#Molecular Pathways

[er-cryptid]

Malate Dehydrogenase 1

Abbreviated MDH1

Oxidizes malate to oxaloacetate

Localized to cytoplasm

Plays a role in malate-aspartate shuttle

Patreon

[meteortrails]

oh fun fact if you’re doing food experiments on flies you can use homogenizers to like. squish them and liquefy them until you have homogenized fly soup. and then you can do pcr on the fly soup to see if they ate the food you tagged with one kind of dna or the other. and if you do qpcr (quantitative pcr, the replication materials you put in there are fluorescent so you can measure the fluorescence of your pcr to see what kinds of DNA had the most starting templates) you can see specifically which food they ate more of. it’s actually really cool and it turns out flies can differentiate between foods with leucine (one specific amino acid out of 20!!!) and foods that don’t, even if the food has ALL THE OTHER AMINO ACIDS. crazy shit bro

[neonnerd17]

Crazy that this is an actual NIH sponsored PubMed article. And that I found it through being sent a meme and trying to Google what the hell a "foidlet" is.

[blueoaknx]

The Connection Between Damaged Mitochondria and Arthritis

Mitochondria are integral organelles responsible for various critical cellular functions, primarily energy production through oxidative phosphorylation. They are involved in maintaining cellular homeostasis, regulating metabolism, modulating calcium levels, and controlling apoptosis. Emerging evidence has highlighted mitochondrial dysfunction as a key contributor to a variety of diseases, including arthritis. This formal overview aims to explore the complex relationship between damaged mitochondria and arthritis, focusing on the molecular mechanisms that link mitochondrial dysfunction to the pathogenesis of inflammatory joint diseases, particularly rheumatoid arthritis (RA) and osteoarthritis (OA).

Mitochondrial Structure and Function

Mitochondria are double-membraned organelles found in eukaryotic cells, and they are crucial for cellular energy metabolism. Their primary role is the production of adenosine triphosphate (ATP) via oxidative phosphorylation, a process that takes place in the inner mitochondrial membrane. During this process, the electron transport chain (ETC) generates a proton gradient across the inner membrane, which drives ATP synthesis through ATP synthase. However, this process also generates reactive oxygen species (ROS) as byproducts, primarily from complexes I and III of the ETC. Under normal physiological conditions, ROS are neutralized by antioxidants, including superoxide dismutase (SOD), catalase, and glutathione. However, under pathological conditions, excessive ROS production can lead to oxidative stress, contributing to cellular damage and dysfunction.

In addition to ATP production, mitochondria have essential roles in calcium buffering, apoptosis regulation, and the maintenance of cellular integrity. Damage to these organelles disrupts these functions, contributing to various diseases, including arthritis.

Mitochondrial Dysfunction in Arthritis

Arthritis is a group of diseases characterized by inflammation and degeneration of the joints. It includes conditions like rheumatoid arthritis (RA), an autoimmune disease, and osteoarthritis (OA), a degenerative disease. In both types of arthritis, mitochondrial dysfunction has been identified as a critical factor that exacerbates disease progression through several mechanisms, including increased oxidative stress, immune activation, and tissue damage.

1. Oxidative Stress and Mitochondrial Damage

Oxidative stress is a hallmark of both RA and OA, and mitochondria are central to its production. In these conditions, mitochondrial dysfunction results in an increase in ROS production, overwhelming the cell’s antioxidant defenses. This oxidative stress leads to the modification of cellular structures, including proteins, lipids, and DNA, causing further mitochondrial damage. In RA, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) stimulate immune cells like macrophages and neutrophils to release large amounts of ROS. These ROS contribute to the local inflammatory environment and accelerate joint destruction by damaging mitochondria and amplifying oxidative stress.

Mitochondrial damage results in a feedback loop where impaired mitochondrial function generates more ROS, further promoting inflammation. For instance, in RA, markers of oxidative damage such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) have been found to correlate with disease activity, suggesting a direct relationship between mitochondrial dysfunction and disease severity.

2. Mitochondrial DNA Damage and Inflammatory Signaling

Mitochondrial DNA (mtDNA) is particularly vulnerable to oxidative damage due to its proximity to the ETC, where ROS are produced during ATP synthesis. Unlike nuclear DNA, mtDNA is not protected by histones and has limited repair mechanisms, making it prone to mutations. Damage to mtDNA impairs mitochondrial function and can lead to the release of mtDNA fragments into the cytoplasm or extracellular space.

In the context of arthritis, mtDNA damage has been implicated in immune activation. When damaged mtDNA is released into the cytoplasm, it is recognized by pattern recognition receptors (PRRs), such as toll-like receptors (TLRs), on immune cells. TLRs, particularly TLR9, activate downstream inflammatory signaling pathways that lead to the production of pro-inflammatory cytokines such as TNF-α and IL-6. This further exacerbates the inflammatory response in joints and contributes to the progression of arthritis. Studies have shown that the presence of mtDNA fragments in the serum of RA patients correlates with disease activity, indicating the role of mtDNA in driving inflammation.

3. Mitochondrial Dynamics and Arthritis Pathogenesis

Mitochondrial dynamics refer to the continuous processes of mitochondrial fission (division) and fusion (joining), which maintain mitochondrial function and integrity. Fission allows for the removal of damaged mitochondria, while fusion helps to integrate mitochondrial contents and maintain a healthy mitochondrial pool. Imbalance between fission and fusion is associated with several diseases, including arthritis.

In the case of RA, excessive mitochondrial fission and reduced fusion have been observed. This imbalance results in mitochondrial fragmentation, which impairs mitochondrial function, increases ROS production, and contributes to cellular stress. Fission is regulated by proteins such as dynamin-related protein 1 (Drp1) and fission 1 protein (Fis1), while fusion is controlled by mitofusins (Mfn1 and Mfn2) and optic atrophy 1 (OPA1). Dysregulation of these proteins in RA leads to a fragmented mitochondrial network, which exacerbates oxidative stress and inflammation in synovial tissues.

4. Mitochondrial-Dependent Cell Death

Mitochondria are also central regulators of programmed cell death, particularly apoptosis. In the pathogenesis of arthritis, excessive or dysregulated apoptosis contributes to joint destruction. Mitochondrial dysfunction plays a critical role in the intrinsic apoptotic pathway by releasing pro-apoptotic factors such as cytochrome c and apoptosis-inducing factor (AIF). These factors activate caspase-dependent and caspase-independent pathways, leading to the death of synovial cells and cartilage cells, which contributes to the progressive tissue damage observed in both RA and OA.

Furthermore, mitochondrial permeability transition pore (mPTP) opening, which is induced by oxidative stress, can lead to necrosis, a form of uncontrolled cell death. Necrotic cell death in the joints increases inflammation and tissue degradation, particularly in OA, where cartilage breakdown is a hallmark feature.

Therapeutic Approaches Targeting Mitochondrial Dysfunction in Arthritis

Given the significant role of mitochondrial dysfunction in the pathogenesis of arthritis, various therapeutic strategies aimed at improving mitochondrial function are under investigation.

1. Mitochondrial Antioxidants

Mitochondrial-targeted antioxidants, such as MitoQ and MitoTEMPO, have been developed to selectively accumulate in mitochondria, where they can neutralize ROS and reduce oxidative stress. These compounds have shown promise in preclinical models of arthritis, where they help to reduce inflammation, protect mitochondrial function, and limit joint damage. The use of mitochondrial antioxidants could be an effective strategy to mitigate oxidative stress in arthritic conditions.

2. Mitochondrial Biogenesis Enhancement

Another potential therapeutic approach is the activation of mitochondrial biogenesis, the process by which new mitochondria are formed to compensate for damaged mitochondria. Agents that activate peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a key regulator of mitochondrial biogenesis, could help restore mitochondrial function in arthritic tissues. Compounds such as resveratrol and NAD+ precursors are under investigation for their ability to promote mitochondrial biogenesis and improve cellular metabolism in arthritis.

3. Mitochondrial Dynamics Modulation

Restoring the balance between mitochondrial fission and fusion is another therapeutic strategy. Inhibiting excessive mitochondrial fission or promoting mitochondrial fusion may help maintain mitochondrial integrity and reduce inflammation in arthritis. Drugs targeting Drp1 or enhancing Mfn1/Mfn2 activity are potential candidates for modulating mitochondrial dynamics in arthritic diseases.

4. Mitophagy Enhancement

Mitophagy, the selective autophagic degradation of damaged mitochondria, is essential for maintaining mitochondrial quality. Enhancing mitophagy through the use of compounds like spermidine or activators of the PINK1/PARK2 pathway could help eliminate dysfunctional mitochondria and reduce inflammation, making it a promising therapeutic approach in arthritis.

Conclusion

Mitochondrial dysfunction plays a critical role in the pathogenesis of arthritis, contributing to oxidative stress, inflammation, and joint damage. The intricate relationship between damaged mitochondria and immune activation highlights the importance of targeting mitochondrial health in the treatment of arthritis. Emerging therapeutic strategies aimed at restoring mitochondrial function, reducing oxidative stress, and modulating mitochondrial dynamics hold promise for improving the management of arthritis and preventing joint destruction. Further research into mitochondrial biology and its role in arthritis is essential for the development of more effective, targeted therapies for these debilitating conditions.

[lifepulse]

Drug resistance in multiple myeloma: When cancer cells say "NO" to treatment

Drug resistance is like a game of cat and mouse. Cancer cells are the cat, and researchers are the mouse. The cat is always trying to find new ways to catch the mouse, but the mouse is always trying to find new ways to avoid getting caught.

Read More

[empyrealoasis]

🪷 Unspoken Facts About the Void State 🍃

1. The Void State and Neuroplasticity

While many people focus on the metaphysical aspects, the void state may have a direct link to neuroplasticity—the brain's ability to rewire itself. The deep focus and detachment from external stimuli in the void can enhance your brain's capacity to form new neural pathways. This means that being in the void isn’t just about manifesting; it’s literally reshaping your mind to align with your desires on a neurological level (and even on a molecular/genetic level).

2. The Void’s Connection to Deep Sleep and Healing

The void state shares similarities with the brain activity observed during non-REM sleep, particularly in stages of deep rest. In this state, your body undergoes repair, and your brain consolidates memories. This suggests that entering the void might accelerate healing processes, as the state mimics the restorative effects of deep sleep while maintaining conscious awareness. Similar to meditation and hypnagogic states.

3. Time Perception in the Void

While in the void, many report losing track of time, but this isn't just a mental trick—it’s tied to how your brain processes sensory input. The void eliminates external stimuli like light, sound, and touch, which are essential for your brain’s internal clock. Without these cues, your sense of time becomes fluid, making hours feel like minutes or vice versa.

4. The Void and Quantum Coherence

The void state aligns intriguingly with concepts in quantum physics, particularly quantum coherence. In quantum systems, coherence describes a state where particles exist in a superposition of possibilities. Similarly, the void state places your mind in a "superposition," where you are simultaneously detached from reality yet capable of accessing infinite possibilities.

5. Entering the Void and Brainwave Frequencies

The void state is strongly associated with theta and delta brainwave states. Theta waves are linked to creativity, intuition, and deep meditation, while delta waves are tied to deep sleep and healing. The unique blend of these brainwaves during the void allows for heightened subconscious access and profound stillness simultaneously. Which is why it is recommended to use these frequencies!

6. Sensory Deprivation and the Void

The void state mirrors the effects of sensory deprivation. When external stimuli are lost, the brain compensates by enhancing internal awareness. This is why many people experience heightened clarity, vivid imagery/mental images, or even sensations of "oneness" while in the void. Essentially, your mind becomes the primary sensory environment and why you lose all of your senses.

7. The Void’s Link to Embryonic Consciousness

Some spiritual theorists compare the void state to the consciousness experienced in the womb. This hypothesis suggests that the void may feel so “pure” because it reflects the state of pre-birth awareness—where one exists in complete with nothingness and infinite potential. This also refers to pure consciousness being your home that you always return to.

8. The Void and Ego Dissolution

A lesser-discussed aspect of the void is its role in ego dissolution. In the void, your sense of self—the “I”—disappears. This detachment from ego allows you to manifest without the usual doubts, fears, or biases that come with personal identity, creating a direct connection between intention and reality. Hence the affirmation "I am" as there's nothing to become, only to "be".

[reasonsforhope]

"A study looking at the bearers of artificial hearts found that a subset of them can regenerate heart muscle tissue—the first time such an observation has ever been made.

It may open the door to new ways to treat and perhaps someday cure heart failure, the deadliest non-communicable disease on Earth. The results were published in the journal Circulation.

A team of physician-scientists at the University of Arizona’s Heart Center in Tucson led a collaboration of international experts to investigate whether heart muscles can regenerate.

According to the Centers for Disease Control and Prevention, heart failure affects nearly 7 million US adults and is responsible for 14% of deaths per year. There is no cure for heart failure, though medications can slow its progression. The only treatment for advanced heart failure, other than a transplant, is a pump replacement through an artificial heart, called a left ventricular assist device, which can help the heart pump blood.

“Skeletal muscle has a significant ability to regenerate after injury. If you’re playing soccer and you tear a muscle, you need to rest it, and it heals,” said Hesham Sadek, director of the University’s Sarver Heart Center.

It was previously thought that when a heart muscle is injured, it could never grow back.

“Irrefutable evidence of heart muscle regeneration has never been shown before in humans,” he said. “This study provided direct evidence.”

The project began with tissue from artificial heart patients provided by colleagues at the University of Utah Health and School of Medicine led by Stavros Drakos, MD, PhD, and a pioneer in left ventricular assist device-mediated recovery.

Teams in Sweden and Germany used their innovative method of carbon dating human heart tissue to track whether these samples contained newly generated cells. The investigators found that patients with artificial hearts regenerated muscle cells at more than six times the rate of healthy hearts.

“This is the strongest evidence we have, so far, that human heart muscle cells can actually regenerate, which really is exciting, because it solidifies the notion that there is an intrinsic capacity of the human heart to regenerate,” Sadek said.

“It also strongly supports the hypothesis that the inability of the heart muscle to ‘rest’ is a major driver of the heart’s lost ability to regenerate shortly after birth. It may be possible to target the molecular pathways involved in cell division to enhance the heart’s ability to regenerate.”

In 2011, Sadek published a paper in Science showing that while heart muscle cells actively divide in utero, they stop dividing shortly after birth to devote their energy to pumping blood through the body nonstop, with no time for breaks.

In 2014, he published evidence of cell division in patients with artificial hearts, hinting that their heart muscle cells might have been regenerating because they were able to rest.

These findings, combined with other research teams’ observations that some artificial heart patients could have their devices removed after experiencing a reversal of symptoms, led him to wonder if the artificial heart provides cardiac muscles the equivalent of bed rest like a person needs when recovering from injury.

“The pump pushes blood into the aorta, bypassing the heart,” he said. “The heart is essentially resting.”

Sadek’s previous studies indicated that this rest might be beneficial for the heart muscle cells, but he needed to design an experiment to determine whether patients with artificial hearts were actually regenerating muscles.

Next, Sadek wants to figure out why only about 25% of patients are “responders” to artificial hearts, meaning that their cardiac muscle regenerates.

“It’s not clear why some patients respond and some don’t, but it’s very clear that the ones who respond have the ability to regenerate heart muscle,” he said. “The exciting part now is to determine how we can make everyone a responder, because if you can, you can essentially cure heart failure.

“The beauty of this is that a mechanical heart is not a therapy we hope to deliver to our patients in the future—these devices are tried and true, and we’ve been using them for years.”"

-via Good News Network, December 31, 2024

[the-winter-spider]

Waiting Room | 3/3

Bucky x avenger!Reader

Word Count: 6.3k

Warnings: Angst......

A/N: Yall i really had no idea where i was gonna take this lol lets remember this was suppose to be a one shot turn into a 3 part mini series lol 😂 not sure if i like this but its whats happening so lmao

Part One

Part Two

----

The med bay was suffocating, a stark, sterile room that felt more like a cage than a place of healing. The white walls reflected the harsh fluorescent lights, the steady hum of machinery filling the space with an oppressive monotony. The faint beeping of monitors, the quiet whir of fans in the equipment, and the faint antiseptic smell in the air were all reminders of where you were—trapped, restrained, and utterly disconnected from the life you once knew.

You laid rigid in the medical bed, your wrists bound by thick restraints bolted to the frame. The straps were reinforced—designed for beings far more powerful than the average soldier. They had to be, for super-soldiers, gods, and now, you. You stared blankly at the far wall, your expression as hollow as your gaze.

Tony and Bruce hovered near their workstations, their faces illuminated by the glow of holograms and screens streaming endless data. They barely spoke, their silence a testament to the weight of what they were trying to undo. Each test they ran came back with the same damning conclusion: the serum coursing through your veins wasn’t just making you stronger, faster, more dangerous. It was chaining you—body and mind—to commands that had been burned into your neural pathways. The serum wasn’t just invasive; it had fused with the super-soldier formula already in your system, weaving itself into the very fabric of who you were.

Bruce leaned back in his chair, rubbing his temples as if trying to massage away the weight of what he was reading. His voice, usually measured, wavered slightly. “This isn’t just physical,” he muttered, glancing at Tony. “It’s neurological. It’s rewriting her instincts, suppressing her emotions… amplifying aggression.”

Tony, who usually filled even the heaviest moments with quips or sarcasm, was silent. His fingers moved rapidly across the keyboard, his brows furrowed in concentration. “Yeah, I see it,” he said finally, his tone clipped and uncharacteristically somber. “This isn’t some dollar-store brainwashing. Whoever did this knew what they were doing. They’re rewriting her at the molecular level. I’ve seen a lot of tech—nothing like this.”

Behind the reinforced glass separating the med bay from the observation room, Bucky sat slumped in a chair. His broad shoulders were hunched, his head bowed slightly, and his metal hand gripped the edge of the seat so tightly the frame creaked. The Bucky they knew was a composed soldier, a man who could compartmentalize his pain and push forward. But now, his mask was gone, his expression stripped down to raw guilt and desperation.

He watched you intently, his eyes never leaving your face. Your blank expression, your lifeless stare—it tore at him, unraveling what little hope he had left. He leaned forward, pressing his elbows to his knees, his voice soft and trembling.

“Sweetheart,” he murmured, his tone cracking with exhaustion. “Please. I know you’re still in there. You’ve gotta fight this. Fight for me… for us.”

His words hung in the air, heavy with longing and heartbreak.

You didn’t react. Not a blink, not a twitch. You were as still as a statue, your chest rising and falling in a mechanical rhythm dictated by the serum coursing through your veins. The vibrant light that once danced in your eyes was gone, replaced by a cold, unfeeling void.

Occasionally, you tilted your head, a small, calculated motion that seemed more analytical than human. It was as if you were studying him, assessing him as an object rather than a person—an obstacle rather than someone who loves you.

The silence between you was deafening, and it crushed Bucky like a vice.

He leaned back, exhaling shakily, running a trembling hand through his hair. His voice dropped to a whisper, as if speaking directly to the version of you he desperately hoped was still buried beneath the serum’s control. “I’m not giving up on you,” he said, though the cracks in his voice betrayed his struggle to believe his own words.

On the other side of the glass, Bruce and Tony exchanged a brief glance. Neither of them said it aloud, but the reality hung between them like a dark cloud: time was running out, and you were slipping further away.

-----

The common room felt as heavy as the med bay, the air thick with unspoken fears and fraying hope. The faint hum of the base’s systems was the only sound until Natasha’s calm, cutting words pierced through the oppressive silence.

“She’s not coming back on her own,” she said again, as if repeating it would make it easier for the others to accept. Her arms were still tightly crossed over her chest, her expression as unreadable as ever, but the way her shoulders were set betrayed her inner turmoil.

Steve stopped pacing and turned toward her, his frown deepening. “Don’t say that,” he said, his voice low but firm, like he could will her to take the words back.

Natasha’s eyes flicked to him, unwavering. “I’m being realistic,” she replied, her tone matter-of-fact but softer now. “You think I want this? Shes my sister! But every day, that serum, whatever it is, digs deeper. You can’t just power through something like this with good intentions. I’ve seen situations like this before, Steve. They don’t end how you want them to.”

Sam shifted forward in his seat, resting his elbows on his knees. “She hesitated at the warehouse,” he said, his voice quieter, almost hesitant. “That means something, doesn’t it? She’s still in there. She’s fighting.”

“Yeah, and that hesitation nearly got us all killed,” Clint snapped, dragging a hand over his face. The frustration in his voice was barely masking the underlying fear. “What happens when she doesn’t hesitate next time? Because there will be a next time.”

Steve’s jaw tightened, and he clenched his fists at his sides. “We’re not giving up on her,” he said with finality, his voice brooking no argument.

Natasha’s sharp gaze softened as she glanced toward the med bay. For a moment, her mask slipped, and a flicker of pain crossed her face. “It’s not about giving up,” she said softly. “It’s about preparing for the possibility… that she isn’t the person we remember anymore and that maybe there is no way to get her back…”

The words lingered in the air, heavy and unrelenting. No one moved.

Then Bucky’s voice cut through the tension like a blade, sharp and trembling. “She’s not gone.”

The team turned as one to see him standing in the doorway, his broad frame silhouetted against the light from the hall. His face was raw, his eyes red-rimmed but blazing with a fierce determination that silenced any response they might have had.

“She’s not gone,” he repeated, stepping into the room. The words were firmer this time, carrying a weight that dared anyone to contradict him. He stopped near the center of the room, his metal hand flexing unconsciously as he looked at each of them in turn.

“And I’m not giving up on her, you shouldn't either” he added, his voice steady but filled with a quiet, devastating pain.

Steve stepped closer, his expression softening as he studied his oldest friend. “Buck—”

Bucky cut him off, his voice rising slightly. “I’m not giving up, Steve. I don’t care how deep that serum’s buried. I don’t care how long it takes. I know her! She’s in there, she’s still in there.” His voice cracked, but he didn’t flinch. “I know she is....”

Natasha pushed off the wall, her arms uncrossing. She held his gaze, her expression unreadable again, but her voice was gentle. “What if she’s not?”

Bucky’s jaw tightened, and for a moment, it seemed like he wouldn’t respond. Then he took a step closer, his voice low but unwavering. “Then we fight until there’s nothing left to fight for. But I’m not stopping... ot until she tells me herself that she’s gone.”

The room fell into silence again, but it wasn’t the same suffocating quiet as before. This silence was heavy, yes, but it carried the weight of something more than grief—it carried resolve.

Steve finally nodded, his voice steady but quiet. “Then we fight.”

Sam looked at Clint, who sighed heavily but gave a small nod. Natasha’s gaze lingered on Bucky for a moment longer before she turned away, her agreement unspoken but clear.

Bucky didn’t thank them, didn’t acknowledge their support. Instead, he turned on his heel and walked back toward the med bay. He didn’t have time for discussions or strategies. He had already made his decision.

As the door slid shut behind him, the others exchanged glances. “He’s not going to let her go,” Sam said quietly.

Steve crossed his arms, his brow furrowed. “Would you?”

Sam didn’t answer. Neither did Clint or Natasha. Because the truth was, none of them would, none of them wanted to.

--------

The lab had become a battlefield of hope and despair. The glowing holograms floating above the table displayed the intricate web of changes the serum had wrought on your body—twisted neurons, altered muscle fibers, and corrupted synaptic pathways that mapped out the story of how the fixer had transformed you into a weapon.

Bruce’s fingers hovered over the holographic display, tracing a complex string of data. His voice was quiet, almost reluctant. “This serum… it’s not just controlling her. It’s fused into everything she is. It’s rewriting her body, her mind. Every instinct, every reaction—it’s all amplified, all his..”

“It’s not just control,” Tony added, his voice devoid of its usual bravado. His face was drawn, his sharp features softened by exhaustion. “It’s enhancement. She’s stronger, faster—more dangerous than any of us combined. And the way it’s fused with the super-soldier serum…” He hesitated, rubbing the back of his neck. “There’s no way to separate them without…”

“Without killing her,” Bruce finished, the words falling like a hammer. He avoided meeting anyone’s gaze.

The room was silent except for the faint hum of machinery. Bucky stood at the edge of the group, his arms crossed tightly, his jaw clenched so hard it was a wonder it didn’t snap.

“Then we don’t separate it,” he said, stepping closer, his voice low and deliberate. “We find another way.”

Tony exhaled sharply, his arms spreading in frustration. “Another way? Bucky, we’re talking about molecular-level integration. This isn’t a wound we can stitch up or a wire we can snip. If we don’t stop her, she’s going to take us all out. That’s not an if—it’s a when.”

Bucky’s eyes locked onto Tony’s, cold and unyielding. “We’re not stopping her, we’re saving her!"

Tony’s gaze didn’t waver, but his voice softened. “And what if there’s no saving her? What if the only thing we can do is stop her before she does something none of us can undo?”

"There's always a choice!" Bucky shouted, his voice raw. "You're supposed to be the smartest guy in the room, Tony. Act like it."

Tony's jaw tightened, but he didn't reply.

The weight of the question hung in the air, heavy and suffocating.

“It not an option,” Bucky said firmly, his tone leaving no room for argument.

Natasha leaned against the table, her voice cutting through the rising tension. “It might have to be.”

Bucky turned to her, his eyes blazing. “You don’t mean that..”

Her expression was calm, but her eyes held a trace of sorrow. “I hope I don’t. But if it comes down to her or everyone else—”

“It won’t!” Bucky snapped, his voice shaking with barely controlled emotion. His fists tightened at his sides, and he took a step forward, his frustration spilling out in a torrent. “Why does it sound like you don’t care? Why do none of you seem to care? It’s Y/N we’re talking about!”

Natasha flinched slightly, but he didn’t stop. His voice rose, trembling with desperation. “The one who knits us matching scarves every Christmas! Who puts Avengers-themed band-aids in all the med kits because she thinks it’ll make us feel better! The one who sings those stupid pop songs on the comms even though they drive you all crazy! The one I love!” His voice cracked, and he exhaled sharply, looking around at the others as if daring them to argue.

“And you’re all just ready to toss her away like she’s nothing,” he continued, his voice breaking. “Like she hasn’t been the glue holding us together. Like she hasn’t saved every one of us a dozen times over!”

No one interrupted. The room was silent except for Bucky’s heavy breathing, his eyes glistening with unshed tears.

“This is my fault,” he said finally, his tone dropping to a whisper. “I pushed her away. I told her....." He trailed off "I thought i was saving her, all I did was drive her straight into the arms of someone who turned her into this. I wasn’t there when she needed me, and now…” His voice cracked again, and he shook his head. “This can’t be how her story ends. This isn’t how our story ends.”

Steve stepped forward cautiously, his voice gentle. “Buck… no one here wants to give up on her. We’re just—”

“No,” Bucky interrupted, his voice rising again. “You don’t get to say that. You’re all standing here talking about stopping her like she’s already gone. But she’s not. I’ve seen her fight…. I know she’s still in there.” He turned back to the holograms, his voice trembling but resolute. “And I’m not going to let her go...I can't”

Steve sighed, his shoulders sagging as he glanced at Natasha and then back to Bucky. “We’ll keep looking. But, Bucky… we’re running out of time....She's running out of time."

That night, Bucky sat in the med bay, staring at the empty bed where you had been just days ago. The sterile light seemed colder, harsher, and the hum of the machines now felt like a mockery of the life you had once filled with warmth.

He sank into the chair beside you, resting his elbows on his knees and running a hand over his face. “I told them,” he murmured after a long moment, his voice raw. “I told them we’re bringing you home. They don’t believe it, not really. But I do. Because I have to. Because if I don’t…”

He trailed off, his throat tightening.

“I told you it was for the better, and it wasn’t,” he continued, his voice trembling. “It was the worst thing I ever did. You deserved better than me pushing you away because I was scared….. And I’m not going to let that mistake be the last thing I ever do for you.”

His metal hand reached out, gently brushing against your wrist. “I’ll fix this. I don’t know how, but I will. I just need you to hang on a little longer, doll. Just a little longer, please."

And so he stayed, watching you in the dim light, his quiet determination the only thing keeping the weight of his guilt at bay.

---

The quiet hum of the med bay filled your ears, the sound of the monitors beeping in rhythm with your heartbeat. You weren’t entirely sure where the sound ended and the signal in your head began. It was constant now—a low, thrumming pulse that vibrated through your skull, tugging at your thoughts, distorting them, and twisting them into something unrecognizable.

You weren’t sure how long you’d been strapped to the bed, the restraints tight against your wrists and ankles. The team—your team???—had been coming in and out for days, speaking to you, pleading with you. You couldn’t remember all the words anymore. They sounded muffled, as though underwater. But one voice pierced through the fog: his.

The fixer’s signal was clear, sharp, and undeniable.

“Come to me. Complete the mission.”

It was like a hook embedded deep in your mind, pulling you with a force you couldn’t resist. You knew where to go. You knew what you had to do. The mission was clear. And yet…

A part of you—small, fragile, buried deep beneath the layers of control—was screaming.

“Don’t go. Don’t leave. Stay.”

You felt it every time Bucky spoke to you, his voice trembling with emotion as he begged you to fight. You felt it when Natasha stood silently by the glass, her arms crossed tightly, the mask of calm slipping just enough to show the hurt in her eyes. It was there in Steve’s steady, quiet resolve as he promised they would bring you back.

You wanted to stay.

But the voice grew louder, overpowering that small, desperate part of you. It wrapped around your thoughts like chains, drowning out everything else. The fixer’s voice wasn’t just in your head anymore—it was in your body, controlling every instinct, every movement.

“They’ll never understand you like I do. You’re meant for more than this. You don’t belong here. Come to me.”

The restraints on the bed groaned as you shifted against them, the serum-enhanced strength coursing through you making the reinforced bindings strain under the pressure. The voice was relentless, urging you forward, telling you that escape was the only answer.

“You need to leave. Now.”

The hum of the med bay sharpened into a buzzing, a dissonance that pressed against your skull like a knife. The monitors flickered faintly, your vitals spiking as the signal reached its crescendo. And then, something inside you snapped.

You didn’t remember breaking free, not really. One moment you were bound, and the next you were standing, the restraints dangling from the bed, bent and broken. The world tilted as you moved—too fast, too quiet, too precise.

“Get out. Go.”

Your body moved on autopilot, fluid and silent as you slipped into the darkened corridors of the compound. The alarms hadn’t started yet. You had time. You knew their rotations, their blind spots. You’d trained with them long enough to anticipate every move, to know exactly where to go.

But with every step, a tiny voice in the back of your mind whispered: Stay.

You passed the common room first, your shadow blending into the dim light spilling out from the slightly open door. Inside, Clint was slumped on the couch, his head tilted back as he stared at the ceiling. Sam sat beside him, his elbows resting on his knees, his gaze distant.

They didn’t see you.

The signal tugged at you again, stronger this time. “Keep going.”

The hallway stretched before you like a tunnel, the exit growing closer with every step. You could feel the pull of freedom, the fixer’s voice growing clearer with every breath.

“They can’t stop you. You’re faster. Stronger. This is what you were meant for.”

But the deeper you moved into the compound, the louder that small, fragile part of yourself became.

“Don’t go. Turn back. You’re one of them. You’re loved.”

The faintest image of Bucky’s face flashed in your mind—his wide, desperate eyes, his trembling voice as he whispered your name like a prayer. You hesitated, your steps faltering for the briefest moment.

But the signal roared back, violent and overwhelming. It drowned out everything else, silencing the tiny part of you that had dared to hope.

You pushed forward.

The armory was your next stop. The door slid open silently, the familiar scent of oil and metal hitting you as you scanned the rows of weapons. You moved with efficiency, your hands grabbing what you needed—a knife, a sidearm, extra ammunition. Everything was automatic, every action mechanical.

The compound was chaos incarnate. The blaring alarms drilled into the team’s ears, the red emergency lights casting jagged shadows that made the corridors feel narrower, more oppressive. Every step echoed with urgency as the Avengers scrambled to find you, to contain you before the situation spiraled further out of control.

You were a ghost, slipping through their defenses with inhuman speed and precision. The enhancements from the serum made your movements impossibly fluid, calculated, and lethal. Every strike you delivered, every dodge you made, was the product of something no longer entirely human.

Bucky was the first to corner you in the armory. His breaths came in ragged bursts as he blocked the exit, his metal arm raised defensively. The flickering lights above cast a faint, uneven glow on his face, emphasizing the desperation in his expression.

“Doll,” he said, his voice steady despite the tremor in his chest. “You don’t have to do this.”

You stood across from him, a silent shadow. Your head tilted slightly, studying him as though he were a puzzle to solve. The cold detachment in your eyes felt like a dagger to his heart.

“Come back with me,” he pleaded, stepping forward cautiously. “We can fix this. I promise we can fix this.”

For a fleeting moment, something in your posture faltered. A twitch of your fingers, a shift in your expression—it was subtle, but enough to make his breath catch. He clung to the flicker of hope as though it could tether you back to him.

But then, as quickly as it came, the flicker disappeared.

You moved first.

Without a word, you lunged at him, your speed a blur.

Bucky barely dodged the first strike, the wind from your punch grazing his face. The second came faster, and his metal arm caught it with a sharp clang. His feet slid back from the force, his boots screeching against the floor.

“Y/N!” he shouted, his voice rising in desperation as you struck again, your attacks relentless. “Stop! This isn’t you!”

His words didn’t reach you.

He didn’t fight back—not really. Every movement was defensive, an attempt to slow you down without hurting you. But you were faster now, stronger. When he grabbed your wrist to stop a blow, you twisted effortlessly, breaking free and delivering a brutal kick to his chest.

The force sent him flying into the wall, the impact knocking the air from his lungs. He crumpled to the floor, gasping, as you turned and disappeared into the shadows of the corridor.

By the time Natasha and Clint arrived moments later, weapons at the ready, you were already gone.

------

The next three weeks stretched like an eternity.

The team threw themselves into the work, pouring over the fixer’s files with a level of intensity that bordered on desperation. Holograms of molecular structures and fragments of decrypted codes hung in the air like ghosts, flickering reminders of how little they’d managed to piece together. Every breakthrough was fleeting, every promising lead dissolved into another dead end.

Bucky barely spoke. He spent most of his time in the gym, taking out his frustration on punching bags or lifting until his muscles screamed for relief. When he wasn’t there, he was in the lab or the common room, lingering just within earshot of the discussions about you. He rarely contributed, but his presence alone was enough to remind the others of what was at stake.

Tony paced back and forth, his hands gesturing sharply as he stared at yet another set of encrypted data on the floating holograms before him. His bloodshot eyes betrayed sleepless nights, his movements jittery from too much caffeine and not enough rest.

“We’re out of time,” he muttered, breaking the heavy silence. The strain was evident in every word, every line of his face.

Steve, standing nearby with his arms crossed, looked up sharply. “What are you saying?”

Tony stopped pacing and turned to the group, his expression grim. “She’s gone after him—the fixer, whatever he calls himself. He’s still alive. And you don’t need me to tell you what that means.”

Sam frowned. “That it’s a trap?”

Tony nodded, his voice clipped. “It’s a trap. He’s counting on us coming after her. But we don’t have a choice.”

“We’ve been chasing shadows for weeks,” Clint said, leaning forward in his chair. “And now, out of nowhere, we have a location? This smells bad.”

Steve’s gaze darkened. “If it’s a trap, we spring it. We’ve dealt with worse before.”

Tony let out a humorless laugh. “Yeah? Worse? This isn’t just some ambush, Cap. That stuff pumping through her—it’s not taking a break. Every second we wait, it’s digging deeper. Taking over every cell, every fiber, everything that makes her her….But if we wait any longer…”

“She’ll be gone,” Natasha said quietly, cutting in. Her voice was calm, but her words carried a sharp edge that made the others glance at her.

The silence that followed was suffocating, broken only by the faint hum of the holograms around them.

Bucky, who had been sitting rigidly in a chair across the room, suddenly shifted. His metal hand gripped the edge of the seat so tightly it creaked.

“She’s not gone,” he said, his voice low and steady, though it trembled faintly at the edges.

Tony hesitated, looking at him. “Bucky—”

“No,” Bucky interrupted, his gaze fixed firmly on the floor. “You don’t get to say that. You don’t get to stand here and talk about her like she’s already dead. She’s not.”

Steve stepped closer, his voice softer now. “We’re not giving up on her. You know that, Buck.”

“Do I?” Bucky snapped, finally looking up. His eyes were bloodshot and glassy, his expression raw. “Because all I’ve been hearing for the past three weeks is what happens if we can’t save her…What happens if she’s too far gone. You’re all ready to bury her, but I’m not. I can’t, I won’t”

Natasha’s voice was quiet but firm. “Bucky, this isn’t about giving up. It’s about being realistic.”

Steve frowned, his tone hardening. “You’re saying we just let her go?”

Natasha’s gaze shifted to him, and her voice softened slightly. “I’m saying we can’t afford to keep chasing her if it means risking everyone else. She’s either going to come back to us, or we’re going to have to stop her. For good.”

The words sent a chill through the room, the weight of their meaning settling heavily over the team.

“None of us want to lose her,” Natasha said, stepping forward. Her voice softened slightly, though her expression remained hard. “But if this is a trap, we have to be ready for what we might find.”

Bucky stood abruptly, his chair screeching against the floor. “What we’ll find is her,” he said, his voice breaking slightly. “And we’re bringing her home. I don’t care what it takes.”

Steve placed a hand on his shoulder, but Bucky shrugged it off, his jaw clenched. “I’m suiting up,” he said flatly. “We’re wasting time.”

-----

The quinjet was a tense, quiet place as it cut through the night sky.

Steve sat in the cockpit, his hands gripping the controls tightly. Sam was strapped in beside him, his gaze fixed on the horizon, his wings folded neatly against his back. Clint and Natasha checked their gear in silence, their movements brisk and mechanical.

Bucky sat alone near the back, staring down at his gloved hands. His foot tapped against the floor, a restless rhythm that matched the pounding in his chest.

“We’ll find her,” Steve said quietly, glancing back.

Bucky didn’t respond.

Natasha looked up from her weapons. “You need to get your head on straight, Barnes. If you lose control out there—”

“I won’t,” Bucky said firmly, cutting her off. He lifted his gaze, his expression hard. “She’s all I’ve got left. I won’t lose her.”

The rest of the ride passed in silence, the team bracing themselves for whatever lay ahead.

When the quinjet touched down, the facility loomed before them like a fortress of steel and concrete. Its towering walls were lined with searchlights, and armed guards patrolled the perimeter in tight formations. The stormy sky above rumbled ominously, lightning flashing in the distance.

“It’s a fortress,” Sam said, his voice low as he peered through the cockpit window.

“It’s a trap,” Natasha said, her tone dry.

“And we’re walking straight into it,” Steve said, standing and grabbing his shield. “Let’s move.”

The team exited the quinjet in silence, their movements practiced and efficient. Bucky fell into step behind Steve, his metal arm flexing as he scanned the facility ahead.

Every fiber of his being screamed that this was wrong, that the odds were stacked too heavily against them. But he couldn’t afford to think about that.

All he could think about was you.

This was it. One way or another, it would end tonight.

The cavernous room was bathed in harsh fluorescent light, a cold and unfeeling illumination that seemed to leech the warmth from everything it touched. The fixer stood at the center, his posture relaxed, his confidence unshaken as the team burst through the double doors, their weapons raised and their eyes scanning the space.

And there you were.

You stood at his side, motionless, your face devoid of emotion. The cold detachment in your eyes sent a chill through the team, freezing them in their tracks. You weren’t holding a weapon yet, but the tension in your posture was enough to set everyone on edge. You looked through them, not at them, as though they weren’t people, just obstacles in the way of your programming.

“Well, well,” the fixer drawled, his voice smooth and mocking as he clasped his hands behind his back. “Took you long enough.”

“Let her go,” Steve barked, his shield raised defensively as he stepped forward. His voice was firm, but there was an edge of desperation in it. “Now.”

The fixer smirked, shaking his head. “Oh, Captain. You’re still under the delusion that this is your game to win.” He gestured toward you, his eyes gleaming with triumph. “She’s not yours anymore. She’s not even hers anymore. She’s mine.”

Bucky’s voice broke through, raw and trembling. “Y/N!” he called out, taking a step toward you despite the warning glance Steve shot him. “You don’t have to do this! Fight it!”

For the briefest moment, your head tilted slightly, your gaze flicking toward him. There was a flicker, something deep in your eyes that might have been recognition.

Then it was gone.

The fixer chuckled, pulling a small remote from his pocket. “Touching. Really, it is. But you’re too late. This is her final mission, it's a great one really, I think you'll all love it: either end the Avengers… or end herself..."

"Or you all die trying." He pressed the button.

A loud beep echoed through the room, followed by a harsh metallic clanking as a digital timer lit up on the far wall. It glowed blood-red, counting down from five minutes.

The fixer gave them a mock salute, his grin widening. “Have fun.”

Before anyone could stop him, he disappeared through a side door.

“Clint, go after him!” Natasha barked, her voice sharp and commanding.

“On it!” Clint was already moving, his bow raised as he sprinted toward the exit.

“Y/N, don’t do this!” Steve shouted, stepping forward with his shield raised. “You don’t have to listen to him!”

But the signal had already taken hold.

Your hand reached for the nearest weapon—a sleek pistol holstered at your side. In one fluid motion, you raised it and fired, the bullet ricocheting off Steve’s shield with a deafening clang.

“Y/N, stop!” Bucky yelled, his voice filled with desperation as he moved to block Natasha. “You don’t want this!”

You didn’t respond. Your movements were sharp, calculated, as though choreographed. You fired again, this time aiming for Tony’s chest. He raised his gauntlet just in time, the repulsor absorbing the bullet.

“She’s not holding back!” Tony shouted, his voice clipped as he dodged another shot.

Steve advanced, his shield up, but his movements were measured, almost hesitant. “Y/N, listen to me! You’re stronger than this—stronger than him!”

You turned on him, your pistol empty now, and dropped it without hesitation. Your hand reached for a knife at your belt as you lunged, the blade flashing in the harsh light.

Steve caught the strike with his shield, but the force of it drove him back a step. “Natasha, help me!”

Natasha moved in from the side, her movements swift and deliberate. She aimed for disarmament, her focus on neutralizing you without causing harm. But every move she made, you countered with ruthless precision, forcing her onto the defensive.

“Damn it, Y/N, fight this!” Natasha snapped, gritting her teeth as she narrowly dodged a high kick.

Meanwhile, Tony and Sam had turned their attention to the timer on the wall.

“Five minutes, huh?” Sam muttered as he landed beside Tony, his wings retracting.

“Four and counting,” Tony corrected, his HUD scanning the device. “And this thing is a beast. Give me a second to figure out how to disarm it.”

“You’ve got three,” Sam quipped, his eyes darting back to the chaos behind them.

Bucky wasn’t fighting. He couldn’t. His metal arm raised instinctively to deflect a stray knife you hurled in his direction, but his voice was soft, pleading.

“Sweetheart, please,” he said, his feet planted firmly between you and Tony. “This isn’t you. I know you’re still in there. You don’t have to do this.”

Your eyes met his briefly, but they were cold, unrecognizable. You moved toward him, your strikes quick and unrelenting, but he didn’t fight back. Instead, he blocked and dodged, his every movement defensive.

“I’m not giving up on you,” he said, his voice cracking. “You hear me? I’m not.”

“Bucky, move!” Natasha shouted, intercepting you with a spinning kick that sent you stumbling back.

You recovered instantly, your hand moving to the explosives strapped to your belt. You hurled one at the team, the small device landing near Steve’s feet.

“Get down!” Steve bellowed, throwing himself over the explosive as it detonated with a deafening boom. Smoke filled the air, momentarily disorienting everyone.

“Two minutes left!” Tony called out, sweat dripping down his face as he worked furiously on the timer. “Sam, hold this!”

Sam took over the wiring Tony handed him, his brow furrowing in concentration. “You sure this won’t blow us all to hell?”

“Not if you don’t mess it up!” Tony snapped, his fingers flying across his gauntlet’s interface.

Natasha and Steve regrouped, their eyes scanning the smoke-filled room for you.

“She’s moving fast,” Natasha said, her voice low as she raised her batons. “Too fast.”

“Nat, on your left!” Steve shouted as you emerged from the haze, a blade in each hand.

Natasha intercepted your strikes with her batons, the crackle of electricity filling the air as she deflected your blows. “Y/N, snap out of it!”

But you didn’t.

Bucky moved closer, his voice cutting through the chaos. “Doll, look at me. It’s me—Bucky. Remember? You know me. You love me, I love you."

Your hands faltered, the knives trembling in your grip. For a moment, the haze in your eyes seemed to clear, and you froze.

“Thirty seconds!” Tony shouted, his voice panicked.

“Y/N,” Bucky whispered, stepping closer, his hands raised. “Come back to me.”

But the signal surged, stronger than ever, and the haze returned. Your grip tightened on the knives as the timer ticked down.

“Twenty seconds!”

“Tony!” Sam shouted.

“I’m on it!” Tony barked.

The final seconds felt like an eternity as the room erupted into chaos once more.

The room was chaos, the countdown timer on the wall casting its blood-red glow over the flickering lights and the frantic movement of the team. The fight raged on around it—blades clashing, bullets ricocheting, and desperate pleas falling on deaf ears.

Bucky blocked another of your strikes, his metal arm catching the blade with a metallic clang. His face was streaked with sweat and dirt, his eyes glassy with unshed tears as he shouted your name again. “Baby, stop! Please, just stop!”

You didn’t respond. Your strikes came fast, precise, unrelenting. It was clear the signal had fully taken hold, driving you like a machine. The fixer’s voice, now silent in the room, still echoed in your mind. “Complete the mission.”

Natasha ducked under one of your swings, slamming her electrified baton against your side, but you twisted out of the way with unnatural speed. Steve joined her, his shield raised, deflecting an incoming strike meant for Natasha.

“We’re running out of time!” Steve called over the din. “Tony, what’s the status on that bomb?”

“Ten seconds!” Tony yelled, his voice tight as his hands flew over the exposed circuitry. “If I screw this up, we’re all toast!”

“You won’t screw it up!” Sam barked from above, sweat dripping from his brow as he hovered near Tony, ready to assist.

“Friday, guide me,” Tony snapped, his voice frantic. The seconds ticked down—nine, eight, seven—and then suddenly the timer went dark.

Tony exhaled sharply, leaning back against the wall. “We’re clear. The bomb’s deactivated.”

Relief washed over the team for a brief moment—but only a moment. You were still fighting, your movements relentless and mechanical. There was no victory here, only desperation.

“Doll, please!” Bucky shouted again, catching your wrist as you lunged at Natasha. His voice cracked, trembling with emotion. “I know you’re in there! Come back to me!” He begged

His words made you falter—just for a moment. Your body stilled, your breathing hitching as you stared at him. Something deep within you flickered, a small light in the overwhelming darkness.

“Doll, it’s me,” he said softly, his voice trembling as he took a cautious step closer. “Remember that time in D.C.? You dragged me out to that diner at two in the morning because you had to try their blueberry pie?” His lips quirked in a small, broken smile. “And then you made me order pancakes just so you could steal them?”

The knife in your hand trembled. Your head tilted slightly, your lips parting as if to respond.

“You told me I made you feel safe,” Bucky continued, his voice barely above a whisper now. “You made me feel safe. Doll, you don’t have to fight anymore. You don’t have to do this. Just come back to me.”

For a moment, everything was still. The haze in your eyes cleared, replaced by something fragile and human. You dropped the knife, and it clattered to the floor.

“Bucky…” you whispered, your voice cracking.

His heart leapt as he stepped closer, reaching out to you. “That’s it,” he murmured, his voice thick with hope. “I’m here. I’ve got you.”

But then the darkness surged again. The fixer’s programming tightened its grip, dragging you back into its depths. Your body stiffened, your breath quickening as the command blared in your head: “Complete the mission.”

“No, no, no!” you gasped, your hands trembling. Your gaze darted wildly, panic etched across your face as you reached for something on your suit. Your fingers closed around a small syringe strapped to your chest.

Natasha’s eyes widened in horror. “She’s got cyanotoxin,” she said sharply, her voice cutting through the tension like a blade. “Y/N, put it down!”

The room froze.

You held the syringe to your neck, your hands shaking violently as tears streamed down your face. “I can feel it,” you said, your voice barely audible. “It’s in me. It’s all I can hear. I can’t stop it, Bucky. I can’t—I can’t!”

“You don’t have to do this!” Bucky’s voice was raw, his steps slow and deliberate as he approached. “We can figure this out! Just put it down, baby please!

Your tear-filled eyes met his, and for a moment, the pain in them was unbearable. “I love you,” you whispered, your voice breaking. ���I love you. I love you. I love you.”

“Y/N, stop!” Bucky screamed, his hand reaching for you. “Don’t do this! Stay with me—stay with me!”

“I’m sorry,” you choked out, your voice trembling. “It’s for the better.”

And then, before anyone could stop you, you plunged the syringe into your neck.

“NO!” Bucky roared, his voice echoing through the chamber.

The syringe fell from your hand as your legs gave out beneath you. You crumpled to the floor, your body already limp and lifeless.

Bucky was at your side in an instant, his arms wrapping around you as he cradled your body against his chest. “No, no, no,” he whispered, his voice shaking. “You’re okay. You’re gonna be okay.”

Tony rushed over, his gauntlet lighting up as he scanned for vitals. “Friday, give me a reading!”

A pause. Then: “No vitals detected,” Friday said quietly.

The words hit Bucky like a hammer. His breath caught, and then a gut-wrenching sob tore from his chest. He held you tighter, his tears falling freely as he rocked back and forth.

“How can any of this be for the better?” he whispered, his voice breaking. “How?”

The team stood frozen, their faces etched with grief as Bucky’s cries filled the room. The weight of your loss settled over them, heavy and suffocating.

For Bucky, the world had stopped. All he could see was you—your lifeless body in his arms, and the memory of your final words echoing in his mind:

“It’s for the better.”

[covid-safer-hotties]

Also preserved in our archive (Daily updates!)

Unlocking the secrets behind immune exhaustion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients is at the center of new Griffith University research.

The study, published Oct. 22 in JCI Insights, investigated immune exhaustion at the molecular level, and offers a crucial step forward in understanding the overlap and differences between ME/CFS and long COVID.

Lead author and Research Fellow at Griffith's National Center for Neuroimmunology and Emerging Diseases (NCNED), Dr. Natalie Eaton-Fitch said the term "immune exhaustion" is new in the area of ME/CFS.

"Our research highlights the importance of investigating different immune pathways to better understand these complex conditions," Dr. Eaton-Fitch said.

"Research is ongoing into overlapping and distinct mechanisms at play for ME/CFS and long COVID.

"While we identified commonalities between the two diseases, there are also distinct immune mechanisms potentially at play which may be indicative of the differences in duration of illness and potential insights into early disease progression."

The study is the first to concurrently analyze immune gene expression in both ME/CFS and long COVID patients, emphasizing the intricate role of immune exhaustion in disease progression for both conditions.

ME/CFS and long COVID are increasingly recognized as serious multisystemic conditions that severely impact quality of life.

This research provides insight into the mechanisms of conditions impacting approximately 250,000 Australians with ME/CFS and 500,000 Australians with long COVID.

NCNED Director, Professor Sonya Marshall-Gradisnik, said, "This research will guide investigators on defining subtypes of ME/CFS and long COVID according to immune gene expression."

"Further investigations into immune gene expression may offer new insights into biomarkers used for identifying disease subtypes or treatment strategies for these chronic conditions," Professor Marshall-Gradisnik said.

"Our team is dedicated to using innovative technologies to further identify the mechanisms of ME/CFS and long COVID.

"Our research goal is to ultimately provide innovative technology to improve diagnosis and treatment for people suffering these conditions."

More information: Natalie Eaton-Fitch et al, Immune exhaustion in ME/CFS and long COVID, JCI Insights (2024). DOI: 10.1172/jci.insight.183810. insight.jci.org/articles/view/183810 insight.jci.org/articles/view/183810

[er-cryptid]

NAD-Linked Glycerol Dehydrogenase

-- part of oxidoreductase family

-- catalyst is NAD+

-- oxidizes glycerol

-- forms glycerone

[amber-tortoiseshell]

Elvtársak, végre.

The orange gene of cats has been identified as the Rho GTPase Activating Protein 36 (Arhgap36) gene.

This protein is part of the pigment production pathway: mutant Arhgap36 triggers the degradation of one of the participating enzymes, leading to red/yellow pheomelanon production instead of black/brown eumelanin.

This means not only that we now know the molecular mechanism of the red color, but also if everything goes well, red and tortie will be finally testable!

[callmedaleelah]

— Pinnacle [ tsukishima kei university au series ]

— so i pay the price of what i lost ; yes it is right that you can handle anything, but you can’t handle everything all at once

author’s notes : no mention of (y/n), written in second person pov, alternative universe, timeskip!tsukishima, college life, not proofread, english is not my first language, long written chapter

[ masterlist ] | [ ask daleelah go to box box 🐭 ]

Winter break felt like a blur of constant assignments, stress, and messages from your mother. You found yourself buried in work, avoiding the outside world—especially your phone, which you knew was filled only with your mom’s relentless reminders to study harder, do better, and aim higher. Tsukishima and Yamaguchi’s contacts had been pushed to the bottom of your recent conversations, untouched since that day in the gym.

You haven’t seen Yamaguchi or Tsukishima since that winter class you skipped to watch their game. That day feels like it happened in a different life—before the semester started to suffocate you, before your every waking moment was consumed by endless biochemistry coursework. You don’t have time to think about anything else anymore, not when every day feels like a battle to keep up with the expectations of your professors and the relentless academic pace.

Classes in the second semester are intense, perhaps even more than you expected. One of your courses, Organic Chemistry II, is particularly demanding. The subject matter dives deep into reaction mechanisms, synthesis pathways, and the stereochemistry of complex molecules. There’s also Molecular Biology, where you’re expected to learn and apply the intricate processes of DNA replication, transcription, and translation. Your third major course, Biophysical Chemistry, focuses on the thermodynamics of biological systems—another subject that stretches your mind to its limit.

It’s only the second week of your new semester in biochemistry, but it feels like you’ve been dragging yourself through months. Everything seems heavier this time—every lecture, every lab session, every assignment. The moment you open your textbooks and class notes, you can feel your brain protesting. There’s an exhaustion that hangs in the air, a feeling like you’re constantly one step behind even when you manage to complete your work on time.

Now, standing outside the lecture hall for Organic Chemistry II, you realized nothing much had changed. The same heavy textbooks, the same tight deadlines, the same competition between your classmates as they all tried to one-up each other. The new semester had brought a new intensity. You were still trying to keep up with your classmates—some of them seemed almost unnaturally gifted, answering the professors’ most complex questions with ease, while you constantly second-guessed yourself, even when you knew the answer.

Professor Saito, a man with a greying beard and an air of calm authority, strode into the room with his usual collected demeanor. His reputation preceded him—tough, no-nonsense, and known for pushing his students to think critically. Today was no different. He picked up a piece of chalk and began scribbling a chemical equation across the board.

Without glancing back, he posed his first question to the room. “Can anyone explain the significance of this reaction in the context of anaerobic respiration in yeast?”

The classroom, filled with second-year students, was eerily silent. Your eyes traced the chemical formula on the board—glucose breaking down into ethanol and carbon dioxide. The answer floated on the surface of your mind, but your heart pounded in your chest as self-doubt crept in. You scanned the room, hoping that one of the top students would break the silence and offer the answer instead. But they remained still, unfazed, as if this question was beneath them.

You bit your lip, feeling the weight of the quiet hanging over you. It was a simple question, one you knew the answer to, but something held you back. You hated this feeling—knowing, yet hesitating, paralyzed by the fear of saying something wrong. The silence stretched on, and finally, despite the knots of anxiety in your stomach, you slowly raised your hand.

Professor Saito turned to face you, his gaze resting on you with a slight lift of his eyebrows. “Yes?”

Your voice wavered as you spoke. “It’s… the fermentation of glucose into ethanol and carbon dioxide,” you said quietly, swallowing back the stammer in your throat. “Yeast uses this anaerobic process to generate energy in the form of ATP when oxygen isn’t available.”

Professor Saito nodded slightly, his expression unreadable. “Correct. And why is this process significant in industrial applications?”

You took a deep breath. “It’s used in brewing to produce alcohol and in baking for the carbon dioxide that helps dough rise.”

He considered your answer for a moment before nodding again. “Yes. Good. Remember, however, that the ATP yield here is significantly lower than in aerobic respiration. That’s the key difference.”

Relief washed over you, and you allowed yourself to relax—just a little. But before you could even savor that small victory, another voice broke the quiet.

“Professor, could you explain the exact mechanism for the stereoselective alkylation of an enolate in asymmetric synthesis?” The voice belonged to Renji, one of the top students in the class. His question was sharp and cutting, a deliberate challenge. “And maybe elaborate on the difference between kinetic and thermodynamic control in that context?”

A ripple of murmurs spread through the room, punctuated by a few suppressed giggles. You stiffened in your seat. The question was far beyond the scope of what you’d covered in class, meant to impress—or worse, embarrass—the professor. Renji’s tone dripped with arrogance, and the way he leaned back in his chair, arms crossed, told you he already knew the answer.

Professor Saito regarded him for a moment, his gaze steady. He began to respond calmly, “In asymmetric synthesis, the stereoselectivity of the alkylation depends on—”

Before he could finish, another voice interrupted. “What about stereoelectronic effects when using Evans' oxazolidinone in highly hindered substrates?” Yumi, another top-tier student, chimed in with a smirk playing at the corner of her lips. She leaned forward slightly, her question laden with the same smug intent—to derail the lesson, to show off her own knowledge.

The air in the room became stifling. You could feel it—the discomfort rippling through the other students, the growing tension as Renji and Yumi sought to outwit the professor rather than learn from him. They weren’t asking to deepen their understanding. No, they were playing a different game, one of one-upmanship and arrogance.

Your stomach twisted with unease as you watched the scene unfold. Professor Saito, usually unflappable, seemed to falter for just a moment. You caught a glimpse of weariness in his eyes as he straightened up, preparing to answer yet another convoluted question. He had always been patient with his students, no matter how difficult the questions, but there was something in the way his shoulders sagged ever so slightly that made your heart ache for him.

You glanced around the room. Some students were fidgeting uncomfortably, others quietly whispering to their neighbors. The whole room had been hijacked by these few who cared more about showing off than learning, and the rest of you were left feeling small, inconsequential. You clenched your fists under the desk, wishing you could say something, do something to stop it, but the words stayed lodged in your throat. What could you say? What could you do?

Professor Saito began explaining the stereoelectronic effects, his voice steady, but you could sense his weariness growing. The air felt oppressive, like the weight of these students’ arrogance had smothered any genuine learning atmosphere. You shifted in your seat, feeling anxiety gnawing at your insides, hating the smug smiles that played on Renji and Yumi’s lips.

Before you could think further, you raised your hand signaling to interrupt the class. Professor Saito caught your motion and stop his explanation. “I’m sorry, Professor, may i speak?” Your voice came out a little shaky but louder than you expected, you can’t stop yourself right now. Every eyes are on you when the professor nodded. You land your gaze to Yumi—her smug faltered as she turned toward your seat. “I don’t see any stereoselective alkylation of enolates in asymmetric synthesis in our syllabus for this entire semester. So, if you’re going to interrupt the class with questions, at least stick to the topic we’re actually supposed to be learning.”

And now you turned to Renji’s seat, his face hardening as the room went deathly quiet. You could feel the eyes of the other students on you, and though your heart pounded in your ears, you pressed on. “And if you’re feeling that generously smart, maybe you should come up there and be the professor yourself. But what do you actually get from trying to make others—let alone the professor—feel small by throwing out questions just to outsmart them?”

Yumi’s smirk vanished, replaced by a look of shock. Renji shifted in his seat, his face hardening, but he remained silent. You could feel the tension swirling in the room, but it wasn’t directed at you anymore—it was directed at the arrogance that had poisoned the air.

Professor Saito stood there for a moment, his expression unreadable. Then, slowly, a small smile tugged at the corners of his lips. He cleared his throat, and the room snapped back to attention.

The room goes quiet, tension crackling in the air. You don’t usually speak up like this, but something about the arrogance in the room pushed you past your breaking point. The student sneers at you, but you don’t flinch. You’ve had enough of people trying to make others feel small just to inflate their own egos.

Professor Saito gives you a small nod of appreciation before continuing his lecture, the class quiet now except for the sound of his chalk against the board.

That evening, you’re back at your desk, struggling to finish another assignment. The words blur together on the screen, and despite your best efforts, you keep having to re-read the same paragraph over and over. You’re exhausted. There’s no other word for it. Even though you’ve tried to catch up on sleep, it never feels like enough. And there’s always another deadline looming, another mountain of work to climb.

Your phone buzzes next to you, but you don’t pick it up. It’s probably your mom again, asking why you haven’t called or berating you for not keeping up with her expectations. You’ve been avoiding her texts and calls lately because you can’t deal with the added pressure. She doesn’t understand how hard this is, how much you’re trying to juggle. Or maybe she does, and just doesn’t care. Either way, you don’t have the energy to explain yourself to her right now.

By the time you finish the assignment and hit submit, it’s nearly 2 AM. You slump back in your chair, staring at the ceiling. Every muscle in your body aches, and there’s a tightness in your chest that hasn’t gone away for days. You feel like you’re sinking deeper into a hole you can’t climb out of.

The thought of opening your phone again fills you with dread, but you do it anyway, more out of habit than anything else. When you do, you see an email from Professor Saito.

Subject: Checking In

I hope this message finds you well. I noticed that you submitted your most recent assignment late last night. While I am aware of the pressures you and many other students are under, I wanted to reach out personally.

Over the past few weeks, I’ve noticed how diligently you’ve participated in my class. I’ve seen how you’ve quietly answered questions, even when you seemed uncertain of yourself. I also noticed how you stepped in during that difficult class discussion the other day and helped refocus the conversation. You have a sharp mind, and I hope you know that.

That said, I am concerned about you. I can tell that you’re pushing yourself hard, and while I appreciate your effort, I also want to remind you that your well-being comes first. I know what it’s like to feel the weight of academic pressure, and I want to encourage you to take care of yourself, too.

If you ever feel overwhelmed or need to talk, please know that my office door is always open to you. You are a valued member of my class, and I believe in your potential.

Take care of yourself, and don’t hesitate to reach out if you need anything.

Warm regards, Professor Saito

As you read the email, you feel a lump form in your throat. You hadn’t realized how much you needed to hear those words until now. For so long, you’ve felt like you were just going through the motions, never sure if you were really doing anything right. But here, someone was telling you that you mattered—that your efforts weren’t invisible.

You close the email and stare at the screen for a long moment. Then, without thinking, you bury your face in your hands. The tears come quickly, a mix of exhaustion, relief, and gratitude. You hadn’t expected this—this kindness, this small bit of recognition in a sea of doubt.

tagslist (free to mention) ; @theweirdfloatything @snowthatareblack @ilovemymomscooking @nayiiryun @knightofmidnight @kozumesphone @scxrcherr

sorry for posting this late, i’ve been super busy with karate practice all weekend—i’ve got a belt test coming up soon, so the training’s been extra intense. i’m exhausted, and my legs hurt so bad i can barely walk, but gotta stay strong and push through! 😣