#Small Drug molecules

[aragenlifesciences]

Fostering Scientific Excellence in Chemistry, Biology, and Development Services. Explore Aragen's Small Molecule APIs & Precision Formulations Expertise.

[mestastop]

At Mestastop, we specialize in cutting-edge research and innovation in Metastasis drug discovery. Our dedicated team focuses on identifying and developing therapies that target metastatic cancer, aiming to revolutionize treatment options for patients. By leveraging advanced scientific methodologies and unique screening platforms, we push the boundaries of precision medicine. With a strong commitment to combating cancer spread, Mestastop stands at the forefront of Metastasis drug discovery, offering tailored solutions for pharmaceutical collaborations and clinical advancements. For more information, visit us at https://mestastop.com/, call us at +91 9177884450, or email us at bd@mestastop.com.  

[luckydige45]

The global RNA targeting small molecule drug discovery market is valued at USD 1.43  Billion in 2023 and is projected to reach a value of USD 7.44 Billion by 2032 at a CAGR (Compound Annual Growth Rate) of 20.11% between 2023 and 2032

[market99sblog]

Clinical Trials Supplies Market Growth Opportunity and Industry Forecast to 2027

The Insight Partners proudly announces the release of the latest market research on “Global Clinical Trials Supplies Market | Size, Share, Statistics, and Forecast” . This trailblazer market research aims to present unparalleled insights into the Clinical Trials Supplies market. This report presents the current market scenario and attempts to forecast future market size, share, and opportunities for businesses.

                                            This analysis is our commitment to deliver strategic business insights to companies willing to strive in competitive dynamic market space. The Insight Partners covered all dynamics of the Clinical Trials Supplies market including key trends, challenges, and several opportunities that businesses might have in the future.

Global Clinical Trials Supplies Market Outlook

This chapter covers several variables that affect business. Future expectations for the Clinical Trials Supplies market are combined with the economies of scale delineated by market size, growth rate, and compound annual growth rate. To examine demand drivers and constraints before other market actors, this chapter is even more crucial. Companies may better manage their goods and place themselves in the market gap by understanding market trends.

Analysis of the business environment based on several models is provided in this section. Businesses must streamline their success and income streams to be competitive in the Clinical Trials Supplies industry. Businesses may map the economic, environmental, and legal issues and update their unique selling propositions.

Know more about our research methodology from our analyst- sales@theinsightpartners.com

Business Impact of Covid-19

Travel restrictions during COVID-19 led to a decline in sales and supply chain metrics resulted in budget cuts. Many manufacturers had to put projects on hold and companies struggled to recover their fixed costs in the absence of revenue streams. Dealing with sharp decline and managing supply-demand equilibrium Clinical Trials Supplies market players responded to the new normal. Through this section, Insight Partners attempts to present an analysis of the impact of Covid-19 on business operations.

[laxmandige05]

The global small molecule drug discovery market size was exhibited at USD 75.98 billion in 2022 and is projected to hit around USD 163.58 billion by 2032, growing at a CAGR of 7.97% during the forecast period 2023 to 2032.

[reasonsforhope]

"People living with diabetes might have a new hope. Scientists have tested a new drug therapy in diabetic mice, and found that it boosted insulin-producing cells by 700% over three months, effectively reversing their disease.

Beta cells in the pancreas have the important job of producing insulin in response to blood sugar levels, but a hallmark of diabetes is that these cells are either destroyed or can’t produce enough insulin. The most common treatment is regular injections of insulin to manage blood sugar levels.

But a recent avenue of research has involved restoring the function of these beta cells. In some cases that’s started with stem cells being coaxed into new beta cells, which are then transplanted into patients with diabetes. Researchers behind this kind of work have described it as a “functional diabetes cure.”

Now, scientists at Mount Sinai and City of Hope have demonstrated a new breakthrough. Previous studies have mostly involved growing new beta cells in a lab dish, then transplanting them into mice or a small device in humans. But this new study has been able to grow the insulin-producing cells right there in the body, in a matter of months.

The therapy involved a combination of two drugs: one is harmine, a natural molecule found in certain plants, which works to inhibit an enzyme called DYRK1A found in beta cells. The second is a GLP1 receptor agonist. The latter is a class of diabetes drug that includes Ozempic, which is gaining attention lately for its side effect of weight loss.

The researchers tested the therapy in mouse models of type 1 and 2 diabetes. First they implanted a small amount of human beta cells into the mice, then treated them with harmine and GLP1 receptor agonists. Sure enough, the beta cells increased in number by 700% within three months of the treatment. The signs of the disease quickly reversed, and stayed that way even a month after stopping the treatment.

“This is the first time scientists have developed a drug treatment that is proven to increase adult human beta cell numbers in vivo,” said Dr. Adolfo Garcia-Ocaña, corresponding author of the study. “This research brings hope for the use of future regenerative therapies to potentially treat the hundreds of millions of people with diabetes.”

The results are intriguing, but of course being an animal study means there’s still much more work to be done before it could find clinical use. So far, harmine alone has recently undergone a phase 1 clinical trial in humans to test its safety and tolerability, while other DYRK1A inhibitors are planned for trials in humans next year.

Perhaps most importantly, the team will soon experiment with combining beta-cell-regenerating drugs with others that modulate the immune system. Ideally this should help overcome a major hurdle: the immune system will continue attacking new beta cells as they’re produced.

The research was published in the journal Science Translational Medicine."

-via New Atlas, July 14, 2024

[aragenlifesciences]

Small molecule Drug discovery companies

Leading the way in pharmaceutical innovations, CDMO pharma companies like Aragen excel in providing comprehensive services. As premier Small molecule Drug discovery companies, they drive the development of groundbreaking therapies, ensuring seamless integration from concept to commercialization.

[auntopossum]

Capital 'T', Capital 'M': The Manager

Saja boys x Gender Neutral! Reader

Content warning: Implied Drug Use, Implied Homophobia

Chapter 2: How to Fight Gentrification: Supernatural Edition

Author's note: 'You will write a normal amount.' I said to myself. 'You will write your normal 1k-2k average word chapter and stop letting this new fandom eat at you' I pleaded to myself. 'You will be normal about the Saja Boys.' I demanded to myself. ....Anywayyyyys, here's 6k for chapter two 👍😎

Chapter 1

Chapter 2: How to Fight Gentrification: Supernatural Edition

“Ughhhhhh.” You groan, lolling your neck to the side and slumping deeper into the battered office chair. You push away from the desk for a moment until the back of your seat meets a hard surface. Looking up, you’re greeted by Romance’s flirtatious smirk. He drapes further over you, the front of his hair tickling your nose. To the left and right of you, Abby and Baby cage you into the small cubicle space. With a roll of his hips against the back of your seat, you’re shoved forward, pinning your soft middle into the firm table with an involuntary Eep!  A bead of sweat rolls down your neck, and you swivel your flushed face back to the task at hand. 

You finished your ‘How to Use a Search Engine for Dummy Demons 101’ course about three hours ago and have since let the boys roam free on the wild west of the internet. Everyone quickly got the hang of it once you explained that it was basically a giant repository of knowledge and ideas. A massive library full of everything. Even the stupid stuff. Especially the stupid stuff. A library with its own archivists (google, bing, duckduckgo). The hardest part was getting them used to a keyboard and mouse. You make a note in your phone to get them personal tablets when you have the funds. 

Mystery and Jinu are in the cubicles next to you. Jinu glowers seriously at a youtube video essay explaining kpop idols, while Mystery peruses online clothing stores like a man on a mission. The screen in front of you blurs before your eyes. The boys’ suffocating proximity is getting to you. Slumping fully onto the desk in a vain effort to restore personal space, you moan out, fanning yourself with the laminated wifi password page. 

“Ughhhhhhhhhhhhh!” The stiff paper does little to relieve you of your plight. Instead, the light breeze spreads the group’s subtle scent of ozone, sulfur, and your reeking sweat deeper into the claustrophobic space. “Why are you guys so hottttt.”

Baby drags your limp arm up and crushes your clammy hand to his feverish face. Tilting with a practiced movement, he batts his eyes in an exaggerated manner. “Awww, thanks Manager!” He coos in a near monotone.

You sneer up at him. “Wasn’t a compliment, pretty boy.” His deathgrip eases for a moment, and you take the opportunity to snake your arm back to your side. “T’was a complaint.”

Gnawing on the plastic of your drink, you suck at the edge in hopes for a single molecule of hydration, glaring back at your monitor. You get three clicks deep before you groan again. Your eyes burn as sweat dribbles past your brow. Swiveling your chair to the side and bashing your knees against Abby, you lift your hips up and dig out your wallet. 

“I can’t do this anymore.” You whine to the group, unfolding the pleather and looking miserably down at your pathetic collection of cash. Jinu’s dainty hen-pecking and Mystery’s keysmashing cease, and you can feel the group hold their nonexistent breath.

You knock your leg up against Abby’s again, reaching for your jacket that’s slung over the back of your chair. As you press your hand against the table to rise, Baby clamps down on your wrist. You twist to raise an eyebrow at him from over your shoulder, and all three lean in closer. Sharing breaths, you scrunch your nose up at the stifling stink of your overheating body.

“Where do you think you're going?” Jinu asks threateningly with a tight, perfect smile, slowly rising from his squeaking seat. The monitors around the room flicker nervously. 

Pushing Romance’s face away from your head, you stare at Jinu incredulously and gesture with your elbows to your overall disheveled and damp appearance.

“Ideally? To go grab something to eat and take a cool shower.” Your arm bends as you struggle against the ram-like determination of Mr. Loverboy. He’s been sniffing your hair this whole time, and you cringe each time he does it, feeling greasier than a french fry.  

“But, you’ll be back, right?” begs Baby in a voice that doesn’t match the sharp pressure of his talons stabbing into your skin. 

You suck in a heavy, humid breath and answer with a long, ambiguous hum, looking around the cafe and eyeing the bored employee at the front. Several large, fat flies hit the radiant neon Open! sign with a tink, tink, tink. One of the bugs finally falls victim to its concussion and drops from the sky, landing directly into the steaming cup of ramen sitting on the check-in desk. You watch, eyes growing wide in disgusted horror, as the employee leans forward and slurps up their meal. Fly and all. 

Your attention is returned by the burning wet feel of something fleshy pressing against your palm. Face still frozen in witnessed extra-protein induced shock, you stare stupidly at Romance licking the hand clasped over his mouth. Your heart flip flops at the sight, and a shiver runs down your spine. Mouth twitching in a wobbly attempt at neutral, you slowly pull your hand away. Wiping the excess spit down the front of his soft shirt, you then tap at your chapped lips in false contemplation.

“Hmmmmmm.” You repeat dramatically, relishing in the suspense, in their attention. Shrugging your jacket into the crook of your arm and putting your wallet away, you poise to strike. “Yes and No.”

Giving them a moment to let your ambiguous words sink in, you seductively pop your pointer finger into your mouth and make a lunge forward. As a reward for disregarding your personal space, Romance is gifted a grand ol’ Wet Willy. The shrieking, AGHH!, flinching effect is exactly what you anticipated, and you take the opportunity to slip out from the suffocating circle, jerking Baby along with you. The needle-like pinpricks of his tightening grip remind you of a kneading cat.

You get three whole steps away before the world tilts drastically, and your ears ring. Crashing skillfully into a free chair, you splay out and pull a pen from your pocket. Using his vice-hold against him, you drag Baby onto your lap, shoving his sweater up to his elbow in his momentary confusion. With a pop! of the cap, you scrawl your apartment address and phone number onto his dry, scorching, porcelain skin. Gesturing the rest closer in hopes for a secret huddle, you whisper conspiratorily, arm wrapping securely around Baby’s waist. 

“This place is a dump, and I feel like I’m going to pass out from heat stroke.” Five gleaming, golden eyes shower you with their full attention and cling to your every word. “I need a break to eat, clean up, and take a nap or something.”

“But, you’ll still help us?” One of them asks quietly. You confidently nod, and the tension in the air eases tremendously.

Swiveling left and right with the extra weight on your legs, you let a full manic grin light up your exhausted face. 

“Can’t get rid of me that easily!” You laugh freely. 

Screeeeeeeeeech! whines the chair as it’s forced to spin with you and your hostage. Agitated by the teeth-aching noise, the swarming flies become frantic, buzzing and bashing against the lights above. Your heart hysterically beats against your chest as your body temperature steadily increases. The cacophony of humming fluorescences, whining machines, and aged speakers drapes over you like a thick, oppressive blanket. Flapping the sandals on your feet, you allow you and your racing thoughts four more full rotations before halting and entering Serious Mode.

“We need to blow this popsicle stand. A good chunk of the stuff I need to do for you guys can’t be done here.” As a treat, you spin once more while the boys puzzle through the first sentence. “I need to go to my apartment. Come over to my place in a few hours.”

“Your home?” Abby asks, pulling Baby’s arm out and reading the inked words.

“Yeah, we can’t use VPNs in cafes like this.” You lament. At their blank expressions, you poorly attempt to clarify. “I’m going to use a VPN, like a type of armor or disguise, so people can’t tell it’s me doing things on the internet. In order to seem legit, Plan A is to obtain social media accounts with followers and age. We would then take a metric fuck-ton of photos, which I will edit to seem like different locations and stuff. With some clever back-dating, we can make the posts seem older than they really are. If you want people to believe you’re a real boy band, you have to pretend you started from humble origins. We need to establish your internet footprint.”

“And this sort of… alibi? Is something you have to do at home?” wonders Jinu, looking a little lost.

“Yeah and depending on what kind of time crunch you’re on, we’ll do Plan D or Plan J afterwards to get our foot in the door.”

“Plan J? Pfft, how many did you come up with?” Abby asks. 

You conk your head against Baby’s and try to spear one of your swimming thoughts. “For getting us to a starting point where you can maximize your charm skills? About to the letter N.”

“What’s Plan N?” Romance says, leaning past the border of your personal bubble. 

“Becoming internet viral by having Abby crush a watermelon with his thighs and then doing something vaguely controversial to get every commentary content creator talking about you.” You gleefully inform, punctuating your sentence with another nerve-grating swivel. 

At Abby’s captured interest, Jinu cuts in. “Ok, so the ‘Game Plan’—” Someone giggles under their breath as Jinu says ‘game plan’ like it’s heavy and foreign on his tongue. He silences them with a piercing glare. “Is to meet you at your house after a few hours, to let you rest and eat, and then we’ll work on creating these…”

“Social media pages.” You finish for him with a nod. Bringing yours and Baby’s clasped hands closer to inspect his nails, you off handedly ask, “I’ve got something we can use as a green screen, but we’re going to need a bunch of outfits for you guys, which I’m assuming, Mystery, you’ve got handled?” 

Your question is answered with a grunt and a pair of sunglasses suddenly appearing on Mystery’s head. With a jerk, they fall from the top to rest on the bridge of his nose. The effect is slightly ruined by the sheer amount of hair already covering his face. You give him an encouraging thumbs up for the theatrical attempt.

“Sickkkkkkkk. Sick. Sick. Sick. Ok. Um…” You spin and spin in tandem with your racing mind. The employee at the check-in desk remains ignorant and unfazed to the shrieking chair and your general buffoonery thanks to their large, over-ear headphones, but the bugs and Saja boys are not if the constant wincing and near-violent buzzing are anything to go by. Baby somehow latches on even tighter, and your craving for water rears its dehydrated head as you thickly swallow. “Hey, sorry to go off topic again, but do you guys get food poisoning?”

“Uhh… No?” Jinu answers nervously, unsure of your direction. “Not really.”

“It’s more of a taste and texture tolerance for us than anything that can actually poison us.” Baby clarifies, wriggling on top of your lap in an effort to increase your spinning velocity.

Much to the relief of the rest of the internet cafe, you stop playing on the chair with a slam of your heels. With a pat, pat, pat, Baby takes your queue to stand, and you follow, digging your wallet back out. With a dramatic flourish, you whip out your credit card and hold it towards Jinu, the most responsible of the party. 

“As a parting gift, I bequeath you the means to a good time.” Sacredly, you tuck the small rectangle into his hand. “Simply tap the indicated machine at the check-out register, and your meal will be paid for, on credit, by my card here.”

Jinu holds the embossed plastic to the light, and the group huddles closer to make out the small numbers. Mystery takes the opportunity to slip his hand in yours, where Baby was seconds ago, not allowing your sweating palms a moment to breathe. You take advantage of the position to check out his cuticles as well. 

Raising your clasped hands, you write another address on the back of Mystery’s. As soon as you’re done, he pulls away, bringing the ink closer for an inspecting sniff. 

With a jerk of your thumb in his direction, you tell your new circus, “If you go there, it’s an all-you-can eat buffet. I’m talking $25 an adult, so about $125, maybe $140 with tax and stuff? You pay as you enter, and as long as you don’t leave, you can eat however much you want until the owners decide to throw you out. Go nuts, and enjoy yourself while you’re up here.” 

At that, you slap a hand on Jinu’s shoulder and walk past them to the exit. Trailing behind you, the Saja Boys look amongst each other wearily. Jinu gives the group an almost imperceptible nod, and excited, fanged grins break out on the rest of their faces. 

The sun’s pounding rays sear into the back of your eyeballs as you step out, and you recoil and hiss loudly. “THE SUN! THE SUN! It burns!” You dramatically cry out and flop an open hand to your forehead, faking a swoon. Abby steadies your shoulders with large, sweltering fingers and gives you a fleeting look of concern. 

Walking through the streets, you step out into the general public and become nearly swarmed by commuters. The boys quietly bicker amongst themselves as they wait with you at the bus stop while you stare into space and come up with plans O through Z. As screeching brakes announce the vehicle’s arrival, you pivot and give the guys a mock salute.

“See you later, alligators!” You shout as you retreat to join the line of people and up the bus’ steps. Packed in like a tin can of sardines thanks to the morning rush, you gaze out the vandalized window and watch your new coworkers/employers disappear in the crowd. Elation and blood boiling joy race through your tired body, and you’re unable to stop bouncing your leg through the entire ride home.

You finally landed a job!

---

Staying awake through the brief journey back to your apartment was a challenge, but somehow, you managed to return to your humble abode alive, in one piece, and freshly employed. As soon as the door slams behind you, you’re peeling off your wet clothes while bee-lining it to your shower. After a not insignificant amount of time, you emerge smelling of your favorite soaps and dressed in your comfiest pair of pajamas. With fuzzy sock adorned feet, you rummage through the kitchen in search of something to celebrate with. 

As you’re elbows deep in your freezer, the handle on your front door begins to rattle violently. Lazily, you slowly turn and eye the chain-latch and lock position. The sound of something furiously whispering eerily creeps in through the thin apartment walls. You raise to your full height with a stretch and groan, rapping your knuckles on the counter surface in a knocking fashion.

“Who is ittt~” You sing out to your unexpected visitor. Immediately, the jangling ceases, and something from behind the wood mimics your knocking pattern once, twice, then thrice.

“It’s Mrs. Lin.” croons the voice of a soft-spoken old woman. “Do you have a moment, sweetie?” 

It’s your neighbor, Mrs. Lin, who has been with this apartment block for decades. She’s a sweet, slightly scary, highly respected member of this residence building. Despite her tendency to appear out of nowhere and at the worst hours of the day, she’s someone whom you always make time for. 

With practiced movements, you open a cabinet and pull out a pile of dish towels. Rolling them into a disorganized wad, you throw the rags onto your dining table as if you were shooting hoops. Several of them tumble off the edge and scatter below on the floor. Turning with a squeak of your heel, you march to the door, trying to school your giddy smile into something more serious and neutral.

“Heyyyyyy, Mrs. Lin. What’s up?” You greet with a flourish. Looking down you see the incredibly petite, old lady. Her hair is in slight disarray, and she’s sporting some sort of murky stain on her mint green winter coat. Just looking at her out of season outfit makes you sweat.

When she doesn’t answer, you peel your unintentionally tight grip from the door and gather her frail fingers in yours. Large bruises bloom over the thin skin of her hand, and something dark red gathers under her jagged, yellowed nails. 

“My gods! Your poor hands are freezing!" You exclaim with real concern. With a lean and shuffle backwards, you draw your neighbor over the threshold and into your apartment. “Come, come in! I’ll brew us some tea, and we can catch up.” 

It’s simple to seat the pliable granny into one of your cheap chairs, tucking her almost non-existent weight into the dining table. She silently bends over, picking up the fallen towels one by one as you start a pot of water. 

Taking a seat across from her wispy form, you get to work peeling fruit. As you place the juicy pieces on a dish in front of her, you ask gently. “So how have things been? How are you?”

With a sharp, whistly inhale and cracking sounds like water freezing, she jerks violently, hunching in on herself. With a sob, she cries into her bony hands, “My husband never came home last night. I’m worried for him! Have you seen him?”

You hum, reaching across the table and starting to fold a few towels. She hesitates, tears evaporating and eyes partially clouding over, before joining in on the chore. The awful, crunching and splintering noises stop, and the kettle resumes its journey to boiling. You glance at a sticky note stuck to the motivational kitten calendar on the side of your fridge. Next to the current month, in big, bold, bleeding sharpie, reads, ‘BUSINESS TRIP TO EUROPE!’. 

“It’s OK , Mrs. Lin. He went on his business trip to Paris two days ago. He should be back sometime later this week.” You soothe, lie rolling off the tongue with ease. Technically, her husband passed away ages ago, but it’s cruel to stress someone out with the reminder that their loved one died before them. You and the other tenants get together each month to ensure the story stays consistent and straight, in case she asks anyone else during her rare moments of lucidity. Standing after a minute to stop the screaming pot, you look away from whatever face she’s making as she absorbs the news.

“O-oh, that’s right.” She stutters with a sickly rasp, raking her dirty fingers through her mangled hair in polite embarrassment. “I’m so sorry to bother you over something so silly. I seem to be getting so forgetful lately.”

“It’s no problem.” You hush, back turned away from your neighbor, pouring the water as slowly as physically possible into a mismatched set of cups. “You can come to me at any time. I’ll do my best to help out.”

For nearly ten minutes, she’s completely silent at the table, and you busy yourself by opening and closing random cabinets and drawers. 

“You’re a good kid.” She finally says, and it’s like a weight is lifted from the room. Standing from your squat under the sink, you look over your shoulder at the empty chair and the neatly folded pile of dish towels. Humming to yourself, you place the rags back where they belong and saunter to your door. Shoving its swollen weight open, you hold it and watch vigilantly as your little neighbor limps, from somewhere in your peripheral, out into the hall. As soon as she vanishes from your sight, the room seems to violently remember that it’s a hot, sweltering summer. Every appliance whirs in overdrive in a desperate effort to remain cool.

You re-lock your door and nearly slip on the humid flooring on your way to your bed. Face planting into your pillow, you let one final thought haunt you before sleep takes over. 

Did you remember to set an alarm?

---

You awake in a cold sweat and with a ringing sound in your ears. Sitting up before you’ve fully returned to the land of the living, you smack your slimy lips together and scratch a bug bite on your ass. 

Checking your phone, your heart jolts in your chest a second time as you check the clock. Shit! The Saja Boys! Diving out of bed, you blindly search for the other half of your sandals, brain still hazy from the poor nap. 

You nearly thump your head against the table you’re checking under when you hear the scream that broke through your dreams again. It continues for a nearly impossible length, echoing throughout the hallways of the complex. The sound is familiar to you, and your body almost relaxes in a honed, pavlovian reaction before you remember. 

SHIT! The Saja Boys!

Mrs. Lin!!!

Barefoot with a singular sandal in hand, you throw yourself out the door with a Bang!  Sprinting down the humid corridor, you head towards the center of the commotion. 

A few meters away from the bottom of the stairway, you see Mrs. Lin’s dark shadow looming over your brightly colored boys. Skipping several steps at a time, you attempt to shout to get everyone’s attention, but you are drowned out by the cacophonous shrieking and hissing. Finally, as your feet hit the bottom damp rug with a smack! and a shudder, you fling yourself past Mrs. Lin and shield the marked form of Abby with your smaller body. 

“Stop!” You try again, to no avail. Your voice goes unheard, but your sudden appearance startles everyone. To make your presence abundantly clear, you throw your sandal at the towering, twisting shape of your neighbor. “Stop it! Stop it! They’re with me, Mrs. Lin!”

With an ugly crack! grind! snap! the ghastly woman shrinks in on herself and reforms into her original appearance. She gives you an incredibly judgemental stare down, peering at you and your group with a single, yellowed eye through the messy mop of her hair. With a shake of her head and a huff, she vanishes in a puff of vapor. 

Awkwardly, you tip-toe over to your fallen footwear and turn to face your invited guests. The boys gawk at you for several long breaths. Nobody moves as the lights flicker back into existence. A door opening and closing somewhere above breaks the spell, and the Saja Boys quickly try to sheath their fangs and claws before anyone else can see.

You wordlessly gesture for them to follow you, traveling together back up to your apartment. Holding the door open, you can’t fight the blush from rising to your face as you realize that you’re still in pajamas. You let them make themselves comfortable while you mumble under your breath, dashing into your bedroom to change. When you emerge, more professionally presentable this time, you find them spread out on the chairs and couch in your living space. Rubbing a hand along the back of your already sweaty neck, you blurt out an apology.  

“Sorry about Mrs. Lin. She’s usually pleasant to deal with, but uh…” You look to the pinks and blues of their outfits on their sprawled forms. “She can be a little… homophobic.” 

Romance holds out a hand before anyone else can speak. Several toothy mouths close with an audible clack!  “I’m sorry, but what?” He asks, bewildered. 

You gesture to their pastel clothes and hair. “Yeah. She’s old fashioned, and like, we’ve had talks with her and all, but she’s really stuck in her ways.”

“She’s a— Why is— What does—?” Romance takes a measured breath, pressing his hands together in prayer and leans forward. Blowing out an unneeded breath, he tries again, wearily asking. “Do you know what she is?”

“She’s my neighbor.” You respond with a serious nod, folding your arms across your chest and frowning. “And I’m really sorry she acted like that. Normally, she’s pretty good with visitors, but like I said…”

“That was a gwishin. A vengeful spirit.” interrupts Jinu. Everyone looks to you with slight concern, not for your safety but your intelligence.

Raising an eyebrow, you shrug. “Yeah? And?” 

“Supernatural beings like that are dangerous to be around.” slowly explains Baby as if you’re a child. He pushes up his sleeves and flexes his talons threateningly. “You should let us—”

You toss a throw pillow at him before he can finish his sentence. “No! No. Absolutely not. Nobody is hurting and doing anything to our dearest Mrs. Lin.” Walking over to your kitchen, but remaining in their line of sight, you huff as you get out 6 cups and start another pot of water. “Ms. Lin is an incredibly important figure to our neighborhood.”

“She’s literally a gwishin!” whines Abby throwing his hands up dramatically, mildly sore from missing out on a good fight. 

The water boils rapidly in the presence of five demons. You ply a plate high with a vast assortment of snacks from around your kitchen.

Clink! Clink! chatters the dishware as you set it before the band. Beep! Beep! chirps the temperature control as you force the central A/C to go full throttle. EEEEEIIII! screams the kettle as you move it from its heating source. 

“Do you know how much I pay in rent for this place?” You nonchalantly ask, pouring everyone a cup of tea and dragging your own chair over. Answering your rhetorical question before any of them can attempt to, you continue. “About 1/6th of what any other place in this area goes for, and I don’t have to pay for utilities or HOA fees. Having Mrs. Lin around lowers the rent by like a LOT, and not only would I personally be upset and disappointed if you harmed her in anyway, but I’m pretty sure everyone else living here would skin me alive and dump my twitching body into the harbor if they found out one of my guests managed to exorcise her.”

“Ok!” Jinu raises his hands and his voice to match your increasingly hysteric tone. “We won’t touch her.”

‘Not unless she picks a fight again.’ You think you hear someone grumble out.

“She’ll also be really useful for us right now.” You quickly add, placing the stack of cups and plates down on the small coffee table. Immediately, everyone lunges for the food as if they didn’t eat a mammoth's worth at the buffet before coming here. You take the time to settle into your own seat.

“Mmmghn?” Abby asks unintelligibly around a mouthful of junk food.

“We’ve got beef with most of the shamans and spirit hunters here.” At their riveted attention, you continue to ramble, waving your cup around as you speak. “Sometimes people come by to bother us and Mrs. Lin. Her presence, hopefully, will mask yours, but either way, those folks should know to piss off if they see me or another tenant coming. You’ll be safe-ish here.”

“You’ve fought off Hunters before?” Romance asks with a deep interest shining in his reflective eyes.

“I’ll have you know I’m an absolute beast with a folding chair. WWE wants me on their roster carnally.” You flex and pose, scalding yourself with a whimper as burning hot tea splashes you amidst your shenanigans.

“Who’s WWE?” Baby whispers to Abby.

“No idea, but now, I really want to see The Manager beat someone with a chair.” He quietly replies. 

A soft guitar rift and series of chimes sounds from your bedroom, and you swear softly to yourself. Clacking the cup back onto the table, you hurry off, without a word, out of the living space. Mystery lunges at the same time as Romance for your abandoned drink, successfully snagging it before anyone else can and chugging the whole boiling beverage down in one go. 

You step out of your room a minute later, earbuds in place and fiddling with your phone. Glancing up, you make a phone hand gesture to your ear then move to shush them. The room falls unnaturally silent as you try and call back your buddy.

“Y’ello! You called me?” You say into your bluetooth microphone, pacing back and forth in front of the guys.

“Yeah~!” A voice slurs out through the tiny speakers, barely imperceptible to the Saja Boy’s supernatural hearing. “You texted lookin’ for a gig?” 

You messaged multiple people recently looking for any and every form of work to keep yourself afloat in these trying times. Out of the corner of your eye, you gauge the band’s reactions to your private conversation, certain they can hear you both. “I did, but let’s hear what it is before I say yes to anything.”

“Oh, you’ll like this one!” They say with a cheer. “My Big Brother got called in on security detail for some rich producer’s house party. It’s tomorrow night, and apparently, the dude who helps set up the sound equipment got arrested. I said I knew someone who’s good with that kind of tech and can keep their head low… and that’s you!”

“Ooooo~ Producer? What kind of producer?” You coo, looking at your phone and rapidly typing out blooming ideas. “Also, how much is the pay?”

“They’re some type of big marketing bigwig. Works with instagram influencers and stuff to sell those really sketchy holistic stuff.” Somewhere in the back of their audio is honking, and you think you hear several engines rev. “Pay’s $600 for the night. You just need to set the crap up and hang out at the place for the duration of the party incase something breaks.”

You freeze in your pacing, and Baby looks up from where he’s picking at a hole in your couch. “$600… is alot…” You say tentatively.

“Yeah, Bro’s gonna be there to help supply the—” They make an exaggerated, long sniffing sound. “Ya’ know? It’s $600 because I trust you to keep your mouth shut about anything you might see.”

“I’ll do it for $500 if you let me bring some friends to enjoy the night with.”

“$450 for the night. You’re to stay sober, and your friends to stay out of our business.”

“Deal.” You declare with a wicked smile, leaning on your kitchen counter with your back turned to your demons.

“Awesome. I’ll text you the address and time. It’s some expensive-ass costume party. Your friends are on their own, but you still have the other half to our Halloween set, right?”

“Yeah.” You snicker, staring at the closet where you shoved the fake, white wings and halo. “I’ve still got the ‘sexy’ angel costume.”

“Perfecttttt. The DJ is going as Jesus because he refuses to cut his hair for this event. This way you guys can sorta theme— Anyways, I’ve got to go, but I’ll talk to you soon!” With a beep! beep! they quickly hang up, and you slowly turn around with a feverish grin.

Raising your phone in the air and plucking the earbuds out of your ears, you sing to your boys. “Guessssss who just got us that chance to use your charm powers~?”

“You?” Baby flatly questions with an eyebrow raised, while Mystery tips an empty chip bag upside down to collect the dust. 

“Meeeee~!” You prance over to them and jump between Abby and Mystery on the couch with a Whump!  The cushions sink under your combined weight, titling the two closer until your thighs and hips touch. Reaching over, you drag a bowl closer and tap at your phone screen furiously. “Rich guy party. It’s costumes, which is perfect because— and I’m being honest here— you guys suck at acting and looking like humans. This is the perfect place to practice and get some influential connections and momentum.”

“And it’s tomorrow night?” Romance asks, confirming that, yes, they can hear conversations that quiet. You make a note in your phone to ensure hearing protection for them when they perform. 

“Yup.” You agree, popping the ‘P’. “Which means we absolutely need to hustle.”

Standing up, you head to where you suddenly spied your missing sandal and rifle around for some scrap paper to write on. The boys perk up and pull themselves to full attention, watching with golden eyes as you fumble around your home.

“Ok, so—” You aggressively scribble out a to-do list for each member. “I’m going to run down to a store and get myself an inhumane amount of caffeine. You guys get set with what you can on each list, and I’ll be back to take the photos. Creativity is rewarded on the internet, so go crazy and have fun with it. If anything, I think we can get about 8 photos each and 10 group pics if I can get us a good set of accounts before I return.”

You hop your other footwear on and shoulder your bag. Fisting your keys in your hand like a weapon, you turn before leaving the boys alone in your home. “I’ll be back as soon as I can! Please don’t set anything on fire, and please, please don’t get in any fights with Mrs. Lin, no matter how rude she is.”

“We won’t.” Jinu promises firmly, placing a hand on Mystery’s and Abby’s shoulders. “We’ll have everything done by the time you come back.”

“Well, do what you’re able to, and don’t push yourself too hard.” You encourage, one foot out the door and hand on the knob. “B.R.B.!” And with that, the door slams, and the demons are left to fumble through your extensive list of tasks alone.

As soon as they hear you walk down the flight of stairs, they all hunch with a sigh and revert back to their hellish forms.

“...I don’t know about you guys, but I can’t get used to today’s slang. Listening to The Manager talk is really making me feel my years.” pouts Romance, who slumps into the plush cushions and glares at the paper in hand.

“That’s what’s making you feel old? Not entirely different way of living, the electricity, or the over abundance of food?” nudges Baby, comparing his list against others.

“Regardless of your guys’ hangups, we need to adapt and learn this stuff fast if we want to do this right.” Jinu affirms, pacing the floor like a mother hen. “Work and practice now. Complaining and gossip later. Let’s go. Chop, chop!”

“Ughhhh, ok. ok.” whines Romance, peeling himself from the softest seat he’s ever been in.

“Always such a taskmaster.” whispers Baby with a roll of his eyes to Abby as they rise together. 

“I think he just wants to impress The Manager.” Abby replies quietly with a muscular shrug. 

“Guys. I can literally hear you.” Jinu growls with his back turned, holding the paper to the light of the window and trying to decipher one of your poorly handwritten words. “Let’s focus here.”

“Do you think I can ask The Manager to spar with me?” Abby buzzes, ignoring Jinu’s long-suffering sigh. “I really, really want to see what they mean about the chair thing.”

“Abby, shut up.” Romance and Baby groan simultaneously. Abby turns to Mystery with a questioning look.

“...I also want to see the ‘chair thing’.” agrees Mystery with a flutter of paper. “But Jinu’s right, let’s get this over with.”

“Thank you.” Jinu sighs.

The room falls silent as each member of the band works on their own assigned project. In the space between their lack of breathing, the city’s bustling noise filters in through the poorly sealed window. After several minutes of intense concentration, Abby speaks up.

“Anyone else dying to know what The Manager’s ‘sexy angel costume’ looks like?”

“Abby, shut up!”

[godihatethiswebsite]

Simon Riley x reader - Hot Cocoa

CW: childhood abuse, implied alcohol and drug usage, angst/comfort

You didn’t know it at the time, but it was more than just a cup of hot cocoa.

Soft hands–so unlike his mothers–never having been braced against the impact of another’s cruelty, yet clutching his with the same maternal insistence as you slip the steaming mug of sweetness between the gnarled, calloused proof of his misfortuned life. 

There is no preamble of cracked leather being drawn from beer stained belt loops; no metal branded welts to be found from a diseased monstrosity who does not care if they are hidden. Simon’s knuckles are intact, not bruised nor split against his sperm donor’s chin. Sentinel instincts are rendered obsolete without the triggering sniffles of his traumatized sibling. No need to keep playing the brave little soldier – the screams of nearby children are not born from brutality.

Doe eyes gaze up at him with an exuberant sparkle, no glassy haze plying you into absent submission. Water molecules of heated breath turning crystalline vapor in the frosty night air hold no trace of ABV – no lingering aroma of whiskey sorrow. The tremble in your bones is from a lack of knitted mittens, not survival induced adrenaline spikes. Frozen fractals catch in silken strands kept immaculate and washed, a polished sheen so unlike her familiar limp straw, reflecting the untarnished soul within he’s done his best to keep pure.

The failure of his mother’s visage haunts his waking past, but the dying warmth of her love renews in an unexpected presence.

He never told you of the act – the ritual of younger nights in a bygone civil hellscape. When the door had finished rattling on rust weathered hinges and the taillights of abuse were all but distant fireflies. When his brother crawled out from his false sanctuary of childhood innocence, having braved the monsters beneath the bed rather than the one he still called ‘papa’. When the woman who should’ve loved them better remembered who she was, the pain of mottled flesh replacing the lucidity of the mind. When he saw his mother for who she was: a woman worn down by sadistic malice. Who was just as much a victim with the scars left on her skin, the pockmarks on her elbows forced there by a stronger hand, the blonde hairs scattered and bloody pulled like cobwebs from her scalp.

Red rimmed eyes spoke wordless apologies for the naivety of her past; for the regrets of choosing wrong the father of her children, the life she wished she had the chance to go back and undo. 

A dead end promise to fix the mistakes of their future – someday.

He clung to the cheap disposable cardboard like the memory of crawling into a threadbare twin, shadows kept at bay with the weak glow from Tommy’s nightlight. The kettle whistled as the pair of them settled, packaged powder dumped into chipped ceramic and brought to them with a shaky smile. He would never voice aloud his own preference for less marshmallows, to give force to the cracks already shattering her resolve. If not for her sake than for his brother’s. 

The expression on your face brings him back from gloomier times, wrapped up in festive cheer all windswept and frost bitten, a backlight of radiance from the bustling market stand you purchased the beverages from. He watches as overeagerness singes your tongue, the small yelp of complaint soothed by a mouthful of whipped cream, the pain doing nothing to retract from the unbridled joy you feel in this simple cherished moment.

You. 

A gift–he knows–sent from heaven by the broken woman he forgave so very long ago. Her promise to him taken physical form.

It’s so much more than just a cup of hot cocoa.

It’s healing.

Masterlist

[mestastop]

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[excalculus]

I saw some mentions of rabies going around again and have no clue what's set it off this time, but given recent scientific developments I want to revisit the idea of curing symptomatic rabies.

First things first: there is still no practical way to do this. The famous Milwaukee Protocol fails far more frequently than it succeeds, and even the successes are not making it out in anything like a normal state. It's been argued that it should no longer be considered a valid treatment [1] due to these issues; any continued use is because there's literally nothing else on the table.

However. There are now two separate studies showing it's possible to cure rabies in mice after the onset of symptoms. The lengths you have to go to in order to pull this off are drastic, to put it mildly, and couldn't really be adapted to humans even if you wanted to. But proof of concept is now on the board.

long post under the cut, warnings for animal experimentation and animal death. full bibliography at the end and first mention of each source links to paper.

Quick recap - rabies is a viral disease of mammals usually transmitted through the saliva of an infected animal. From a contaminated bite wound, it propagates slowly for anywhere from days to months until it reaches the central nervous system (CNS). Post-exposure vaccination can head it off during this phase, but once it reaches the CNS and neurological symptoms appear it's game over. There will typically be a prodromal phase where the animal doesn't act right - out at the wrong time of day, disoriented, abnormally friendly, etc. This will then progress to the furious (stereotypical "mad dog" disease) and/or paralytic phases, with death eventually caused by either seizures or paralysis of the muscles needed for breathing.

That's the course we're familiar with in larger animals. Mice, though, are fragile little creatures with fast metabolisms.

In the first study's rabies infection model, lab mice show rabies virus in the spinal cord by day 4 after infection and in the brain by day 5. Weight loss and slower movement start by day 7, paralysis starting from the hind limbs from day 8 on, and if not euthanized first they're dead by day 10-13. [2]

This study (fittingly conducted at the Institut Pasteur) had two human monoclonal antibodies, and wanted to see if there was any possibility they could be used to cure rabies after what we think of as the point of no return.

Injecting the antibodies into muscle saved some mice if done at days 2 or 4, and none if done later, even at high doses of 20 milligrams per kilogram of body weight of each. Conclusion: targeting the virus out in the rest of the body is no use if it's already replicating in the CNS.

Getting a drug past the blood-brain barrier is, to use a highly technical term, really fucking hard. It's the sort of problem that even the best-funded labs and biggest companies in the world routinely fail at. And that's for small molecule drugs, which are puny compared to antibodies.

But this isn't drug development for a clinical trial. This is a very, very early proof-of-concept attempt, which means you're willing to ignore practicality to see if this idea is even remotely workable. So you can do things like brute force the issue by cutting through the skull to implant a microinfusion pump, which lets you deliver the antibodies directly into the normally-protected space around the brain. Combine this with the normal injections, and you can treat both the CNS and the rest of the body at the same time. Here's a survival graph of treated mice. X axis is days, Y axis is percentage of mice in that group still alive.

Figure 2A from reference 2, accessed February 2024

The fact that the blue, green, and purple lines did anything other than sink horribly to zero is unheard of. When the combination treatment was started at day 6, 100% of the mice survived. Started at day 7 (prodromal phase), 5 out of 9 mice recovered and survived. Started at day 8 (solidly symptomatic, paralysis already starting to set in), 5 of 15 mice recovered and survived. And when they say "survived", they kept these mice all the way to day 100 to make sure. Some of them had permanent minor paralysis but largely they were back to being normal mice doing normal mouse things. So, success, but by pretty extreme means.

Enter the second paper [3]. This was a different approach using a single human monoclonal antibody against Australian bat lyssavirus (ABLV - closely related to rabies, similar symptoms in humans) to try for a cure without needing to deliver treatments directly into the CNS. They also made a luminescent version of ABLV that let them directly image viral activity, so they could see both where the virus was replicating and how much there was in a live mouse.

Figure 1 from reference 3, accessed February 2024

Mice infected with ABLV start showing symptoms around day 8. You can see in the figure that at day 3 there's viral replication in the foot at the site of infection, which has shifted into the spine and brain by day 10. So what happens if you give one of these doomed mice one single injection of the antibody into the body?

Done at day 3, the virus doesn't make it to the brain until day 14, and while disease does set in after that around 30% of the mice survive. Days 5 and 7 are much more interesting. Those mice still develop symptoms at day 8, but the imaging shows the amount of virus in their spines and brains never gets anywhere near the levels seen in untreated controls, and within days it starts to decrease. Around 80% of day 5 and 100% of day 7 mice survive.

Okay, sure, you can stop another lyssavirus, but technically you did start treatment before symptoms appeared. What about symptomatic rabies?

The rodent-adapted rabies strain CVS-11 starts causing symptoms as early as day 3 after infection, and untreated mice die between days 8 and 11. The same single dose of antibody saved 67% of mice treated on day 5 and 50% of mice treated on day 7. Without making the luminescent version of the virus there's no real-time imaging of the infection, but you can still track symptoms.

Figure 2 from reference 3, accessed February 2024. CVS-11 is the name of the rodent rabies strain and F11 is the name of the antibody.

Disease score is a combination of several metrics including things like whether the mice are behaving normally and whether they show signs of paralysis. In untreated mice it goes up and up, and then they die. If one of those lines starts coming back down and continues past day 10 or so, that's a mouse that recovered. The success rate isn't as good as against ABLV, but again, this is a rabies strain specifically adapted to rodents and treatment wasn't started until it was well-established in the CNS.

So how on earth is this happening? The antibody neutralizes both ABLV and rabies really well in a test tube, but we've already established that there's no way a huge lumbering antibody is making it past the blood-brain barrier without serious help. Something about the immune response is clearly making it in there though. And it turns out that if you start trying this cure in mice missing various parts of their immune systems, mice without CD4+ T cells don't survive even with the treatment. By contrast mice without CD8+ T cells take longer to work through the infection, but they eventually manage it and are immune to reinfection afterwards.

To grossly oversimplify the immune system here, CD4+ are mature helper T cells, which work mostly by activating other immune cells like macrophages (white blood cells) and CD8+ T cells (killer T cells) against a threat.

Normally, T cells are also kept out by the blood-brain barrier, but we know that in certain specific cases including viral infection they can pass it to migrate into the brain. In the brains of the infected mice for which antibody treatment either wasn't given or didn't work, you can find a roughly even mix of CD8+ and CD4+ T cells along with a whole lot of viral RNA. But in the brains of those successfully fighting off the infection, there's less viral RNA and the cells are almost exclusively CD4+. So the antibody doesn't work by neutralizing the virus directly - something about it is activating the animal's own immune system in a way that gives it a fighting chance.

Again, neither of these proof of concept treatments is really workable yet as a real world cure. The first one is almost hilariously overkill and still has a pretty good chance of failure. The second is less invasive but careful sequencing still shows both low-level viral replication and signs of immune response in the brains of the survivors even at day 139, so it may not be truly clearing the virus so much as trading a death sentence for life with a low-level chronic infection. But now we know that 1. curing rabies after symptoms begin is at least theoretically possible, and 2. we have some clues as to mechanisms to investigate further.

Not today. Not tomorrow. But maybe not never, either.

References:

Zeiler, F. A., & Jackson, A. C. (2016). Critical appraisal of the Milwaukee protocol for rabies: this failed approach should be abandoned. Canadian Journal of Neurological Sciences, 43(1), 44-51.

de Melo, G. D., Sonthonnax, F., Lepousez, G., Jouvion, G., Minola, A., Zatta, F., ... & Bourhy, H. (2020). A combination of two human monoclonal antibodies cures symptomatic rabies. EMBO molecular medicine, 12(11), e12628.

Mastraccio, K. E., Huaman, C., Coggins, S. A. A., Clouse, C., Rader, M., Yan, L., ... & Schaefer, B. C. (2023). mAb therapy controls CNS‐resident lyssavirus infection via a CD4 T cell‐dependent mechanism. EMBO Molecular Medicine, 15(10), e16394.

[hellsite-proteins]

idk if this is a fair ask cause it's about a real peptide but. I saw your post about the 6 aa peptide and was wondering if alphafold can show a 5 aa peptide. There's the Extracellular Death Factor (EDF) which is NNWNN and I really wanted to see how it looked like and what you thought of it based on the structure alone

very cool! i know peptides don't make good drugs, but something about a molecule small enough that it makes sense to look at its chemical structure feels to me like it would be used that way (or maybe i've just taken too many classes with units about drug design?)

AF3 was able to make something for this little structure, but i'm not sure how useful it is

letter sequence in this ask matching protein-coding amino acids:

NNWNN

protein guy analysis:

this is small enough that ChimeraX initially opens it as a stick structure and not a cartoon, which makes sense because the cartoon is pretty underwhelming. it is too small to really make any secondary structure, which does also mean that the predicted confidence is incredibly high. overall, this is just a little guy and its very neat :)

predicted protein structure:

stick representation

cartoon representation