#PharmSky

@shihcheng.bsky.social

1 hour ago

https://doi.org/10.1001/jamapsychiatry.2026.0086 No description available

New JAMA Psychiatry paper: Clozapine is tested after 1 antipsychotic failure in FEP. Study spans 7 sites in China, 2 randomizations! PMID:41811299, JAMA Psychiatry 2026, @JAMAPsych https://doi.org/10.1001/jamapsychiatry.2026.0086 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Shicheng Guo

@shihcheng.bsky.social

2 hours ago

Cancer cachexia in STK11/LKB1-mutated non-small cell lung cancer is dependent on tumor-secreted GDF15 | Nature Communications Cachexia is a wasting syndrome involving adipose, muscle, and body weight loss in cancer patients. Tumor loss-of-function mutations in STK11/LKB1, a regulator of AMP-activated protein kinase, induce cancer cachexia (CC) in preclinical models and are linked to weight loss in non-small cell lung cancer (NSCLC) patients. This study examines the role of the integrated stress response (ISR) cytokine growth differentiation factor 15 (GDF15) in regulating cachexia using patient-derived and engineered STK11/LKB1-mutant NSCLC lines. Tumor cell-derived serum GDF15 levels are elevated in mice bearing these tumors. Treatment with a GDF15-neutralizing antibody or silencing GDF15 from tumor cells prevents adipose/muscle loss, strength decline, and weight reduction, identifying tumors cells as the GDF15 source. Restoring wild-type STK11/LKB1 in NSCLC lines with endogenous STK11/LKB1 loss reverses the ISR and reduces GDF15 expression rescuing the cachexia phenotype. Collectively, these findings implic

GDF15 is key to cachexia in STK11/LKB1-mutant lung cancer. Blocking it could halt muscle, fat, and weight loss. Insights from patient-derived models. PMID:41617691, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-68702-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Shicheng Guo

@shihcheng.bsky.social

5 hours ago

De novo design of GPCR exoframe modulators | Nature G-protein-coupled receptors (GPCRs) are important therapeutic targets and have been targeted mainly through their orthosteric site, where the endogenous agonist binds1. However, allosteric modulation has emerged as a promising and innovative strategy in the realm of GPCR drug discovery1. Here, drawing inspiration from the natural regulation of GPCRs by transmembrane proteins, we have developed GPCR exoframe modulators (GEMs), de novo designed proteins that specifically target the transmembrane domain of GPCRs. Utilizing a hallucination-like design approach, we crafted GEMs with three strategic structural prompts to achieve the desired binding modes. We selected the dopamine D1 receptor as a prototypical model and systematically investigated four GEMs. Structural studies and functional assays revealed that these GEMs bind to the transmembrane domains and function as diverse allosteric modulators, including agonist-positive allosteric modulator, negative allosteric modulator and biased a

Innovative GPCR exoframe modulators tune allosteric sites for precise targeting. De novo proteins open pathways for future solutions in drug discovery. PMID:41699180, Nature 2026, @Nature https://doi.org/10.1038/s41586-025-09957-1 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Shicheng Guo

@shihcheng.bsky.social

15 hours ago

Composite SMG5-SMG6 PIN domain formation is essential for NMD | Nature Communications Nonsense-mediated mRNA decay (NMD) relies on the coordinated assembly and action of multiple protein factors. Degradation of target mRNAs begins with endonucleolytic cleavage near premature stop codons, but the mechanisms of endonuclease activation and regulation remain unclear. Using structural predictions, biochemical in vitro assays, and cell-based NMD analysis, we show that SMG5 and SMG6 interact via their PIN domains to form a composite interface (cPIN) with full endonuclease activity. In vitro reconstituted SMG5-SMG6 cPIN heterodimers show high activity, as SMG5 completes the SMG6 active site and substrate binding site. Mutations in residues at their predicted interaction surfaces, RNA-binding sites, or active site attenuate or abolish cPIN activity in vitro and impair cellular NMD. Our findings demonstrate how paralogous PIN domains complement each other to assemble a highly active endonuclease in NMD, providing a structural and mechanistic explanation for efficient NMD sub

New insights into NMD: SMG5 and SMG6 form a composite PIN domain, critical for mRNA decay via endonucleolytic cleavage near premature stop codons. PMID:41714610, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69819-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Pharmacists United for Truth & Transparency

@truthrx.org

15 hours ago

Taxes are paid to the government - Not pharmacies

Every time legislation is introduced that can restrict PBMs from running local pharmacies out of business while fleecing #patients & #taxpayers - out come the misinformation campaigns.🙄

It's Time to STOP Their Lies.

#PBMreform #Kansas #Pharmacy #MedSky #PharmSky

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Euan Reid

@euanreid.pharmsky.app

22 hours ago

Statement: RPS opposes the Assisted Dying Bill in Scotland | Royal Pharmaceutical Society | RPS

The correct decision @rpharms.com

RPS opposes the Assisted Dying Bill in Scotland.
#Pharmsky

www.rpharms.com/about-us/new...

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Shicheng Guo

@shihcheng.bsky.social

22 hours ago

LLM-assisted systematic review of large language models in clinical medicine | Nature Medicine Clinical evaluations of large language models (LLMs) have rapidly expanded since 2022, yet their evidence base remains opaque. The overwhelming volume of studies creates challenges for manual curation and review. However, LLMs themselves offer the scalability and capability to evaluate the ever-growing evidence base. This LLM-assisted review identified 4,609 peer-reviewed studies in clinical medicine between January 2022 and September 2025, equating to roughly 3.2 papers per day. Only 1,048 studies used real-world patient data and of these only 19 were prospective randomized trials; most addressed simulated scenarios (n = 1,857) or exam-style tasks (n = 1,704). ChatGPT and related OpenAI models constitute 65.7% of evaluated models, with Gemini/Bard a distant second constituting 13.1% of evaluated models. Patient-facing communication and education comprised 17% of tasks, followed by knowledge retrieval, and education and assessment simulation. Across 1,046 head-to-head comparisons, LLMs

Exploring LLMs in clinical medicine: 4,609 studies reviewed from Jan 2022-Sep 2025, averaging 3.2 papers/day. Only 1,048 detailed. PMID:41776077, Nat Med 2026, @NatureMedicine https://doi.org/10.1038/s41591-026-04229-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

5 1 0 0

Paulb

@paulb3964.bsky.social

23 hours ago

Have to say there wasn’t much enthusiasm for this election, which could tuen out to be the most important one for decades, yet only 11.1% of members/fellows in England voted.

Is that the worst turnout ever?

#PharmSky

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Shicheng Guo

@shihcheng.bsky.social

1 day ago

Light-induced assembly and repeatable actuation in Ca2+-driven chemomechanical protein networks | Nature Communications Programming rapid, repeatable motions in soft materials has remained a challenge in active matter and biomimetic design. Here, we present a light-controlled chemomechanical network based on Tetrahymena thermophila calcium-binding protein 2 (Tcb2), a Ca2+-sensitive contractile protein. These networks—driven by Ca2+-triggered structural rearrangements—exhibit dynamic self-assembly, spatiotemporal growth, and contraction rates comparable to actomyosin systems. By coupling light-sensitive chelators for optically triggered Ca2+ release, we achieve precise growth and repeatable mechanical contractility of Tcb2 networks, revealing emergent phenomena such as boundary-localized active regions and density gradient-driven reversals in motion. A coupled reaction-diffusion and elastic model explains these dynamics, highlighting the interplay between chemical network assembly and mechanical response. We further demonstrate active transport of particles via network-mediated forces in vitro and implem

Discover proteins that mimic muscle movements: Tcb2 networks show rapid, repeatable Ca²⁺-triggered actions with light control, rivaling actomyosin speeds. PMID:41723139, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69651-2 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Shicheng Guo

@shihcheng.bsky.social

1 day ago

Roles of microtubules and LIS1 in dynein transport machinery assembly | Nature Cytoplasmic dynein-1, a microtubule (MT)-based motor protein, requires dynactin and a coiled-coil adaptor to form the processive dynein–dynactin–adaptor (DDA) complex1,2. The roles of MTs and dynein regulator lissencephaly-1 (LIS1) in DDA assembly have remained elusive. Here we use cryo-electron microscopy to determine the structural basis of MT- and LIS1-mediated DDA assembly. We show that an adaptor-independent dynein–dynactin complex spontaneously forms on MTs with an intrinsic 2:1 stoichiometry in a highly efficient manner, driven by parallel alignment of dynein tails upon MT binding. Adaptors can wedge into and exchange within the assembled MT-bound dynein–dynactin complex; these processes are enabled by relative rotations between dynein and dynactin and facilitated by the dynein light-intermediate chains that assist the adaptor ‘search’ mechanism. Although LIS1 is dispensable for efficient DD(A)–MT assembly, its presence expands the conformational landscape of DD(A) assemblies on

Study reveals dynein motor protein spontaneously forms a 2:1 dynein-dynactin complex on microtubules. LIS1's role in this assembly unveiled via cryo-EM. PMID:41708859, Nature 2026, @Nature https://doi.org/10.1038/s41586-026-10153-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

15 5 0 0

Shicheng Guo

@shihcheng.bsky.social

1 day ago

https://www.cell.com/ajhg/fulltext/S0002-9297(26)00029-7 No description available

Exciting insights from the 2025 ASHG address in Boston: advancing genetics with 10 key breakthroughs impacting 7 diseases! #HumanGenetics PMID:41795467, Am J Hum Genet 2026, @AJHGNews www.cell.com/ajhg/fulltext/S0002-9297... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

5 1 1 0

Shicheng Guo

@shihcheng.bsky.social

1 day ago

https://doi.org/10.1093/nar/gkaf1524 No description available

Discover how Cdn1's structural flexibility allows it to bind multiple cOA types and activate CRISPR defenses in prokaryotes! 📖🔬🧬 PMID:41569151, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkaf1524 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Shicheng Guo

@shihcheng.bsky.social

2 days ago

Integrase anchors viral RNA to the HIV-1 capsid interior | Nature HIV-1 integrase (IN) promotes encapsulation of viral genomic RNA into mature viral cores, and this function is a target for ongoing antiretroviral drug development efforts1–3. Here we determined the cryogenic electron microscopy (cryo-EM) structure of a primate lentiviral IN in a complex with RNA, revealing a linear filament made of IN octamer repeat units, each comprising a pair of asymmetric homotetramers. The assembly is stabilized through IN–RNA interactions involving mainly the IN C-terminal domains and RNA backbone. The spacing and orientation of the IN filament repeat units closely matched those of consecutive capsid (CA) hexamers within the mature CA lattice. Using cryo-EM images of native purified HIV-1 cores, we refined the structure of the IN filament as it propagates along the luminal side of the CA lattice. Each IN tetramer within the filament nestled in a CA hexamer, engaging closely with the major homology regions. Substitutions of residues involved in IN–CA co

Cryo-EM reveals HIV-1 integrase forms linear octameric filaments encapsulating viral RNA, crucial for drug design. Explore this structural insight! PMID:41708858, Nature 2026, @Nature https://doi.org/10.1038/s41586-026-10154-x #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Shicheng Guo

@shihcheng.bsky.social

2 days ago

https://doi.org/10.1126/science.adw4937 No description available

Poxvirus M3.1 triggers an antiviral NF-κB response in human monocytes, revealing an effector-triggered immunity (ETI) pathway. Fascinating insight! PMID:41678605, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.adw4937 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

8 4 0 0

YSUBassoon

@bassoonysu.bsky.social

2 days ago

I think it's bridged like with warfarin or enoxaparin. Not sure the dosing since that was always handled by others, especially in the Coumadin clinics.

#PharmSky #MedSky

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Shicheng Guo

@shihcheng.bsky.social

2 days ago

https://doi.org/10.1093/nar/gkag021 No description available

BAF phosphorylation is crucial for anchoring centromeric heterochromatin to the NE, affecting genome organization in eukaryotes. PMID:41569157, Nucleic Acids Res 2026, @NAR_Open https://doi.org/10.1093/nar/gkag021 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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ASPET Journals

@aspetjournals.bsky.social

2 days ago

Trying to land a job in pharmacology? Join our two-part online workshop and learn how to create high-performing resumes, and how to maximize job search strategies with AI. These sessions are presented in cooperation with Recruitomics. Learn more: https://ow.ly/pHT550YsOQV
#Pharmsky 🧪

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ASPET

@aspet-org.bsky.social

2 days ago

Trying to land a job in pharmacology? Join our two-part online workshop and learn how to create high-performing resumes, and how to maximize job search strategies with AI. These sessions are presented in cooperation with Recruitomics. Learn more: https://ow.ly/pHT550YsOQV
#Pharmsky 🧪

1 0 0 0

Shicheng Guo

@shihcheng.bsky.social

3 days ago

https://doi.org/10.1001/jamadermatol.2025.5973 No description available

A man in his 30s with 2-month scalp and lateral eyebrow hair loss. Negative hair-pull test. Diagnosis? Share thoughts! PMID:41671003, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2025.5973 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

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Veronica Zafonte

@veezaff.bsky.social

3 days ago

Does any use #cefoxitin 3g for surgical prophylaxis in obesity?
#IDSky #RxSky #PharmSky

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Stanford Antimicrobial Safety & Sustainability Program

@stanfordasp.bsky.social

3 days ago

🌟 ABX Pearl of the Day

💡 Q: My patient is admitted with an acute biliary infection. Is empiric metronidazole needed in this and other IAI?

#IDsky #MedSky #PharmSky #SkyRX #AMSsky

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ASPET Journals

@aspetjournals.bsky.social

3 days ago

Sign up for today's FREE webinar, hosted in partnership with the Association of Medical School Pharmacology Chairs, and open to anyone interested in the future of pharmacology!

Learn more: https://ow.ly/Tc5X50Yn0ya
🧪#pharmsky

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ASPET

@aspet-org.bsky.social

3 days ago

Sign up for today's FREE webinar, hosted in partnership with the Association of Medical School Pharmacology Chairs, and open to anyone interested in the future of pharmacology!

Learn more: https://ow.ly/Tc5X50Yn0ya
🧪#pharmsky

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Shicheng Guo

@shihcheng.bsky.social

3 days ago

Comprehensive profiling of CRISPR/dCas9 epigenome editors indicates a complex link between on and off target effects | Genome Biology | Springer Nature Link CRISPR/dCas9-based epigenome editing systems, including DNA methylation epimodifiers, have greatly advanced molecular functional studies, revolutionizing t

CRISPR/dCas9 epigenome editors show complex on-target and off-target effects, prompting better design for precision. Optimization is key! PMID:41620608, Genome Biol 2026 @OTSociety @NAR_Open https://doi.org/10.1186/s13059-026-03967-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

4 2 0 0

Shicheng Guo

@shihcheng.bsky.social

3 days ago

https://doi.org/10.1038/s41556-026-01876-1 No description available

THY1⁺ CSCs drive metastasis via a pseudohypoxic state. Key roles: IL-6-MYC signaling, neutrophil mitochondria. Multi-omics reveal! PMID:41680445, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01876-1 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

3 1 0 0

Shicheng Guo

@shihcheng.bsky.social

4 days ago

https://doi.org/10.1126/science.adx1616 No description available

Explore sugarcane's complexity: 9-genome pangenome graph, 47-57 haplotypes/chromo, 74K-271K alleles. Revolutionizes multiomics! PMID:41643009, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.adx1616 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

3 1 0 0

ASPET Journals

@aspetjournals.bsky.social

4 days ago

Registered for ASPET 2026? Sign up for this a hands-on workshop to help develop your career! Led by ASPET Secretary/Treasurer-Elect Allyn Howlett, PhD, FASPET, on Sunday, May 17. Learn more: https://ow.ly/2QOE50YrsY4
🧪#pharmsky

1 1 0 0

ASPET

@aspet-org.bsky.social

4 days ago

Registered for ASPET 2026? Sign up for this a hands-on workshop to help develop your career! Led by ASPET Secretary/Treasurer-Elect Allyn Howlett, PhD, FASPET, on Sunday, May 17. Learn more: https://ow.ly/2QOE50YrsY4
🧪#pharmsky

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UW–Madison School of Pharmacy

@uwmadpharmacy.bsky.social

4 days ago

A group of people in white coats sit around tables, engaging in a lively discussion. The room is filled with papers, folders, and educational materials. Some individuals are smiling and holding documents. The setting appears to be a classroom or workshop. Crayola markers are visible on one of the tables.

The UW–Madison School of Pharmacy’s new #MentalHealth Skills lab is destigmatizing the conversation around suicide — preparing student #pharmacists to identify risks, be comfortable in conversation, and connect patients with the right resources. https://bit.ly/4r3ui5o
#PharmSky #SuicidePrevention

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American Journal of Drug and Alcohol Abuse

@ajdaajournal.bsky.social

4 days ago

#PsychSciSky #DrugSky #PharmSky #MedSky #AddictionSci #NeuroSky #EpiSky #StatsSky #HealthPolicy @tandfresearch.bsky.social #methadone #buprenorphine #HarmReduction #HealthEquity #PublicHealth

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Posts tagged #PharmSky