Shicheng Guo

@shihcheng.bsky.social

2 hours ago

CRISPR-Cas12a activity enhanced! Reversible crRNA scaffold remodeling via short DNA blockers boosts precision and control. PMID:41784267, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag167 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

4 hours ago

Detect disease origins and therapy responses from just 50μl of plasma with cf-EpiTracing! Profiles histone mods, integrates chromatin states, uses AI. PMID:41781618, Nature 2026, @Nature https://doi.org/10.1038/s41586-026-10224-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

5 hours ago

Quality-oriented diet therapy for chronic kidney disease | Nature Reviews Nephrology Traditional dietary advice for people living with chronic kidney disease (CKD) focused predominantly on the quantity of energy and protein provided by the diet as well as restricting the consumption of single micronutrients. However, flaws in the assumptions that underlie this quantity-based approach have led to re-examination of medical nutrition therapy for kidney-related conditions, with a shift towards recommending more varied and liberalized plant-rich diets with a focus on dietary quality. Although clinical practice guidelines for patients with CKD have cautiously acknowledged this shift, less advice is available on how to translate new knowledge into practical and feasible recommendations that describe which foods patients should be advised to eat. In this Review, we provide a framework for the delivery of quality-oriented diet therapy for people with CKD based on the dietary principles of balance, variety and moderation. This approach also requires consideration of the manner i

Revised CKD diet therapy: Move from rigid nutrient limits to diverse, plant-rich focus for improved nutrition quality! PMID:41491876, Nat Rev Nephrol 2026, @NatRevNeph https://doi.org/10.1038/s41581-025-01034-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

6 hours ago

Health of adipose tissue: oestrogen matters | Nature Reviews Endocrinology Menopausal women are more likely than premenopausal women to gain weight in the form of excess adipose tissue, which becomes preferentially deposited in the viscera. This body composition shift, largely driven by declining oestrogen levels, increases cardiometabolic disease risk. Oestrogens are key hormones involved in many metabolic processes, including in adipose tissue. Given the strong influence that adipose tissue health has on systemic metabolism, additional insights into mechanisms by which oestrogens affect adipose tissue phenotype and function are critical. Not only is adipose tissue affected by oestrogen signalling, adipose tissue is also a major source of circulating oestrogens, and the only appreciable source of oestrogens for men and postmenopausal women. Therefore, women with obesity have higher circulating levels of oestrogens, but whether this fact contributes to the diverse comorbidities of obesity (such as, cancer, metabolic syndrome and osteoporosis) remains unclear.

Menopause ups visceral fat, often due to lower oestrogen, raising cardiometabolic risk in women. Insights needed! PMID:41006902, Nat Rev Endocrinol 2026, @NatureRevEndo https://doi.org/10.1038/s41574-025-01180-2 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

19 hours ago

Prime Editing corrects delGT in NCF1 for p47^phox-deficient CGD. Two participants received stem-cell therapy PM359 with busulfan prep. PMID:41358590, N Engl J Med 2026, @NEJM https://doi.org/10.1056/NEJMoa2509807 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

21 hours ago

Programmable macromolecule delivery via engineered trogocytosis | Nature Cell Biology Trogocytosis, the transfer of plasma membrane fragments during cell–cell contact, offers potential for macromolecular delivery but is limited by the uncertain fate of trogocytosed molecules, restriction to membrane cargo and unclear generalizability. Here we demonstrate that donor cells engineered with designed receptors specific to surface ligands can transfer proteins to recipient cells through direct contact. We identified key engineering principles for enhancing transfer and ensuring cargo functionalization, including receptor design, pH-responsive membrane fusion, inducible cargo localization and release, and subcellular translocation. The method is broadly applicable across diverse cell types and operates through a dynamin- and endosome acidification-dependent pathway. Exploiting these findings, we developed TRANSFER, a versatile delivery system with programmable cell type specificity and tunability. TRANSFER can sense multiple ligand inputs, deliver large therapeutic protein car

New tech for macromolecule transfer: Engineered receptors enable direct protein delivery between cells via trogocytosis! #BiotechRevolution PMID:41922519, Nat Cell Biol 2026, @NatureCellBio @Stanford https://doi.org/10.1038/s41556-026-01920-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

22 hours ago

DPEP2 cuts sepsis death risk, regulating inflammation via macrophage metabolism. Reduced DPEP2 in sepsis correlates with severe inflammation and outcomes. PMID:41803155, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70466-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

1 day ago

Glucocorticoids in the ED for migraine may pose risks; not advised as first-line for adults or kids. Use with caution! PMID:41661582, JAMA Neurol 2026, @JAMANeuro https://doi.org/10.1001/jamaneurol.2025.5493 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

2 days ago

Discover how a new protein family, designed via deep learning and physics methods, achieves nanomolar to low micromolar affinities for 6 small molecules! PMID:41904144, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70953-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

2 days ago

A study finds NANP inhibition radiosensitizes glioblastoma by a TNFR1-driven mesenchymal shift, potentially improving GBM therapy. PMID:41851195, Nat Commun 2026, @NatureComms @OTSociety @NAR_Open https://doi.org/10.1038/s41467-026-70853-x #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

2 days ago

Magnetic resonance microscopy maps widespread effects of Alzheimer’s disease on brain structures and behavior in mice | Nature Neuroscience Alzheimer’s disease has widespread effects on brain structure, function and behavior, but we lack a systematic dissection of its impact across hundreds of forebrain and brainstem regions. Here, using diffusion tensor MRI at 25 µm, we mapped the global consequences of mutations in APP and PSEN1 across 231 regions of interest (ROIs) in male and female 5×FAD BXD hybrid mice at 14 months. Over half of the ROIs change in volume along rostrocaudal and mediolateral axes of the CNS, with unexpected swelling in the neocortex, hippocampus and amygdala of up to 10%, counterbalanced by shrinkage in the thalamus, brainstem and most white matter tracts. Yet, total brain volume is unaltered. Variation in individual ROI volumes is highest in females. Differences in fear acquisition and contextual memory performance covary with volumes of several regions and can have opposite polarities between cases and controls. These structural benchmarks establish a foundation for testing therapeutic interventions

Alzheimer's mutations in APP/PSEN1 alter over 50% of 231 brain regions in 5×FAD BXD mice. Detailed MRI maps reveal vast changes at 25μm. PMID:41748785, Nat Neurosci 2026, @NatureNeuro https://doi.org/10.1038/s41593-025-02199-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

2 days ago

Chronic kidney disease affects ~10% globally, challenging the single-cause approach. Reassessing kidney capacity-workload balance is key. PMID:41491877, Nat Rev Nephrol 2026, @NatRevNeph https://doi.org/10.1038/s41581-025-01038-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

2 days ago

CRISPR/Cas9 screening unveils PABPN1 at APA's core. A dBFPR strategy spots APA regulators, boosting detection efficiency. PMID:41755634, Nucleic Acids Res 2026, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkag172 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

3 days ago

Woman, 60s, with 3-year pulmonary hypertension, 2-month dyspnea, and abdominal distension. Possible diagnosis? Let's discuss! 🎯 PMID:41879764, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0019 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

3 days ago

Reimagine “skin of color” in dermatology—shift to a pigment-focused approach, embracing biological nuances and socio-context sans race. PMID:41848719, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0151 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

4 days ago

An agentic system for rare disease diagnosis with traceable reasoning | Nature Rare diseases affect more than 300 million people worldwide1–3, yet timely and accurate diagnosis remains an urgent challenge1,3–5. Patients often endure a prolonged ‘diagnostic odyssey’ exceeding 5 years, marked by repeated referrals, misdiagnoses and unnecessary interventions, leading to delayed treatment and substantial emotional and economic burden4,5. Here we present DeepRare—a multi-agent system for rare disease differential diagnosis decision support6–8 powered by large language models, integrating more than 40 specialized tools and up-to-date knowledge sources. DeepRare processes heterogeneous clinical inputs, including free-text descriptions, structured human phenotype ontology terms and genetic testing results to generate ranked diagnostic hypotheses with transparent reasoning linked to verifiable medical evidence. Evaluated across nine datasets from literature, case reports and clinical centres across Asia, North America and Europe spanning 14 medical specialties, DeepRare d

DeepRare transforms rare disease diagnosis. It cuts the 5+ year "diagnostic odyssey", reducing emotional and economic costs for 300M affected globally. PMID:41708847, Nature 2026, @Nature https://doi.org/10.1038/s41586-025-10097-9 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

4 days ago

Base barrier cells provide compartmentalization of choroid plexus, brain and CSF | Nature Neuroscience The choroid plexus (ChP), located in the brain ventricles, is largely composed of ChP epithelial cells that produce the cerebrospinal fluid (CSF) and form the blood–CSF barrier. At the ChP–brain attachment sites, we have discovered unique fibroblasts referred to as ChP base barrier cells (BBCs). We show that ChP BBCs originate from meningeal mesenchymal precursors, arrive early during development, remain throughout life and are conserved across species. ChP BBCs are transcriptionally similar to meningeal arachnoid barrier cells and are interconnected by both adherens and tight junctions. Notably, we provide evidence that the BBCs function as a barrier, controlling communication between the periphery and central nervous system. Moreover, during inflammatory insult, we observed a loss of barrier integrity and immune cell crossing. Altogether, our research revealed a barrier at the ChP base, crucial in protecting the central nervous system by compartmentalizing the ChP stroma, brain paren

Choroid plexus base barrier cells, derived from meningeal mesenchymal precursors, form blood-CSF barrier, exist lifelong! PMID:41680326, Nat Neurosci 2026, @NatureNeuro https://doi.org/10.1038/s41593-025-02188-7 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

4 days ago

Man in 90s: granulomatous dermatitis treated with topical delgocitinib. Successful outcome highlighted in JAMA Derm report! PMID:41811334, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2025.6123 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

4 days ago

Preventing HFS in cancer patients: A meta-analysis of 21 RCTs shows promise in pharmacologic strategies against chemotherapy-induced HFS. PMID:41779386, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0042 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

5 days ago

Cardiotoxicity of T cell immunotherapies | Nature Reviews Cardiology T cell immunotherapies offer a new approach to cancer therapy. Chimeric antigen receptor (CAR) T cell therapy is the most prolific of these treatments, leveraging genetically engineered T cells to augment the antitumour response. Bispecific antibodies, T cell receptor-engineered T cells and tumour-infiltrating lymphocytes have also emerged as novel T cell therapies with therapeutic benefit. As the variety of T cell therapies and indications for their use expand, a nuanced understanding of potential haemodynamic sequelae and cardiovascular toxicities is required. T cell activation can lead to massive cytokine release and excessive inflammation, termed cytokine release syndrome (CRS). Like other inflammatory syndromes, CRS can lead to cardiovascular complications, including arrhythmias, myocardial infarction and heart failure, with an incidence of cardiovascular events as high as 20% among patients who develop high-grade CRS. In this Review, we summarize the mechanisms, epidemiology and

T cell immunotherapies, like CAR T cells and bispecific antibodies, boost cancer treatment but can risk heart toxicity. PMID:41730987, Nat Rev Cardiol 2026, @NatRevCardiol https://doi.org/10.1038/s41569-026-01265-z #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

5 days ago

AI's potential in melanoma diagnostics explored: Analysis of dermoscopy, AI, and AI-assisted dermatology shows promising results for future clinical use. PMID:41879756, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0217 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

5 days ago

Post-pandemic changes in population immunity have reduced the likelihood of emergence of zoonotic coronaviruses | Nature Communications Infections by endemic viruses, and the vaccines used to control them, often provide cross-protection against related viruses, potentially altering the transmission dynamics and likelihood of emergence of new zoonotic viruses with pandemic potential. Here, we investigate how population immunity after the COVID-19 pandemic has impacted the likelihood of emergence of a novel sarbecovirus, termed SARS-CoV-X. To this end, we combined empirical cross-neutralisation data with mathematical modelling to identify key immunological and epidemiological factors shaping sarbecovirus emergence. We show that sera from individuals with different COVID-19 immunological histories contained cross-neutralising antibodies against the spike (S) protein of multiple zoonotic sarbecoviruses. Simulations parameterised by these data predict that the likelihood of emergence of a novel sarbecovirus has been reduced significantly by population cross-immunity, with outcomes determined by the extent of cross-protectio

Post-COVID population immunity lowers new zoonotic coronavirus risk. Study: Cross-neutralization data + models show reduced SARS-CoV-X threat. PMID:41876522, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69988-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

5 days ago

NCBP1 stress signaling drives alternative S6K1 splicing inhibiting translation | Nature Chemical Biology Subcellular stress profoundly influences protein synthesis. However, both the nature of spatiotemporally restricted chemical cues and local protein responders to these cues remain elusive. Unlocking these mechanisms requires the ability to functionally map in living systems locale-specific stress responder proteins and interrogate how chemical modification of each responder impacts proteome synthesis. We resolved this problem by integrating precision localized electrophile generation and genetic code expansion tools. Upon examination of four distinct subcellular locales, only nuclear-targeted electrophile stress stalled translation. We discovered that NCBP1—a nuclear-resident protein with multifaceted roles in eukaryotic mRNA biogenesis—propagated this nuclear stress signal through a single cysteine (C436) from among its 19 conserved cysteines. This NCBP1(C436)-specific modification elicited alternative splicing of more than 250 genes. Mechanistically, global protein synthesis stall wa

NCBP₁ stress signaling alters S6K₁ splicing, hindering translation. Researchers integrated localized electrophile methods. PMID:41667655, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-025-02135-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

5 days ago

CDK9 phosphorylates NF-κB p65 in cardiomyocytes, fueling inflammation and remodeling in hypertensive heart failure. Potential target: Thr-186 site. PMID:41876530, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70410-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

5 days ago

EBV alters the transcriptome and immunopeptidome in HLA-DR15+ B cells, enhancing myelin peptide presentation, potentially driving MS pathogenesis. PMID:41534530, Cell 2026, @Cell www.cell.com/cell/fulltext/S0092-8674... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

6 days ago

Ewing sarcoma proteomics: 10,000+ proteins studied in 170 tumor samples from 74 patients, offering key insights into prognosis and chemoresistance. PMID:41813675, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70449-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

6 days ago

Mast cell extracellular granules are bioactive condensates assembled by heparin and polyamine | Nature Chemical Biology Biomolecular condensates are membraneless bodies that organize biochemical reactions typically within cells. However, the roles of condensates in extracellular space—where conditions differ substantially from intracellular space—remain poorly understood. Here we report that mast cell extracellular granules (MCEGs), a stable membraneless entity, are condensates assembled through electrostatic interactions between glycosaminoglycans and polyamines. Disrupting polyamine synthesis or trafficking blocks MCEG formation and compromises the storage of proteases and cytokines. Granules reconstituted with heparin and spermine are sufficient to enrich mediators such as carboxypeptidase A3 (CPA3) and tumor necrosis factor (TNF), maintaining an elevated pH and higher concentrations of calcium and zinc compared to the extracellular milieu. This unique environment enhances CPA3 enzymatic activity. Furthermore, the granules increase TNF binding and its bioactivity toward endothelial cells. Together, w

Mast cell extracellular granules (MCEGs) are bioactive condensates formed by heparin and polyamines, crucial for immune responses. PMID:41760814, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-026-02165-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

6 days ago

Discover MULTI-evolve: a rapid evolution method efficiently engineering protein multimutants using AI. Transform lengthy, costly trials! PMID:41712694, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.aea1820 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

6 days ago

RNA-specific local translation is patterned by condensates for multinucleate cell growth | Nature Cell Biology Coordination between growth and nuclear division is a common cell feature. In some syncytia, nuclei divide asynchronously throughout the cell but growth occurs only at discrete locations, raising the question how the processes are locally regulated and globally coordinated. In the syncytial fungus Ashbya gossypii, both cell cycle progression and hyphal elongation require condensates formed by the protein Whi3 in complex with distinct mRNA species. Here we show that Whi3 condensates are enriched for translation regulators and are associated with local, spatially patterned translation of specific target RNAs near nuclei and growth sites. Whi3–RNA condensates can both promote and repress mRNA translation in an RNA- and condensate size-dependent manner in vitro. Condensate interfaces are sites of translation, tunable by condensate composition, RNA valency and protein charge state in vitro. Together, these data suggest that Whi3 condensates can generate a continuum of translation states tha

In Ashbya gossypii, Whi3 protein forms RNA condensates to synchronize nuclear division and growth in multinucleate cells. PMID:41772090, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01887-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Shicheng Guo

@shihcheng.bsky.social

1 week ago

Discover the promise: Intralesional interleukin-2 therapy shows potential in treating high-risk or sensitive cSCC cases! 🎯📊 PMID:41848721, JAMA Dermatol 2026 https://doi.org/10.1001/jamadermatol.2026.0181 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪