Shicheng Guo

Eighteen million years of diverse enamel proteomes from the East African Rift | Nature Research into the palaeobiology of extinct taxa through ancient DNA and proteomics has been mostly limited to Plio-Pleistocene fossils1–9, due to molecular breakdown over time, which is exacerbated in tropical settings1–3. Here we sample small proteomes from the interior enamel of fossils at palaeontological sites from the Pleistocene to the Oligocene in the Turkana Basin, Kenya, which has produced a rich record of Cenozoic mammalian evolution10. Through a mass-spectrometry-based proteomic workflow, and using criteria to locate diagenetiforms derived from enamel, we recover fragments of enamelin, ameloblastin, matrix metalloprotease-20 and dentin matrix acidic phosphoprotein 1 from an Early Miocene rhinocerotid and several proboscideans collected from the sites of Buluk (16 million years ago; Ma) and Loperot (18 Ma). Diagenetiform counts decline in progressively older fossils, and we observe variability in Early Miocene preservation across sites. Phylogenetic analyses reveal the contri

Discovering 18M years of enamel proteomes in Kenya's Turkana Basin offers new insights into mammalian evolution, breaking limits in ancient biomolecule research! PMID:40634615, Nature 2025, @Nature https://doi.org/10.1038/s41586-025-09040-9 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

How stem cells respond to infection, inflammation and ageing | Nature Reviews Immunology Stem cells maintain tissue architecture by replacing differentiated cells at steady state and upon injury. Implementing this cornerstone role requires protection of stem cells from pathogens and from the toxic effects of immune system activation. However, the pro-inflammatory innate immune mechanisms that protect differentiated cells from infection are poorly functional in stem cells. Instead, stem cells employ other specific defence mechanisms, such as antiviral RNA interference. At steady state, the proliferation and differentiation of tissue stem cells is regulated by multiple cell types, including immune cells. Following sterile tissue injury or during infection, the immune response — in addition to controlling pathogens and clearing cell debris — orchestrates tissue repair by fine-tuning stem cell activity, through direct cell–cell contacts and via inflammatory mediators such as cytokines. There is thus stem–immune cross-talk that is fundamental to the maintenance of tissue homeos

Stem cells replace cells but need protection from pathogens. Their pro-inflammatory defenses are limited, using RNAi instead. PMID:40707693, Nat Rev Immunol 2025, @NatRevImmunol https://doi.org/10.1038/s41577-025-01203-z #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A role for microglia in mediating the microbiota–gut–brain axis | Nature Reviews Immunology Microglia, the resident immune cells of the brain, are now recognized as being active participants in the onset and progression of many neurological and neuropsychiatric disorders. As a result, substantial effort has been made in finding ways to target, deplete or modulate the aberrant phenotypes of the microglia that are present in these different disease states, albeit with varied levels of success. The gut microbiota has recently emerged as a master regulator of microglia throughout the lifespan; here, we propose that this microbiota–microglia cross-talk may have major implications for our understanding of neurological disorders and neuropsychiatric diseases. We focus on the latest advances in understanding gut–microglia communication in the context of microglial heterogeneity and microglia-related functions, as well as considering the evidence for effects of these pathways on diseases and disorders of the central nervous system. We also address the challenges, opportunities and cli

Microglia, brain's immune cells, influenced by gut microbiota, play roles in neurological disorders. Potential target for therapy. PMID:40506470, Nat Rev Immunol 2025, @NatRevImmunol https://doi.org/10.1038/s41577-025-01188-9 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

5 authors reveal misattributed paternity (MP) findings, critiquing 15 guidelines from medical organizations for 10 key hazards. #MPDiscovery PMID:39904342, Am J Hum Genet 2025, @AJHGNews https://www.cell.com/ajhg/fulltext/S0002-9297(25)00006-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A DNA-gated molecular guard controls bacterial Hailong anti-phage defence | Nature Animal and bacterial cells use nucleotidyltransferase (NTase) enzymes to respond to viral infection and control major forms of immune signalling including cGAS-STING innate immunity and CBASS anti-phage defence1–4. Here we discover a family of bacterial defence systems, which we name Hailong, that use NTase enzymes to constitutively synthesize DNA signals and guard against phage infection. Hailong protein B (HalB) is an NTase that converts deoxy-ATP into single-stranded DNA oligomers. A series of X-ray crystal structures define a stepwise mechanism of HalB DNA synthesis initiated by a C-terminal tyrosine residue that enables de novo enzymatic priming. We show that HalB DNA signals bind to and repress activation of a partnering Hailong protein A (HalA) effector complex. A 2.0-Å cryo-electron microscopy structure of the HalA–DNA complex reveals a membrane protein with a conserved ion channel domain and a unique crown domain that binds the DNA signal and gates activation. Analysing Hailon

Discover the Hailong defense: NTase enzyme HalB turns deoxy-ATP into DNA oligomers to protect bacteria from phages. A groundbreaking insight in immunology! PMID:40306316, Nature 2025, @Nature https://doi.org/10.1038/s41586-025-09058-z #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Explore L2S2, a web tool featuring 1.678M gene sets from 248 cell lines affected by 33,621 compounds & 7,508 CRISPR KOs. Discover insights fast! PMID:40308216, Nucleic Acids Res 2025, @NAR_Open https://doi.org/10.1093/nar/gkaf373 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Polyglycine aggregates disrupted tRNA processing in GGC repeat disorders by incorporating FAM98B, affecting neurodegeneration. PMID:40674500, Science 2025, @ScienceMagazine https://doi.org/10.1126/science.ado2403 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Lutetium-177–PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial | Nature Medicine The prostate-specific membrane antigen (PSMA)-targeted radioligand [¹⁷⁷Lu]Lu–PSMA-617 is a new standard treatment for metastatic castration-resistant prostate cancer (mCRPC), but predictive genomic biomarkers informing its rational use are unknown. We performed detailed dissection of prostate cancer driver genes across 290 serial plasma cell-free DNA samples from 180 molecular imaging-selected patients with mCRPC from the randomized TheraP trial of [¹⁷⁷Lu]Lu–PSMA-617 (n = 97) versus cabazitaxel chemotherapy (n = 83). The primary endpoint was PSA50 biochemical response, with secondary endpoints of progression-free survival (PFS) and overall survival (OS). In this post-hoc biomarker analysis, a low pretreatment circulating tumor DNA (ctDNA) fraction predicted a superior biochemical response (100% versus 58%, P = 0.0067) and PFS (median 14.7 versus 6.0 months; hazard ratio 0.12, P = 2.5 × 10−4) on [¹⁷⁷Lu]Lu–PSMA-617 independent of predictive PSMA–positron emission tomography imaging param

Study of 177Lu-PSMA-617 vs cabazitaxel in 180 mCRPC patients reveals circulating tumor DNA insights from 290 plasma samples! PMID:40425844, Nat Med 2025, @NatureMedicine https://doi.org/10.1038/s41591-025-03704-9 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Labelizer: systematic selection of protein residues for covalent fluorophore labeling | Nature Communications Attaching fluorescent dyes to biomolecules is essential for assays in biology, biochemistry, biophysics, biomedicine and imaging. A systematic approach for the selection of suitable labeling sites in macromolecules, particularly proteins, is missing. We present a quantitative strategy to identify such protein residues using a naïve Bayes classifier. Analysis of >100 proteins with ~400 successfully labeled residues allows to identify four parameters, which can rank residues via a single metric (the label score). The approach is tested and benchmarked by inspection of literature data and experiments on the expression level, degree of labelling, and success in FRET assays of different bacterial substrate binding proteins. With the paper, we provide a python package and webserver ( https://labelizer.bio.lmu.de/ ), that performs an analysis of a pdb-structure (or model), label score calculation, and FRET assay scoring. The approach can facilitate to build up a central open-access databas

Discover a method to select protein sites for dye labeling using a Naïve Bayes classifier. Analyzed 100+ proteins and ~400 residues for optimal picks. PMID:40319045, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-58602-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Innovative approach creates proteins targeting 39 diverse intrinsically disordered regions, unlocking new potential in complex systems! PMID:40674483, Science 2025, @ScienceMagazine https://doi.org/10.1126/science.adr8063 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

CBM588 showed 42% improved recovery post-CRC surgery! 🎉 #CBM588 #ColorectalCancer PMID:40633539, Cell Rep Med 2025 https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00307-6?rss=yes&utm_source=dlvr.it&utm_medium=twitter #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Identifying fibroblast-derived sFRP2 as a therapeutic target and engineering siRNA therapy for uterine scarring | Nature Communications Uterine scarring is a common complication following uterine injury, characterized by abnormal wound healing in the endometrial or myometrial tissue. However, the underlying mechanisms contributing to scar formation remain unclear, impeding the development of effective drugs for uterine scarring. Here, we identify that secreted frizzled-related protein 2 (sFRP2) is highly expressed in human and mouse uterine tissues with uterine scarring, particularly in uterine fibroblasts. Using female mouse models, we demonstrate that sFRP2 overexpression in the healthy uterus induces uterine scarring features and exacerbates surgery-induced fibrosis, while sFRP2 knockdown inhibits uterine scarring development and fibrotic transformation in uterine fibroblasts, highlighting the pivotal role of sFRP2 as an initiating driver in uterine scarring pathogenesis. Mechanistically, sFRP2 promotes uterine scar formation by activating the non-canonical Wnt signaling pathway and calcium influx in uterine fibrobl

Discovering that sFRP2 is highly expressed in uterine scarring, a potential drug target emerges! siRNA therapy may revolutionize treatment. Your thoughts? PMID:40715133, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-62248-1 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cryo-EM structure of native honey bee vitellogenin | Nature Communications Vitellogenin (Vg) is the main yolk precursor lipoprotein in almost all egg-laying animals. In addition, along its evolutionary history, Vg has developed a range of new functions in different taxa. In the honey bee, Vg has functions related to immunity, antioxidant protection, social behavior and longevity. However, the molecular mechanisms underlying Vg functionalities are still poorly understood. Here, we report the cryo-EM structure of full-length honey bee Vg, one-step purified directly from hemolymph. The structure provides structural insights into the overall domain architecture, including the lipid binding cavity and the previously uncharacterized von Willebrand factor type D domain. A domain of unknown function has been identified as a C-terminal cystine knot domain based on structural homology. Information about post-translational modifications, cleavage products, metal and lipid binding allow an improved understanding of the mechanisms underlying the range of Vg functionalitie

Discover the cryo-EM structure of honey bee vitellogenin, revealing insights into its roles in immunity, antioxidant defense, behavior, & longevity. PMID:40593495, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-58575-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Allosteric modulation and biased signalling at free fatty acid receptor 2 | Nature Free fatty acid receptor 2 (FFA2) is a G protein-coupled receptor (GPCR) that is a primary sensor for short-chain fatty acids produced by gut microbiota. Consequently, FFA2 is a promising drug target for immunometabolic disorders1–4. Here we report cryogenic electronic microscopy structures of FFA2 in complex with two G proteins and three distinct classes of positive allosteric modulators (PAMs), and describe noncanonical activation mechanisms that involve conserved structural features of class A GPCRs. Two PAMs disrupt the E/DRY activation microswitch5 and stabilize the conformation of intracellular loop 2 by binding to lipid-facing pockets near the cytoplasmic side of the receptor. By contrast, the third PAM promotes the separation of transmembrane helices 6 and 7 by interacting with transmembrane helix 6 at the receptor–lipid interface. Molecular dynamic simulations and mutagenesis experiments confirm these noncanonical activation mechanisms. Furthermore, we demonstrate the molecula

Discover how FFA2, a key GPCR sensing short-chain fatty acids, is structurally influenced by 2 G-proteins and 3 PAMs. Unveiling new drug pathways! PMID:40533560, Nature 2025, @Nature https://doi.org/10.1038/s41586-025-09186-6 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Economic analysis shows hidradenitis suppurativa unroofing costs rose from 2005 to 2020, critical amid rising medical inflation. PMID:40332903, JAMA Dermatol 2025 https://doi.org/10.1001/jamadermatol.2025.0819 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Natural variation of AcEGY3 mediates chloroplastic ROS homeostasis to confer kiwifruit thermotolerance | Nature Communications The genus of Actinidia consists of the popular kiwifruits consuming worldwide. Most kiwifruit species are naturally distributed in warm and moist environments. So, they are vulnerable to high levels of heat stress. Till now, genetic basis of kiwifruit thermotolerance has remained largely unexplored. Here, we uncover a natural variation responsible for thermotolerance in kiwifruit species. We reveal that thermotolerant kiwifruit species have increased expression of AcEGY3, a gene encoding a chloroplast-localized protein, which can promote expression of nuclear thermotolerance genes via H2O2-dependent retrograde signaling. We show that natural variation in the promoter of AcEGY3 constitute a binding site for the heat stress-inducible transcription factor AcGATA1. The increased expression of AcEGY3 is regulated by AcGATA1 and its possible interaction with another transcription factor AcHSFA2-2. This natural variation is absent from the thermosensitive kiwifruit species. Collectively, our

Kiwifruits' thermotolerance linked to AcEGY3 gene. Higher expression in resilient species helps maintain chloroplastic ROS homeostasis under heat stress. 🍃 PMID:40615434, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-61593-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Discover BEscreen: a dynamic tool for designing sgRNA libraries for base editing. Create scalable, versatile genetic screens today! PMID:40384567, Nucleic Acids Res 2025, @NAR_Open https://doi.org/10.1093/nar/gkaf406 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Structural insights into the roles of PARP4 and NAD+ binding in the human vault cage | Nature Communications Vault is a massive ribonucleoprotein complex found across Eukaryota. The major vault protein (MVP) oligomerizes into an ovular cage, which contains several minor vault components (MVCs) and is thought to transport transiently bound “cargo” molecules. Vertebrate vaults house a poly (ADP-ribose) polymerase (known as PARP4 in humans), which is the only MVC with known enzymatic activity. Despite being discovered decades ago, the molecular basis for PARP4’s interaction with MVP remains unclear. In this study, we determined the structure of the human vault cage in complex with PARP4 and its enzymatic substrate NAD+. The structures reveal atomic-level details of the protein-binding interface, as well as unexpected binding sites for NAD+ and related nucleotides within the interior of the vault cage. In addition, proteomics data show that human vaults purified from wild-type and PARP4-depleted cells interact with distinct subsets of proteins. Our results thereby support a model in which PARP4’s

Explore vault mysteries: Structural insights reveal PARP4 binds with vault's MVP, using NAD+ to potentially influence cargo transport in 1 massive complex! PMID:40691181, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-61981-x #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Surveying 50+ NHS clinical scientists at CanVIG-UK revealed barriers to MAVE adoption: 85% citing need for robust validation! #Genetics PMID:40480200, Am J Hum Genet 2025, @AJHGNews https://www.cell.com/ajhg/fulltext/S0002-9297(25)00147-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

AI agents developed in a virtual lab design new SARS-CoV-2 nanobodies. This innovation overcomes interdisciplinary barriers, enhancing research collaboration. PMID:40730228, Nature 2025, @Nature https://doi.org/10.1038/s41586-025-09442-9 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A microRNA-based dynamic risk score for type 1 diabetes | Nature Medicine Identifying individuals at high risk of type 1 diabetes (T1D) is crucial as disease-delaying medications are available. Here we report a microRNA (miRNA)-based dynamic (responsive to the environment) risk score developed using multicenter, multiethnic and multicountry (‘multicontext’) cohorts for T1D risk stratification. Discovery (wet and dry lab) analysis identified 50 miRNAs associated with functional β cell loss, which is a hallmark of T1D. These miRNAs measured across n = 2,204 individuals from four contexts (4C: Australia, Denmark, Hong Kong SAR People’s Republic of China, India) led to a four-context, miRNA-based dynamic risk score (DRS) that effectively stratified individuals with and without T1D. Generative artificial intelligence was used to create an enhanced four-context, miRNA-based DRS, which offered good predictive power (area under the curve = 0.84) for T1D stratification in a separate multicontext validation dataset (n = 662), and accurately predicted future exogenous

Study unveils a dynamic miRNA-based risk score for T1D. Analyzing 50 miRNAs, it offers improved risk stratification across diverse cohorts. PMID:40473952, Nat Med 2025, @NatureMedicine https://doi.org/10.1038/s41591-025-03730-7 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Neoadjuvant ARX788 plus pyrotinib versus trastuzumab, pertuzumab, docetaxel and carboplatin for HER2-positive breast cancer: a randomised phase 2b trial | Nature Communications Antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) are widely used for HER2-positive metastatic breast cancer, but their efficacy in the neoadjuvant setting remains under investigation. The MUKDEN 06 trial (NCT05426486), a multicentre, randomised, phase 2b study, compared ARX788 (anti-HER2 ADC) plus pyrotinib (TKI) with the standard neoadjuvant regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCbHP) in female patients with early or locally advanced HER2-positive breast cancer. The primary endpoint was the pathological complete response (pCR, ypT0/is, ypN0) rate, analyzed in the intention-to-treat population. pCR was achieved in 70.6% (48/68) of patients receiving ARX788 plus pyrotinib, compared to 51.5% (35/68) in the TCbHP group, with a significant absolute difference of 19.1% (95% CI, 2.7–34.6; p = 0.023). No treatment-related deaths occurred. The most common grade 3–4 adverse events were diarrhea and hepatic dysfunction in the ARX788 plus pyrotinib

MUKDEN 06 trial: ARX788 + Pyrotinib vs. TCbHP for HER2+ breast cancer in neoadjuvant setting. Phase 2b results: promising efficacy and safety. PMID:40593759, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-61213-2 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Phase separation instead of binding strength determines target specificities of MAGUKs | Nature Chemical Biology Homologous proteins often have distinct functions, even if they share overlapping binding targets. PSD-95 and MAGI-2, two membrane-associated guanylate kinase (MAGUK)-family scaffolds in neuronal synapses, exemplify this. With unknown mechanisms, the two MAGUKs are localized at distinct subsynaptic compartments with PSD-95 inside the postsynaptic density (PSD) and MAGI-2 outside. Here we demonstrate that MAGI-2 forms condensates through phase separation. When coexisting with PSD proteins, the MAGI-2 condensate can enrich the extrasynaptic N-cadherin–β-catenin adhesion complex and the MAGI-2 condensates are immiscible with the PSD-95 condensates. Surprisingly, phosphorylated SAPAP is selectively enriched in the PSD-95 condensate, even though it binds to MAGI-2 with a higher affinity. The specific localization of SAPAP is because of the higher network complexities of the PSD-95-containing condensate than the MAGI-2 condensate. Thus, phase-separation-mediated molecular condensate formatio

Discover how MAGUKs differentiate: phase separation, not binding strength, guides target specificity. PSD-95 & MAGI-2 roles decoded! PMID:40494974, Nat Chem Biol 2025, @nchembio https://doi.org/10.1038/s41589-025-01925-0 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Discover scleroderma: symptoms, diagnosis, and treatments boiled down! Dive into the essentials: skin hardening, Raynaud's, lung issues. 🩺 PMID:40238140, JAMA Dermatol 2025 https://doi.org/10.1001/jamadermatol.2024.5291 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Guselkumab (100 mg) shows promise for moderate-severe scalp psoriasis in skin of color. 48-week VISIBLE trial data on efficacy & safety. PMID:40560554, JAMA Dermatol 2025 https://doi.org/10.1001/jamadermatol.2025.1849 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

The impact of library size and scale of testing on virtual screening | Nature Chemical Biology Virtual ligand libraries for ligand discovery have recently increased 10,000-fold. Whether this has improved hit rates and potencies has not been directly tested. Meanwhile, typically only dozens of docking hits are assayed, clouding hit-rate interpretation. Here we docked a 1.7 billion-molecule virtual library against β-lactamase, testing 1,521 new molecules and comparing the results to a 99 million-molecule screen where 44 molecules were tested. In a larger screen, hit rates improved twofold, more scaffolds were discovered and potency improved. Fifty-fold more inhibitors were found, supporting the idea that the large libraries harbor many more ligands than are being tested. In sampling smaller sets from the 1,521, hit rates only converged when several hundred molecules were tested. Hit rates and affinities improved steadily with docking score. It may be that as the scale of docking libraries and their testing grows, both ligands and our ability to rank them will improve. The docking

A study docked 1.7B molecules against β-lactamase, testing 1,521 vs. a 99M screen with 44. Larger screens offer insights on hit rates. PMID:39753705, Nat Chem Biol 2025, @nchembio https://doi.org/10.1038/s41589-024-01797-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

In a phase 3 trial, Trastuzumab Deruxtecan (6.4 mg/kg) was compared as 2nd-line treatment vs Ramucirumab+Paclitaxel in HER2+ gastric cancer. PMID:40454632, N Engl J Med 2025, @NEJM https://doi.org/10.1056/NEJMoa2503119 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cryo-EM reveals human telomerase dimer structure at 4.2 Å, showing H/ACA RNP roles in dimerization beyond monomers. PMID:40638752, Science 2025, @ScienceMagazine https://doi.org/10.1126/science.adr5817 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer | Nature Communications Ovarian cancer has the highest mortality rate among gynecologic tumors worldwide, with unclear underlying mechanisms of pathogenesis. RNA-binding proteins (RBPs) primarily direct post-transcriptional regulation through modulating RNA metabolism. Recent evidence demonstrates that RBPs are also implicated in transcriptional control. However, the role and mechanism of RBP-mediated transcriptional regulation in tumorigenesis remain largely unexplored. Here, we show that the RBP heterogeneous ribonucleoprotein L (hnRNPL) interacts with chromatin and regulates gene transcription by forming phase-separated condensates in ovarian cancer. hnRNPL phase separation activates PIK3CB transcription and glycolysis, thus promoting ovarian cancer progression. Notably, we observe that the PIK3CB promoter is transcribed to produce a non-coding RNA which interacts with hnRNPL and promotes hnRNPL condensation. Furthermore, hnRNPL is significantly amplified in ovarian cancer, and its high expression predicts

Discover how hnRNPL's phase separation activates PIK3CB transcription, boosting glycolysis in ovarian cancer. Find insights into its deadly mechanisms! PMID:40413189, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-60115-7 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation | Nature Communications Atrial fibrillation (AF) is a common cardiac arrhythmia with strong genetic components, yet its underlying molecular mechanisms and potential therapeutic targets remain incompletely understood. We conducted a cross-population genome-wide meta-analysis of 168,007 AF cases and identified 525 loci that met genome-wide significance. Two loci of PITX2 and ZFHX3 genes were identified as shared across populations of different ancestries. Comprehensive gene prioritization approaches reinforced the role of muscle development and heart contraction while also uncovering additional pathways, including cellular response to transforming growth factor-beta. Population-specific genetic correlations uncovered common and unique circulatory comorbidities between Europeans and Africans. Mendelian randomization identified modifiable risk factors and circulating proteins, informing disease prevention and drug development. Integrating genomic data from this cross-population genome-wide meta-analysis with pro

Cross-population GWAS of 168,007 AF cases reveals 525 significant loci! Key shared loci: PITX2 & ZFHX3, hinting at potent targets. Molecular insights grow. PMID:40645996, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-61720-2 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪