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Yang, W.

Publications and source records attributed to Yang, W..

At least 19 recordsLinked to original sources

Enhancing Visuomotor Reaction during Dark Transition via Model-Optimized Transcutaneous Vagus Nerve Stimulation

Sudden reductions in ambient illuminance temporarily impair visuomotor performance due to the inherent latency of dark adaptation, posing significant risks in operational environments such as tunnel entry. To mitigate this degradation, we propose a model-based neuromodulation framework using transcutaneous vagus nerve stimulation (tVNS), which is known to accelerate and augment pupil dilation and potentially enhance sensorimotor processing by activating the locus coeruleus-norepinephrine (LC-NE) system. First, we characterized the temporal dynamics of the tVNS-induced pupillary response and developed a predictive model using a long short-term memory (LSTM) network in standard lighting. The model demonstrated efficacy in reproducing nonlinear physiological characteristics even under sudden dark exposure. Second, we derived optimized stimulation sequences using a genetic algorithm to maximize pupil dilation during immediate adaptation to darkness. Pupillary evaluations during bright-to-dark transitions revealed that the optimized tVNS additively increased pupil diameter. The improvement in visuomotor choice-reaction performance was highly correlated with the amount of tVNS-induced increase in pupil diameter during dark transition across healthy young adults. These findings suggest that the model-optimized tVNS approach may effectively mitigate the degradation of visuomotor performance during dark transitions via LC-NE activation as well as subsequent sensorimotor enhancement. Furthermore, the experimental results demonstrate the potential of the transient pupil response to tVNS to serve as a robust physiological indicator for predicting behavioral improvement.

bioengineering↗

Conserved molecular compatibility for MIZ1 function in cytokinin signaling in land plants

Plant roots adjust their growth direction toward water through hydrotropism, a process that in Arabidopsis thaliana requires the endoplasmic reticulum (ER)-associated protein MIZU-KUSSEI1 (MIZ1). Nonetheless, MIZ1 orthologues occur throughout land plants, including lineages lacking true roots, raising questions about the ancestral function of this protein family. Here, we investigated the evolutionary conservation and functional diversification of MIZ1-like proteins across land plants. MIZ1 orthologues from evolutionarily distant land plants failed to restore hydrotropism or cytokinin sensitivity in the Arabidopsis miz1 mutant, despite conserved protein structure and ER localization. In the liverwort Marchantia polymorpha, loss of MpMIZ1a led to altered cytokinin sensitivity and cytokinin-mediated development in both the sporophyte and gametophyte. These phenotypes and gene expression analyses imply a conserved role of MIZ1 in cytokinin-related processes. Despite this functional similarity, protein-protein docking and bimolecular fluorescence complementation revealed species-specific interactions between MIZ1 proteins and their cognate cytokinin histidine kinase receptors in Arabidopsis and Marchantia. Together, our findings indicate that MIZ1 proteins represent ancient land plant regulators of cytokinin-dependent development whose molecular compatibility and developmental outputs have diverged during evolution. We propose that the role of MIZ1 in root hydrotropism represents a derived recruitment of this ancestral module into root-specific environmental response pathways.

plant biology↗

An N-Terminally Acetylated Degron Specifically Recognized by the CTLHMKLN1-FAM72A E3 Ubiquitin Ligase for Regulatory Protein Degradation

N-terminal acetylation of cellular proteins has been implicated in their proteasomal degradation through the Ac/N-degron pathway. Despite representing a major branch of the N-degron system, only a limited number of degrons and their motifs have been identified and characterized in this pathway, and the mechanism underpinning the recognition of N-terminal acetylation has remained largely elusive. Here, by interrogating FAM72A-mediated degradation of UNG2, we pinpointed the N-terminally acetylated sequence of UNG2 as a bona fide Ac/N-degron specifically recognized by the CTLHMKLN1-FAM72A E3 ubiquitin ligase. Rather than relying solely on a single acetylated N-terminal residue, this degron features a consensus Nt-AcM1-[ILV]2-G3 motif that governs both E3 targeting and the intracellular stability of the neo-substrates uncovered through proteomic screenings. Cryo-EM structure of the UNG2-FAM72A-MKLN1 complex further elucidated the molecular details supporting the high specificity of degron recognition. Notably, this degron pathway is subject to multilayered regulation, highlighting the characteristic conditionality of degron system. Our findings thus define a distinct AcM-[ILV]-G/N-degron pathway and provide mechanistic insights into degron recognition dictated by both N-terminal acetylation and sequence motif context.

biochemistry↗

Mechanistic Investigation of Reversible Hibernation-Driven Immune Suppression in Thirteen-Lined Ground Squirrels

Torpor in mammals imposes extreme energetic constraints, yet how it reshapes the immune system remains poorly understood. Here we combined single-cell RNA sequencing with quantitative image analysis of immune cell populations in splenic tissues to define immune remodeling during torpor in a natural hibernator, 13-lined ground squirrels. The torpid spleen showed a significant contraction of white pulp with a preferential reduction of B cell- and T cell-rich adaptive niches and relative preservation of innate myeloid populations. Across immune cell lineages, a conserved transcriptional program of metabolic downscaling emerged, marked by suppression of glycolysis, cell-cycle progression, RNA processing, and translation, together with reduced glucose transporter expression and induction of cold-shock RNA-binding proteins. Despite this pervasive metabolic quiescence, immune cells maintain lineage identity, with B cells undergoing numerical and transcriptional contraction linked to follicular remodeling and T cells adopting a quiescent, stress-resistant state without apoptotic enrichment. Innate cell populations remained numerically enriched but transcriptionally restrained, consistent with low-energy tissue surveillance rather than inflammatory activation. These findings identified torpor as a coordinated, multi-tiered state of reversible immune suppression, in which hierarchical metabolic and lineage-specific programs conserve energy while preserving essential immune infrastructure for rapid restoration. Our identified key molecules and pathways in immune suppression at the cellular and transcriptional levels have important implications for future development of targeted treatment for autoimmune diseases, cancers, and infectious diseases.

immunology↗

A SUN1-ApoD feedback loop promotes cellular aging via microtubule-nuclear mechanotransduction

Alterations in nuclear envelope proteins such as SUN1 and prelamin A are known hallmarks of cellular aging, but how they cause aging phenotypes beyond the expressing cells is unknown. With a tissue culture version of parabiosis, we found that aged fibroblasts secrete an activity that induces aging-related polarity defects in young fibroblasts. Secretomics identified the factor as apolipoprotein D (ApoD), a circulating protein whose levels are known to rise with age. ApoD increased SUN1 levels and disrupted polarity in fibroblasts via SUN1-promoted coupling of microtubules to the nucleus. In turn, elevated SUN1 enhanced ApoD expression and secretion, forming a feedback loop that promotes acquisition of aged phenotypes. In mice, ApoD induced aging-related phenotypes in muscle. Elevated ApoD expression required coupling between SUN1, its outer nuclear membrane binding partner nesprin-2, and microtubules. Broader analysis revealed that this pathway regulates hundreds of genes. These findings define microtubule-nuclear coupling as a direct mechanotransduction pathway controlling gene expression and promoting aging-associated phenotypes.

cell biology↗

Hydrophobic Patch Spacing Produces Nonmonotonic Compaction in Intrinsically Disordered Proteins

The conformational ensembles of intrinsically disordered proteins (IDPs) are encoded by the distribution of physicochemical interactions along their sequences. Although hydropathy-based descriptors capture average chain dimensions across diverse IDPs, the consequences of spacing localized hydrophobic patches remain poorly understood. Coarse-grained simulations of fixed-composition FUS-derived sequence variants reveal maximal compaction at an intermediate patch spacing. Analysis of simplified model peptides identifies this nonmonotonic behavior as one of three spacing responses: monotonic expansion, nonmonotonic compaction, and monotonic compaction. Their occurrence depends on interaction strength, effective interaction length scale, and patch architecture, with nonmonotonicity emerging only when hydrophobic attractions are sufficiently strong. A conformational-class decomposition resolves these responses into weighted patch-contact and patch-noncontact contributions to the ensemble-averaged chain dimensions. In attractive regimes, the contact contribution decreases with spacing while the noncontact contribution increases, and the changing balance between these opposing effects produces maximal compaction at an intermediate spacing. In the steric-dominated regime, separating the patches instead compacts the dominant noncontact conformations by relieving steric frustration. These steric- and attraction-dominated limits show that similar spacing responses can arise from distinct microscopic mechanisms. These findings establish a unified framework for understanding how interaction regime and hydrophobic patch spacing jointly shape IDP conformational ensembles.

biophysics↗

Programmable De Novo Design of Mesoporous Protein Crystal Frameworks

Three-dimensional protein crystals are ordered, porous macroscopic materials with potential applications in catalysis, biosensing, and biomedicine. However, most protein crystals are obtained by empirical screening, providing limited control over the lattice architecture, pore geometry or component composition that determine material function. Here, we present a modular strategy for the programmable design of highly porous, framework-like protein crystals using predefined protein-protein interactions. This strategy yielded over 30 distinct protein crystals, including single-component and multicomponent P213 and I213 lattices that grow to over 100 micrometers in size. Small-angle X-ray scattering and electron microscopy showed close agreement between experimental lattices and computational models. RFdiffusion-guided design generated isomorphous variants with matched lattice parameters, enabling coherent protein crystal alloys, epitaxial core-shell growth and reversible shell assembly. The designed crystals exhibit tunable mesoporous architectures, with limiting apertures of 2-18 nm, and support genetically encoded incorporation of fluorescent protein guests. These results establish a general route to programmable lattice engineering of protein crystals and position them as genetically encoded, compositionally tunable mesoporous materials.

synthetic biology↗

PASTRI: Resolving Stage-Specific Cell-State Dynamics from Annotated Cell Lineage Trees

Cellular transitions between phenotypic states are fundamental to development and disease, yet quantitative analysis of their dynamics remains challenging. Here we present PASTRI (Phylogenetic Adjacency-based State Transition Rate Inference), a computational framework that infers transition rates from cell lineages/phylogenies annotated with terminal phenotypic states, such as single-cell transcriptomes. We validate PASTRI using simulated lineages and the Caenorhabditis elegans embryonic lineage. Importantly, by leveraging cell pairs at varying phylogenetic distances, PASTRI accurately resolves stage-specific transition rates, circumventing the issue of developmental changes in dynamics. Applied to three cell phylogeny datasets from our lineage-tracing experiments spanning diverse developmental/disease models and tracing systems, PASTRI uncovers rate-limiting steps in the activation of hepatic stellate cells and the differentiation of primordial lung progenitors, as well as attractor states that support cancer cell proliferation. PASTRI thus opens up a venue for dissecting cell state transition dynamics from annotated cell lineage/phylogeny.

bioinformatics↗

MiRNA let-7a-5p Ameliorates Pulmonary Fibrosis by Suppressing TGFBR1-Mediated Endothelial-to-Mesenchymal Transition

Background Idiopathic Pulmonary Fibrosis (IPF) is a fatal chronic lung disease with limited therapeutic options. While alveolar epithelial injury and fibroblast activation are well-studied, endothelial-mesenchymal transition (EndoMT) is emerging as a critical pathogenic mechanism. The regulatory role of exosomal miRNAs in pulmonary fibrosis remains unclear. This study investigates serum exosomal miRNAs, particularly let-7a-5p, in modulating EndoMT during the onset of pulmonary fibrosis. Methods Clinical cohorts of IPF patients and healthy controls were enrolled. Serum exosomal miRNAs were profiled, followed by differential expression and functional enrichment analyses. In vitro experiments involved human pulmonary artery endothelial cells (HPAECs) transfected with let-7a-5p mimic or inhibitor. Dual-luciferase reporter assays confirmed the binding between let-7a-5p and TGFBR1. HPAECs were co-cultured with lung epithelial cells to examine paracrine signaling. In vivo studies used a bleomycin-induced mouse model with let-7a-5p agomir administration. Assessments included histopathological staining, hydroxyproline content, Western blot, qPCR, micro-CT, and pulmonary function tests. Results Let-7a-5p was significantly downregulated in serum exosomes from IPF patients, correlating with clinical indicators. Mechanistically, let-7a-5p directly bound the TGFBR1 3'UTR to inhibit its expression. Inhibition of let-7a-5p upregulated -SMA, FN1, smad2/3 phosphorylation, and collagen I, while downregulating CD31 and VE-cadherin. Therapeutically, let-7a-5p mimic reversed bleomycin-induced EndoMT and suppressed epithelial-mesenchymal transition (EMT) via paracrine signaling. Mice administered agomir showed reduced fibrosis, improved lung function, and suppressed TGF-{beta}/Smad signaling. Conclusion Serum exosomal let-7a-5p suppresses pulmonary fibrosis by targeting TGFBR1 to inhibit EndoMT. Its downregulation in IPF patients correlates with disease progression, highlighting its biomarker potential.

molecular biology↗

Patient-Derived Liver Cancer Organoids Reflect Tumor Biology and Their Growth Phenotype Correlates with Clinical Outcomes

Liver cancer remains a major global health burden with high mortality and limited treatment response prediction tools. Patient-derived cancer organoids have emerged as promising preclinical models that recapitulate tumor heterogeneity; however, the biological significance of morphological diversity within established organoids remains poorly characterized in hepatocellular carcinoma (HCC). In this exploratory study, we investigated whether distinct organoid growth phenotypes reflect underlying tumor biology and correlate with clinical outcomes. We established liver cancer organoids from resected tumor tissues of 27 patients and analyzed their clinical, histological, and genomic characteristics. Organoids were classified morphologically into cystic and solid types. Whole exome sequencing (WES) was conducted on six matched tumor-organoid pairs to assess genomic fidelity. Associations between organoid establishment, growth characteristics, and clinical parameters were statistically evaluated. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and univariate Cox proportional hazards regression. Organoids were successfully established in 13 of 27 cases (48.1%). Solid-type organoids were significantly associated with shorter PFS compared to cystic types (HR = 13.91; p = 0.0039, log-rank test). Organoid establishment was more frequent in older patients (>70 years), those with HBV infection, and tumors with positive {beta}-catenin expression. WES analysis demonstrated high concordance in somatic mutation profiles and variant allele frequency distributions between tissues and corresponding organoids. In univariate Cox regression, organoid growth pattern (solid vs. cystic) showed a significant association with PFS within this exploratory cohort (p = 0.0207). Patient-derived liver cancer organoids preserved the genomic and histopathological features of the original tumors. Notably, solid morphology was associated with shorter PFS, suggesting that organoid growth phenotype may serve as a supplementary indicator of tumor biological behavior in HCC. Given the modest cohort size and the absence of multivariate analysis, these preliminary findings should be interpreted with caution and warrant further large-scale validation.

cancer biology↗

Structure-guided design of a CD81-binding mini-protein that blocks hepatitis C virus entry

Despite the success of direct-acting antivirals, preventing hepatitis C virus (HCV) reinfection remains a critical global challenge. To address this, we leveraged deep learning-based de novo protein design to engineer mini-proteins targeting the large extracellular loop (LEL) of the HCV co-receptor CD81. These mini-proteins are predicted to precisely dock into CD81-LEL, occluding the critical binding interface required for the HCV E2 glycoprotein. Through biophysical screening, we identified mini-19, a lead candidate with sub-nanomolar affinity (KD = 0.5 nM) and high thermostability up to 95{degrees}C. Flow cytometry and super-resolution imaging confirmed that mini-19 specifically recognizes the native topology of CD81 on cells and extracellular vesicles. Functionally, mini-19 neutralized HCVcc infection (IC50 = 1.2 nM). Molecular dynamics simulations demonstrated that mini-19 acts as a structural clamp, restricting the fusogenic conformational plasticity of the receptor. By targeting a conserved host factor rather than the rapidly mutating viral envelope, mini-19 provides a high genetic barrier to resistance. Beyond offering a prophylactic strategy against HCV, our findings establish a stable biologic platform for targeting tetraspanin-enriched microdomains and modulating host-pathogen interactions.

bioengineering↗

Chromosome-level genome assembly of Calotes wangi with dynamic colour variation

The Wangs garden lizard, Calotes wangi, is a widely distributed agamid species in Southern China and Northern Vietnam and exhibits pronounced colour variation and rapid body colour change. Despite increasing interest in the genomic basis of colour variation, chromosome-level genomic resources remain limited in agamid lizards. Here, we generated a chromosome-level reference genome of C. wangi using PacBio HiFi sequencing and Hi-C scaffolding. The final genome assembly was approximately 1.66 Gb in size and comprised 6 macrochromosomes and 11 microchromosomes, with a contig N50 of 110.09 Mb and 98.9% complete BUSCO genes. A total of 20,442 protein-coding genes were annotated. Comparative genomic analyses identified 297 significantly expanded gene families, with enriched functions associated with steroid metabolism, chromatin regulation, and epigenetic processes. This high-quality genome assembly provides an important genomic resource for future studies of colour variation, phenotypic plasticity, and evolutionary diversification in agamid lizards.

evolutionary biology↗

APOBEC3-driven neoantigen-rich cancers co-opt 1q23.3 amplification for tumor-intrinsic immune cloaking

Hypermutational processes, including those driven by the APOBEC3 family of cytidine deaminases, generate abundant neoantigens yet give rise to tumors that evade immune recognition. Here, using multi-omics analyses followed by functional validation, we identified a tumor-intrinsic immune-cloaking mechanism in neoantigen-rich epithelial cancers, characterized by coordinated suppression of antigen presentation, immune-recruiting cytokines and immune-checkpoint programs. In bladder cancer, genome-wide copy-number analysis identified recurrent 1q23.3 amplification as a genomic feature of a neoantigen-high/CD8-low tumor state. Within this locus, NECTIN4 emerged as the dominant candidate effector, outperforming extrachromosomal DNA status as a predictor of immune-neoantigen discordance. Similar associations were observed across breast and lung cancers. Functional studies demonstrated that NECTIN4 was sufficient to establish a T-cell-poor tumor microenvironment and confer resistance to PD-1 blockade in immunocompetent mice. Mechanistically, NECTIN4 engaged a DDR1-SHP2 axis that suppressed STAT1 phosphorylation, silencing tumor-cell immune-engagement programs. NECTIN4 blockade restored STAT1 activity and reduced tumor growth, indicating that the cloaked state is pharmacologically reversible. Mutational signature, breakpoint motif, timing and clonality analyses, together with APOBEC3B expression and germline genetic evidence, linked APOBEC3-mediated mutagenesis to recurrent 1q23.3 amplification encompassing NECTIN4. These findings reveal how neoantigen-generating mutational processes can be coupled to structural genome evolution to enable tumor-intrinsic immune cloaking through a therapeutically targetable NECTIN4-DDR1-SHP2 axis.

cancer biology↗

An engineered IdeS variant with enhanced activity and performance for IgG degradation

IgG-degrading enzymes have emerged as innovative therapeutic agents for treating conditions driven by pathogenic antibodies. Here, we used structure-guided rational design to engineer IdeSM33, a double mutant (K167R/D226E) of the IgG-specific bacterial protease IdeS from Streptococcus pyogenes, with improved catalytic efficiency. Biolayer interferometry revealed a fourfold increase in binding affinity relative to wild-type IdeS (IdeSWT). This enhancement is likely attributable to mutations that strengthen hydrogen bonding at the enzyme-IgG Fc interface. In vitro, IdeSM33 has higher performance than IdeSWT in cleaving serum IgG. In vivo studies in rabbits demonstrated that IdeSM33 effectively depleted circulating IgG and showed better performance at a dose of 0.005 mg/kg than the IdeSWT. Although doses greater than 0.2 mg/kg demonstrated higher plasma concentrations of IdeS and a larger AUClast, they did not show a significant enhancement in the pharmacodynamics of IgG degradation. Importantly, a single dose of IdeSM33 (0.2 mg/kg) potently degraded binding and neutralizing antibodies against AAV9 within 1-2 days and restored hepatic AAV9 transduction in pre-immunized animals. Together, these findings highlight IdeSM33 as a potent and safe engineered enzyme with therapeutic potential for autoimmune disorders, transplant rejection, and overcoming pre-existing humoral immunity in gene therapy.

bioengineering↗

Non-contact direct sensing of material properties of biomolecular condensate using Scanning Ionic Conductance Microscopy

Biomolecular condensates are important regulators of cellular compartmentalization and biochemical processes. Understanding their material properties is critical to elucidate how they control molecular organization and dynamics within cells. However, quantitatively probing these properties remains challenging due to the wide range of length scales, concentrations, and timescales over which condensates operate, as well as the limited force ranges accessible to current nanoscale mechanical mapping methods. We explored the use of a non-contact 3D imaging tool Scanning Ion Conductance Microscopy (SICM) for stiffness measurements of liquid-liquid phase-separated biomolecular condensates. We focus on the Dhh1 protein, which is a regulator of cytoplasmic processing bodies (PBs) membrane-less cytoplasmic condensates that control the storage and degradation of untranslated mRNA. In our study, we investigate the properties of mCherry2- or His-mCherry2-tagged full-length Dhh1 and N- or C-terminus tail-deletion constructs, as well as the catalytically inactive mutant DQAD, under different pH and incubation times. We mapped both spatial and temporal changes in the material properties of the condensates, highlighting the capabilities of the instrument. We found that the removal of either of the two tails led to an increase in condensate stiffness upon shifting the pH from a stress-associated cellular environment (pH 6.5) to physiological conditions (pH 7.5). Additionally, the choice of protein tags led to vastly different results depending on the pH where mCherry2-Dhh1 exhibited a stiffening going from pH 6.0 to 6.5 while the double-tagged His-mCherry2 did not. Our measurements are verified and corroborated by established techniques such as optical tweezer-based fusion assays and fluorescence recovery after photobleaching (FRAP). Furthermore, we were able to track the same biomolecular condensate sample for up to 20 days getting insights on the ageing and evolution of the condensates. Overall, our study demonstrates the applicability of SICM for direct measurement of the material properties of biomolecular condensate.

biophysics↗

The b0+ Amino Acid Transporter Defines a Selenium-utilization Enterocyte Program in the Human Intestine

Selenium is an essential trace element incorporated into selenoproteins as selenocysteine, yet the intestinal cellular programs associated with selenium utilization remain poorly defined. Here, we performed a large-scale single-cell transcriptomic analysis of 169,068 human enterocytes from 105 donors to systematically profile nine candidate selenium transporter systems and their relationship to selenoprotein expression. Among all transporters examined, the b0+ amino acid transporter system (SLC3A1/SLC7A9) showed the strongest and most maturation-independent association with selenoproteins, including SELENOP (Spearman r = 0.489) and GPX4 (r = 0.392), with enrichment across 21 of 24 detected selenoproteins in b0+-complete versus transporter-negative enterocytes. These associations were robust across individual donors and confirmed by pseudobulk validation, and were only partially explained by enterocyte maturation state, intestinal segment, and sequencing depth after covariate adjustment, indicating both differentiation-dependent and differentiation-independent components. Furthermore, enterocytes carrying the b0+ complex expressed a non-canonical LRP repertoire (LRP1, LRP5 and LRP6) rather than the canonical SELENOP receptors LRP2 and LRP8; this co-expression was maturation-dependent, nominating these LRPs as candidate intestinal SELENOP-handling receptors. Together, these single-cell data identify b0+ transporter expression as a marker of a selenoprotein-enriched enterocyte state in the human intestine.

molecular biology↗

Microinjection-based Single-Cell Toxicological Assessment Reveals How Physiological Levels of PFOS Impair Oocyte Maturation and Developmental Competence

Perfluorooctanesulfonic acid (PFOS) is a persistent environmental contaminant widely detected in human serum and follicular fluid and has been associated with reduced implantation rates and female fertility. However, its direct effects on mammalian oocyte maturation remain poorly understood. Here, we developed a microinjection-based single-oocyte toxicological assay to directly evaluate how physiologically relevant PFOS concentrations affect mouse oocyte maturation and early embryonic development. Microinjection of PFOS at follicular-fluid level (5.6 nM) and occupational exposure level (60 nM) significantly reduced germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) rates compared with water-injected controls. Notably, all tested concentrations (2.4 nM serum level, 5.6 nM, and 60 nM) induced abnormal polar-body formation, disrupted meiotic spindle morphology, and increased the proportion of unhealthy oocytes. PFOS exposure also significantly elevated intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential at 5.6 nM, indicating oxidative stress and mitochondrial dysfunction. Cytological analyses revealed chromosome misalignment and widened metaphase I plates, suggesting chromosome missegregation and subsequent prometaphase II arrest with defective polar bodies. Single-cell RNA sequencing of PFOS-treated oocytes exhibiting abnormal small polar bodies identified distinct transcriptional signatures, including dysregulation of genes involved in mRNA processing, chromosome segregation, mitochondrial function, and cell division. Functionally, these oocytes failed to progress beyond the 2-cell stage following in vitro fertilization, indicating loss of developmental competence. Collectively, these findings demonstrate that PFOS directly disrupts meiotic progression through spindle defects, oxidative stress, and transcriptional dysregulation, ultimately compromising oocyte quality even at environmentally relevant exposure levels. Environmental ImplicationPFOS is a persistent environmental contaminant widely detected in human serum and follicular fluid. Our findings demonstrate that PFOS at physiologically relevant levels can impair oocyte maturation, disrupt meiotic chromosome segregation, and compromise early embryonic development. By using a single-oocyte toxicological assay, we reveal that even low-dose PFOS exposure can induce oxidative stress and transcriptional dysregulation. These results highlight the potential reproductive risks of chronic PFOS exposure and underscore the importance of stricter environmental monitoring and regulation to protect female reproductive health and fertility. This novel assay also has the potential to redefine safety thresholds for other environmental toxicants.

cell biology↗

Revisiting CPUs for Protein Folding: Xeon-Based Acceleration of AlphaFold2

Protein structure prediction via AlphaFold2 has revolutionized drug discovery, yet its end-to-end execution remains computationally intensive. While GPUs are traditionally favored for deep learning, the AlphaFold2 algorithm consists of heterogeneous phases -- preprocessing with sparse database searches and model inference with low-arithmetic-intensity attention modules -- that present unique architectural challenges. In this work, we address these bottlenecks by introducing Open-Omics-AlphaFold2, a highly optimized implementation for Intel(R) Xeon(R) CPU. By leveraging the CPUs versatility in handling both sparse preprocessing algorithms and dense matrix operations via Intel Advanced Matrix Extensions (AMX), we accelerate the entire pipeline end-to-end. Our optimization strategy employs multi-level parallelism -- spanning multiprocessing, multi-threading, and vectorization -- alongside cacheaware tiling and operator fusion. Our results demonstrate that, on a Xeon CPU, Open-Omics-AlphaFold2 achieves 2 7.58 speedup for preprocessing and 19.8 29.2 speedup for model inference over baseline Deepmind-AlphaFold2. Moreover, for a proteome of 391 proteins, Open-Omics-AlphaFold2 running on a dual-socket Intel Xeon 6980P system achieves a remarkable 76% higher through-put over the state-of-the-art GPU-accelerated solution, FastFold, running on a single-socket Intel Xeon 6980P CPU with an NVIDIA H100 offioad. Code availabilityBaremetal: https://github.com/IntelLabs/open-omics-alphafold Containerized: https://github.com/IntelLabs/Open-Omics-Accelera tion-Framework/tree/main/pipelines/alphafold2-based-protein-folding

genomics↗