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Biology subjects

Jia, S.

Publications and source records attributed to Jia, S..

At least 37 records · Page 2Linked to original sources

Plasma-Activated Water: An Emerging Technology for the Control of Eggshell-Associated Biofilms

Biofilm formation on eggshell surfaces poses a significant food safety concern by promoting bacterial persistence and facilitating cross-contamination, contributing to foodborne illness outbreaks worldwide. Beyond public health impacts, bacterial contamination also drives spoilage, food loss, and waste, together placing substantial strain on healthcare systems and economic infrastructures. This study evaluated the anti-biofilm efficacy of plasma-activated water (PAW), a reactive oxygen and nitrogen species (RONS)-rich solution generated through the interaction of cold atmospheric plasma with water. 50 bacterial isolates were recovered from chicken eggshells, and the biofilm-forming capacities of eight representative species (Staphylococcus arlettae, Lysinibacillus fusiformis, Priestia megaterium, Peribacillus frigoritolerans, Acinetobacter lwoffii, Escherichia coli, Pseudomonas fulva, and Pseudomonas stutzeri) were characterised in vitro. All isolates formed biofilms, exhibiting variable culturable cell populations, biomass, and extracellular polymeric substance (EPS) matrix presence and composition. EPS analyses identified polysaccharides, extracellular DNA, and proteins as key matrix components, with relative abundance varying with biofilm maturity. PAW efficacy was assessed under short exposure times (1, 5, and 15 minutes) using freshly generated, 1-week-old, and 4-week-old PAW. Fresh PAW demonstrated potent anti-biofilm activity, achieving complete inactivation of E. coli and P. stutzeri biofilms below the limit of detection within 1 min, while biofilms of Gram-positive bacteria, L. fusiformis and P. megaterium, were generally more tolerant. Reduced efficacy of aged PAW was likely associated with RONS decay. Mechanistic analyses, including scanning electron microscopy and intracellular reactive oxygen species assays, linked PAW treatment to biofilm disruption and intracellular oxidative stress. This study provides the first detailed evaluation of biofilm formation by under-investigated eggshell-associated bacteria and elucidates mechanisms underlying PAW-mediated biofilm inactivation. Overall, PAW shows strong potential as a sanitising technology for the egg industry, supporting safer food production and reduced reliance on conventional antimicrobial agents amid rising global antimicrobial resistance rates.

microbiology↗

Scalable spike sorting across thousands of neurons by modeling neural dynamics with NeuroSort

Neural circuit research requires resolving the functional coding mechanisms at the single-neuron scale. However, neural signals captured from extracellular recordings are inherently complex, shaped both by electrode properties and the spatially distributed neural population activity across recording sites. These factors introduce strong signal mixing and waveform variation, making it diffcult for existing spike sorting methods to reliably isolate individual neurons from large-scale recodings. To address this, we develop NeuroSort, which fuses spatiotemporal information through a contrastive learning strategy to adaptively model neural dynamics. NeuroSort is a GPU-enabled, highly efficient spike sorting framework, enabling the isolating of up to thousands of neurons. We validated NeuroSort on in vivo extracellular recordings, including Utah array data from rhesus macaques performing motor tasks and Neuropixels 1.0 probe data from a rat during rest. Moreover, in a recording collected by the 1,024-channel Neuroscroll probe, NeuroSort sorted the largest number of well-isolated neurons from different brain areas while achieving a 2-8 times speedup over other methods. Taken together, NeuroSort generalizes across recording conditions, providing an interpretable and scalable paradigm for whole-brain dynamic analysis.

neuroscience↗

Augmented prediction of multi-species protein--RNA interactions using evolutionary conservation of RNA-binding proteins

AbstractRNA-binding proteins (RBPs) play critical roles in gene expression regulation. Recent studies have begun to detail the RNA recognition mechanisms of diverse RBPs. However, given the array of RBPs studied so far, it is implausible to experimentally profile RBP-binding peaks for hundreds of RBPs in multiple non-model organisms. Here, we introduce MuSIC (Multi-Species RBP-RNA Interactions using Conservation), a deep learning-based framework for predicting cross-species RBP-RNA interactions by leveraging label smoothing and evolutionary conservation of RBPs across 11 diverse species ranging from human to yeast. MuSIC outperforms state-of-the-art computational methods, and provides predicted RBP-binding peaks across species with high accuracy. The prediction confidence is higher in the closely related species, partially due to the RBP conservation patterns. Finally, the effects of homologous genetic variants on RBP binding can be computationally quantified across species, followed by experimental validations. The target transcripts with disrupted binding events are enriched with the ubiquitination-associated pathways. To summarize, MuSIC provides a useful computational framework for predicting RBP-RNA interactions cross-species and quantifying the effects of genetic variants on RBP binding, offering novel insights into the RBP-mediated regulatory mechanisms implicated in human diseases. HighlightsO_LIMuSIC integrates RBP-binding peaks with conservation-weighted label smoothing to predict RBP-RNA interactions across eleven species C_LIO_LIMuSIC outperforms state-of-the-art computational methods in predicting cross-species RBP-RNA interactions C_LIO_LICross-species prediction accuracy of RBP-binding peaks correlates with the conservation of RBPs C_LIO_LIMuSIC quantifies the effects of homologous SNVs on RBP binding with experimental validation in mouse C_LI

bioinformatics↗

JointMap identified SERPINA3+ chondrocytes as a therapeutic target for osteoarthritis

BackgroundOsteoarthritis (OA) is a prevalent degenerative joint disease that affects nearly half of the population aged over 65. Recent single-cell transcriptional studies have identified heterogeneous OA-specific chondrocyte subtypes, yet a unified subtype-classification remains incomplete. MethodsIn this study, we integrated a total of 545,946 cells to develop JointMap, an interspecies atlas. The chondrocyte subtypes were analyzed using machine learning algorithms were validated via human samples, animal models, and in vitro cell culture. We performed KAS-seq and analyzed the spatial characters for JointMap. ResultsBased on clinical diagnosis and cross-omic indexes, we identified a novel OA-elevated chondrocyte subtype, SERPINA3+ chondrocytes. Notably, we uncovered their upregulated chondrogenesis function and intercellular communication patterns as potential therapeutic targets. ConclusionsIn summary, JointMap provides a unified framework for the systematic annotation of chondral tissues across species and helps in the identification of druggable networks for articular diseases.

bioinformatics↗

Real-time, High-throughput Super-resolution Microscopy via Panoramic Integration

We introduce super-resolution panoramic integration (SPI), an on-the-fly microscopy technique enabling instantaneous generation of subdiffractional images concurrently with scalable, high-throughput screening. SPI leverages multifocal optical rescaling, high-content sweeping, and synchronized line-scan readout while preserving minimal post-processing and compatibility with epi-fluorescence settings. We demonstrate SPI for various subcellular and populational morphology, function, and heterogeneity. This versatile platform offers a practical pathway toward biological insights beyond traditional optical and computational constraints.

bioengineering↗

Rationally Engineered Coronavirus-mimicking Protein Nanocage Platform for Glioblastoma Targeted Delivery and Immunity Regulation

Glioblastoma (GBM) is one of the most aggressive and treatment-resistant brain tumors, owing to the dual challenges of the blood-brain barrier (BBB) and a profoundly immunosuppressive tumor microenvironment. However, few existing strategies are capable of simultaneously overcoming these two barriers, underscoring a critical scientific gap and the need for innovative therapeutic platforms that enable both effective BBB traversal and tumor immune reprogramming. Here, we present a coronavirus-mimicking protein nanocage platform (EcomPC) derived from Thermotoga maritima encapsulin, rationally engineered for the targeted and sustained delivery of interferon- (IFN-) to GBM lesions. Through strategic insertion of flexible linkers, cysteine-to-serine mutations, and modular surface functionalization via SpyTag/SpyCatcher chemistry, EcomPC enables intracellular self-assembly of IFN- and glioma-specific targeting. In orthotopic GBM models, EcomPC-IFN demonstrates efficient BBB translocation, selective tumor accumulation, and potent anti-tumor efficacy. Mechanistically, localized IFN- release induces tumor cell apoptosis and reprograms the immune microenvironment--characterized by increased CD8 T cell infiltration, decreased Foxp3 regulatory T cells, and a favorable chemokine shift. These therapeutic effects are not recapitulated by free IFN- or untargeted nanocages, underscoring the essential role of both structural mimicry and ligand-guided delivery. Collectively, this work establishes EcomPC as a programmable, virus-inspired protein delivery platform capable of overcoming key physiological barriers in brain tumor immunotherapy, and lays the foundation for its broader application in CNS-targeted biologic delivery.

bioengineering↗

DNA framework array enables ultra-high throughput DNA synthesis

High-throughput DNA synthesis has revolutionized synthetic biology, molecular diagnostics, genome engineering, and DNA data storage by enabling the scalable and precise construction of nucleotide-based information systems. However, existing high-throughput synthesis technologies rely on top-down fabrication strategies to maximize throughput, yet they are inherently constrained by physical limitations. These constraints make it exceedingly difficult to achieve single-molecule level synthesis control that is essential for advancing next-generation DNA synthesis. Here, we present a DNA framework-based bottom-up enzymatic synthesis strategy that enables single-molecule level control of DNA synthesis with high-throughput. Leveraging the nanoscale addressability of DNA frameworks, we achieved a synthesis site pitch of 10.9 nm--183-fold smaller than that of previously reported electrode arrays. Theoretical projections suggest that this approach could scale synthesis throughput to 5.3 x 1011 sequences per square centimeter, representing a four-order-of-magnitude improvement over existing synthesis arrays. This approach lays the foundation for gigabyte-scale DNA writing and offers a highly accessible pathway toward large-scale DNA synthesis for emerging applications such as molecular data storage.

synthetic biology↗

Deep Volumetric Localization Super-Resolution Microscopy

Super-resolution microscopy, particularly localization-based methods, necessitates careful balancing of optical complexity, computational demands, and user accessibility. Conventional strategies typically adopt either deterministic or learning-based approaches, overlooking opportunities to leverage their syn-ergistic strengths. In this work, we introduce deep volumetric localization microscopy (VLM), a super-resolution methodology that integrates instrumental and algorithmic advancements for high-fidelity 3D single-molecule imaging. VLM employs a wavefront-optimized light-field configuration to capture single-molecule data, while a cascaded neural network reconstructs 3D volumes and extracts molecular coordinates at a 10 nm and 25 nm localization precision in the lateral and axial dimensions, respectively, across an imaging depth exceeding 5 {micro}m. Unlike existing methods, VLM is trained exclusively with system-aware intrinsic point-spread functions, bypassing dependencies on external imaging modalities or sample-specific data training. We validate VLM across diverse biological specimens, demonstrating hardware simplicity, data efficiency, and minimal phototoxicity. We anticipate VLM will overcome current limitations in fluorescence microscopy, empowering broader advancements in biomedical research.

bioengineering↗

Genetic architecture of the S-locus supergene revealed in a tetraploid distylous species

SummaryO_LIHeterostyly is a polymorphic floral adaptation controlled by supergenes and maintained in populations by disassortative mating. The molecular basis of distyly has been investigated in several unrelated families. Previous studies have been limited to diploid species and have not included Rubiaceae, which has the highest number of heterostylous species. C_LIO_LIHere, we investigate the genetic architecture of tetraploid Schizomussaenda henryi (Rubiaceae) to identify candidate style-length genes, evidence for hemizygosity and the potential role of gene duplication in the evolution of the S-locus. Chromosome-level genome assemblies and transcriptomic approaches identified the S-locus region comprised of four hemizygous genes. C_LIO_LIThe candidate gene SchzAUX22 may regulate style length and filament growth by acting in the auxin signaling pathway. Comparative studies of the two sub-genomes of S. henryi indicated strong similarities and no significant sub-genome dominance, as expected from autotetraploidy. Evidence from haplotype-resolved assemblies of a short-styled plant indicated that it possessed the ssSS genotype, consistent with autotetraploidy, which was estimated to have originated [~]3.6 Mya. Analysis of Ks values between S-locus genes and their paralogs indicated that the S-locus likely originated through stepwise duplication. C_LIO_LIOur study provides comprehensive genomic analysis of distyly in a polyploid and demonstrates that despite whole genome doubling the S-locus supergene remains intact and functional as an outbreeding mechanism. Our results contrast with many other heterostylous lineages where polyploidy is associated with breakdown of the polymorphism and transitions to self-fertilization. C_LI

plant biology↗

A reference genome assembly of the alpine forage grass Elymus nutans

Elymus nutans Griseb. (Poaceae: Triticeae, 2n=6x=42) is a dominant perennial plant species in the Qinghai-Tibetan Plateau in China, which is an important forage resource in high-altitude and cold regions and is the most popular species used for high yield artificial grassland planting because of its rich nutritional value and good palatability for herbivorous ruminant animals. In this study, using advanced sequencing technology, we generated an allohexaploid reference genome for E. nutans, representing the three sets of chromosomes (subgenomes St, Y, and H). This is the first study to our knowledge to confirm the origin of the Y subgenome, which shares a close relationship with the V subgenome. We predict that E. nutans arose via two-step hybridization and that its speciation occurred [~]3.16 MYA. The whole genome in this study will update the Triticeae family genomics information and provide theoretical basis for the evolutionary of its related speicies.

plant biology↗

Crucial roles of mesenchymal Gata2 in murine epididymal development

Androgens drive the morphogenesis and differentiation of the Wolffian duct (WD) into the epididymis, an essential organ for male reproduction, by binding to the androgen receptor (AR). However, it remains unclear whether other transcriptional programs operate beyond the central androgen/AR signaling in promoting WD development. We discovered that mesenchyme-specific deletion of the transcription factor Gata2 resulted in defective epididymal coiling in the corpus and caudal regions. The defective coiling in the absence of mesenchymal Gata2 did not result from androgen signaling deficiency, as there were no abnormalities in testicular morphology, androgen production, or AR/Ar expression, and dihydrotestosterone supplementation did not restore epididymal coiling in cultured WDs. Instead, Gata2 deletion reduced the expression of the mesenchyme- derived factor Inhba and epithelial proliferation, both of which play critical roles in epididymal coiling. The epididymal defect persisted into adulthood, with the uncoiled corpus and caudal epididymis exhibiting abnormal epithelial morphology and lumen environments, resulting in an unfavorable environment for sperm storage. Our results demonstrate the androgen-independent role of mesenchymal GATA2 in promoting epididymal development through Inhba induction and highlight the importance of proper fetal development in male reproduction. Significance StatementTesticular androgens drive the maintenance and differentiation of the Wolffian duct into a coiled and functional epididymis during male sexual differentiation. Our study, however, reveals that the Wolffian duct failed to develop into a coiled and functional epididymis in the absence of mesenchymal Gata2. This defect is not due to androgen signaling deficiency but rather to reduced expression of the mesenchyme-derived factor Inhba and decreased epithelial proliferation. Our results demonstrate the crucial role of GATA2-mediated transcriptional programs beyond the central androgen/androgen receptor signaling in Wolffian duct development.

developmental biology↗

Chimeric Collagen-like Proteins with Tunable Structural Heterogeneity for Precise Control and Targeted Doxorubicin Delivery

Protein-based drug delivery systems offer advantages such as genetic tunability, structural homogeneity, and high biocompatibility. However, precisely controlling the assembly of protein nanoparticles and establishing correlations between their macroscopic properties and molecular architecture remain significant challenges. Here, inspired by chimeric collagen-like proteins, we rationally designed a series of de novo chimeric proteins comprising an N-terminal globular domain fused to a linear collagen-like domain. These structurally heterogeneous proteins were conjugated with doxorubicin (DOX) and homogenized to form chimeric collagen-like protein-DOX nanocomplexes (CDCNs). By fine-tuning the protein structure and domain organization, we achieved precise control over CDCN architecture and drug release kinetics. Furthermore, to enhance tumor specificity, triple-negative breast cancer (TNBC)- and glioblastoma (GBM)-targeting peptides were genetically fused to the chimeric proteins, respectively. In both in vitro and in vivo models of TNBC and GBM, CDCNs facilitated selective tumor accumulation, enhanced cellular uptake, and promoted apoptosis while minimizing off-target toxicity. This work establishes a strategy for designing protein-based nanoplatforms with programmable structures and tunable functionalities, offering promising potential for precisely controlling of protein-based delivery system.

bioengineering↗

Short Polysialic Acid Counteracts Age-Related Synaptic and Cognitive Deficits

Impaired activity of glutamate transporters, elevated concentration of extrasynaptic glutamate and hyperactivity of extrasynaptic GluN2B-containing NMDA receptors are common features in aging and several neurological conditions, including Alzheimers disease (AD). Previous studies revealed that polysialic acid (polySia), a glycan predominantly carried by the neural cell adhesion molecule NCAM, inhibits extrasynaptic NMDA receptors and supports synaptic plasticity in healthy adult brains. Moreover, intranasal delivery of polySia with the degree of polymerization 12 (NANA12) rescued synaptic plasticity and cognitive functions in models of tauopathy and amyloidosis associated with AD. Here, we comparatively studied the effects of NANA12 in young (4 months) old (26 months) and very old (29 months) mice. Strikingly, NANA12 promoted cognitive flexibility in attentional set-shifting (ASST) tests and spatial memory in the Barnes maze in very old mice. To capture fine-grained effects undetectable by conventional methods, we introduced a novel trial-wise data analysis approach for evaluating ASST performance. The observed cognitive improvements were not due to changes in the size of hippocampal memory engrams, visualized by c-Fos immunolabeling after reactivation of spatial memory in the probe trial. Five-day treatment with NANA12 did not affect neuronal structure (MAP2 levels), expression of senescence (lipofuscin) or neuroinflammation (microglial Iba1) markers, activation of BDNF receptors (p-TrkB) or expression of endogenous polySia in the hippocampus of very old mice. However, cognitive improvements correlated with the normalized size of CD68+ microglial lysosomes and reduced amounts of pre- and postsynaptic proteins at these structures. Thus, our data demonstrate the potential of short polySia to reduce synaptic phagocytosis and restore key cognitive functions attenuated in aging.

neuroscience↗

Toti: an integrated multi-omics database to decipher the epigenetic regulation of gene expression in totipotent stem cells

Totipotent cells (TSCs), the origin of mammalian life and foundation to early mammalian embryogenesis, are characterized by the highest differentiation capacity and extensive developmental potential. However, none of the existing embryonic databases have provided epigenetic and transcriptomic resources on totipotency, greatly limiting our understanding of the mechanisms governing the establishment and exit of totipotency. Here, we present Toti, a pioneering multi-omics database exclusively developed for totipotency, covering in vivo, in vitro and genome-edited human and mouse embryonic TSCs, TSC-like cells, pluripotent cells (PSCs), and embryos spanning preimplantation stages, with a total of 8,265 samples. Toti facilitates an in-depth exploration of the molecular mechanisms underlying totipotency by offering Search, Browse and Analysis modules available at http://toti.zju.edu.cn/.

developmental biology↗

Highly efficient organ-targeting transport through the ventral midline interstitial channels injection: a new development of interstitium

How to improve the drugs bioavailability has always been a hot and difficult topic. Conventional drug delivery methods, such as oral administration and the blood circulation system, suffer from issues such as low targeting efficiency, low bioavailability, and high side effects. Recently, interstitium has gradually been recognized as an important new organ. Interstitial injection allows small molecules to move through interstitial channels with interstitial fluid flow and be transported to organs, providing new possibilities for drug delivery. In this study, using fluorescein sodium as a drug model, we systematically investigated the distribution of the fluorescein sodium in organs and body surface of the rats after ventral midline interstitial channels injection. In addition, we observed the microstructure of the ventral midline interstitial channels of abdominal wall and the effects of channels ligation on fluorescein sodium delivery and target organs, to explore the mechanism of interstitial injection. We found that fluorescein sodium can be efficiently transported to the uterus and ovaries along the ventral midline interstitial channels, and the parallel fibers and interconnected interstitial spaces of the channels facilitate long-distance transport of solutes. Additionally, the blockage of the transmission through those channels had results in a significant decrease in targeted transport efficiency over long distances, a decrease in oestrogen levels, organ coefficients, and body weights in female rats. Therefore, the ventral midline interstitial channels with free fluid flow may be a potential communication pathway between body surface and organs. These findings have significant value in the development of drug delivery.

physiology↗

Development of a novel peripherally acting alpha2A-adrenergic receptor antagonist for anti-diabetic

Yohimbine, a potent alpha2A-adrenergic receptor (2AAR) antagonist, was found therapeutic potential for type 2 diabetes through improving insulin release. However, the adverse side effects mediated by its actions in the brain hampered its use. Here, based on molecular docking analysis and structural modification, we have developed a novel peripherally acting yohimbine derivative (CDS479-2). CryoEM data found that yohimbine and CDS479-2 have similar interactions with the structure of 2AAR. Importantly, CDS479-2 shows similar 2AAR antagonist activity as yohimbine, but with very limited access to the brain, and thus avoiding the unwanted central effects such as hypertension and anxiety. Acute administration of CDS479-2 by injection or gavage lowered blood glucose levels and improved glucose tolerance in the high-fat diet-induced obesity (DIO) mice, an animal model for human type 2 diabetes. Remarkably, DIO mice received 2 weeks of daily administration of CDS479-2, but not yohimbine, exhibited sustained normoglycaemia, and increased density of the insulin-producing beta cells, in which important proliferation genes were found upregulated. Moreover, the overall protein expression levels of their pancreas were more similar to that of the healthy chow-fed mice. Thus, CDS479-2 may indicate a new direction for type 2 diabetes treatment. Importantly, the strategy we employed in this study will inspire the optimization for drugs that with both peripheral and central targets. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=166 HEIGHT=200 SRC="FIGDIR/small/628818v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1d3d7corg.highwire.dtl.DTLVardef@1afbad3org.highwire.dtl.DTLVardef@12a1aborg.highwire.dtl.DTLVardef@1341a02_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma

As the core, tumorigenic downstream effectors of the Hippo signalling pathway, YAP/TAZ and the TEAD family of transcription factors represent attractive targets for drug discovery efforts within cancer research. This is particularly true within the context of pleural mesothelioma, in which there are many recent preclinical developments and clinical trials evaluating the efficacy of TEAD inhibitors. The range of inhibitors have shown great promise, but comparisons of their performances are so far limited. Here we develop a high content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors. We take advantage of isogenic cellular models that enable us to examine inhibitor specificity. We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer relevant assays in a clinically relevant cellular model.

cancer biology↗

CILP from Cartilage Intermediate Zone Inhibits Hyaline Cartilage Fibrosis and Chondrocyte Ferroptosis via Keap1-Nrf2 Axis in Early Osteoarthritis Exercise Therapy

By analyzing the single-cell RNA-Seq libraries, the roles of cartilage intermediate layer protein (CILP) and the cartilage intermediate zone in early osteoarthritis (OA) exercise therapy were explored. An early OA rat model was established via a 4-week anterior cruciate ligament transection. The effect of moderate exercise was confirmed using histology, the open-field test, and gait analysis. The response of the cartilage intermediate zone to mechanical stimulation was explored using multiplex fluorescent immunohistochemical staining. Radiomics was used to evaluate the relatively damaged and undamaged areas in the cartilage of patients with OA. CILP was OE and KD in early OA chondrocytes, and quantitative proteomics, yeast one-hybrid, co-immunoprecipitation, Nrf2 and ubiquitination assays were used to investigate its mechanism. We found that moderate exercise upregulates CILP in the cartilage intermediate zone. CILP recovers the type II/I collagen, Sox9, and -SMA expression ratios, and reduces Keap1-Nrf2 dimer stability, inhibiting Nrf2 ubiquitination and promoting Nrf2 nuclear translocation. Nrf2 nuclear translocation activates SLC7A11, HO-1, GPX4, and SOD-1 expression, decreases MDA content, and increases GSH content, inhibiting chondrocyte ferroptosis and promoting fibrocartilage hyalinization. In conclusion, the exercise-induced cartilage intermediate zone and CILP-Keap1-Nrf2 axis inhibit hyaline cartilage fibrosis and chondrocyte ferroptosis to alleviate early OA.

cell biology↗