Biology subjects

zhang, x.

Publications and source records attributed to zhang, x..

13 recordsLinked to original sources

bioRxiv2026

Chronic kidney disease promotes anxiety susceptibility through an angiotensin II central amygdala axis

Background: Neuropsychiatric comorbidities are highly prevalent in chronic kidney disease (CKD), yet the underlying neural mechanisms remain poorly defined. Methods: We established multiple mouse models of CKD and identified an adenine-induced model as the most suitable platform to study neurobehavioral alterations. Anxiety susceptibility was operationalized as the emergence of anxiety-like behavior after subthreshold unpredictable stress (SUS) and was assessed using the SUS paradigm combined with behavioral assays. Region-focused c-Fos mapping, fiber photometry, and chemogenetic manipulation were used to interrogate neural circuit activity. Pharmacological and genetic approaches were applied to investigate the role of angiotensin II (Ang II) signaling. Finally, hypothalamic paraventricular nucleus (PVN) activation was used to explore brain-to-kidney feedback by using in vivo multiphoton microscopy imaging techniques. Results: CKD mice showed no consistent baseline anxiety-like phenotype across standard assays but developed robust anxiety-like behavior after subthreshold unpredictable stress. Region-focused c-Fos profiling and fiber photometry identified the central amygdala (CeA) as a stress-sensitized limbic node in CKD. Chemogenetic inhibition of CeA GABAergic neurons attenuated anxiety-like behavior, supporting a functional role for CeA activity. Mechanistically, CKD elevated circulating Ang II and enhanced CeA accumulation of peripherally administered FAM-Ang II-associated signal. CeA-specific Agtr1a knockdown attenuated anxiety-like behavior and exaggerated stress evoked CeA calcium responses. Exploratory experiments further showed that sustained PVN glutamatergic activation aggravated early renal injury markers in a mild renal injury model. These findings support a kidney-to-brain model in which CKD primes CeA stress circuits, while local Ang II AT1R signaling contributes to the behavioral expression of stress-induced anxiety-like behavior, with a potential brain to kidney feedback component. Conclusions: CKD promotes stress-induced anxiety susceptibility through a CeA-centered mechanism involving local Ang II AT1R signaling. These findings identify CeA Ang II AT1R signaling as a potential contributor to CKD-associated stress-related affective vulnerability.

animal behavior and cognition↗

bioRxiv2026

An electron-bifurcating hydrogenase-like activity associated with mitochondrial Complex I under hypoxia in vascular plants

Abstract Molecular hydrogen (H2) evolution by higher plants under oxygen limitation was reported more than six decades ago, yet its origin, biochemical basis and physiological significance have remained unresolved. Here, we localize this activity to a mitochondrial, Complex I-associated electron-transfer system. Mitochondrial fractions from etiolated Vigna radiata hypocotyls accumulated H2 under hypoxia and mildly acidic conditions. H2 accumulation was nearly abolished by rotenone and was sensitive to perturbations of Complex II, quinone-pool turnover, terminal oxidases and protonmotive force. NADH-generating substrates and succinate-fumarate supplementation stimulated H2 accumulation, while metabolic profiling linked H2 production to succinate and NADH accumulation. Cumulative H2 production exceeded the measured NADH pool by approximately two orders of magnitude, requiring sustained NADH regeneration. These findings support a division-of-labour model involving coexisting mature Complex I and CI*, a Complex I assembly or remodeling state. TCA-cycle dehydrogenation and succinate-driven reverse electron transfer (RET) through mature Complex I replenish the matrix NADH pool, whereas CI* consumes NADH through an H2-evolving branch, regenerating NAD. This model identifies a potential conditional redox function for CI* and an electron outlet coupled to continuous NADH cycling. Unlike mammalian RET, which can generate pronounced reactive oxygen species (ROS), diversion of reducing equivalents into H2 could attenuate the corresponding ROS signature, potentially helping explain the elusive physiological evidence for plant RET. The data establish a RET-compatible supply route, not direct reverse electron flux. Structural and computational analyses support an FMN-Fe-S branched mechanism whose catalytic steps remain unverified. More broadly, Complex I assembly may not merely build the respiratory machinery; under specific physiological conditions, its intermediate states may reshape electron fate, exposing latent hydrogenase-related chemistry associated with Complex I's evolutionary ancestry.

biochemistry↗

bioRxiv2026

A Phospho-Switch for Cell Fate Control

Cell fate control is thought to be complex, likely involving both cell intrinsic and extrinsic factors, and remains ill-defined at the molecular level. Here we show a phospho-switch controls cell fate both in vitro and in vivo. We first show that SALL4 is phosphorylated at multiple sites, but only T903 as the primary one as SALL4T903A lost BAF interaction and [~]90% activity in reprogramming. Mechanistically, we demonstrate that SALL4pT903 is sensitive to BMP4 signaling through DUSP9 axis. Finally, we show by tetraploid embryo complementation that mESCs harboring SALL4T903A can sustain embryo development but with severe defects including cranial hypoplasia and flattened skull vault after birth. A genome wide search identifies 608 transcription factors harboring the same HTG motif sandwiched by two zinc fingers, suggesting that this phospho-switch may be a conserved mechanism to control cell fate. In briefA phosphorylation switch, pT903, in SALL4 governs cell fate by modulating BAF complex interaction in response to BMP4-DUSP9 signaling, as its dephosphorylation abrogates reprogramming and causes cranial defects in mice, suggesting that such switches may broadly regulate cell fate machinery. HighlightsO_LIA T903 phospho-switch in SALL4 gates BAF interaction to orchestrate gene activation and reprogramming C_LIO_LIBMP4-DUSP9 signaling converges on SALL4pT903 dephosphorylation to couple extracellular cues with cell fate determination C_LIO_LIDisrupting the SALL4-T903 phospho-switch causes severe postnatal developmental defects in mice. C_LIO_LIThe HTGE motif may function as a central switch on key transcription factors for sensing upstream signals C_LI

developmental biology↗

bioRxiv2025

Enhanced Hydrogen Production Through Two-Stage Fermentation Coupling Clostridium pasteurianum and Rhodobacter sphaeroides

Biological H2 production via dark fermentation is constrained by low yields and inhibitory metabolite accumulation. Coupling dark and photo fermentation effectively overcomes these issues by enhancing substrate utilization and reducing wastewater pollution, yet scalable systems for industrial application remain rare. This study presents a 10-L two-stage fermentation system (5L dark/5L photo bioreactors) using Clostridium pasteurianum DSM 525 and Rhodobacter sphaeroides ZX-5. Dark fermentation generated 3372 mL H2 from glucose, yielding effluent with 1.29 g/L acetic and 3.11 g/L butyric acids. After centrifugation, pH adjustment, and clinoptilolite deamination ([≥]60% efficiency), ammonium was reduced to <100 mg/L. The pretreated effluent, supplemented with concentrated RCVBN medium, served as photo-fermentation substrate. A butyric acid feeding strategy extended the process by 120 h, boosting H2 yield by 16.4%. The coupled system produced 6480 mL H2 (80% increase), degrading 50% acetic acid and 42% butyric acid. This work demonstrates a scalable bioreactor configuration integrating efficient biohydrogen production with value-added wastewater treatment for industrial bioenergy applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/694164v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1f324a4org.highwire.dtl.DTLVardef@1eab711org.highwire.dtl.DTLVardef@98e50dorg.highwire.dtl.DTLVardef@1e5f02e_HPS_FORMAT_FIGEXP M_FIG Graphic abstract C_FIG

bioengineering↗

bioRxiv2025

A perturbation proteomics-based foundation model for virtual cell construction

Building a virtual cell requires comprehensive understanding of protein network dynamics of a cell which necessitates large-scale perturbation proteome data and intelligent computational models learned from the proteome data corpus. Here, we generate a large-scale dataset of over 38 million perturbed protein measurements in breast cancer cell lines and develop a neural ordinary differential equation-based foundation model, namely ProteinTalks. During pretraining, ProteinTalks gains a fundamental understanding of cellular protein network dynamics. Our model encodes protein networks and exhibits consistently improved predictive accuracy across various downstream tasks, highlighting its generalization capabilities and adaptability. In cancer cells, ProteinTalks robustly predicts drug efficacy and synergy, identifies novel drug combinations, and, through its interpretability, uncovers resistance-associated proteins. When applied to more complex system, patient-derived tumor xenografts, ProteinTalks predicts potential responses to drugs. Its integration with clinical patient data enhances the prognosis prediction of breast cancer patients. Collectively, we present a foundational model based on proteome dynamics, offering potential for various downstream applications, including drug discovery, and providing a basis for developing virtual cells.

systems biology↗

bioRxiv2024

Apelin-13 in the paraventricular nucleus protects myocardium from ischemia via V1a receptor of the paraventricular nucleus and GABAA receptor γ2 of the nucleus tractus solitarii in rats

BackgroundApelin system plays a significant role in central blood pressure regulation, but its role in neural control of myocardial injury protection is poorly understood. Thus, this study was undertaken to evaluate the effects of apelin-13 in the paraventricular nucleus (PVN) on myocardial infarction (MI) and ischemia/reperfusion (I/R). MethodsThe cardiac functions were assessed after microinjecting or transferring the apelin-13 gene into the paraventricular nucleus (PVN) of rat models with myocardial infarction (MI) or ischemia/reperfusion (I/R). ResultsIn MI rats, we showed that apelin-13 expression decreased in PVN, V1a receptor expression increased in PVN and nucleus tractus solitarii (NTS), and GABAA receptor (GAR) {gamma}2 expression increased in NTS. In primary cultured hypothalamus and medulla oblongata neurons, V1a receptor expression was downregulated by APJ receptor antagonist or GAR agonist, indicating that there are interactions between these receptors in neurons. Apelin-13 overexpression in PVN significantly improved cardiac function of MI and I/R rats, including left-ventricular end-diastolic diameter, left-ventricular end-systolic diameter, left-ventricular ejection fraction, and left-ventricular fractions shortening, accompanied by decreased noradrenaline and increased vasopressin plasma levels. Myocardial ischemia-related apoptotic and inflammatory pathway markers (Bcl-1, Bax, TGF-{beta}1, CCR5, Smad2) were downregulated and four neuropeptides of the parasympathetic endocrine system (somatostatin, cholecystokinin, glucagon-like peptide 1, vasoactive intestinal peptide) were increased in serum correspondingly with cardiac function improving. V1a receptor antagonist in PVN or NTS and GAR agonist in NTS decreased the effects of apelin-13 overexpression on cardiac function of MI and I/R rats. ConclusionsOverexpression of apelin-13 in PVN leads to cardiac function improvement via V1a receptor in PVN and NTS, and GAR{gamma}2 in NTS. Parasympathetic endocrine system and myocardial ischemia-related apoptotic and inflammation signaling pathways are involved in apelin-13 in PVN-mediated cardiac function regulation, which provides evidence for neural regulation of cardiovascular diseases.

neuroscience↗

bioRxiv2024

A Novel Computational Pre-Procedural Planning Model for Coronary Interventions Based on Coronary CT Angiography

In percutaneous coronary intervention (PCI), the ability to predict post-PCI fractional flow reserve (FFR) and stented vessel informs procedural planning. However, highly precise and effective methods to quantitatively simulate coronary intervention are lacking. This study developed a validated virtual coronary intervention (VCI) technique for non-invasive physiological and anatomical assessment of PCI. In this study, patients with substantial lesions (pre-PCI FFR of less than 0.80) were enrolled. VCI framework was used to predict vessel reshape and post-PCI FFR. The accuracy of predicted post-VCI FFR, luminal cross-sectional area (CSA) and centreline curvature was validated with post-PCI computed tomography (CT) angiography datasets. Overall, 21 patients were selected for the study, of which 9 patients (9 vessels) were included in the analysis. The average time for PCI simulation was 24.92 {+/-} 1.00 s on a single processor. The calculated post-PCI FFR was 0.92 {+/-} 0.09 and the predicted post-VCI FFR was 0.90 {+/-} 0.08 (mean difference: -0.02 {+/-} 0.05 FFR unit; limits of agreement: -0.08 to 0.05). Morphologically, the predicted CSA is 16.36 {+/-} 4.41 mm2 and post-CSA is 17.91 {+/-} 4.84 mm2 (mean difference: -1.55 {+/-} 1.89 mm2; limits of agreement: -5.22 to 2.12), the predicted centreline curvature of stented region is 0.15 {+/-} 0.04 mm{square}1 and post-PCI centreline curvature is 0.17 {+/-} 0.03 mm{square}1 (mean difference: -0.02 {+/-} 0.06 mm{square}1; limits of agreement: -0.12 to 0.09). The proposed VCI technique achieves non-invasive pre-procedural anatomical and physiological assessment of coronary intervention. The proposed model has the potential to optimize PCI pre-procedural planning and improve the safety and efficiency of PCI. HighlightsO_LIPresent a computational pre-procedural planning model for coronary interventions. C_LIO_LIDevelop a computational framework to predict post-PCI FFR. C_LIO_LIValidation of the model with post-PCI CT angiography datasets. C_LIO_LIThe proposed model has the potential to optimize PCI pre-procedural planning. C_LI

bioengineering↗

bioRxiv2024

Human DDIT4L intron retention contributes to cognitive impairment and amyloid plaque formation.

Cognitive impairment and amyloid plaques are the most important clinical and neuropathological feature for dementia, especially in Alzheimers disease (AD). However, the etiology of dementia is complicated. The present study reveals that an aberrant splicing of DDIT4L, the isoform DDIT4L intron retention (DIR), occurs in AD patients. Homozygous DIR-knock-in (KI) mice showed DIR expression in hippocampal neurons, marked cognitive impairment, augmented A{beta} deposition and enhanced Tau phosphorylation. The DIR colocalized with thioflavin S-positive plaques and gelsolin in AD patients. The DIR induced A{beta} deposition and cognitive impairment by interacting with gelsolin. Moreover, DIR interacted with GluA1, the subunit of the AMPA receptor, contributing to synaptic deficiency and cognitive impairment. Furthermore, an anti-DIR monoclonal antibody (mAb) alleviated cognitive impairment and reduced A{beta} deposition and Tau phosphorylation. Thus, DIR contributes to cognitive impairment and amyloid plaques, and could be a potential therapeutic target for dementia.

neuroscience↗

bioRxiv2021

DNA metabarcoding Uncover the Diet of Subterranean Rodents in China

ObjectiveIn the past, the zokor, which lived in northern China, caused great harm to agriculture and forestry production due to its large and sophisticated diet. Since the rat lives underground for most of its life, researchers know little about its dietary habits. Further understanding of its diet in the field is of important meaning for developing green and sustainable control strategies for the rat. MethodsLongde County in Liupan Mountain area of Ningxia Hui Autonomous Region was selected as the interest area to capture zokor and investigate the species of habitat plants.We selected chloroplast trnL gene and eukaryotic internal transcription spacer 1 (ITS 1) primers to amplify DNA from the gastric contents of zokor,and then sequenced on Illumina Miseq PE300 platform. ResultsThe gastric contents of Eospalax smithii (n=16) and E.cansus(n=9) were analyzed by operational taxonomic units (OTU) clustering and amplicon sequence variants(ASVs).The OTU clustering method obtained 2,995 OTUs, and the ASV method obtained 4,657 ASVs. The ASV method was better than the OTU clustering method, and the ASV method was adopted in the subsequent analysis. The food list of 32 families, 80 genera and 154 species was obtained by ASV method after the error was removed. The food composition of zokor was evaluated by relative abundance(%RA) method and frequency of occurrence(%ROO) method. At the Family level, it was found that zokor mainly fed on Asteraceae, Poaceae, Rosaceae, Pinaceae, Brassicaceae, Apiaceae, etc. At the Genus level, they are mainlyEchinops, Littledalea,Artemisia,Picea, Cirsium, Elymus and so on. The diet alpha diversity of E.cansus was slightly higher than that of E.smithii (P > 0.05). The correlation coefficient between Sobs index of alpha diversity and body weight of zokor was -0.382 (P = 0.059). The diet beta diversity proved that most zokors (22/25) clustered together, with low heterogeneity. They fed positively on Calamagrostis, Cirsium, Echinops, Medicago, Sanguisorba and Taraxacum. We found that zokor mainly fed on the roots of perennial herbs(PH), which were rich in water, carbohydrate, fat and protein, which provided an important energy source for its survival. ConclusionHigh-throughput sequencing(HTS) based DNA metabarcoding technology has well revealed the diet of zokor, which are generalist.

ecology↗

bioRxiv2020

VIL1, a Polycomb-associated protein, modulates high ambient temperature response via H3K27me3 and H2A.Z in Arabidopsis thaliana

Adapting to the everchanging environment is key to a successful life for an organism. Eukaryotes reprogram their transcriptome in order to adapt to an unfavorable environment. To achieve this reprogramming, plants and animals employ multiple responses including epigenetic regulation. In the search for mutations compromised in high ambient temperature response, we found that VIL1, a PHD finger protein displays aberrant development at high temperature. RNA-seq analysis shows that vil1 fails to downregulate heat suppressed genes. H2A.Z ChIP-seq showed that unlike wild type, vil1 fails to evict H2A.Z from heat responsive genes. We also found that vil1 suppresses constitutive thermo-morphogenic phenotype of arp6. Supporting this phenotype, RNA-seq analysis revealed that constitutive heat responsive transcriptome of arp6 reverted back to the wild-type levels in arp6vil1. This observation suggests an antagonistic relationship between VIL1 and ARP6. We found that this antagonism can be explained in part by interaction between H3K27me3 and H2A.Z.

plant biology↗

bioRxiv2019

The co-stimulation of anti-CD28 and IL-2 enhances the sensitivity of ELISPOT assays for detection of neoantigen-specific T cells in PBMC

Neoantigen-based cancer immunotherapies hold the promise of being a truly personalized, effective treatment for diverse cancer types. ELISPOT assays, as a powerful experimental technique, can verify the existence of antigen specific T cells to support basic clinical research and monitor clinical trials. However, despite the high sensitivity of ELISPOT assays, detecting immune responses of neoantigen specific T cells in a patient or healthy donors PBMCs is still extremely difficult, since the frequency of these T cells can be very low. We developed a novel experimental method, by co-stimulation of T cells with anti-CD28 and IL-2 at the beginning of ELISPOT, to further increase the sensitivity of ELISPOT and mitigate the challenge introduced by low frequency T cells. Under the optimal concentration of 1g/mL for anti-CD28 and 1U/ml for IL-2, our new method can increase sensitivity by up to 5 folds comparing to a conventional ELISPOT, and outperforms other cytokine stimulation alternatives. To the best of our knowledge, this is the first report that the co-stimulation of anti-CD28 and IL-2 is able to significantly improve the sensitivity of ELISPOT assays, indicating that anti-CD28 and IL-2 signaling can act in synergy to lower the T cell activation threshold and trigger more neoantigen-specific T cells.

immunology↗

bioRxiv2019

Dynamic response of RNA editing to temperature in Grape by RNA deep-sequencing

RNA editing is a post-transcriptional process of modifying genetic information on RNA molecules, which provides cells an additional level of gene expression regulation. Unlike mammals, in land plants, RNA editing converts C to U residues in organelles. However, its potential role in response to different stressors (heat, salt and so on) remains unclear. Grape is one of the most popular and economically important fruits in the world, and its production, like other crops, must deal with abiotic and biotic stresses, which cause reductions in yield and fruit quality. In our study, we tested the influence of the environmental factor temperature on RNA processing in the whole mRNA from grape organelle. In total, we identified 123 and 628 RNA editing in chloroplast and mitochondria respectively with the average editing extent nearly ~60%. The analyses revealed that number of non-synonymous editing sites were higher than that of synonymous editing sites, and the amino acid substitution type tend to be hydrophobic. Additionally, the overall editing level decreased with the temperature rises, especially several gene transcripts in chloroplast and mitochondria (matK, ndhB etc.). 245 sites were furthermore determined as stress-responsive sites candidates. We also found that the expression level of PPR genes decreased with the temperature rises, which may contribute to the loss of RNA editing at high temperature. Our findings suggest that the RNA editing events are very sensitive to high temperature, the changes of amino acid in these genes may contribute to the stress adaption for grape.

plant biology↗

bioRxiv2018

A novel amidase signature family amidase from the marine actinomycete Salinispora arenicola CNS-205

We cloned a new gene from the amidase signature (AS) family, designated am, from the marine actinomycete Salinispora arenicola CNS-205. As indicated by bioinformatics analysis and site-directed mutagenesis, the AM protein belonged to the AS family. AM was expressed, purified, and characterised in Escherichia coli BL21 (DE3), and the AM molecular mass was determined to be 51 kDa. The optimal temperature and pH were 40 {degrees}C and pH 8.0, respectively. AM exhibited a wide substrate spectrum and showed amidase, aryl acylamidase, and acyl transferase activities. AM had high activity towards aromatic and aliphatic amides. The AM substrate specificity for anilides was very narrow; only propanil could be used as an effective substrate. The extensive substrate range of AM indicates it may have broad potential applications in biosynthetic processes and biodegradation.

molecular biology↗