Biology subjects

Lin, Y.-H.

Publications and source records attributed to Lin, Y.-H..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Exogenous Methylglyoxal Improves Maize Yield by Alleviating Plant Diabetes and leaf senescence under Drought

Drought-induced leaf senescence is related to high sugar levels in leaves, photosynthesis inhibition, and ultimate yield loss. This physiological phenomenon in leaves bears resemblance to the symptom of diabetes in human disease. However, the underlying mechanisms of plant diabetes on carbon imbalance in maize leaf and corresponding detoxification strategy have not been well understood. In this study, we demonstrated that foliar application of exogenous methylglyoxal (MG) delayed leaf senescence and promoted photoassimilation, retrieved 14% yield loss induced by drought stress during grain filling stage. Transcriptome and metabolite analysis revealed that drought increased sugar accumulation in leaf with inhibition of sugar transporters facilitating phloem loading. This further lead to disequilibrium of glycolysis and over-accumulation of endogenous MG. Contrarily, exogenous MG significantly upregulated glycolytic flux and glyoxalase system catabolizing endogenous MG and advanced glycation end products toxicity, ultimately alleviating plant diabetes. Besides, the genes facilitating anabolism and catabolism of trehalose- 6-phosphate were promoted and suppressed by drought, respectively, whereas exogenous MG reversed the effect. Moreover, exogenous MG activated phenylpropanoid biosynthetic pathway, likely promoting cell structural integrity. Collectively, these results suggest that exogenous MG alleviates the toxic effect from drought-induced sugar accumulation and activates the defense-related pathway, thereby maintaining leaf function and yield production. HighlightExogenous methylglyoxal stimulates glycolytic flux and glyoxalase system, providing a potential insight to alleviate plant diabetes under drought condition.

physiology↗

bioRxiv2023

Rapid assessment of changes in phage bioactivity using dynamic light scattering

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-year-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web-application (Phage-ELF) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and non-destructive tool for quality control of phage preparations in academic and commercial settings. Significance StatementPhages are promising for use in treating antibiotic-resistant infections, but their decay over time in refrigerated storage and higher temperatures has been a difficult barrier to overcome. This is in part because there are no suitable methods to monitor phage activity over time, especially in clinical settings. Here, we show that Dynamic Light Scattering (DLS) can be used to measure the physical state of phage preparations, which provides accurate and precise information on their lytic function - the key parameter underlying clinical efficacy. This study reveals a "structure-function" relationship for lytic phages and establishes DLS as a method to optimize the storage, handling, and clinical use of phages.

biophysics↗

bioRxiv2023

Anaplerotic nutrient stress drives synergy of angiogenesis inhibitors with therapeutics targeting tumor metabolism

Tumor angiogenesis is a cancer hallmark, and its therapeutic inhibition has provided meaningful, albeit limited, clinical benefit. While anti-angiogenesis inhibitors deprive the tumor of oxygen and essential nutrients, cancer cells activate metabolic adaptations to diminish therapeutic response. Despite these adaptations, angiogenesis inhibition incurs extensive metabolic stress, prompting us to consider such metabolic stress as an induced vulnerability to therapies targeting cancer metabolism. Metabolomic profiling of angiogenesis-inhibited intracranial xenografts showed universal decrease in tricarboxylic acid cycle intermediates, corroborating a state of anaplerotic nutrient deficit or stress. Accordingly, we show strong synergy between angiogenesis inhibitors (Avastin, Tivozanib) and inhibitors of glycolysis or oxidative phosphorylation through exacerbation of anaplerotic nutrient stress in intracranial orthotopic xenografted gliomas. Our findings were recapitulated in GBM xenografts that do not have genetically predisposed metabolic vulnerabilities at baseline. Thus, our findings cement the central importance of the tricarboxylic acid cycle as the nexus of metabolic vulnerabilities and suggest clinical path hypothesis combining angiogenesis inhibitors with pharmacological cancer interventions targeting tumor metabolism for GBM tumors.

cancer biology↗

bioRxiv2023

High-Dimensional Spectral Cytometry Reveals Therapeutically Relevant Immune Subtypes in Gastric Cancer

Identification of locally advanced gastric cancer (GC) patients who might potentially benefit from immune-based strategies is limited by both the poor predictive quality of existing biomarkers, including molecular subtypes, tumor mutational burden, and PD-L1 expression, as well as inadequate understanding of the gastric cancer immune microenvironment. Here, we leveraged high-dimensional spectral cytometry to re-classify locally advanced gastric tumors based on immune composition. The gastric cancer microenvironment was comprised of a diverse immune infiltrate including high proportions of plasmablasts, macrophages, and myeloid-derived suppressor cells. Computational cell typing and sample clustering based on tiered broad immune and T-cell focused phenotyping identified three distinct immune subtypes. The most immunogenic subtype exhibited high proportions of activated CD4+ T-cells and plasmablasts and included tumors that would have been classified as non-immunogenic based on prior classifications. Analysis of gastric cancer patients treated with immune checkpoint blockade indicates that patients who responded to immunotherapy had a pre-treatment tumor composition that corresponded to higher immune scores from our analysis. This work establishes a novel immunological classification of gastric cancer including identification of patients and immune networks likely to benefit from immune-based therapies.

cancer biology↗

bioRxiv2023

Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease

Somatic mutations in non-malignant tissues accumulate with age and insult, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate mutations found in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to non-alcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7, a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance. Next, we induced pooled mosaicism in 63 known NASH genes, allowing us to trace mutant clones side-by-side. This in vivo tracing platform, which we coined MOSAICS, selected for mutations that ameliorate lipotoxicity, including mutant genes identified in human NASH. To prioritize new genes, additional screening of 472 candidates identified 23 somatic perturbations that promoted clonal expansion. In validation studies, liver-wide deletion of Bcl6, Tbx3, or Smyd2 resulted in protection against NASH. Selection for clonal fitness in mouse and human livers identifies pathways that regulate metabolic disease. HighlightsO_LIMosaic Mboat7 mutations that increase lipotoxicity lead to clonal disappearance in NASH. C_LIO_LIIn vivo screening can identify genes that alter hepatocyte fitness in NASH. C_LIO_LIMosaic Gpam mutations are positively selected due to reduced lipogenesis. C_LIO_LIIn vivo screening of transcription factors and epifactors identified new therapeutic targets in NASH. C_LI

cell biology↗

bioRxiv2023

A Weakly Supervised U-Net Model for Precise Whole Brain Immunolabeled Cell Detection

Cell segmentations low precision due to the intensity differences hinders widespread use of whole brain microscopy imaging. Previous studies used ResNet or CNN to account for this problem, but are unapplicable to immunolabeled signals across samples. Here we present a semiauto ground truth generation and weakly-supervised U-Net-based Deep-learning precise segmentation pipeline for whole brain immunopositive c-FOS signals, which reveals the distinct neural activity maps with different social motivations.

neuroscience↗

bioRxiv2022

NAD+ biosynthesis as a collateral lethality target for precision oncology

Genomic deletion of tumor suppressor genes (TSG) often encompasses neighboring genes which may be members of multi-gene families encoding cell essential functions. These genomic events create targetable cancer-specific vulnerabilities, termed "collateral lethality" as illustrated by homozygous deletion of the glycolytic gene ENO1, which sensitizes glioblastoma (GBM) cells to inhibition of its paralog ENO2. Here, we sought to generalize the concept by validating a second multi-gene family in an unrelated metabolic pathway. Nicotinamide-nucleotide adenylyltransferase (NMNAT) is an essential and (unlike the more extensively studied NAMPT) non-bypassable step in NAD biosynthesis encoded by three paralogs, one of which, NMNAT1, is homozygously deleted as part of the 1p36 tumor suppressor locus in TCGA data of GBM, Cholangiocarcinoma and Hepatocellular carcinoma (with near zero expression of found in several other malignancies). In a glioma cell line (Gli56) with homozygous deletion of NMNAT1 expressing NMNAT2 and NMNAT3, shRNA-mediated knockdown of NMNAT2 is selectively toxic to Gli56 NMNAT1-deleted but not ectopically rescued cells. As NMNAT1 and NMNAT2 are predominantly localized in the nucleus and cytosol, respectively, these data suggest a functionally common pool of cytosolic and nuclear NAD+. Inducible shRNA-mediated extinction of NMNAT2 decreases NAD+ levels and selectively kills NMNAT1-deleted, but not NMNAT1-rescued cells in vitro and eradicates intracranial tumors in vivo. Thus, collateral lethality is a generalizable framework for the development of new classes of targeted agents with an informed clinical development path in cancer. Statement of significanceAn ongoing challenge in precision oncology is the translation of genomic data into actionable therapeutic opportunities with clear clinical benefit. We have demonstrated that genes homozygously deleted by virtue of chromosomal proximity to major tumor suppressor genes can confer cancer-specific vulnerabilities, termed "collateral lethality". While our previous work validated one such collateral lethality target in glycolysis, we now provide empirical in vitro and in vivo evidence that this concept applies to another deleted gene governing an altogether distinct biochemical pathway. The generalization of collateral lethality may expand the spectrum of molecular targets in cancer with a genomically-informed path for accurate clinical development.

cancer biology↗

bioRxiv2022

A versatile method to archive and delipidate brain tissues for ensuing multiplexed immunolabeling and organ-level imaging

Tissue clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain, and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

bioengineering↗

bioRxiv2022

IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration

While midlobular hepatocytes in zone 2 are a recently identified cellular source for liver homeostasis and regeneration, these cells have not been exclusively fate mapped. We generated a Igfbp2-CreER knockin strain, which specifically labels midlobular hepatocytes. During homeostasis over 1 year, zone 2 hepatocytes increased in abundance from occupying 21% to 41% of the lobular area. After either pericentral injury with carbon tetrachloride or periportal injury with DDC, IGFBP2+ cells replenished lost hepatocytes in zones 3 and 1, respectively. IGFBP2+ cells also preferentially contributed to regeneration after 70% partial hepatectomy, as well as liver growth during pregnancy. Because IGFBP2 labeling increased substantially with fasting, we used single nuclear transcriptomics to explore zonation as a function of nutrition, revealing that the zonal division of labor shifts dramatically with fasting. These studies demonstrate the contribution of IGFBP2-labeled zone 2 hepatocytes to liver homeostasis and regeneration. HighlightsO_LILineage tracing showed that midlobular hepatocytes proliferate during homeostasis. C_LIO_LIZone 2 cells were protected from portal and centrilobular injuries and replaced lost hepatocytes. C_LIO_LIFasting induced significant changes in liver zonation. C_LI eTOC statementThe liver consists of different zones with spatial heterogeneity in their metabolic functions. Here, a new Igfbp2-CreER line enabled direct tracing of midlobular hepatocytes, which showed that IGFBP2+ cells serve as a source of new hepatocytes during normal homeostasis and regeneration.

developmental biology↗

bioRxiv2022

A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness

BackgroundFor almost a century, it has been recognized that influenza A virus (IAV) infection can promote the development of secondary bacterial infections (SBI) mainly caused by Streptococcus pneumoniae (Spn). Recent observations have shown that IAV is able to directly bind to the surface of Spn. To gain a foundational understanding of how direct IAV-Spn interaction alters bacterial biological fitness we employed combinatorial multi-omic and molecular approaches. ResultsHere we show IAV significantly remodels the global transcriptome, proteome and phosphoproteome profiles of Spn independently of host effectors. We identified Spn surface proteins that interact with IAV proteins (hemagglutinin, nucleoprotein, and neuraminidase). In addition, IAV was found to directly modulate expression of Spn virulence determinants such as pneumococcal surface protein A, pneumolysin, and factors associated with antimicrobial resistance among many others. Metabolic pathways were significantly altered leading to changes in Spn growth rate. IAV was also found to drive Spn capsule shedding and the release of pneumococcal surface proteins. Released proteins were found to be involved in evasion of innate immune responses and actively reduced human complement hemolytic and opsonizing activity. IAV also led to phosphorylation changes in Spn proteins associated with metabolism and bacterial virulence. Validation of proteomic data showed significant changes in Spn galactose and glucose metabolism. Furthermore, supplementation with galactose rescued bacterial growth and promoted bacterial invasion, while glucose supplementation led to enhanced pneumolysin production and lung cell apoptosis. ConclusionsHere we demonstrate that IAV can directly modulate Spn biology without the requirement of host effectors and support the notion that inter-kingdom interactions between human viruses and commensal pathobionts can promote bacterial pathogenesis and microbiome dysbiosis.

microbiology↗

bioRxiv2021

Maize AFP1 confers antifungal activity by inhibiting chitin deacetylases from a broad range of fungi

Adapted plant pathogenic fungi deacetylate chitin to chitosan to avoid host perception and disarm the chitin-triggered plant immunity. Whether plants have evolved factors to counteract this fungal evasion mechanism in the plant-pathogen interface remains obscure. Here, we decipher the underlying mechanism of maize cysteine-rich receptor-like secreted proteins (CRRSPs)-AFP1, which exhibits mannose-binding dependent antifungal activity. AFP1 initials the action by binding to specific sites on the surface of yeast-like cells, filaments, and germinated spores of the biotrophic fungi Ustilago maydis. This could result in fungal cell growth and cell budding inhibition, delaying spore germination and subsequently reducing fungal viability in a mannose-binding dependence manner. The antifungal activity of AFP1 is conferred by its interaction with the PMT-dependent mannosylated chitin deacetylases (CDAs) and interfering with the conversion of chitin. Our finding that AFP1 targets CDAs from pathogenic fungi and nonpathogenic budding yeast suggests a potential application of the CRRSP in combating fungal diseases and reducing threats posed by the fungal kingdom.

microbiology↗

bioRxiv2021

The master energy homeostasis regulator PGC-1alpha couples transcriptional co-activation and mRNA nuclear export

PGC-1 plays a central role in maintaining the mitochondrial and energy metabolism homeostasis, linking external stimuli to the transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and a putative RNA recognition motif, however potential RNA-processing role(s) have remained elusive for the past 20 years. Here, we show that the RS domain of human PGC-1 directly interacts with RNA and the nuclear RNA export factor NXF1. Inducible depletion of endogenous PGC-1 and expression of RNAi-resistant RS-deleted PGC-1 further demonstrate that the RNA-binding activity is required for nuclear export of co-activated transcripts and mitochondrial homeostasis. Moreover, a quantitative proteomics approach confirmed PGC-1-dependent RNA transport and mitochondrial-related functions, identifying also novel mRNA nuclear export targets in age-related telomere maintenance. Discovering a novel function for a major cellular homeostasis regulator provides new directions to further elucidate the roles of PGC-1 in gene expression, metabolic disorders, ageing and neurodegenerative diseases.

molecular biology↗

bioRxiv2021

A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export suppresses neurodegeneration

Hexanucleotide repeat expansions in C9ORF72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a spectrum of incurable debilitating neurodegenerative diseases. Here, we report a novel ALS/FTD drug concept with in vivo and in vitro therapeutic activity in preclinical models of C9ORF72-ALS/FTD. Our data demonstrate that supplementation or oral administration of a cell-penetrant peptide, which competes with the SRSF1:NXF1 interaction, confers neuroprotection by inhibiting the nuclear export of pathological C9ORF72-repeat transcripts in various models of disease including primary neurons, patient-derived motor neurons and Drosophila. Our drug-like rationale for disrupting the nuclear export of microsatellite repeat transcripts in neurological disorders provides a promising alternative to conventional small molecule inhibitors often limited by poor blood-brain barrier penetrance.

molecular biology↗

bioRxiv2021

An all-solid-state heterojunction oxide transistor for the rapid detection of biomolecules and SARS-CoV-2 spike S1 protein

Solid-state transistor sensors that can detect biomolecules in real time are highly attractive for emerging bioanalytical applications. However, combining cost-effective manufacturing with high sensitivity, specificity and fast sensing response, remains challenging. Here we develop low-temperature solution-processed In2O3/ZnO heterojunction transistors featuring a geometrically engineered tri-channel architecture for rapid real-time detection of different biomolecules. The sensor combines a high electron mobility channel, attributed to the quasi-two-dimensional electron gas (q2DEG) at the buried In2O3/ZnO heterointerface, in close proximity to a sensing surface featuring tethered analyte receptors. The unusual tri-channel design enables strong coupling between the buried q2DEG and the minute electronic perturbations occurring during receptor-analyte interactions allowing for robust, real-time detection of biomolecules down to attomolar (aM) concentrations. By functionalizing the tri-channel surface with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) antibody receptors, we demonstrate real-time detection of the SARS-CoV-2 spike S1 protein down to attomolar concentrations in under two minutes.

bioengineering↗

bioRxiv2020

Degenerated virulence and irregular development of Fusarium oxysporum f. sp. niveum induced by successive subculture

Successive cultivation of fungus has been reported to cause the sectorization, which leads to degeneration of developmental phenotype, and virulence. Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon Fusarium wilt, demonstrated that successive cultivation formed the degenerated sectors. In the present research, we demonstrated that subculture with aged mycelium increased the incidence of degenerations. To further investigate the differences between the Fon wild type (sporodochial type, ST) and variants (MT: mycelium type and PT: pionnotal type), developmental phenotypes and pathogenicity to watermelon were examined. Results have shown that degeneration variants (PT2, PT3, PT11 and MT6) were different from ST with mycelium growth, conidia production and chlamydospore formation. Virulence of degenerated variants on susceptible watermelon Grand Baby (GB) cultivar was determined after inoculated with Fon variants and Fon ST. In root dipping methods, all Fon variants showed slightly increased disease severity than ST. Conversely, all Fon variants showed a significant decrease in disease progression compared with ST through infested soil inoculation. The contrary results of two inoculation methods suggest that the changes of successive cultural degeneration may lead to the loss of pathogen virulence-related factors of the early stage of Fon infection process. Therefore, Cell wall-degrading enzymes (CWDEs; cellulase, pectinase, and xylanase) activities of different variants were analysed. All Fon degenerated variants demonstrated significantly decreased of CWDEs activities compared with ST. Additionally, transcripts level of 9 virulence-related genes (fmk1, fgb1, pacC, xlnR, pl1, rho1, gas1, wc1 and fow1) were assessed in normal state. The degenerated variants demonstrated a significantly low level of tested virulence-related genes transcripts except for fmk1, xlnR and fow1. In summary, the degeneration of Fon is triggered with successive subculture through aged mycelium. The degeneration showed significant impacts on virulence to watermelon, which caused by the reduction of CWDEs activities and declining expression of a set of virulence-related genes.

microbiology↗

bioRxiv2020

Accelerated erythrocyte senescence causes dose-limiting anemia of antimalarial enolase inhibitors

Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase - a critical enzyme in glycolysis - and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather than direct hemolysis. We apply our model of red cell toxicity to address questions regarding erythrocyte glycolytic disruption in the context of Plasmodium falciparum malaria pathogenesis. Our study provides a framework for understanding red blood cell homeostasis under normal and disease states and clarifies the importance of erythrocyte reductive capacity in malaria parasite growth.

pharmacology and toxicology↗

bioRxiv2020

Netome: The Molecular Characterization of Neutrophil Extracellular Traps (NETs)

Neutrophils are the most abundant type of white blood cells in humans with biological roles relevant to inflammation and fighting infections. The release of neutrophil extracellular DNA aims to control invasion by bacteria, viruses, fungi, and tissue damage. Neutrophil Extracellular Traps (NETs) act as antimicrobial agents triggering immune signaling through the release of the nuclear content into the extracellular space. Although intense investigations have elucidated the pathways preceding NET formation, the exact molecular composition of released NETs has not been mapped. We aimed to decode the sequences of DNA and proteins from NETs. With emerging needs to understand neutrophil functions precisely, we open the field of NETOMIC studies through isolation of NETs in combination with omics approaches including shotgun genomics and proteomics. Our in vitro NET isolation methodology allowed for unprecedented replicability with induction in a sterile inflammation model system. Enrichment of mitochondrial DNA and telomere sequences are significantly expressed in NET genomes. This study revealed that the genomic sequence released in the extracellular milieu is not stochastically serving as a scaffold for a repertoire of proteins involved in neutrophil protective functions. Collectively, we established the gene and protein signatures exclusive to the extracellular NETs in comparison to undifferentiated and differentiated neutrophil states, further guiding future detection of specific regions needed for diagnostics and targeted therapies of NET related conditions.

immunology↗

bioRxiv2020

The global proteome and phosphoproteome landscape of sepsis-induced kidney injury

Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, while AKI has been recognized as a disease with long-term sequelae, partly due to the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2,950 phosphosites through multi-proteomics analyses. Here we denote the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.AbbreviationsAKIAcute kidney injuryBADBcl2-associated agonist of cell death proteinCKDChronic kidney diseaseCLPCecal ligation and punctureDAMPsDamage-associated molecular patternsELISAEnzyme-linked immunosorbent assayESCRTEndosomal sorting complexes required for transportFADDFAS-associated death domain proteinFCFold changeFDRFalse discovery rateGOGene OntologyGsdmdGasdermin DICUIntensive care unitKEGGKyoto Encyclopedia of Genes and GenomesLFQLabel-free quantitationNGALNeutrophil gelatinase-associated lipocalin proteinPAMPsPathogen-associated molecular patternsPASPeriodic acid-SchiffPCAPrinciple component analysisS-AKISepsis-induced acute kidney injurySLCSolute carrier proteinsSTrapSuspension TrappingTLRsToll-like receptorsView Full Text

pathology↗