To select the core target (RAB13) in sepsis patients\' peripheral blood and investigate its molecular functions and possible mechanisms. The peripheral blood of sepsis patients (n = 21) and healthy individuals (n = 9) within 24 h after admission were collected for RNA-seq, and differential gene screening was performed by iDEP online analysis software (P < 0.01; log2FC ≥ 2) and enrichment analysis, the potential core target RAB13 was screened out. The association between RAB13 expression and sepsis severity was explored using multiple datasets in the GEO database, and survival analysis was conducted. Subsequently, peripheral blood mononuclear cells (PBMCs) from sepsis and control groups were isolated, and 10 × single-cell sequencing was used to identify the main RAB13-expressing cell types. Finally, LPS was used to stimulate THP1 cells to construct a sepsis model to explore the function and possible mechanism of RAB13. We found that RAB13 was a potential core target, and RAB13 expression level was positively associated with sepsis severity and negatively correlated with survival based on multiple public datasets. A single-cell sequencing indicated that RAB13 is predominantly localized in monocytes. Cell experiments validated that RAB13 is highly expressed in sepsis, and the knockdown of RAB13 promotes the polarization of macrophages towards the M2 phenotype. This mechanism may be associated with the ECM-receptor interaction signaling pathway. The upregulation of RAB13 in sepsis patients promotes the polarization of M2-like macrophages and correlates positively with the severity of sepsis.

Mounting evidence in animal experiments proves that early life stage exposure to organophosphate flame retardants (OPFRs) affects the locomotor behavior and changes the transcriptions of central nervous system genes. Unfortunately, their effect on human motor neuron (MN) development, which is necessary for body locomotion and survival, has not yet characterized. Here, we utilized a spinal cord MN differentiation model from human embryonic stem cells (ESCs) and adopted this model to test the effects of two typical OPFRs tris (2-butoxyethyl) phosphate (TBEP) and tris (2-chloroethyl) phosphate (TCEP), on MN development and the possible mechanisms underlying. Our findings revealed TBEP exerted a much more inhibitory effect on MN survival, while TCEP exhibited a stronger stimulatory effect on ESCs differentiation into MN, and thus TBEP exhibited a stronger inhibition on MN development than TCEP. RNA sequencing analysis identified TBEP and TCEP inhibited MN survival mainly by disrupting extracellular matrix (ECM)-receptor interaction. Focusing on the pathway guided MN differentiation, we found both TBEP and TCEP activated BMP signaling, whereas TCEP simultaneously downregulated Wnt signaling. Collectively, this is the first study demonstrated TBEP and TCEP disrupted human MN development by affecting their survival and differentiation, thereby raising concern about their potential harm in causing MN disorders.

This study aimed to identify genes shared by metabolic dysfunction-associated fatty liver disease (MASH) and diabetic nephropathy (DN) and the effect of extracellular matrix (ECM) receptor interaction genes on them. Datasets with MASH and DN were downloaded from the Gene Expression Omnibus (GEO) database. Pearson\'s coefficients assessed the correlation between ECM-receptor interaction genes and cross talk genes. The coexpression network of co-expression pairs (CP) genes was integrated with its protein-protein interaction (PPI) network, and machine learning was employed to identify essential disease-representing genes. Finally, immuno-penetration analysis was performed on the MASH and DN gene datasets using the CIBERSORT algorithm to evaluate the plausibility of these genes in diseases. We found 19 key CP genes. Fos proto-oncogene (FOS), belonging to the IL-17 signalling pathway, showed greater centrality PPI network; Hyaluronan Mediated Motility Receptor (HMMR), belonging to ECM-receptor interaction genes, showed most critical in the co-expression network map of 19 CP genes; Forkhead Box C1 (FOXC1), like FOS, showed a high ability to predict disease in XGBoost analysis. Further immune infiltration showed a clear positive correlation between FOS/FOXC1 and mast cells that secrete IL-17 during inflammation. Combining the results of previous studies, we suggest a FOS/FOXC1/HMMR regulatory axis in MASH and DN may be associated with mast cells in the acting IL-17 signalling pathway. Extracellular HMMR may regulate the IL-17 pathway represented by FOS through the Mitogen-Activated Protein Kinase 1 (ERK) or PI3K-Akt-mTOR pathway. HMMR may serve as a signalling carrier between MASH and DN and could be targeted for therapeutic development.

Deoxynivalenol (DON) is one of the frequent Fusarium mycotoxins and poses a serious threat to public health worldwide. DON-induced weight loss is tightly connected with its ability to decrease feed intake by influencing gastrointestinal tract (GIT) motility. Our previous reports indicated that DON interfered with intestinal motility by injuring the contractility of enteric smooth muscle cells (SMC). Here, we further explored the potential mechanisms by employing a complementary method of transcriptomics and proteomics using the porcine enteric smooth muscle cell line (PISMC) as an experimental model. The transcriptomic and proteomic data uncover that the expression of numerous extracellular matrix (ECM) proteins and multiple integrin subunits were downregulated in PISMC under DON exposure, suppressing the ECM-integrin receptor interaction and its mediated signaling. Furthermore, DON treatment could depress actin polymerization, as reflected by the upregulated expression of Rho GTPase-activating proteins and cofilin in PISMC. Meanwhile, the expression levels of downstream contractile apparatus genes were significantly inhibited after challenge with DON. Taken together, the current results suggest that DON inhibits enteric SMC contractility by regulating the ECM-integrin-actin polymerization signaling pathway. Our findings provide novel insights into the potential mechanisms behind the DON toxicological effects in the GIT of humans and animals.

Light traps have been widely used to monitor and manage pest populations, but natural enemies are also influenced. The Dastarcus helophoroides Fairmaire is an important species of natural enemy for longhorn beetles. However, the molecular mechanism of D. helophoroides in response to light exposure is still scarce. Here, integrated behavioral, comparative transcriptome and weighted gene co-expression network analyses were applied to investigate gene expression profiles in the head of D. helophoroides at different light exposure time. The results showed that the phototactic response rates of adults were 1.67%-22.5% and females and males displayed a negative phototaxis under different light exposure [6.31 × 1018 (photos/m2/s)]; the trapping rates of female and male were influenced significantly by light exposure time, diel rhythm, and light wavelength in the behavioral data. Furthermore, transcriptome data showed that a total of 1,052 significantly differentially expressed genes (DEGs) were identified under different light exposure times relative to dark adaptation. Bioinformatics analyses revealed that the \"ECM-receptor interaction,\" \"focal adhesion,\" \"PI3K-Akt signaling,\" and \"lysosome\" pathways were significantly downregulated with increasing light exposure time. Furthermore, nine DEGs were identified as hub genes using WGCNA analysis. The results revealed molecular mechanism in negative phototactic behavior response of D. helophoroides under the light exposure with relative high intensity, and provided valuable insights into the underlying molecular response mechanism of nocturnal beetles to light stress.

The aberrant expression of mRNAs participates in the pathogenesis of hepatic fibrosis. However, the precise mechanisms regulated by microRNAs (miRNAs) remain unclear. This study aims to investigate the functions about differentially expressed mRNAs (DEMs) in liver fibrosis and their regulatory mechanisms. The DEMs datasets about hepatic stellate cells (HSCs) obtained from hepatic fibrosis mice versus HSCs obtained from normal mice were downloaded from the GEO database (GSE120281). According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the GSE120281 datasets, ECM-receptor interaction was the most significant enrichment pathway that was correlated with hepatic fibrosis, and the fibronectin 1 (FN1) gene was upregulated most significantly in the signaling pathway. Downregulation of the expression of the FN1 gene by transfecting with FN1-siRNA alleviated the activity of HSCs. Four different bioinformatics web-based tools were used to predict that microRNA-96-5p (miR-96-5p) would directly target FN1, and a luciferase assay further confirmed this. Moreover, miR-96-5p was declined in activated HSCs and FN1, whereas laminin γ1 (LAMC1), collagen 1α1 (COL1A1) in the ECM-receptor interaction pathway, and the fibrosis marker α-smooth muscle actin (α-SMA) could be reduced by upregulation of the miRNA. Additionally, miR-96-5p expression was low in CCl4-induced liver fibrosis mice. Increased miR-96-5p expression alleviated liver fibrosis, improved liver function, and inhibited the expression of α-SMA, FN1, COL1A1, and LAMC1. In conclusion, this study indicated that upregulation of miR-96-5p could reduce HSC activation and relieve hepatic fibrosis by restraining the FN1/ECM-receptor interaction pathway.

BACKGROUND: Ganoderma lucidum polysaccharide (GLP) has many biological properties, however, the anti-fibrosis effect of GLP is unknown at present.
OBJECTIVE: This study aimed to examine the anti-fibrogenic effect of GLP and its underlying molecular mechanisms in vivo and in vitro.
METHODS: Both CCl4-induced mouse and TGF-β1-induced HSC-T6 cellular models of fibrosis were established to examine the anti-fibrogenic effect of a water-soluble GLP (25 kDa) extracted from the sporoderm-removed spores of G. lucidum..
METHODS: Serum markers of liver injury, histology and fibrosis of liver tissues, and collagen formation were examined using an automatic biochemical analyzer, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, ELISA, Western blotting, and qRT-PCR. RNA-sequencing, enrichment pathway analysis, Western blotting, qRT-PCR, and flow cytometry were employed to identify the potential molecular targets and signaling pathways that are responsible for the anti-fibrotic effect of GLP.
RESULTS: We showed that GLP (150 and 300 mg/kg) significantly inhibited hepatic fibrogenesis and inflammation in CCl4-treated mice as mediated by the TLR4/NF-κB/MyD88 signaling pathway. We further demonstrated that GLP significantly inhibited hepatic stellate cell (HSCs) activation in mice and in TGF-β1-induced HSC-T6 cells as manifested by reduced collagen I and a-SMA expressions. RNA-sequencing uncovered inflammation, apoptosis, cell cycle, ECM-receptor interaction, TLR4/NF-κB, and TGF-β/Smad signalings as major pathways suppressed by GLP administration. Further studies demonstrated that GLP elicits anti-fibrotic actions that are associated with a novel dual effect on apoptosis in vivo (inhibit) or in vitro (promote), suppression of cell cycle in vivo, induction of S phase arrest in vitro, and attenuation of ECM-receptor interaction-associated molecule expressions including integrins ITGA6 and ITGA8. Furthermore, GLP significantly inhibited the TGF-β/Smad signaling in mice, and reduced TGF-β1 or its agonist SRI-011381-induced Smad2 and Smad3 phosphorylations, but increased Samd7 expression in HSC-T6 cells.
CONCLUSIONS: This study provides the first evidence that GLP could be a promising dietary strategy for treating liver fibrosis, which protects against liver fibrosis and HSC activation through targeting inflammation, apoptosis, cell cycle, and ECM-receptor interactions that are mediated by TGF-β/Smad signaling.

Acyl-coenzyme A synthetase medium chain family member 1 (ACSM1) is a medium chain Acyl-CoA Synthetase family member and plays an important role in fatty acid metabolism. The oncogenic roles of ACSM1 are largely unknown. Using comprehensive approaches, we analyzed gene expression profiles and genomic datasets and identified that the expression of ACSM1 was specifically increased in prostate cancer in comparison to the adjacent non-tumor tissues. The increased expression of ACSM1 was associated with increased risks of poor prognosis and shorter survival time. Moreover, genomic copy number alterations of ACSM1, including deletion, amplification, and amino acid changes were frequently observed in prostate cancers, although these mutations did not correlate with gene expression levels. However, ACSM1 gene amplifications were significantly corrected with increased risks of prostate cancer metastasis, and ACSM1 genetic alterations were significantly associated with worse disease-free. And progress-free survival. Gene function stratification and gene set enrichment analysis revealed that the oncogenic roles of ACSM1 in prostate cancer were mainly through metabolic pathways and extracellular matrix (ECM)-receptor interaction signaling pathways, but not associated with microenvironmental immunological signaling pathways, and that ACSM1 expression was not associated with immune cell infiltration in the cancer microenvironment or prostate cancer immune subtypes. In conclusion, the present work has demonstrated that ACSM1 can be specifically and significantly elevated in prostate cancer. ACSM1 gene expression and genomic amplification exhibit important clinical significance through metabolic and ECM-receptor interaction signaling pathways. Thus, ACSM1 may be a novel oncogene and serve as a biomarker for prostate cancer screening and prognosis prediction, and/or a therapeutic target.

As a common mycotoxin, deoxynivalenol (DON) contaminates cereal grains and feed in field or during processing and storage. DON elicits a spectrum of adverse effects in animals including anorexia and growth retardation. Especially, the presence of DON has also been detected in muscle, suggesting that DON may has the potential to affect the development of muscle. However, the relevant research is very rare and the molecular mechanism remains unclear. Myoblasts differentiation into multinucleated myotubes is one of the crucial steps of skeletal muscle development. In the present study, we investigated the effects of DON on differentiation of myoblasts using murine C2C12 cells model. The results indicated that DON dose-dependent inhibited the formation of myotubes in C2C12 cells. After performing omics techniques, a total of 149 differentially expressed genes were identified. The expression of cytoskeleton proteins and extracellular matrix (ECM) proteins were downregulated by DON. Furthermore, DON significantly downregulated the expression of integrin αv and integrin β5, leading to inhibition of the ECM-integrin receptor interaction. The focal adhesion kinase (FAK) and phosphorylated forms, ras-related C3 botulinum toxin substrate (RAC) and p21-activated kinases 1 (PAK1) were also downregulated by DON. Taken together, our findings suggest that DON has the potent to affect the differentiation of myoblasts via downregulating of cytoskeleton and ECM-integrin-FAK-RAC-PAK signaling pathway.

Occipital cortical malformation (OCCM) is a disease caused by malformations of cortical development characterized by polymicrogyria and pachygyria of the occipital lobes and childhood-onset seizures. The recessive or complex heterozygous variants of the LAMC3 gene are identified as the cause of OCCM. In the present study, we identified novel complex heterozygous variants (c.470G > A and c.4030 + 1G > A) of the LAMC3 gene in a Chinese female with childhood-onset seizures. Cranial magnetic resonance imaging was normal. Functional experiments confirmed that both variant sites caused premature truncation of the laminin γ3 chain. Bioinformatics analysis predicted 10 genes interacted with LAMC3 with an interaction score of 0.4 (P value = 1.0e-16). The proteins encoded by these genes were mainly located in the basement membrane and extracellular matrix component. Furthermore, the biological processes and molecular functions from gene ontology analysis indicated that laminin γ3 chain and related proteins played an important role in structural support and cellular processes through protein-containing complex binding and signaling receptor binding. KEGG pathway enrichment predicted that the LAMC3 gene variant was most likely to participate in the occurrence and development of OCCM through extracellular matrix receptor interaction and PI3K-Akt signaling pathway.