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Cyclin-dependent kinase-like 3 (CDKL3) has been identified as an oncogene in certain types of tumors. Nonetheless, its function in hepatocellular carcinoma (HCC) is poorly understood. In this study, we conducted a comprehensive analysis of CDKL3 based on data from the HCC cohort of The Cancer Genome Atlas (TCGA). Our analysis included gene expression, diagnosis, prognosis, functional enrichment, tumor microenvironment and metabolic characteristics, tumor burden, mRNA expression-based stemness, alternative splicing, and prediction of therapy response. Additionally, we performed a cell counting kit-8 assay, TdT-mediated dUTP nick-end Labeling staining, migration assay, wound healing assay, colony formation assay, and nude mouse experiments to confirm the functional relevance of CDKL3 in HCC. Our findings showed that CDKL3 was significantly upregulated in HCC patients compared to controls. Various bioinformatic analyses suggested that CDKL3 could serve as a potential marker for HCC diagnosis and prognosis. Furthermore, CDKL3 was found to be involved in various mechanisms linked to the development of HCC, including copy number variation, tumor burden, genomic heterogeneity, cancer stemness, and alternative splicing of CDKL3. Notably, CDKL3 was also closely correlated with tumor immune cell infiltration and the expression of immune checkpoint markers. Additionally, CDKL3 was shown to independently function as a risk predictor for overall survival in HCC patients by multivariate Cox regression analysis. Furthermore, the knockdown of CDKL3 significantly inhibited cell proliferation in vitro and in vivo, indicating its role as an oncogene in HCC. Taken together, our findings suggest that CDKL3 shows promise as a biomarker for the detection and treatment outcome prediction of HCC patients.

Continuous cropping obstacles seriously constrained the sustainable development of the ginseng industry. The allelopathic autotoxicity of ginsenosides is the key “trigger” of continuous cropping obstacles in ginseng. During harvest, the ginseng plants could be broken and remain in the soil. The decomposition of ginseng residue in soil is one of the important release ways of ginsenosides. Therefore, the allelopathic mechanism of ginsenosides through the decomposed release pathway needs an in-depth study. To investigate this allelopathic regulation mechanism, the integrated analysis of transcriptomics and metabolomics was applied. The prototype ginsenosides in ginseng were detected converse to rare ginsenosides during decomposition. The rare ginsenosides caused more serious damage to ginseng hairy root cells and inhibited the growth of ginseng hairy roots more significantly. By high-throughput RNA sequencing gene transcriptomics study, the significantly differential expressed genes (DEGs) were obtained under prototype and rare ginsenoside interventions. These DEGs were mainly enriched in the biosynthesis of secondary metabolites and metabolic pathways, phytohormone signal transduction, and protein processing in endoplasmic reticulum pathways. Based on the functional enrichment of DEGs, the targeted metabolomics analysis based on UPLC-MS/MS determination was applied to screen endogenous differential metabolized phytohormones (DMPs). The influence of prototype and rare ginsenosides on the accumulation of endogenous phytohormones was studied. These were mainly involved in the biosynthesis of diterpenoid, zeatin, and secondary metabolites, phytohormone signal transduction, and metabolic pathways. After integrating the transcriptomics and metabolomics analysis, ginsenosides could regulate the genes in phytohormone signaling pathways to influence the accumulation of JA, ABA, and SA. The conclusion was that the prototype ginsenosides were converted into rare ginsenosides by ginseng decomposition and released into the soil, which aggravated its allelopathic autotoxicity. The allelopathic mechanism was to intervene in the response regulation of genes related to the metabolic accumulation of endogenous phytohormones in ginseng. This result provides a reference for the in-depth study of continuous cropping obstacles of ginseng.

In order to explore the antagonistic mechanism of Lysinibacillus sphaericus AEB18 against Nocardia seriolae, the whole genome of strain AEB18 was sequenced, and the effect of strain AEB18 in controlling nocardiosis of hybrid snakehead was verified in vitro and in vivo. Strain AEB18 genome was a circular DNA of 4,653,716 base pairs (bp) and GC content of 37.4%, predicting 4,529 coding genes, 108 tRNAs, 37 rRNAs, and 95 non-coding (nc)RNAs. The eggNOG (Non-supervised Orthologous Groups), GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) and the CAZy (Carbohydrate-Associated Enzyme) database annotated the strain AEB18 genome to 3,965, 3,325, 2,061, and 112 genes, respectively. Furthermore, nine gene clusters, including polyketones, non-ribosomal synthetic peptides, β-lactones, terpenes, ribosomal synthetic peptides, and other secondary metabolites with bacteriostatic effect were obtained through the prediction of secondary metabolites of strain AEB18. After the addition of L. sphaericus AEB18 (1 × 109 CFU/g) with a mass fraction of 1% to the basal diet for 21 days, the weight gain rate and the activity of amylase in intestinal chyme of hybrid snakehead were significantly increased (P< 0.05). In addition, hybrid snakehead fed with L. sphaericus AEB18 supplemented diets showed significantly reduced mortality rate (P< 0.05) after N. seriolae infection, compared with the control group (mortality rate was 100%). Overall, L. sphaericus AEB18 positively affected hybrid snakeheads, promoted growth and reduced mortality rate of hybrid snakeheads with nocardiosis. Taken together, the L. sphaericus AEB18 possesses great potential as a biocontrol agent, which can be commercially developed to improve disease control in freshwater aquaculture.

PurposeRapid eye movement sleep behavior disorder (RBD) affects 30%–40% of patients with Parkinson’s disease (PD) and has been linked to a higher risk of cognitive impairment, especially executive dysfunction. The aim of this study was to investigate the brain activation patterns in PD patients with RBD (PD-RBD+) compared to those without RBD (PD-RBD−) and healthy controls (HCs), and to analyze the correlation between changes in cerebral cortex activity and the severity of RBD.MethodsWe recruited 50 PD patients, including 30 PD-RBD+, 20 PD-RBD−, and 20 HCs. We used functional near infrared spectroscopy during a verbal fluency task (VFT-fNIRS) and clinical neuropsychological assessment to explore the correlation between PD-RBD+ and executive function and changes in neural activity.ResultsThe VFT-fNIRS analysis revealed a significant reduction in activation among PD-RBD+ patients across multiple channels when compared to both the PD-RBD− and HC groups. Specifically, PD-RBD+ patients exhibited diminished activation in the bilateral dorsolateral prefrontal cortex (DLPFC) and the right ventrolateral prefrontal cortex (VLPFC) relative to their PD-RBD− counterparts. Furthermore, compared to the HC group, PD-RBD+ patients displayed reduced activation specifically in the right DLPFC. Significantly, a noteworthy negative correlation was identified between the average change in oxygenated hemoglobin concentration (ΔHbO2) in the right DLPFC of PD-RBD+ patients and the severity of their RBD.ConclusionOur study offers compelling evidence that RBD exacerbates cognitive impairment in PD, manifested as executive dysfunction, primarily attributed to reduced prefrontal activation. These aberrations in brain activation may potentially correlate with the severity of RBD.

Two patients with refractory nephrotic syndrome were treated with peritoneal dialysis (PD) for diuretic resistance, anasarca and acute kidney injury. Following PD, their fluid overload was promptly alleviated, accompanied by an increase in urine volume and an improvement in renal function. PD as an adjuvant approach enabled them to resume corticosteroids and immunosuppressive agents. Eventually, both patients could be withdrawn from PD and achieved remission of proteinuria.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by the Dabie bandavirus (DBV), and it has become a global public health threat. Cytokine storm is considered to be an important pathogenesis of critical SFTS. Tripartite motif-containing 3 (TRIM3), as a member of the TRIM protein family, may contribute to the regulation of the immune and inflammatory responses after viral infection. However, whether TRIM3 plays a major role in the pathogenesis of SFTS has not yet been investigated.MethodsTRIM3 mRNA levels were detected in PBMCs between 29 SFTS patients and 29 healthy controls by qRT-PCR. We established the pathogenic IFNAR−/− SFTS mouse model successfully by inoculating subcutaneously with DBV and testing the expression levels of TRIM3 mRNA and protein by qRT-PCR and immunofluorescence in the livers, spleens, lungs, and kidneys. TRIM3OE THP-1 cells and peritoneal macrophages extracted from TRIM3−/− mice were infected with DBV. The effect of TRIM3 on cytokines was detected by qRT-PCR and ELISA. Then we examined Toll-like receptor 3 (TLR3) and protein phosphorylation in the MAPK pathway after DBV infection using Western blot. Flow cytometry was used to verify TLR3 expression on peripheral blood monocytes in SFTS patients. We further explored the interaction between TRIM3 and TLR3 using CO-IP and Western blot.ResultsCompared to healthy controls, TRIM3 mRNA expression in PBMCs is decreased in SFTS patients, especially in severe cases. TRIM3 mRNA and protein were synchronously reduced in the livers, spleens, lungs, and kidney tissues of the IFNAR−/− SFTS mice model. In the DBV-infected cell model, TRIM3 overexpression can inhibit the DBV-induced release of IL-1β, IL-6, and TNF-α, the expression of TLR3, and protein phosphorylation in the MAPK pathway, which plays an anti-inflammatory role, while TRIM3 deficiency exacerbates the pro-inflammatory effects. We further found that TRIM3 can promote TLR3 degradation through K48-linked ubiquitination.ConclusionTRIM3 can inhibit the production of cytokines by regulating the degradation of TLR3 through K48-linked ubiquitination, which can be a therapeutic target for improving the prognosis of SFTS.

IntroductionRoxadustat treatment in PD patients is equivalent to ESAs in increasing hemoglobin (Hb). But blood pressure, cardiovascular parameters, cardio-cerebrovascular complications and prognosis in the two groups before and after treatment has not been sufficiently discussed.MethodsSixty PD patients who were treated with roxadustat for renal anemia in our PD center recruited from June 2019 to April 2020 as roxadustat group. PD patients treated with rHuEPO were enrolled at a 1:1 ratio as rHuEPO group using the method of propensity score matching. Hb, blood pressure, cardiovascular parameters, cardio-cerebrovascular complications and prognosis were compared between the two group. All patients were followed up for at least 24 months.ResultsThere were no significant differences in baseline clinical data or laboratory values between roxadustat group and rHuEPO group. After 24 months of follow-up, there was no significant difference in Hb levels (p > 0.05). There were no significant changes in blood pressure, or the incidence of nocturnal hypertension before and after treatment in roxadustat group (p > 0.05), while blood pressure significantly increased in rHuEPO group after treatment (p

Imatinib (IMB), an anticancer drug, is extensively used for chemotherapy to improve the quality of life of cancer patients. The aim of therapeutic drug monitoring (TDM) is to guide and evaluate the medicinal therapy, and then optimize the clinical effect of individual dosing regimens. In this work, a highly sensitive and selective electrochemical sensor based on glassy carbon electrode (GCE) modified with acetylene black (AB) and a Cu (II) metal organic framework (CuMOF) was developed to measure the concentration of IMB. CuMOF with preferable adsorbability and AB with excellent electrical conductivity functioned cooperatively to enhance the analytical determination of IMB. The modified electrodes were characterized using X-rays diffraction (XRD), X-ray photoelectron spectroscopy (XPS), fourier transform infrared (FT-IR), ultraviolet and visible spectrophotometry (UV-vis), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), energy dispersive X‐ray spectroscopy (EDS), brunauer‒emmett‒teller (BET) and barrett‒joyner‒halenda (BJH) techniques. Analytical parameters such as the ratio of CuMOF to AB, dropping volumes, pH, scanning rate and accumulation time were investigated through cyclic voltammetry (CV). Under optimal conditions, the sensor exhibited an excellent electrocatalytic response for IMB detection, and two linear detection ranges were obatined of 2.5 nM-1.0 μM and 1.0–6.0 μM with a detection limit (DL) of 1.7 nM (S/N = 3). Finally, the good electroanalytical ability of CuMOF-AB/GCE sensor facilitated the successful determination of IMB in human serum samples. Due to its acceptable selectivity, repeatability and long-term stability, this sensor shows promising application prospects in the detection of IMB in clinical samples.

Lotus (Nelumbo) leaves are rich in polyphenols and dietary fiber, which have the potential as a high-quality fiber material in functional food. However, lotus leaves exhibit dense structure and poor taste, it is vital to develop appropriate modification methods to improve the properties of lotus leaves dietary fiber. In this study, the effects of three modification methods with shear emulsifying (SE), ball milling (BM), and autoclave treatment (AT) on structure, physicochemical properties, phenolic compounds, and antioxidant capacity of lotus leave dietary fiber (LDF) were evaluated. SEM indicated that there were significant differences in the microstructure of modified LDFs. FT-IR spectra and X-ray diffraction pattern of modified LDFs revealed similar shapes, while the peak intensity and crystalline region changed by modification. SE showed the greatest effect on crystallization index. SE-LDF had the highest water holding capacity, water swelling capacity, and bound phenolic content in LDFs, which increased by 15.69, 12.02, and 31.81%, respectively, compared with the unmodified LDF. BM exhibited the most dramatic effect on particle size. BM-LDF had the highest free phenolic and total phenolic contents in LDFs, which increased by 32.20 and 29.05% respectively, compared with the unmodified LDF. Phenolic compounds in LDFs were mainly free phenolic, and modifications altered the concents of flavonoids. The BM-LDF and SE-LDF exhibited higher antioxidant capacity than that of AT-LDF. Overall, SE-LDF showed better physical properties, and BM-LDF showed better bioactive components. SE and BM were considered to be appropriate modification methods to enhance the properties of LDF with their own advantages.

DNA methylation is a critical epigenetic modification that dynamically regulates gene expression in organisms facing abiotic stress. However, few studies have comprehensively examined the role of DNA methylation in marine fish during environmental adaptation. Therefore, this study explored the methylome dynamics and DNA methylation regulation mechanisms in large yellow croaker (Larimichthys crocea) during low-salinity adaption. The methylation level in the gills was notably raised in the S-group (5‰ salinity) compared to C-group (25‰ salinity). A total of 109 differentially methylated promoter target genes and 581 differentially expressed genes were identified via whole-genome bisulfite sequencing (WGBS) and RNA-seq of gills in the two salinity groups, respectively. Moreover, 23 hypo-methylated/up-regulated differentially methylated genes (DMGs) and 28 hyper-methylated/down-regulated DMGs were identified through integrative analysis, which were mainly enriched in signal transduction, ion exchange, energy metabolism, and cytoskeleton system and other biological processes. Collectively, our findings suggested that low-salinity stress can induce adaptive genome-wide DNA methylation changes, which can in turn affect the transcription of genes in large yellow croaker during low-salinity adaptation. Therefore, our findings provide new insights into the regulatory mechanisms of marine fish in response to rapid environmental changes.

Designing and preparing highly active oxygen evolution reaction (OER) electrodes are essential for improving the overall efficiency of water splitting. Increasing the number of active sites is the simplest way to enhance OER performance. Herein, we present a dealloy-etched Ni–Fe foam with a hierarchical nanoporous structure as integrated electrodes with excellent performance for OER. Using the dealloying method on the Ni–Fe foam framework, a nanoporous structure is produced, which is named nanoporous Ni–Fe@Ni–Fe foam (NP-NF@NFF). Because of the peculiarities of the dealloying method, the NP-NF@NFF produced contains oxygen vacancies and heterojunctions. As a result, NP-NF@NFF electrode outperforms state-of-the-art noble metal catalysts with an extremely low overpotential of 210 and 285 mV at current densities of 10 and 100 mA cm−2, respectively. Additionally, the NP-NF@NFF electrode shows a 60-h stability period. Therefore, NP-NF@NFF provides new insights into the investigation of high-performance transition metal foam electrodes with effective active sites for efficient oxygen evolution at high current densities.

Histone post-translational modifications (HPTMs) are essential epigenetic mechanisms that affect chromatin-associated nuclear processes without altering the DNA sequence. With the application of mass spectrometry-based proteomics, novel histone lysine acylation, such as propionylation, butyrylation, crotonylation, malonylation, succinylation, glutarylation, and lactoylation have been successively discovered. The emerging diversity of the lysine acylation landscape prompted us to investigate the function and mechanism of these novel HPTMs in health and disease. Recently, it has been reported that β-hydroxybutyrate (BHB), the main component of the ketone body, has various protective roles beyond alternative fuel provision during starvation. Histone lysine β-hydroxybutyrylation (Kbhb) is a novel HPTMs identified by mass spectrometry, which regulates gene transcription in response to carbohydrate restriction or elevated BHB levels in vivo and vitro. Recent studies have shown that histone Kbhb is strongly associated with the pathogenesis of metabolic cardiovascular diseases, kidney diseases, tumors, neuropsychiatric disorders, and metabolic diseases suggesting it has different functions from histone acetylation and methylation. This review focuses on the writers, erasers, sites, and underlying functions of histone Kbhb, providing a glimpse into their complex regulation mechanism.

Alcohol-induced osteonecrosis of the femoral head (AIONFH) is a complicated refractory bone disease seen in the clinic. The pathogenesis of AIONFH is still controversial. Extrachromosomal circular DNA (eccDNA) elements have been indicated ubiquitously exist in eukaryotic genomes. However, the characteristics and biological functions of eccDNAs remain unclear in AIONFH. In this study, eccDNAs from AIONFH samples (n = 7) and fracture of femoral neck samples as a control (n = 7) were purified by removing linear DNA and rolling circle amplification. High-throughput sequencing and bioinformatics analysis were performed to study the characterization and biofunction of eccDNAs. We identified more than 600,000 unique eccDNAs. The number of detected eccDNAs in AIONFH was less than that in the control, and eccDNA formation may be related to transcription or other characteristics of coding genes. The eccDNA lengths are mainly distributed between 0.1 kb and 1 kb, with a major peak in 0.358 kb. The bioinformatic analysis showed that 25 significant genes were detected, including MAP3K1, ADCY1, CACNA1S, and MACF1, which contributed to regulating bone formation. GO and KEGG analyses suggested that the related genes derived from exons mainly affected metabolic processes and signal transduction, and bone metabolism-related pathways, such as the MAPK pathway and TGF-β pathway, were enriched. EccDNAs in AIONFH are common and may play an important role in pathogenesis by regulating bone metabolism.

African swine fever (ASF) is a hemorrhagic and often fatal disease occurring in domestic pigs and wild boars. ASF can potentially greatly impact the global trade of pigs and pork products and threaten global food security. Outbreaks of ASF must be notified to the World Organization for Animal Health. In this study, we analyzed the feasibility of applying propidium monoazide (PMA) pretreatment-based infectious virus detection technology to ASF prevention and control and investigated the prospects of applying this technology for epidemic monitoring, disinfection effect evaluation, and drug development. PMA as a nucleic acid dye can enter damaged cells and undergo irreversible covalent crosslinking with nucleic acid under halogen light to prevent its amplification. Although this technology has been widely used for the rapid detection of viable bacteria, its application in viruses is rare. Therefore, we analyzed the theoretical feasibility of applying this technology to the African swine fever virus (ASFV) in terms of gene and cell composition. Rapid infectious ASFV detection technology based on PMA pretreatment would greatly enhance all aspects of ASF prevention and control, such as epidemic monitoring, disinfection treatment, and drug development. The introduction of this technology will also greatly improve the ability to prevent and control ASF.

Background: Bladder cancer (BCa), among the world’s most common malignant tumors in the urinary system, has a high morbidity and mortality. Though cuproptosis is a new type of cell death mediated by lipoylated tricarboxylic acid (TCA) cycle proteins, the role of cuproptosis-related long noncoding RNAs (crlncRNAs) in bladder tumors awaits further elucidation. In this paper, we tried to explore how important crlncRNAs are for BCa.Methods: The crlncRNAs were first obtained through Pearson correlation analysis of the RNA-seq data and corresponding clinical data downloaded from The Cancer Genome Atlas (TCGA). Then, three lncRNAs were acquired by Cox regression and Lasso regression to build a prognostic model of crlncRNAs for verification. In the meantime, clinicopathological correlation analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, principal component analysis (PCA), immunoassay, and half-maximal inhibitory concentration prediction (IC50) were carried out. Then, an entire tumor was classified into two clusters by crlncRNA expression to further discuss the differences in prognosis, immune status and drug susceptibility among different subgroups.Results: We obtained a total of 152 crlncRNAs and built a risk model for screened crlncRNAs. We validated the model and found that calibration charts feature a high consistency in verifying nomogram prediction. Receiver operating characteristic (ROC) curve and univariate and multivariate Cox regression suggested that this model can be applied as an independent prognostic factor of bladder cancer due to its high accuracy. According to KEGG analysis, high-risk groups were enriched in cancer and immune-related pathways. During tumor immunoassay, noticeable differences were observed in both immune infiltration and checkpoints between high- and low-risk patients. Of the two subgroups divided among patients by consensus clustering, cluster 2 had a better prognosis, whereas cluster 1 had higher immunoreactivity scores, more immune cell infiltrations and immune checkpoint expressions, and different sensitivities to drugs.Conclusion: The research findings demonstrate that crlncRNAs can be used to predict the prognosis and immune microenvironment of patients suffering from BCa, and differentiate between BCa subgroups to improve the individual therapy of BCa.

Whether under anaerobic or aerobic conditions, glycolysis results in production of lactate. Increasing evidence suggests that lactate serves as a multifunctional signaling molecule that develops non-metabolic activities in addition to serving as a key metabolite to link glycolysis and oxidative phosphorylation. Histone posttranslational modification patterns (HPTMs) are essential epigenetic processes controlling a variety of biological activities. Proteomics based on mass spectrometry (MS) has been used to progressively reveal new HPTMs. Recent discoveries of histone lactylation modification mediated by lactate and subsequent research demonstrating its involvement in cancer, inflammation, lung fibrosis, and other conditions suggest that it plays a significant role in immune regulation and homeostasis maintenance. This review provides a brief overview of the complicated control of histone lactylation modification in both pathological and physiological conditions.

BackgroundCurrently, few studies have explored the heterogeneity of symptoms and functions in patients with breast cancer. This study aimed to identify the subgroups of symptoms and functions in women receiving chemotherapy for breast cancer and determine whether the subgroups differed in demographic and clinical characteristics.MethodsA cross-sectional multicenter survey involving five hospitals in Zhejiang, Shanghai, Shandong, and Guangxi provinces of Mainland China was implemented between August 2020 to December 2021. Participants completed questionnaires that included the PROMIS-57, PROMIS cognitive function short form, and demographic and clinical characteristics. Latent class analysis was performed, followed by chi-square test and analysis of variance. Subsequently, significant variables were included in multinomial logistic regression.ResultsA total of 1,180 patients were investigated, with an average age of 48.9 years. Three classes were identified: low symptom burdens and functions group (26.2%, Class 1), moderate symptom burdens and functions group (16.9%, Class 2), and low symptom burdens and high functions group (56.9%, Class 3). Compared with patients in Class 1 and 3, those in Class 2 consistently showed a higher tendency of having urban employee health insurance (odds ratio = 2.506, P < 0.05) and rural health insurance (odds ratio = 2.207, P < 0.05). Additionally, patients in Class 2 tended to be in their fourth cycle of chemotherapy. However, receiving chemotherapy and surgery increased the likelihood of belonging to Class 1.ConclusionsA high proportion of patients experienced varying degrees of symptom and function issues, suggesting that attention is warranted for women with breast cancer undergoing chemotherapy. Patients with the urban employee basic medical system, the new rural cooperative medical system and in the early stage of chemotherapy cycles were more likely to have symptom burdens. Middle-aged postmenopausal women reported varying degrees of cognitive issues. Additionally, surgery increased the presence of potential long-term effects in functional levels.

Diabetic kidney disease (DKD) remains the leading cause of the end-stage renal disease and is a major burden on the healthcare system. The current understanding of the mechanisms responsible for the progression of DKD recognizes the involvement of oxidative stress, low-grade inflammation, and fibrosis. Several circulating metabolites that are the end products of the fermentation process, released by the gut microbiota, are known to be associated with systemic immune-inflammatory responses and kidney injury. This phenomenon has been recognized as the “gut–kidney axis.” Butyrate is produced predominantly by gut microbiota fermentation of dietary fiber and undigested carbohydrates. In addition to its important role as a fuel for colonic epithelial cells, butyrate has been demonstrated to ameliorate obesity, diabetes, and kidney diseases via G-protein coupled receptors (GPCRs). It also acts as an epigenetic regulator by inhibiting histone deacetylase (HDAC), up-regulation of miRNAs, or induction of the histone butyrylation and autophagy processes. This review aims to outline the existing literature on the treatment of DKD by butyrate in animal models and cell culture experiments, and to explore the protective effects of butyrate on DKD and the underlying molecular mechanism.

H3K4me3 is an important histone modification that could influence DNA replication and RNA translation in response to abiotic stress. Here, RNA-seq analyses were conducted in gill tissues of large yellow croaker to identify the function of H3K4me3 under low salinity stress. Additionally, CUT&Tag analyses were performed to identify the genome-wide dynamic changes in H3K4me3 and explore the mechanisms by which H3K4me3 regulates gene expression. A total of 201 differentially expressed genes (DEGs) were identified between the 5‰ low salinity group (S-group) and 25‰ normal salinity group (C-group), among which 23 DEGs (11 up-regulated H3K4me3 targets and 12 down-regulated targets) were directly regulated by H3K4me3. Our findings thus describe the epigenetic regulatory landscape of H3K4me3 in gill of large yellow croaker during low salinity stress, and provide novel insights into the regulation mechanisms of H3K4me3 mediating the responses of aquatic animals to abiotic stress.

BackgroundIt has been reported that there is a correlation between the level of ubiquitin-specific protease 22 (USP22) and the clinicopathological parameters and prognosis of gastric cancer (GC) patients, but the conclusions are inconsistent. Hence, a meta-analysis must be conducted to clarify the relationship between USP22 expression and clinicopathological and prognostic value of GC patients to provide more accurate evidence.MethodsAccording to the predetermined selection criteria, systematic file retrieval was performed. The hazard ratio (HR) or odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the relationship between USP22 expression and clinicopathological and prognostic value of GC patients.ResultsIn a total of 802 patients, those with GC were finally included in 6 studies. The pooled results demonstrated that the expression of USP22 was significantly increased in GC tissues compared with control tissues (OR = 9.947, 95% CI, 6.074–16.291, P = 0.000), and USP22 expression was related to lymph node metastasis (OR = 2.415, 95% CI, 1.082, P = 0.031), distant metastasis (OR = 3.956, 95% CI, 1.365–11.464, P = 0.011) and TNM stage (OR = 2.973, 95% CI, 1.153–7.666, P = 0.024). Nevertheless, the expression of USP22 was not correlated with gender (OR = 1.202, 95% CI, 0.877–1.648, P = 0.253), age (OR = 1.090, 95% CI, 0.811–1.466, P = 0.568), tumor size (OR = 0.693,95% CI, 0.348–1.380, P = 0.297), tumor differentiation (OR = 1.830, 95%CI, 0.948–3.531, P = 0.072) and depth of invasion (OR = 2.320, 95% CI, 0.684–7.871, P = 0.177). Moreover, a high expression of USP22 predicted a poor overall survival (OS) in GC patients (HR = 2.012, 95% CI, 1.522–2.658, P = 0.000). The database of Kaplan–Meier plotter confirmed that a high expression of USP22 was correlated with poor prognostics in GC patients (HR = 1.41, 95% CI, 1.18–1.68, P

BackgroundRecurrent implantation failure (RIF) is a disease associated with endometrial receptivity dysfunction. Retinoic acid receptor alpha (RARα) is an important protein in many biological processes, such as differentiation and development. However, the exact underlying mechanism whereby RARα affects RIF remains unknown. This study investigated RARα expression and its contribution in the mid-luteal phase endometria of patients with RIF.MethodsThe expression levels of RARα and CCAAT/enhancer-binding protein (C/EBP) β in the endometria of the RIF and normal group were investigated using western blotting and immunohistochemistry. In in vitro experiments, immortal telomerase-transformed human endometrial stromal cells (T-HESCs) were incubated with medroxyprogesterone-17-acetate (MPA) and cyclic adenosine monophosphate (cAMP) for 4 days to induce decidualization. The expression levels of the decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein-1 (IGFBP-1) were determined using quantitative polymerase chain reaction. RARα was knocked down using a small interfering RNA, and C/EBPβ was overexpressed from an adenoviral vector. The transcriptional regulation of CEBPB by RARα was determined by chromatin immunoprecipitation (ChIP) assay and luciferase assays.ResultsWe found that the expression levels of RARα decreased in the mid-luteal endometria of RIF patients. After 4 days of decidualization induction in vitro, RARα knockdown impaired the decidualization of T-HESCs and downregulated the expression of C/EBPβ. The restoration of C/EBPβ expression rescued the RARα knockdown-induced suppression of T-HESC decidualization. In ChIP analysis of lysates from decidualized T-HESCs, the CEBPB promoter region was enriched in chromatin fragments pulled down using an anti-RARα antibody. However, the relationship between CEBPB transcription and RARα expression levels was only observed when the decidualization of T-HESCs was induced by the addition of cAMP and MPA. To identify the binding site of RARα/retinoid X receptor α, we performed luciferase assays. Mutation of the predicted binding site in CEBPB (-2,009/-1,781) decreased the transcriptional activity of the reporter. To confirm this mechanism, the expression levels of C/EBPβ in the mid-luteal endometria of RIF patients were determined and found to decrease with decreased RARα expression levels.ConclusionA deficiency of RARα expression in the mid-luteal endometrium inhibits decidualization due to the downregulation of CEBPB transcription. This is a potential mechanism contributing to RIF.

AimsYes-associated protein (YAP), a downstream protein in the Hippo signaling pathway, plays an important role in tumor proliferation, including in hepatocellular carcinoma (HCC). α-hederin, a monodesmosidic triterpenoid saponin isolated from Fructus akebiae, displayed anti-cancer effects on several cancer cell lines but the precise mechanism has not been ascertained. In the present study, we explored the effects of α-hederin on cell proliferation and apoptosis in human HCC cell lines and the underlying mechanisms.Main MethodCell proliferation and apoptosis were assessed using 5-ethynyl-2’-deoxyuridine staining, colony formation, flow cytometry. The expression patterns of components of Hippo signaling pathway and apoptotic genes were further examined via RT-qPCR and immunoblotting. A xenograft tumor model in nude mice was used to evaluate the anti-HCC effects of α-hederin in vivo.Resultsα-hederin promoted the apoptosis and inhibited the proliferation of SMMC-7721 and HepG2 cells in vitro, and remarkably inhibited the tumor size and weight in the xenograft mouse model. Additionally, α-hederin increased the expression of pro-apoptosis proteins and suppressed the expression of anti-apoptosis proteins. Moreover, α-hederin treatment upregulated the expression of Hippo signaling pathway-related proteins and genes, while, effectively reduced the level of nuclear YAP, which resulted in the inhibition of proliferation and the induction of apoptosis of HCC cells. Finally, the effects of α-hederin on HCC cell proliferation and apoptosis were alleviated by XMU-MP-1, a Mst1/2 inhibitor in vitro.SignificanceWe identified α-hederin is a novel agonist of Hippo signaling pathway and possesses an anti-HCC efficacy through inhibiting YAP activity.

It is difficult to treat cardiorenal syndrome (CRS) in clinical practice, which is the common reason for the death of patients. This report aimed to describe the effects of sacubitril/valsartan treatment on cardiac and renal functions of a patient with cardiorenal syndrome type 4 (CRS4) after more than 3 years of follow-up. A 77-year-old Chinese woman was admitted to our hospital because of CRS4 and stage 5 chronic kidney disease (CKD), who had a history of long-term proteinuria and renal failure. The patient's cardiothoracic ratio (CTR) measured by chest X–ray was 0.6. Cardiac ultrasonography showed that the left ventricular ejection fraction (LVEF) was 0.40. The patient had been treated for heart failure (HF) for 5 months, but there was no improvement in clinical manifestations, and the renal function gradually deteriorated. In our hospital, she received sacubitril/valsartan treatment for at least 40 months. The symptoms of HF relieved, and the indices of cardiac function improved. In addition, the patient's renal function was stable. During the treatment, the dosage of sacubitril/valsartan needed to be adjusted to achieve the optimal therapeutic effect. Follow-up results showed that she achieved cardiac function of New York Heart Association (NYHA) class II with an ejection fraction of 0.60 and E/A > 1 indicated by echocardiogram, and did not develop hyperkalemia. In summary, the improvement of cardiac and renal functions of the CRS4 patient was associated with the long-term sacubitril/valsartan treatment.

Emerging evidence shows that m6A is the most abundant modification in eukaryotic RNA molecules. It has only recently been found that this epigenetic modification plays an important role in many physiological and pathological processes, such as cell fate commitment, immune response, obesity, tumorigenesis, and relevant for the present review, gametogenesis. Notably the RNA metabolism process mediated by m6A is controlled and regulated by a series of proteins termed writers, readers and erasers that are highly expressed in germ cells and somatic cells of gonads. Here, we review and discuss the expression and the functional emerging roles of m6A in gametogenesis and early embryogenesis of mammals. Besides updated references about such new topics, readers might find in the present work inspiration and clues to elucidate epigenetic molecular mechanisms of reproductive dysfunction and perspectives for future research.

ObjectiveTo investigate the effects of glial cell-derived neurotrophic factor (GDNF), GDNF family receptor alpha 1 (GFRα1), and glial fibrillary acidic protein (GFAP) on colonic motility in a mouse model of intestinal neuronal dysplasia by intervention with Bifidobacterium and to explore the influence of Bifidobacterium on enteric glial cells (EGCs).MethodsWestern blotting and qRT-PCR were employed to detect the expression of GFRα1 and GFAP in colonic tissues of mice with or without Tlx2 mutations, and ELISA was used to detect the expression of GDNF in serum. IHC was used to detect the appearance of the ganglion cells. Subsequently, Tlx2 homozygous mutant (Tlx2−/−) mice were treated with Bifidobacterium. Colonic motility was measured before and after intervention by measuring the glass bead expelling time. The variations in abdominal circumference and GDNF, GFRα1, and GFAP expression were measured. In addition, 16SrRNA gene sequencing was performed to detect the abundance of the intestinal microbiota.ResultsThe mRNA and protein expression of GFRα1 and GFAP was decreased in the colonic tissues of Tlx2−/− mice and GDNF expression was decreased in serum compared with Tlx2+/− and WT mice. After confirming the colonization of Bifidobacterium by 16S rRNA gene sequencing, the expelling time and abdominal distension were ameliorated, and the expression of GFAP, GDNF, and GFRα1 was increased.ConclusionsThe expression of GDNF, GFRα1, and GFAP is associated with colonic motility. The altered expression of EGC-related factors suggested that Bifidobacterium may be involved in the EGC activation process. The amelioration of IND symptoms after intervention with Bifidobacterium prompted the elicitation of adjuvant therapy.

Objective: The aim of this study was to explore the development of enteric glial cells (EGCs) in different segments of Hirschsprung's disease (HSCR).Methods: Colonic specimens from 35 children with HSCR were selected to analyze the relative expression of glial fibrillary acidic protein and S100 calcium-binding protein B using Western blotting and real-time fluorescence quantitative PCR. Immunofluorescence and immunohistochemical staining were performed to determine the distribution of myenteric EGCs and neuronal cells in different segments of HSCR.Results: There was a trend of diminished protein and mRNA expression of glial fibrillary acidic protein and S100 calcium-binding protein B from the proximal, dilated, and transitional segments to the aganglionic segment (p < 0.05). Immunofluorescence and immunohistochemistry showed that the EGCs in the aganglionic, transitional, and dilated colonic muscles were morphologically abnormal, which was consistent with the dysplasia of myenteric neurons.Conclusion: Aberrant development of myenteric EGCs was observed in the colon of HSCR, which may affect the survival of enteric neurons.

The circadian rhythm has a great impact on the growth, metabolism and development of animals, but little is known about the circadian rhythm of marine bivalves. Understanding of the feeding rhythm is of great significance to increase the yield of razor clam Sinonovacula constricta, an economically important bivalve mollusk. The aim of this experiment was to study the effects of circadian rhythm of feeding time on digestive enzymes activities and their gene expression in S. constricta within a light (ZT8-ZT20)/dark (ZT20-ZT8) cycle. The present results showed that circadian rhythm of feeding rate (FR) was highly associated with digestive enzyme activities and relative expression of their genes. The highest values of FR were basically observed in the night from ZT0-ZT2 and ZT6-ZT8, which were significantly higher than those values in the daytime from ZT12-ZT14 and ZT18-ZT20 (P < 0.05). The digestive enzymes activities displayed the highest values at ZT2 and ZT8, and the lowest at ZT14 and ZT20. Among them, cellulase and pepsin were found to have significantly different activities (P < 0.05), rather than amylase and lipase. Notably, the relative expression of digestive enzyme genes shared the similar pattern with the activities of digestive enzymes. The highest values of relative gene expression of amylase (AMY), lipase (LIP), cellulase (CEL), and pepsin (PEP) were found at ZT2 and ZT8 in the night, while the lowest values were found at ZT14 during the day. It is therefore suggested that the biological clock may regulate the process from feeding to digestion. Furthermore, it might be better to feed at night to reduce cultivating cost and increase economic benefits in the farming industry of S. constricta.

BackgroundThe clinicopathological and prognostic significance of SRY-box transcription factor 9 (SOX9) expression in gastric cancer (GC) patients is still controversial. Our aim is to investigate the clinicopathological and prognostic value of SOX9 expression in GC patients.MethodsA systemic literature search and meta-analysis were used to evaluate the clinicopathological significance and overall survival (OS) of SOX9 expression in GC patients. The Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between SOX9 expression and OS of stomach adenocarcinoma (STAD) patients.ResultsA total of 11 articles involving 3,060 GC patients were included. In GC patients, the SOX9 expression was not associated with age [odds ratio (OR) = 0.743, 95% CI = 0.507–1.089, p = 0.128], sex (OR = 0.794, 95% CI = 0.605–1.042, p = 0.097), differentiation (OR = 0.728, 95% CI = 0.475–1.115, p = 0.144), and lymph node metastasis (OR = 1.031, 95% CI = 0.793–1.340, p = 0.820). SOX9 expression was associated with depth of invasion (OR = 0.348, 95% CI = 0.247–0.489, p = 0.000) and TNM stage (OR = 0.428, 95% CI = 0.308–0.595, p = 0.000). The 1-year OS (OR = 1.507, 95% CI = 1.167–1.945, p = 0.002), 3-year OS (OR = 1.482, 95% CI = 1.189–1.847, p = 0.000), and 5-year OS (OR = 1.487, 95% CI = 1.187–1.862, p = 0.001) were significantly shorter in GC patients with high SOX9 expression. TCGA analysis showed that SOX9 was upregulated in STAD patients compared with that in normal patients (p < 0.001), and the OS of STAD patients with a high expression of SOX9 is poorer than that in patients with low expression of SOX9, but the statistical difference is not obvious (p = 0.31).ConclusionSOX9 expression was associated with the depth of tumor invasion, TNM stage, and poor OS of GC patients. SOX9 may be a potential prognostic factor for GC patients but needs further study.Systematic Review RegistrationPROSPERO, ID NUMBER 275712.

Hypertension is caused by polygenic inheritance and the interaction of various environmental factors. Abnormal function of the renin-angiotensin-aldosterone system (RAAS) is closely associated with changes in blood pressure. As an essential factor in the RAAS, angiotensin II (Ang II) contributes to vasoconstriction and inflammatory responses. However, the effects of overproduction of Ang II on the whole body-metabolism have been unclear. In this study, we established a hypertensive mouse model by micro-osmotic pump perfusion of Ang II, and the maximum systolic blood pressure reached 140 mmHg after 2 weeks. By ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, the metabolites in the serum of hypertensive model and control mice were analyzed. Partial least squares discriminant analysis (PLS-DA) in both positive and negative ionization modes showed clear separation of the two groups. Perfusion of Ang II induced perturbations of multiple metabolic pathways in mice, such as steroid hormone biosynthesis and galactose metabolism. Tandem mass spectrometry revealed 40 metabolite markers with potential diagnostic value for hypertension. Our data indicate that non-targeted metabolomics can reveal biochemical pathways associated with Ang II-induced hypertension. Although researches about the clinical use of these metabolites as potential biomarkers in hypertension is still needed, the current study improves the understanding of systemic metabolic response to sustained release of Ang II in hypertensive mice, providing a new panel of biomarkers that may be used to predict blood pressure fluctuations in the early stages of hypertension.

Transient receptor potential vanilloid 4 (TRPV4) channels are widely expressed in systemic tissues and can be activated by many stimuli. TRPV4, a Ca2+-permeable cation channel, plays an important role in the vasculature and is implicated in the regulation of cardiovascular homeostasis processes such as blood pressure, vascular remodeling, and pulmonary hypertension and edema. Within the vasculature, TRPV4 channels are expressed in smooth muscle cells, endothelial cells, and perivascular nerves. The activation of endothelial TRPV4 contributes to vasodilation involving nitric oxide, prostacyclin, and endothelial-derived hyperpolarizing factor pathways. TRPV4 activation also can directly cause vascular smooth muscle cell hyperpolarization and vasodilation. In addition, TRPV4 activation can evoke constriction in some specific vascular beds or under some pathological conditions. TRPV4 participates in the control of vascular permeability and vascular damage, particularly in the lung capillary endothelial barrier and lung injury. It also participates in vascular remodeling regulation mainly by controlling vasculogenesis and arteriogenesis. This review examines the role of TRPV4 in vascular function, particularly in vascular dilation and constriction, vascular permeability, vascular remodeling, and vascular damage, along with possible mechanisms, and discusses the possibility of targeting TRPV4 for therapy.

Zhi-zi-chi Decoction (ZZCD), composed of Fructus Gardeniae (Zhizi in Chinese, ZZ in brief) and Semen sojae praeparatum (Dandouchi in Chinese, DDC in brief), has been used as a drug therapy for depression for thousands of years in China. However, the antidepressant mechanism of ZZCD still remains unknown. This study was aimed at exploring antidepressant effects of ZZCD from the aspect of neuroprotection based on herb compatibility. Glutamate-treated PC12 cells and chronic unpredictable mild stress (CUMS)-induced rats were established as models of depression in vitro and in vivo respectively. Cell viability, lactate dehydrogenase (LDH), apoptosis rate, reactive oxygen species (ROS), glutathione reductase (GR) and superoxide dismutase (SOD), and the expressions of Bax, Bcl-2 and cyclic adenosine monophosphate-response element binding protein (CREB) were measured to compare neuroprotection among single herbs and the formula in vitro. Behavior tests were conducted to validate antidepressant effects of ZZCD in vivo. Results showed that the compatibility of ZZ and DDC increased cell viability and activities of GR and SOD, and decreased the levels of LDH, apoptosis cells and ROS. Besides, the expressions of Bcl-2 and CREB were up-regulated while that of Bax was down-regulated by ZZCD. Furthermore, the compatibility of ZZ and DDC reversed abnormal behaviors in CUMS-induced rats and displayed higher efficacy than any of the single herbs. This study revealed that the antidepressant effects of ZZCD were closely associated with neuroprotection and elucidated synergistic effects of the compatibility of ZZ and DDC based on it.

Chemotherapeutic patients with leukemia often relapse and produce drug resistance due to the existence of leukemia stem cells (LSCs). Fibroblast growth factor receptor 3 (FGFR3) signaling mediates the drug resistance of LSCs in chronic myeloid leukemia (CML). However, the function of FGFR3 in acute myeloid leukemia (AML) is less understood. Here, we identified that the loss of FGFR3 reprograms MLL-AF9 (MA)-driven murine AML cells into weakly pathogenic CD117-positive leukemia stem-like cells by activating the FGFR1-ERG signaling pathway. FGFR3 deletion significantly inhibits AML cells engraftment in vivo and extends the survival time of leukemic mice. FGFR3 deletion sharply decreased the expression of chemokines and the prolonged survival time in mice receiving FGFR3-deficient MA cells could be neutralized by overexpression of CCL3. Here we firstly found that FGFR3 had a novel regulatory mechanism for the stemness of LSCs in AML, and provided a promising anti-leukemia approach by interrupting FGFR3.

In this report, we studied the vitellogenin gene family in the whiteleg shrimp Litopenaeus vannamei by transcriptomics, bioinformatics, and molecular biology methods. At least three moderately homologous vitellogenin (Vg) genes (i.e. LvVg1, LvVg2, and LvVg3) were identified in the genome. The deduced LvVg proteins consisted of a vitellogenin_N domain, a DUF1943 domain, and a VWD domain typical of most vitellogenins from oviparous animals. LvVg1 was the most abundant Vg expressed in the hepatopancreas and ovary of maturing females. Furthermore, multiple isoforms of LvVg1 were evolved presumably due to the need for rapid Vg production during the rapid phase of vitellogenesis. LvVg transcripts were detected in different larval stages, juveniles, and subadults. During the non-reproductive cycle, LvVg expression in the hepatopancreas peaked at the intermolt stages. During the female vitellogenesis cycle, a two-phase expression pattern of LvVg1 gene was observed in the hepatopancreas and ovary. Moreover, the eyestalk optic nerve, brain, and thoracic ganglion consisted of factors that differentially regulated the expression of the three Vg genes. In addition to their reproduction-related roles, Vg may also be involved in growth and molt-related processes. Phylogenetic analysis revealed the early expansion and separation of these Vg genes, and it is most likely correlated with the expansion of Vg’s function. In conclusion, the evolution of multiple LvVg1 isoforms and the acquisition of different Vg genes (i.e. LvVg2 and LvVg3) may occur universally in most decapods. Full information on the total number of Vg genes and precise knowledge on the expression pattern and endocrine regulation of each Vg during all life cycle stages are crucial for us to understand the roles of this emerging gene family in the control of shrimp reproduction and other non-reproductive processes.

Acquisition of the blaNDM–1 gene by Proteus mirabilis is a concern because it already has intrinsic resistance to polymyxin E and tigecycline antibiotics. Here, we describe a P. mirabilis isolate that carries a pPrY2001-like plasmid (pHFK418-NDM) containing a blaNDM–1 gene. The pPrY2001-like plasmid, pHFK418-NDM, was first reported in China. The pHFK418-NDM plasmid was sequenced using a hybrid approach based on Illumina and MinION platforms. The sequence of pHFK418-NDM was compared with those of the six other pPrY2001-like plasmids deposited in GenBank. We found that the multidrug-resistance encoding region of pHFK418-NDM contains ΔTn10 and a novel transposon Tn6625. Tn6625 consists of ΔTn1696, Tn6260, In251, ΔTn125 (carrying blaNDM–1), ΔTn2670, and a novel mph(E)-harboring transposon Tn6624. In251 was first identified in a clinical isolate, suggesting that it has been transferred efficiently from environmental organisms to clinical isolates. Genomic comparisons of all these pPrY2001-like plasmids showed that their relatively conserved backbones could integrate the numerous and various accessory modules carrying multifarious antibiotic resistance genes. Our results provide a greater depth of insight into the horizontal transfer of resistance genes and add interpretive value to the genomic diversity and evolution of pPrY2001-like plasmids.

A scorpion peptide reported to exhibit both analgesic and antitumor activity in animal models may present as an alternative therapeutic agent for breast cancer. We aimed to investigate the effect of Buthus martensii Karsch antitumor-analgesic peptide (BmK AGAP) on breast cancer cell stemness and epithelial-mesenchymal transition (EMT). We treated MCF-7 and MDA-MB-231 cells with different concentrations of rBmK AGAP and observed that rBmK AGAP inhibited cancer cell stemness, epithelial-mesenchymal transition (EMT), migration, and invasion. Analysis by qPCR, ELISA, western blot, immunofluorescence staining, sphere formation, colony assay, transwell migration, and invasion assays demonstrated rBmK AGAP treatment decreased the expressions of Oct4, Sox2, N-cadherin, Snail, and increased the expression of E-cadherin. rBmK AGAP inhibited breast cancer cell stemness, EMT, migration, and invasion by down-regulating PTX3 through NF-κB and Wnt/β-catenin signaling Pathway in vitro and in vivo. Xenograft tumor model confirmed inhibition of tumor growth, stem-like features, and EMT by rBmK AGAP. Thus, rBmK AGAP is a potential therapeutic agent against breast cancer and related pain.

Isoflavones, presenting in leguminous plants and the normal chow diet, are known to alter intestinal microbiota, yet their deficiency has not been widely studied for its effect on constipation in biochemical state of rats. Our previous study discovered the differences in pharmacokinetic traits of isoflavones from Semen sojae praeparatum fed with normal chow diet (ISO) and non-isoflavones diet (NISO). To gain insight into the key role of intestinal microbiota in constipation and metabolic differences caused by isoflavones deficiency, we observed a significant decrease in fecal pellet numbers, fecal water content, intestinal transit rate together with the serum concentrations of substance P (SP) and vasoactive intestinal peptide (VIP) in NISO group, compared with those in the ISO group. Following 16S rRNA compositional sequencing, results excluded the changes in intestinal microbiota over time and highlighted that a total of 5 phyla and 21 genera changed significantly, among which Firmicutes, Bacteroidetes, Blautia, Prevotella, Lactobacillus and Bifidobacterium were closely related to constipation. In addition, Lactobacillus, produceing β-glucosidase which contribute to biotransform glycosides into aglycons and exert the bioactivities consequently, was decreased after non-isoflavones diet intake. Meanwhile, predicted metagenomics indicated that the pathway of glycan biosynthesis and metabolism was markedly down-regulated after non-isoflavones diet intake. Taken together, the findings suggested that the changes in the dietary components could alter the biochemical state of rats, which may be triggered by the abnormal modifications facilitated by β-glucosidase-producing bacteria. Our study shed a new strategy to explore the relationship among disease phenotypes (D), intestinal microbiota (I), enzymes (E) and traits of metabolism (T) named as “DIET,” which can provide a reference for further study of the mechanism in regulation of intestinal bacteria-mediated diet on diseases.

This work performed a large scale assessment for organophosphorus pesticides (OPPs) degradation activity of 121 Lactobacillus (L.) plantarum strains. Six L. plantarum strains (P9, IMAU80110, IMAU40100, IMAU10585, IMAU10209, and IMAU80070) were found to possess high capacity of degrading three commonly used OPPs, namely dimethoate, phorate, and omethoate; and they were selected for more detailed characterization. Moreover, the three OPPs were mainly detected in the culture supernatants but not in the cell extracts, further confirming that the OPPs were degraded rather than absorbed by the cells. Among the six selected strains, P9 was most tolerant to gastrointestinal juices and bile. We thus used ultra-high performance liquid chromatography electron spray ionization coupled with time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) to generate the metabolomic profiles of the strain P9 growing in MRS medium with and without containing phorate. By using orthogonal partial least squares discriminant analysis, we identified some potential phorate-derived degradative products. This work has identified novel lactic acid bacteria resources for application in pesticide degradation. Our results also shed light on the phorate degradation mechanism by L. plantarum P9.

BackgroundA possible relationship between oral lichen planus (OLP) and thyroid disease has received attention in recent years.ObjectiveThis study aimed to evaluate the correlation between OLP and thyroid diseases in Chinese ethnic patients.Methods192 OLP patients, 123 patients with oral lichenoid lesions (OLLs), and 162 controls were recruited in this case–control study. All participants received screening for thyroid function and underwent ultrasound. Sex and age of the patients in the three groups were matched. The prevalence of thyroid diseases in the subjects was analyzed. Using logistic regression, the odds ratio (OR) with 95% confidence intervals was appraised for associations between OLP, OLL, and different types of thyroid diseases [Hashimoto’s thyroiditis (HT), hypothyroidism, and thyroid nodule].ResultsThe prevalence of thyroid diseases in the OLP group (72.4%) and OLL group (68.3%) was higher than the control group (49.4%) with statistical significance. The OR of HT was 3.16 (1.87–5.33) for OLP, 2.09 (1.18–3.70) for OLL, while the OR of thyroid nodule was 2.31 (1.30–4.09) for OLP.ConclusionOur study suggested a close relationship between OLP/OLL and HT and thyroid nodule in a Chinese population. The possible mechanism behind this association warrants further investigation.

Sepsis is a major cause of death for hospitalized patients and is characterized by massive overreaction of immune responses to invading pathogens which is mediated by cytokines. For decades, there has been no effective treatment for sepsis. Sialic acid-binding, Ig-like lectin-9 (Siglec-9), is an immunomodulatory receptor expressed primarily on hematopoietic cells which is involved in various aspects of inflammatory responses and is a potential target for treatment of sepsis. The aim of the present study was to develop a human anti-Siglec-9 Fab fragment, which was named hS9-Fab03 and investigate its immune activity in human macrophages. We began by constructing the hS9-Fab03 prokaryotic expression vector from human antibody library and phage display. Then, we utilized a multitude of assays, including SDS-PAGE, Western blotting, ELISA, affinity, and kinetics assay to evaluate the binding affinity and specificity of hS9-Fab03. Results demonstrated that hS9-Fab03 specifically bind to Siglec-9 antigen with high affinity, and pretreatment with hS9-Fab03 could attenuate lipopolysaccharide (LPS)-induced TNF-α, IL-6, IL-1β, IL-8, and IFN-β production in human PBMC-derived macrophages, but slightly increased IL-10 production in an early time point. We also observed similar results in human THP-1-differentiated macrophages. Collectively, we prepared the hS9-Fab03 with efficient activity for blocking LPS-induced pro-inflammatory cytokines production in human macrophages. These results indicated that ligation of Siglec-9 with hS9-Fab03 might be a novel anti-inflammatory therapeutic strategy for sepsis. [ABSTRACT FROM AUTHOR]