Teachers' Emotional Intelligence and Organizational Commitment: A Moderated Mediation Model of Teachers' Psychological Well-Being and Principal Transformational Leadership.

Given the global challenge of increasing teacher attrition and turnover rates, the exploration of factors and mechanisms that improve teachers' organizational commitment has become a pivotal topic in educational research. In this context, the present study examines the influence of teachers' emotional intelligence on their organizational commitment, with a specific inquiry into the mediating role of teachers' psychological well-being and the moderating role of principal transformational leadership, as informed by the broaden-and-build theory of positive emotions and the trait activation theory. We verified this study's hypotheses based on 768 valid questionnaires collected from Chinese primary and secondary school teachers. The results reveal that teachers' emotional intelligence can predict their organizational commitment both directly and indirectly through the mediating role of psychological well-being. Additionally, principal transformational leadership amplifies the positive effect of teachers' emotional intelligence on psychological well-being and, subsequently, organizational commitment. These findings theoretically deepen our understanding of the psychological pathways and the boundary conditions linking teachers' emotional intelligence to their organizational commitment, while also offering valuable practical implications for building a stable and effective teaching workforce.

Association between Dietary Intake of Live Microbes and Chronic Constipation in Adults.

BACKGROUND: Chronic constipation (CC) is a common gut health problem, and the role of live dietary microbes in CC is unclear. OBJECTIVE: This study aimed to investigate the relationship between dietary live microbes consumption and CC. METHODS: Using the National Health and Nutrition Examination Survey data (2005-2010), 11,170 adults who completed the 24-h face-to-face dietary recall and bowel health questionnaire were identified. CC was defined by the Bristol Stool Form Scale. Dietary live microbes intake was classified as low, medium, and high. Additionally, combined medium and high categories (MedHi) were analyzed. Multivariate regression models were constructed to assess the association between dietary intake of live microbes and CC. RESULTS: In the weighted sample, the age-adjusted CC prevalence was 7.06% (95% confidence interval [CI]: 6.45, 7.67). In multivariate regression models, after controlling for potential confounders race/ethnicity, sex, body mass index, education, poverty, depression, caffeine intake, and alcohol intake, a significant inverse association between dietary live microbes consumption and CC was observed (odds ratio [OR]: 0.77, 95% CI: 0.61, 0.97, P-trend = 0.061). CONCLUSIONS: Our findings suggest that a high dietary live microbes consumption may be associated with lower odds of CC. However, further prospective studies are essential to confirm its effectiveness in reducing CC occurrence.

Lifting the veils on transmembrane proteins: Potential anticancer targets.

Cancer, as a prevalent cause of mortality, poses a substantial global health burden and hinders efforts to enhance life expectancy. Nevertheless, the prognosis of patients with malignant tumors remains discouraging, owing to the lack of specific diagnostic and therapeutic targets. Therefore, the development of early diagnostic indicators and novel therapeutic drugs for the prevention and treatment of cancer is essential. Transmembrane proteins (TMEMs) are a class of proteins that can span the phospholipid bilayer and are stably anchored. They are associated with fibrotic diseases, neurodegenerative diseases, autoimmune diseases, developmental disorders, and cancer. It has been found that the expression levels of TMEMs were elevated or reduced in cancer cells, exerting pro/anticancer effects. These aberrant expression levels have also been linked to the prognostic and clinicopathological features of diverse tumors. In this review, the structures, functions, and roles of TMEMs in cancer were discussed, and the scientific perspectives were described. This review also explored the potential of TMEMs as tumor drug candidates from the perspective of targeted therapies, and the challenges that need to be overcome in a wide range of preclinical and clinical anticancer research were summarized.

Multi-omics analysis of fecal microbiota transplantation's impact on functional constipation and comorbid depression and anxiety.

BACKGROUND: Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted. METHODS: We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro. RESULTS: Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells. CONCLUSION: FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.

Comparative Study on the Resistance of Beta-Cypermethrin Nanoemulsion and Conventional Emulsion in Blattella germanica.

OBJECTIVE: This study aimed to compare the resistance rates of Blattella germanica to beta-cypermethrin nanoemulsion and conventional emulsion and establish reference values via biochemical detection for conventional emulsion. METHODS: We conducted experiments using subcultured Blattella germanica and applied the micro-drop method for treatment. Subsequently, the activity of metabolic enzymes was measured using spectrophotometry. Profile analysis was employed to study the resistance rates of beta-cypermethrin nanoemulsion and beta-cypermethrin emulsion. RESULTS: The regression equation for the relationship between generation and resistance factor in Blattella germanica treated with beta-cypermethrin nanoemulsion was as follows: y1 = 0.091x1 + 0.991, with an r-value of 0.990 (F = 95.184, p = 0.01 < 0.05). Similarly, the regression equation for Blattella germanica treated with emulsion was y2 = 0.376x2 + 1.051, with an r-value of 0.993 (F = 141.094, p = 0.007 < 0.05). The comparison of slopes between these two regression equations yielded an F-value of 8.61, indicating a significant difference (p = 0.001 < 0.05). CONCLUSION: Our findings suggest that the resistance factor in Blattella germanica treated with beta-cypermethrin nanoemulsion differs from that treated with beta-cypermethrin emulsion. Specifically, the resistance factor of beta-cypermethrin nanoemulsion increased at a slower rate compared to beta-cypermethrin emulsion.

Characterization of gut microbiota in adults with coronary atherosclerosis.

Background: Cardiovascular disease, which is mainly caused by coronary atherosclerosis, is one of the leading causes of death and disability worldwide. Gut microbiota likely play an important role in coronary atherosclerosis. This study aims to investigate the microbiota profile of adults with coronary atherosclerosis to provide a theoretical basis for future research. Methods: Fecal samples were collected from 35 adult patients diagnosed with coronary atherosclerosis and 32 healthy adults in Nanjing, China, and the V3-V4 region of 16S rDNA genes was sequenced using high-throughput sequencing. Differences in alpha diversity, beta diversity, and gut microbiota composition between the two groups were then compared. Results: A beta diversity analysis revealed significant differences between adults with coronary atherosclerosis and controls, but there was no statistical difference in alpha diversity between the two groups. There were also differences in the composition of the gut microbiota between the two groups. The genera, Megamonas, Streptococcus, Veillonella, Ruminococcus_torques_group, Prevotella_2, Tyzzerella_4, were identified as potential biomarkers for coronary atherosclerosis. Conclusion: There are some differences in the gut microbiota of adults with coronary atherosclerosis compared to healthy adults. The insights from this study could be used to explore microbiome-based mechanisms for coronary atherosclerosis.

Integrated metagenomics and targeted-metabolomics analysis of the effects of phenylalanine on loperamide-induced constipation in rats.

Functional constipation is a common functional gastrointestinal disease. In our previous study, we found that the gut microbiota structure was disordered and the level of phenylalanine (Phe) in serum was decreased in constipated women. We conducted the present study to elucidate the role of Phe in remodeling the composition of gut microbiota and the relationship between gut microbiota and serum metabolites. Here, we demonstrated that Phe treatment significantly enhanced intestinal motility, suppressed inflammatory responses, and prevented intestinal barrier damage in rats with loperamide (Lop)-induced constipation. By metagenomic sequencing, the disbalanced gut microbial profile was analyzed in constipated rats. Phe treatment reversed changes in the abundance of several gut bacteria at the phylum, genus, and species levels. Further, we observed distinct metabolic patterns in constipated rats through targeted metabolomics and identified constipation-related gut microbial species linked to changes in circulating neurotransmitter metabolites. The abundances of species s_Lactobacillus murinus, s_Enterococcus italicus, s_Lactobacillus animalis, s_Lactobacillus apodemi, s_Enterococcus faecalis, and s_Lactobacillus backii were positively correlated with L-asparagine, L-Glutamic acid, Putrescine, and Spermidine levels. The abundances of s_Lactobacillus johnsonii and s_Butyricimonas virosa were negatively correlated with L-asparagine, L-Glutamic acid, Putrescine, and Spermidine levels. Taken together, our findings suggest that Phe can ameliorate the development of Lop-induced constipation in rats by remodeling the gut microbial community structure and changing metabolite levels.

A prognostic signature of pyroptosis-related lncRNAs verified in gastric cancer samples to predict the immunotherapy and chemotherapy drug sensitivity.

Background: Pyroptosis is a recently identified mode of programmed inflammatory cell death that has remarkable implications for cancer development. lncRNAs can be involved in cellular regulation through various pathways and play a critical role in gastric cancer (GC). However, pyroptosis -related lncRNAs (PRlncRNAs) have been rarely studied in GC. Methods: Pyroptosis-related gene were abstracted from the literature and GSEA Molecular Signatures data resource. PRlncRNAs were obtained using co-expression analysis. LASSO Cox regression assessment was employed to build a risk model. Kaplan-Meier (KM), univariate along with multivariate Cox regression analysis were adopted to verify the predictive efficiency of the risk model in terms of prognosis. qRT-PCR was adopted to validate the expression of PRlncRNAs in GC tissues. In addition, immune cell infiltration assessment and ESTIMATE score evaluation were adopted for assessing the relationship of the risk model with the tumor immune microenvironment (TME). Finally, immune checkpoint gene association analysis and chemotherapy drug sensitivity analysis were implemented to assess the worthiness of our risk model in immunotherapy and chemotherapy of GC. Results: We identified 3 key PRlncRNAs (PVT1, CYMP-AS1 and AC017076.1) and testified the difference of their expression levels in GC tumor tissues and neighboring non-malignant tissues (p < 0.05). PRlncRNAs risk model was able to successfully estimate the prognosis of GC patients, and lower rate of survival was seen in the high-GC risk group relative to the low-GC risk group (p < 0.001). Other digestive system tumors such as pancreatic cancer further validated our risk model. There was a dramatic difference in TMB level between high-GC and low-GC risk groups (p < 0.001). Immune cell infiltration analysis and ESTIMATE score evaluation demonstrated that the risk model can be adopted as an indicator of TME status. Besides, the expressions of immunodetection site genes in different risk groups were remarkably different (CTLA-4 (r = -0.14, p = 0.010), VISTA (r = 0.15, p = 0.005), and B7-H3 (r = 0.14, p = 0.009)). PRlncRNAs risk model was able to effectively establish a connection with the sensitivity of chemotherapeutic agents. Conclusion: The 3 PRlncRNAs identified in this study could be utilized to predict disease outcome in GC patients. It may also be a potential therapeutic target in GC therapy, including immunotherapy and chemotherapy.

Alteration of Serum Metabolites in Women of Reproductive Age with Chronic Constipation.

BACKGROUND Chronic constipation is a common gastrointestinal disease. Our previous studies confirmed that there are differences in the composition and function of gut microbiota between women of reproductive age with chronic constipation and healthy controls. However, little is known about the differences in the metabolic profile of the 2 groups. The aim of this study was to observe changes in serum metabolites and identify potential metabolic pathways in the development of chronic constipation. MATERIAL AND METHODS A total of 50 participants were included in this study: 25 female patients of childbearing age with chronic constipation who met the inclusion and exclusion criteria and 25 healthy participants as a control group. Serum samples of these participants were collected; 1 portion of the serum sample was used for clinical biochemical analysis, and the other was used for non-targeted metabolomic testing. RESULTS Compared with the control group, serum 2-hydroxyphenylacetic acid levels were higher (P<0.05) and DL-phenylalanine levels were lower (P<0.05) in the constipation group. Other amino acids, such as 5-hydroxy-l-lysine and l-pipecolic acid, were upregulated, and L-valine, glycine, L-leucyl-L-proline, and N-formylmethionine were downregulated in the constipation group. In addition, levels of the bile acid, 3b-hydroxy-5-cholenoic acid, were higher in the constipation group than in the control group. Pathway analysis showed that the significantly altered pathways were phenylalanine metabolism and glycine, serine, and threonine metabolism. CONCLUSIONS These results strongly suggest that serum metabolites and pathways are significantly altered in women of reproductive age with chronic constipation.

Prefoldin and prefoldin-like complex subunits as predictive biomarkers for hepatocellular carcinoma immunotherapy.

BACKGROUND: Prefoldin complex subunits (PFDNs) and prefoldin-like complex subunits (PFDLNs) collaborate in protein folding, modulate endoplasmic reticulum stress. The association between PFDN/PFDLN and the immune microenvironment of HCC remains unclear. We investigated the biological significance of PFDNs and PFDLNs in HCC using bioinformatics. METHODS: The relationship between PFDNs/PFDLNs and HCC was analysed using TCGA, and Human Protein Atlas. The protein-protein interaction (PPI) network was performed through String and Cytoscape. In addition, mutations in PFDNs and PFDLNs were analysed using cBioPortal. Clinical correlation analysis, survival analysis was conducted by using UALCAN and Kaplan-Meier analysis. The protein-protein interaction (PPI) network was performed through String and Cytoscape. The GO and KEGG enrichment analyses were also carried out. CCK-8 and Flow cytometry analysis were used to detect the proliferation and apoptosis of PFDN1 and UXT knockdown HCC cells. Immune infiltrates analyses was were conducted using the TIMER and TISIDB to determine whether PFDNs/PFDLNs are predictive biomarkers of immune cell infiltration. RESULTS: We observed that PFDNs and PFDLNs were significantly overexpressed in HCC tissues compared to normal liver tissues. This abnormal expression was associated with worse clinicopathological features and negatively affected patient survival. PFDNs and PFDLNs have varying degrees of mutations in HCC, which may be related to their abnormal expression. In addition, up-regulated PFDN1 and UXT were found to promote HCC proliferation and inhibit apoptosis in vitro. Finally, the expression of certain PFDNs and PFDLNs in the tumour microenvironment was positively correlated with the level of tumour-infiltrating immune cells and significantly enhanced the infiltration of immune cells in the microenvironment. CONCLUSIONS: PFDNs and PFDLNs are valuable predictive biomarkers for immune infiltration in HCC and may assist in tumour immunotherapy research and prognosis prediction in the future.

MicroRNA-203-3p inhibits the proliferation, invasion and migration of pancreatic cancer cells by downregulating fibroblast growth factor 2.

Aberrant expression of fibroblast growth factor 2 (FGF2) is a major cause of poor prognosis in patients with pancreatic cancer. MicroRNA (miRNA/miR) miR-203-3p is a newly identified miRNA that can affect the biological behavior of tumors. The present study investigated the function of miR-203-3p on the regulation of FGF2 expression, and its role in pancreatic cancer cell proliferation, apoptosis, invasion and migration. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of miR-203-3p and FGF2 in vitro. Cell Counting Kit-8, Annexin V-APC/7-AAD double-staining Apoptosis Detection kit, wound healing and Transwell assays were used to determine the proliferation, apoptosis, migration and invasion of pancreatic cancer cells. The binding of miR-203-3p to FGF2 was assessed by a luciferase reporter assay. The results demonstrated that miR-203-3p expression was downregulated in pancreatic cancer cells. Gain- and loss-of-function experiments indicated that miR-203-3p inhibited the proliferation, migration and invasion, and promoted the apoptosis of pancreatic cancer cells in vitro. In addition, it was found that alteration of miR-203-3p abolished the promoting effects of FGF2 on pancreatic cancer cells. The present study demonstrated that FGF2 significantly promoted the proliferation, invasion and migration of pancreatic cancer cells. The mechanism involved the binding of miR-203-3p to the 3'-untranslated region of FGF2 mRNA, resulting in the downregulation of FGF2. In conclusion, miR-203-3p inhibited FGF2 expression, regulated the proliferation and inhibited the invasion and migration of pancreatic cancer cells.

The effects of psyllium husk on gut microbiota composition and function in chronically constipated women of reproductive age using 16S rRNA gene sequencing analysis.

Chronic constipation is a common gastrointestinal disorder that occurs in the elderly and in women. Psyllium husk is widely used to treat this condition. Recent studies have shown that psyllium husk can improve the clinical symptoms of constipation by regulating gut microbiota, but its clinical effects and potential mechanisms in constipated women of reproductive age have not been previously investigated. We compared fecal microbiota after treatment with placebo (n = 29) and psyllium husk (n = 25) using 16S ribosomal ribonucleic acid (rRNA) gene sequencing analysis. Psyllium husk relieved the symptoms of constipated women of reproductive age. Sequencing results showed that the psyllium husk group exhibited a different gut microbiota composition compared to that of the placebo group. Moreover, network analysis indicated more significant correlations and clustering of operational taxonomic units (OTUs) in the psyllium husk group. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis showed that the relative abundances of metabolism-related KEGG pathways were enriched in the psyllium husk group. In conclusion, these findings suggest that the composition of gut microbiota was altered and that symptoms of constipation were alleviated via psyllium husk intervention. The changes in metabolic function might be related to constipation. Furthermore, these studies are warranted to elucidate the potential metabolic mechanisms contributing to chronic constipation.

The Collective Effect of MIP-3α and FL Promotes Dendritic Cell Function Within the Immune Microenvironment of Murine Liver Cancer.

Hepatocellular carcinoma is a highly malignant and lethal tumor. In addition to surgery, immunotherapy is currently a more effective treatment for hepatocellular carcinoma. The tumor immune microenvironment (TIME) largely determines the efficacy of cancer immunotherapy. Based on the universal targeting of TIME modulators in clinical treatment, TIME modulators are promising targets for tumor immunotherapy. We investigated the effect of a double gene expression vector (recombinant galactose-terminal glycol-poly-L-lysine coupled MIP-3α-FL) on dendritic cells (DCs) regulation within the TIME of mice with liver cancer. H22 cells were transfected with a recombinant MIP-3α-FL plasmid to induce DCs differentiation and chemotaxis. The effects of transfection were investigated by flow cytometry following the modified Boyden's method. Cytokine-induced killer (CIK) cells co-culture revealed changes in the antigen presentation ability of DCs. Further, tumor-bearing mice were injected with the recombinant double gene vector via the tail vein. We compared the survival time, tumor volume, weight of the mice, as well as the number and phenotype of tumor-infiltrating DCs (TIDCs) between groups. The supernatant of transfected H22 cells promoted the phenotypic maturation of DCs, enhancing their chemotaxis. Further, treated DCs promoted the cytokine secretion and killing ability of CIK cells. The survival time of mice injected with the double gene vector was significantly prolonged, while their tumor weight and volume were relatively reduced. Flow cytometry revealed that the number of TIDCs (as well as CD80 and CD86 expression) in the MouseMIP-3α-FL group, were significantly higher than in the control group. The combination of MIP-3α and FL can significantly promote DCs aggregation, maturation, and enhance their antigen presentation ability. The coupling of the double gene vector with glycosylated polylysine can improve the precise targeting of the liver and inhibit tumor growth in vivo, providing a novel approach for immune therapy in liver cancer.

Alterations of intestinal microbiota in liver cirrhosis with muscle wasting.

OBJECTIVES: The intestinal microbiota plays an important role in the nutritional status and energy metabolism of the host. Liver cirrhosis is accompanied by muscle wasting or sarcopenia. The aim of this study was to to explore the changes in intestinal microbiota in patients with liver cirrhosis and muscle wasting by using metagenomics. METHODS: This was a cross-sectional study of patients with (n = 30) and without (n = 30) muscle wasting and age- and sex-matched healthy controls (n = 30) to evaluate changes in intestinal microbiota by metagenomic gene sequencing. Muscle wasting was determined by the third lumbar vertebrae skeletal muscle index (L3 SMI). RESULTS: The Shannon index, which represents species diversity, of patients in the muscle-wasting group (2.11 ± 0.88) was lower than in the non-muscle-wasting group (2.64 ± 0.68; P = 0.039), which was significantly lower than in the healthy control group (2.70 ± 0.53; P = 0.023). There were 17 microbial species with significant differences in relative abundance between the two groups (linear discriminant analysis score >2; P < 0.05). The relative abundance of Escherichia coli, Peptostreptococcus stomatis, and Bacteroides uniformis showed the most significant association with L3 SMI. CONCLUSIONS: There were compositional alterations in intestinal microbiota in patients with liver cirrhosis and muscle wasting. L3 SMI is closely related to E. coli, P. stomatis, and B. uniformis in liver cirrhosis. Further interventional studies are needed to confirm whether improving intestinal microbiota can improve the nutritional status of patients with liver cirrhosis.

Mitochondrial redox-driven mitofusin 2 S-glutathionylation promotes neuronal necroptosis via disrupting ER-mitochondria crosstalk in cadmium-induced neurotoxicity.

Reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress and mitochondrial dysfunction are known to affect the structural and functional damage in the neural system. Cadmium (Cd) is an environmental contaminant that is widely found in numerous environmental matrices and exhibits potential neurotoxic risk. However, it remains unclear how mitochondrial redox status induces, and whether Cd destabilizes, the ER-mitochondria crosstalk to have a toxic effect on the nervous system. Herein, in our present study, bioinformatics analysis revealed an important role of protein interaction and mitochondrial machinery in brain samples from Alzheimer's disease (AD) patients. Furthermore, we established a neurotoxicity model in vivo and in vitro induced by cadmium chloride (CdCl2). We demonstrated that CdCl2 exposure disrupts the balance in mitochondrial redox represented by enhanced mitochondrial ROS (mitoROS) levels, which enhance mitofusin 2 (Mfn2) S-glutathionylation and interrupt the mitochondria-associated ER membranes (MAMs) for crosstalk between the ER and mitochondria to induce neuronal necroptosis. Mechanistically, it was shown that CdCl2 exposure significantly enhances the mitochondria-associated degradation (MAD) of Mfn2 via S-glutathionylation, which inhibits Mfn2 localization to the MAMs and subsequently leads to the formation of the RIPK1-RIPK3-p-MLKL complex (a key component of the necrosome) at MAMs, to promote neuronal necroptosis. Furthermore, the glutaredoxin 1 (Grx1) catalyzed and Mfn2 overexpression restored S-glu-Mfn2, MAMs perturbation, necrosome formation, and necroptosis in neurons induced by CdCl2 exposure in vitro. Moreover, the intervention with antioxidants to reduce mitochondrial redox, such as N-acetyl-l-cysteine (NAC) and mitochondria-targeted antioxidant Mito-TEMPO, reduced the S-glutathionylation of Mfn2 involved in the antagonism of CdCl2-induced necroptosis and neurotoxicity in vivo and in vitro. Taken together, our results are the first time to demonstrate that S-glutathionylation of Mfn2 promotes neuronal necroptosis via disruption of ER-mitochondria crosstalk in CdCl2-induced neurotoxicity, providing the novel mechanistic insight into how hazardous chemical-induced adverse effects in various organs and tissues could be interpreted by intraorganellar pathways under the control of MAMs components in neurons.

Analysis of CNOT Family Gene Expression, Clinicopathological Features, and Prognosis Value in Hepatocellular Carcinoma.

The carbon catabolite repressor 4-negative on TATA (CCR4-NOT) complex, abbreviated CNOT, has deadenylation and 3'-5' exonuclease activity, mediates deadenylation in the degradation of RNA, initiates the exonuclease degradation pathway, and participates in tumor gene regulation. CNOT proteins comprise a family of global transcriptional regulators that are evolutionarily conserved in eukaryotic cells. Several subunit types of the CNOT complex have been discovered; however, little is known about the role of different subunits in tumorigenesis and development. We observed overexpression of CNOT1-11 in liver cancer and correlations with clinicopathological characteristics. The expression of some CNOTs subunits was associated with histological grades, lymph node metastasis, and tumor stages in patients with hepatocellular carcinoma (HCC). Our data suggested that some CNOTs can be used as predictors of poor prognosis in HCC patients. At the same time, we conducted an analysis of CNOTs mutations in HCC patients. Moreover, we selected CNOT6, CNOT10, and CNOT11 for protein interaction network analysis and Gene Ontology enrichment analysis to investigate their related biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, the results of western blot and quantitative reverse transcription-PCR (qRT-PCR) experiments were consistent with the database findings. Results of this study suggest that CNOT6, CNOT10, and CNOT11, acting as regulators of transcription, may play an important role in the development of HCC and may serve as biological markers in the diagnosis and prognosis of HCC.

Gut Microbiota Composition Changes in Constipated Women of Reproductive Age.

Background: Chronic constipation is one of the most prevalent functional gastrointestinal disorders, yet its etiology is multifactorial, and the pathophysiological mechanism is still unclear. Previous studies have shown that the gut microbiota of constipated patients differs from healthy controls; however, many discrepancies exist in the findings, and no clear link has been confirmed between chronic constipation and changes in the gut microbiota. Growing evidence indicates that age, gender, and hormone levels can affect the composition of gut microbiota. The aim of this study is to examine the overall changes in gut microbiota within a specific sub-population of patients, namely, constipated women of reproductive age. Methods: We carried out a cross-sectional study comparing the fecal microbial composition of 30 healthy women and 29 constipated women using 16S rRNA gene sequencing. Only women of reproductive age were recruited to reduce the effects of age, gender, and hormone levels on the microbiome, and to prevent conflating the impact of these factors with the effects of constipation. Results: There were obvious differences in the gut microbiota in constipated women of reproductive age compared with the healthy controls, manifesting mainly as a significant increase in the abundance of Bacteroides (p < 0.05) and a significant decrease in the abundance of Proteobacteria (p < 0.01). The overall composition of the gut microbiota in each group was different, which was reflected in the ratios of Firmicutes to Bacteroidetes (F/B), which was 1.52 in the constipated group vs. 2.21 in the healthy group. Additionally, there was a significant decrease in butyrate-producing bacteria, like Roseburia and Fusicatenibacter (p < 0.01). Conclusion: The overall composition of the gut microbiota changed in constipated women of reproductive age, characterized by a loss in Proteobacteria and an increase in Bacteroidetes. Furthermore, the abundance of some butyrate-producing bacteria also reduced. These changes may reflect the unique interactions between host and some bacteria, or some bacterial metabolic products, which may be important targets for future studies to explore the pathogenesis of constipation.

Cyclooxygenase-2 modulates ER-mitochondria crosstalk to mediate superparamagnetic iron oxide nanoparticles induced hepatotoxicity: an in vitro and in vivo study.

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are central microdomains of the ER that interact with mitochondria. MAMs provide an essential platform for crosstalk between the ER and mitochondria and play a critical role in the local transfer of calcium (Ca2+) to maintain cellular functions. Despite the potential uses of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in biomedical applications, the hepatotoxicity of these nanoparticles (NPs) is not well characterized and little is known about the involvement of MAMs in ER-mitochondria crosstalk. We studied SPIO-NPs-associated hepatotoxicity in vitro and in vivo. In vitro, human normal hepatic L02 cells were exposed to SPIO-NPs (2.5, 7.5, and 12.5 µg/mL) for 6 h and SPIO-NPs (12.5 µg/mL) was found to induce apoptosis. In vivo, SPIO-NPs induced liver injury when mice were intravenously injected with 20 mg/kg body weight SPIO-NPs for 24 h. Based on both in vitro and in vivo studies, we found that the structure and Ca2+ transport function of MAMs were perturbated and an accumulation of cyclooxygenase-2 (COX-2) in MAMs fractions was increased upon treatment of SPIO-NPs. The interaction between COX-2 and the components of MAMs, in terms of IP3R-GRP75-VDAC1 complex, was also revealed. Furthermore, the role of COX-2 in SPIO-NPs-associated hepatotoxicity was investigated by modifying the expression of COX-2. We demonstrated that COX-2 increases the structural and functional ER-mitochondria coupling and enhances the efficacy of ER-mitochondria Ca2+ transfer through the MAMs, thus sensitizing hepatocytes to a mitochondrial Ca2+ overload-dependent apoptosis. Taken together, our findings link SPIO-NPs-triggered hepatotoxicity with ER-mitochondria Ca2+ crosstalk which is mediated by COX-2 and provide mechanistic insight into the impact of interorganelle ER-mitochondria communication on hepatic nanotoxicity.

Lactational exposure to environmentally relevant benzo(a)pyrene causes astrocytic activation and anxiety-like behavior in male mice.

Previous studies have shown the adversely neurodevelopmental effects of exposure to benzo(a)pyrene (BaP) at early life stage. However, it is unclear the effects of lactational exposure to environmentally relevant BaP on anxiety-like behavior and the molecular mechanisms related. In this study, lactational exposure to 1 and 10 µg/kg bw BaP from postnatal day 3-21 caused anxiety-like behavior and alterations of the expressions of the neurodevelopment and anxiety-related genes in adolescence male mice using O cycle maze. Moreover, BaP exposure increased the expression level of glial fibrillary acidic protein, a typical marker of astrocytes, in hippocampus of male offspring. The release of pro-inflammatory cytokines interleukin 6 and tumor necrosis factor α was also elevated in BaP-treated offspring. Further, lactational exposure to BaP decreased the level of glutathione and the expressions of antioxidant genes (Thioredoxin 1 and Glutaredoxin 2) in male offspring. Our study demonstrated that environmentally relevant BaP lactational exposure caused anxiety-like behavior in male offspring involved in astrocytic activation, neuroinflammation, and antioxidant capability dysfunction.