Epigallocatechin-3-gallate Alleviates Ethanol-Induced Endothelia Cells Injury Partly through Alteration of NF-κB Translocation and Activation of the Nrf2 Signaling Pathway.

Ethanol (alcohol) is a risk factor that contributes to non-communicable diseases. Chronic abuse of ethanol is toxic to both the heart and overall health, and even results in death. Ethanol and its byproduct acetaldehyde can harm the cardiovascular system by impairing mitochondrial function, causing oxidative damage, and reducing contractile proteins. Endothelial cells are essential components of the cardiovascular system, are highly susceptible to ethanol, either through direct or indirect exposure. Thus, protection against endothelial injury is of great importance for persons who chronic abuse of ethanol. In this study, an in vitro model of endothelial injury was created using ethanol. The findings revealed that a concentration of 20.0 mM of ethanol reduced cell viability and Bcl-2 expression, while increasing cell apoptosis, intracellular reactive oxygen species (ROS) levels, mitochondrial depolarization, and the expression of Bax and cleaved-caspase-3 in endothelial cells. Further study showed that ethanol promoted nuclear translocation of nuclear factor kappa B (NF-κB), increased the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 in the culture medium, and inhibited nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway. The aforementioned findings suggest that ethanol has a harmful impact on endothelial cells. Nevertheless, the application of epigallocatechin-3-gallate (EGCG) to the cells can effectively mitigate the detrimental effects of ethanol on endothelial cells. In conclusion, EGCG alleviates ethanol-induced endothelial injury partly through alteration of NF-κB translocation and activation of the Nrf2 signaling pathway. Therefore, EGCG holds great potential in safeguarding individuals who chronically abuse ethanol from endothelial dysfunction.

Perinatal exposure to bisphenol A impairs cognitive function via the gamma-aminobutyric acid signaling pathway in male rat offspring.

Bisphenol A (BPA) is a common synthetic endocrine disruptor that can be utilized in the fabrication of materials such as polycarbonates and epoxy resins. Numerous studies have linked BPA to learning and memory problems, although the precise mechanism remains unknown. Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the vertebrate central nervous system, and it is intimately related to learning and memory. This study aims to evaluate whether altered cognitive behavior involves the GABA signaling pathway in male offspring of rats exposed to BPA during the prenatal and early postnatal periods. Pregnant rats were orally given BPA (0, 0.04, 0.4, and 4 mg/kg body weight (BW)/day) from the first day of pregnancy to the 21st day of breastfeeding. Three-week-old male rat offspring were selected for an open-field experiment and a new object recognition experiment to evaluate the effect of BPA exposure on cognitive behavior. Furthermore, the role of GABA signaling markers in the cognition affected by BPA was investigated at the molecular level using western blotting and real-time polymerase chain reaction (RT-PCR). The research demonstrated that BPA exposure impacted the behavior and memory of male rat offspring and elevated the expression of glutamic acid decarboxylase 67 (GAD67), GABA type A receptors subunit (GABAARα1), and GABA vesicle transporter (VGAT) in the hippocampus while decreasing the expression levels of GABA transaminase (GABA-T) and GABA transporter 1 (GAT-1). These findings indicate that the alteration in the expression of GABA signaling molecules may be one of the molecular mechanisms by which perinatal exposure to BPA leads to decreased learning and memory in male rat offspring.

Prenatal exposure to low-dose bisphenol A disrupts hippocampal DNA methylation and demethylation in male rat offspring.

Earlier research has demonstrated that developmental exposure to bisphenol A (BPA) has persistent impacts on both adult brain growth and actions. It has been suggested that BPA might obstruct the methylation coding of the genes in the brain. In this study, the methylation changes in the hippocampus tissue of male rat pups were examined following prenatal BPA exposure. Pregnant Sprague-Dawley rats were treated with either vehicle (tocopherol-stripped corn oil) or BPA (4, 40, or 400 µg/kg·body weight/day) throughout the entire duration of gestation and lactation. At 3 weeks of age, the male rat offspring were euthanized, and the hippocampus were dissected out for analysis. The expression levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and DNA demethylases (TET1, Gadd45a, Gadd45b, and Apobec1) were analyzed in the hippocampus by means of quantitative real-time polymerase chain reaction and Western blotting, respectively. The results showed that prenatal exposure to BPA upregulated the expression of enzymes associated with DNA methylation and demethylation processes in the hippocampus of male rat offspring. These findings suggest that prenatal exposure to a low dose of BPA could potentially disrupt the balance of methylation and demethylation in the hippocampus, thereby perturbing epigenetic modifications. This may represent a neurotoxicity mechanism of BPA.

Pan-Cancer Study of the Prognosistic Value of Selenium Phosphate Synthase 1.

Objective: This study sought to determine the mean prognostic usefulness of seleniumphosphate synthase (SEPHS1) by investigating its expression in 33 human malignancies and its relationship to tumor immunity.Methods: The expression of selenophosphate synthase 1 (SEPHS1) in 33 human malignant tumors was examined using the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), and TIMER databases. Furthermore, the TCGA cohort was used to investigate relationships between SEPHS1 and immunological checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs). To establish independent risk factors and calculate survival probabilities for liver hepatocellular carcinoma (LIHC) and brain lower-grade glioma (LGG), Cox regression models and Kaplan-Meier curves were utilized. Eventually, the Genomics of Cancer Drug Sensitivity (GDSC) database was used to evaluate the drug sensitivity in LGG and LIHC patients with high SEPHS1 expression.Results: Overall, in numerous tumor tissues, SEPHS1 was highly expressed, and it significantly linked with the prognosis of LGG, ACC, and LIHC (P < .05). Furthermore, in numerous cancers, SEPHS1 expression was linked to tumor-infiltrating immune cells (TIICs), TMB, MSI, and MMRs. According to univariate and multivariate Cox analyses, SEPHS1 expression was significant for patients with LGG and LIHC.Conclusion: High SEPHS1 expression has a better prognosis for LGG, while low SEPHS1 expression has a better prognosis for LIHC. Chemotherapy was advised for LGG patients, particularly for those with high SEPHS1 expression because it can predict how responsive patients will be to 5-Fluorouracil and Temozolomide. This interaction between SEPHS1 and chemoradiotherapy has a positive clinical impact and may be used as evidence for chemotherapy for LGG and LIHC patients.

Benefits of successful percutaneous coronary intervention in chronic total occlusion patients with diabetes.

BACKGROUND: Diabetes was commonly seen in chronic total occlusion (CTO) patients but data regarding the impact of successful percutaneous coronary intervention (PCI) on clinical outcome of CTO patients with diabetes was controversial. And importantly, no studies have compared quality of life (QOL) after CTO-PCI in patients with and without diabetes. METHODS: Consecutive patients undergoing elective CTO-PCI were prospectively enrolled from Apr. 2018 to May 2021. Patients were subdivided into 2 groups: Diabetes and No Diabetes. Detailed baseline characteristics, assessment of symptoms and QOL, angiographic and procedural details, in-hospital complications, and 1 month and 1 year follow-up data were collected. These data were analyzed accordingly for risk predictors of clinical outcome in patients who have diabetes and received successful CTO-PCI. RESULTS: A total of 1076 patients underwent CTO-PCI attempts. Diabetes was present in 374 (34.76%) patients, who had more hypertension, previous PCI and stroke. Regarding the coronary lesions, diabetic patients suffered more LCX lesion, multivessel disease, number of lesions per patient, blunt stump, calcification and higher J-CTO score (p < 0.05). In-hospital major adverse cardiac event (MACE) (4.13% vs. 5.35%; p = 0.362) was similar in the two groups. At 1 month and 1 year follow-up after successful CTO-PCI, the incidence of MACE and all-cause mortality were also similar in the two groups (p > 0.05). Number of lesions per patient was an independent risk factor of MACE and all-cause mortality (p < 0.001) 1 year after successful CTO-PCI. Symptom and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up, and importantly, patients with diabetes showed similar degrees of improvement to those without diabetes (P > 0.05). CONCLUSIONS: Successful CTO-PCI could represent an effective strategy improving clinical outcome, symptoms and QOL in CTO patients with diabetes.

A novel model for detecting advanced fibrosis in patients with nonalcoholic fatty liver disease.

AIMS: The study aimed to develop a novel noninvasive model to detect advanced fibrosis based on routinely available clinical and laboratory tests. MATERIALS AND METHODS: A total of 309 patients who underwent liver biopsy were randomly divided into the estimation group (n = 201) and validation group (n = 108). The model was developed using multiple regression analysis in the estimation group and further verified in the validation group. Diagnostic accuracy was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: The model was named NAFLD Fibrosis Index (NFI): -10.844 + 0.046 × age - 0.01 × platelet count + 0.19 × 2h postprandial plasma glucose (PG) + 0.294 × conjugated bilirubin - 0.015 × ALT + 0.039 × AST + 0.109 × total iron binding capacity -0.033 × parathyroid hormone (PTH). The area under the ROC curve (AUC) of NFI was 0.86 (95% CI: 0.79-0.93, p < 0.001) in the estimation group and 0.80 (95% CI: 0.69-0.91, p < 0.001) in the validation group, higher than NFS, FIB4, APRI, and BARD, and similar to FibroScan (NFI AUC = 0.77, 95% CI: 0.66-0.89, p = 0.001 vs. FibroScan AUC = 0.76, 95% CI: 0.62-0.90, p = 0.002). By applying the low cut-off value (-2.756), advanced fibrosis could be excluded among 49.3% and 48% of patients in the estimation group (sensitivity: 93.1%, NPV: 97.9%, specificity: 55.2%, and PPV: 26.0%) and validation group (sensitivity: 81.3%, NPV: 94.2%, specificity: 53.3%, and PPV: 23.2%), respectively, allowing them to avoid liver biopsy. CONCLUSIONS: The study has established a novel model for advanced fibrosis, the diagnostic accuracy of which is superior to the current clinical scoring systems and is similar to FibroScan.

A comparison of NAFLD and MAFLD diagnostic criteria in contemporary urban healthy adults in China: a cross-sectional study.

BACKGROUND: A recently proposed diagnostic criteria of metabolic dysfunction-associated fatty liver disease (MAFLD) is more available for various clinical situations than nonalcoholic fatty liver disease (NAFLD), but understanding about differences between NAFLD and MAFLD in clinical practice remains limited in the general adult urban population in China. METHODS: A total of 795 subjects were recruited from Wu Song Branch of Zhongshan Hospital who participated in the general health assessment. Examination results was obtained through analysis of blood samples and abdominal ultrasonography. Participants were divided into four subgroups according to whether they had NAFLD or MAFLD (NAFLD- MAFLD-, NAFLD + MAFLD-, NAFLD- MAFLD + and NAFLD + MAFLD+). RESULTS: Among the urban healthy adults investigated, 345 people (43.4%) were diagnosed with NAFLD and 356 people (44.8%) with MAFLD. No significant differences in the prevalence, age, fasting blood glucose, glycosylated hemoglobin, liver enzyme examination, percentage of overweight, hypertension or dyslipidaemia were found between NAFLD and MAFLD patients. Patients with MAFLD had worse metabolic disorders than NAFLD + MAFLD- patients. The NAFLD fibrosis score (NFS) of the NAFLD- MAFLD + group was higher than that of the NAFLD + MAFLD- group. Higher proportion of patients in the NAFLD- MAFLD + group have NFS ≥-1.455. CONCLUSION: MAFLD criteria have similar prevalence and patient characteristics compared with previous NAFLD but help to identify a group of patients with high risks of metabolic disorders and liver fibrosis who have been missed with NAFLD, and has superior utility.

Involvement of spinal cannabinoid receptor type 2 in the analgesia effect of hyperbaric oxygen treatment on paclitaxel-induced neuropathic pain.

BACKGROUND: Chemotherapy-induced neuropathic pain (CINP) is intractable, and spinal cannabinoid receptors (CBRs) are potential therapeutic targets for CINP. Previous studies demonstrated that hyperbaric oxygen (HBO2) may contribute in alleviating specific peripheral neuropathic pain. However, neither CINP nor CBR have been clarified. We hypothesized that HBO2 is capable of alleviating CINP, and the effect could be explained by the activation of spinal CBRs. METHODS: A series of paclitaxel-induced CINP models were established on male Sprague-Dawley rats. Then HBO2 treatment was administered for seven consecutive days at 2.5 atmospheres absolute. Two groups were treated with AM251 (an antagonist of CBR type-1, CBR1) or AM630 (an antagonist of CBR type-2, CBR2) respectively 30 minutes before each HBO2 treatment. The mechanical withdrawal threshold was assessed before, during and at two weeks after HBO2 treatment. Lumbar spinal cords were collected for Western blot analysis of CBR1, CBR2, GFAP and CD11b, and ELISA analysis of proinflammatory cytokines IL-1ß and TNF-α. RESULTS: A mechanical allodynia was successfully exhibited and the spinal GFAP, CD11b, IL-1ß and TNF-α significantly increased after the modeling, and these effects could be further reversed by HBO2 treatment, which could be blocked by AM630, other than AM251. CONCLUSION: HBO2 treatment can alleviate paclitaxel-induced neuropathic pain, and be mediated by CBR2. Spinal glial cells and proinflammatory cytokines are involved in this process.

Biological Functions of Selenoprotein Iodothyronine Deiodinase and its Expression in Osteoarthritis.

Objective Iodothyronine deiodinases (DIOs) are important selenoproteins that play a key role in the bone and joint diseases. Osteoarthritis (OA) is the most prevalent joint disease especially in elders. This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis. Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques, including GenCLip 3.0, Database for Annotation, Visualization and Integrated Discovery (DAVID), STRING, Cytoscape, and Network Analyst. The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus (GEO) database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3. Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine; GO analysis showed that DIOs were mainly involved in biological processes, such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling; SULT1A1 was the core node of the PPI network; miRNAs and thyroid hormones had some iterations with DIO1and DIO2; Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients (SMD = 0.31, 95%CI: 0.03, 0.59, P = 0.03). Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone. And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.

[Effect of Selenoprotein Thioredoxin Reductase 3 on the Survival Prognosis of Tumor Patients].

Objective To investigate the expression of thioredoxin reductase 3(TXNRD3),a selenoprotein,in 33 human malignant tumors and then analyze its effect on the survival prognosis.Methods We employed the genotype-tissue expression project database,the cancer cell line encyclopedia,and the cancer genome atlas to explore the expression of TXNRD3 gene in 33 human malignant tumors and analyze its impact on the survival prognosis.Further,we explored the correlations of TXNRD3 with immune cells and immune infiltration in the tumor microenvironment,as well as with neoantigens,immune checkpoint genes,tumor mutational burden,and microsatellite instability.Subsequently,human samples were classified into high-and low-expression groups according to TXNRD3 gene expression levels,and the enrichment analysis of biological functions and signaling pathways was performed.Results The analysis with multiple databases showed that TXNRD3 was highly expressed in 15 tumors.The survival analysis showed that TXNRD3 was significantly associated with poor prognosis in pancreatic cancer patients.In addition,the expression level of TXNRD3 was correlated with immune infiltration in tumor microenvironment,neoantigens,immune checkpoint genes,tumor mutational burden,and microsatellite instability.TXNRD3 affected the expression of DNA mismatch repair genes.The gene set enrichment indicated that TXNRD3 was involved in regulating multiple signaling pathways associated with tumor metabolism and tumor immunity.Conclusion TXNRD3 is widely expressed in tumors and has a clinical value for the survival prognosis prediction and treatment of multiple tumors,demonstrating the potential of being a promising biomarker for targeted treatment of multiple tumors.

[Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients].

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

[Expression and Regulatory Mechanism of Autophagy-related Genes in Synovial Tissues of Patients with Rheumatoid Arthritis].

Objective To investigate the expression regulation of autophagy-related genes(ATG)and the mechanism of autophagy in rheumatoid arthritis(RA).Methods The differentially expressed genes(DEG)of RA were identified from GSE55235 and GSE55457,on the basis of which the differentially expressed autophagy-related genes(DE-ATG)were selected from the Human Autophagy Database.STRING 11.0 and GeneMANIA were used to establish protein-protein interaction networks.Further,the transcription factor-gene-miRNA co-expression network was established via NetworkAnalyst and Cytoscape.Finally,receiver operating characteristic(ROC)curve and DrugBank were employed to evaluate the efficacy of the predicted biomarkers and the performance of drugs targeting DE-ATG.GraphPad Prism 8.2.1 and R 4.0.3 were used for statistical analysis and graphics.Results A total of 485 DEG were enriched in signaling pathways such as T cell activation,hormone regulation,osteoclast differentiation,RA,and chemokines.Eleven DE-ATG regulated the expression of RUNX1,TP53,SOX2,and hsa-mir-155-5p in synovial tissues of RA patients and were involved in the response to environmental factors such as 2,3,7,8-tetrachlorodibenzodioxin and silicon dioxide.The ROC curve analysis identified the DE-ATG with good sensitivity and specificity,such as MYC,MAPK8,CDKN1A,and TNFSF10,which can be used to distinguish certain phenotypes and serve as novel biomarkers for RA.Conclusions In RA,down-regulated DE-ATG expression may promote apoptosis and lysis of chondrocytes.The identified novel biomarkers provides new ideas and methods for diagnosing and treating RA.The establishment of transcription factor-miRNA-gene co-expression network provides direct evidence for dissecting synovial inflammation and articular cartilage destruction.

Glutathione peroxidase family and survival prognosis in patients with renal cell carcinoma. / è°·èƒ±ç”˜è‚½è¿‡æ°§åŒ–ç‰©é ¶å®¶æ—ä¸Žè‚¾ç»†èƒžç™Œæ‚£è€ ç”Ÿå­˜é¢„åŽçš„å ³ç³».

OBJECTIVES: Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis. METHODS: The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene. RESULTS: The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59. CONCLUSIONS: GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.

[Clinical Investigation of Key Parameter Range of AMG Muscle Relaxant Monitor].

The accelerometry(AMG) muscle relaxant monitor is the most widely used quantitative muscle relaxant monitor to assess the degree of neuromuscular at present. In this study, the ulnar nerve was stimulated by using train of four stimulation(TOF) mode of the AMG muscle relaxant monitor, and the movement of the adductor pollicis muscle was monitored. In this way, the distribution range of key parameters (acceleration peak value, response time, and TOF ratio) of the adductor pollicis muscle during the use of muscle relaxant in clinical practice is analyzed and will provide a practical basis for the development and improvement of the muscle relaxant monitor.

Maternal exposure to low doses of bisphenol A affects learning and memory in male rat offspring with abnormal N-methyl-d-aspartate receptors in the hippocampus.

Bisphenol A (BPA), a component of polycarbonate and epoxy resins, has been reported to induce learning and memory deficits. However, the mechanisms have not been fully elucidated. Growing evidence has suggested that N-methyl-d-aspartate receptors (NMDARs) are involved in cognitive impairments. In this study, BPA was administered to female Sprague-Dawley rats (six per dose group) at concentrations of 0 (control), 4, 40, and 400 µg/kg·body weight/day from gestation day 1 through lactation day 21. Spatial learning was evaluated using the Morris water maze on postnatal day 22. Expression levels of NMDARs were determined using real-time polymerase chain reaction and Western blot. The results showed that male offspring exposed to BPA exhibited increased latency in reaching the platform and reduced time in the target quadrant, and the number of crossing the platform was less, as compared with the control group. The mRNA and protein expression levels of NMDARs in the hippocampus were significantly downregulated when compared with the control group of male offspring. The data showed that maternal exposure to BPA at low dosage can cause cognitive deficits in male rat offspring, probably due to a decrease in NMDARs in the hippocampus.

CRISPR/Cas9-mediated mutagenesis of Clpsk1 in watermelon to confer resistance to Fusarium oxysporum f.sp. niveum.

KEY MESSAGE: CRISPR/Cas9-mediated editing of Clpsk1 enhanced watermelon resistance to Fusarium oxysporum. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has proven to be an effective genome-editing tool for crop improvement. Previous studies described that Phytosulfokine (PSK) signalling attenuates plant immune response. In this work, we employed the CRISPR/Cas9 system to knockout Clpsk1 gene, encoding the PSK precursor, to confer enhanced watermelon resistance to Fusarium oxysporum f.sp. niveum (FON). Interactions between PSK and FON were analysed and it was found that transcript of Clpsk1 was significantly induced upon FON infection. Meanwhile, application of exogenous PSK increased the pathogen growth. Then, one sgRNA, which targeted the first exon of Clpsk1, was selected for construction of pRGEB32-CAS9-gRNA-Clpsk1 expression cassette. The construct was then transformed to watermelon through Agrobacterium tumefaciens-mediated transformation method. Six mutant plants were obtained and three types of mutations at the expected position were identified based on Sanger sequencing. Resistance evaluation indicated that Clpsk1 loss-of-function rendered watermelon seedlings more resistant to infection by FON. These results indicate that CRISPR/Cas9-mediated gene modification is an effective approach for watermelon improvement.

Bioinformatic Analysis of Differentially Expressed Genes in Peripheral Blood of Human Immunodeficiency Virus/Tubercle Bacilli Co-infected Patients.

Objective To analyze the differentially expressed genes in peripheral blood of human immunodeficiency(HIV)/tubercle bacilli co-infected patients and explore the biological regulatory mechanism and network of key proteins,so as to provide new evidence for early diagnosis and clinical treatment of HIV/TB co-infected patients. Methods Microarray gene chip data of HIV/TB co-infected patients were downloaded from public databases GEO and imported into the analysis software GEO,STRING,PANTHER,and GenClip. The gene expression profiles,protein interaction networks,processes of molecular biology,and gene functions were analyzed. Results The expression profiles of 15 529 genes between the two groups of patients were similar,and gene expression profiles from 44 subjects were highly correlated. The 251 differentially expressed genes had good diagnostic capabilities in the differential diagnosis of HIV/TB infection. RPLP1 might be a key gene in the diagnosis of HIV/TB infection. The differentially expressed genes and positive regulators showed certain functions such as external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological and other relevant functionalities. Meanwhile,they may also be involved in free radical-related apoptosis,inflammation,and activation pathways. Conclusions A total of 251 differentially expressed genes are found to be able to distinguish simple HIV infection from HIV/TB infection. Protein-protein interaction network of top 40 differential expression genes includes RPLP1 gene,which is possibly associated with HIV/TB co-infection and may be involved in and the positive regulation of external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological functions. These findings may provide certain evidence for the diagnosis and treatment of HIV/TB infection.

Operando Colorations from Real-Time Growth of 3D-Printed Nanoarchitectures.

While artificial 3D nanostructures can generate precise and flexible coloration, their real-time color changes during 3D nanoprinting remain unexplored owing to the inherent challenges of in situ transient measurements and observations. In this study, a 3D-printing system which supports the operando observation/measurement of the color dynamics of subwavelength metallic nanoarchitectures fabricated in real time is developed and evaluated. During 3D printing, the dimensions and geometries of the 3D nanostructures grow over time, producing a large library of optical spectra associated with real-time color changes. Only a timer is needed to define the expected colors from a single 3D print run. Fin-like nanostructures are used to toggle colors based on the polarization effect and produce color gradients. Based on structural coloration, nanoarchitectures are designed and printed to animate desired color patterns. Moreover, the resulting color dynamics can also serve as an operando identifier for real-time structural information during 3D nanoprinting. A single print run enables the efficient creation of a comprehensive library of desired colorations owing to the flexibility in time-dependent controllability and 3D geometries at the subwavelength scale. 3D nanoprinted plasmonic structures exhibiting time-varying colorations (4D printing of colors) uniquely redefines the coloring stategy, offering considerable potential for numerous applications.

Icariin ameliorates osteoporosis by activating autophagy in ovariectomized rats.

BACKGROUND: Osteoporosis (OP) is a major problem that increases the mortality and disability rate worldwide. With an increase in the aging population, OP has become a major public threat to human health. Searching for effective and suitable targets for drug treatment in OP has become an urgent need. OBJECTIVES: Osteoporosis is a metabolic bone disease characterized by reduced bone mass and density as well as micro-architectural deterioration. Icariin is a flavonoid extracted from plants of the genus Epimedium and has been shown to exert potential anti-OP activity. The present study was designed to observe the effect of icariin on OP and to clarify the underlying mechanisms in ovariectomized (OVX) rats. MATERIAL AND METHODS: Hematoxylin and eosin (H&E) staining, von Kossa staining and micro-computed tomography (micro-CT) confirmed significant bone loss in the OVX group. Protein expression level was detected with western blot analysis. RESULTS: Icariin reversed a trend of increased bone turnover by reducing serum alkaline phosphatase (ALP), procollagen type I N-terminal propeptide (PINP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and C-telopeptide of type I collagen (CTX-I). Furthermore, icariin decreased sequestosome 1 (p62) and increased microtubule-associated protein 1 light chain 3II/microtubule-associated protein 1 light chain 3I (LC3II/LC3I), autophagy-related protein 7 (Atg7), and Beclin 1 in the femur of OVX rats, improving the indicators of impaired autophagy in OP. CONCLUSIONS: Icariin reversed the significant upregulation of the serine/threonine protein kinase (Akt), mammalian target of rapamycin (mTOR) and unc-51-like autophagy activating kinase 1 (ULK1) at Ser757, and the downregulation of p-AMP-activated protein kinase (p-AMPK) and ULK1 phosphorylated at Ser555 in the OVX rats, suggesting that the mechanism of icariin action in OP treatment involves the activation and suppression of the AMPK/ULK1 and AKT/mTOR/ULK1 autophagy pathways, respectively.

Selenoprotein GPX3 is a novel prognostic indicator for stomach adenocarcinoma and brain low-grade gliomas: Evidence from an integrative pan-cancer analysis.

Background: The antioxidant enzyme GPX3 is a selenoprotein that transports selenium in blood and maintains its levels in peripheral tissues. Aberrant GPX3 expression is strongly linked to the development of some tumors. However, there is a scarcity of studies examining the pan-cancer expression patterns and prognostic relevance of GPX3. Methods: GPX3 expression levels in normal tissues and multiple tumors were analyzed using TCGA, CCLE, GTEx, UALCAN and HPA databases. Forest plots and KM survival curves were utilized to evaluate the correlation between GPX3 expression and the outcome of tumor patients. The prognostic value of GPX3 in LGG was assessed utilizing the CGGA datasets, and that in STAD was tested by TCGA and GEO databases. A nomogram was then constructed to predict OS in STAD using R software. Additionally, the impact of GPX3 on post-chemoradiotherapy OS in patients with LGG and STAD was evaluated using the KM method. The multiplicative interaction of GPX3 expression, chemotherapy and radiotherapy on STAD and LGG was analyzed using logistic regression models. The correlation of GPX3 with the immune infiltration, immune neoantigens and MMR genes were investigated in TCGA cohort. Results: GPX3 exhibited downregulation across 21 tumor types, including STAD, with its decreased expression significantly associated with improved OS, DFS, PFS and DSS. Conversely, in LGG, low levels of GPX3 expression were indicative of a poorer prognosis. Univariate and multivariate Cox models further identified GPX3 as an independent predictor of STAD, and a nomogram based on GPX3 expression and other independent factors showed high level of predictive accuracy. Moreover, low GPX3 expression and chemotherapy prolonged the survival of STAD. In LGG patients, chemoradiotherapy, GPX3 and chemotherapy, and GPX3 and chemoradiotherapy may improve prognosis. Our observations reveal a notable connection between GPX3 and immune infiltration, immune neoantigens, and MMR genes. Conclusions: The variations in GPX3 expression are linked to the controlling tumor development and could act as a promising biomarker that impacts the prognosis of specific cancers like STAD and LGG.