Systematic analysis of cuproptosis abnormalities and functional significance in cancer.

BACKGROUND: Cuproptosis is a recently discovered type of cell death, but the role and behavior of cuproptosis-related genes (CuRGs) in cancers remain unclear. This paper aims to address these issues by analyzing the multi-omics characteristics of cancer-related genes (CuRGs) across various types of cancer. METHOD: To investigate the impact of somatic copy number alterations (SCNA) and DNA methylation on CRG expression, we will analyze the correlation between these factors. We developed a cuproptosis index (CPI) model to measure the level of cuproptosis and investigate its functional roles. Using this model, we assessed the clinical prognosis of colorectal cancer patients and analyzed genetic changes and immune infiltration features in different CPI levels. RESULTS: The study's findings indicate that the majority of cancer-related genes (CuRGs) were suppressed in tumors and had a positive correlation with somatic copy number alterations (SCNA), while having a negative correlation with DNA methylation. This suggests that both SCNA and DNA methylation have an impact on the expression of CuRGs. The CPI model is a reliable predictor of survival outcomes in patients with colorectal cancer and can serve as an independent prognostic factor. Patients with a higher CPI have a worse prognosis. We conducted a deeper analysis of the genetic alterations and immune infiltration patterns in both CPI positive and negative groups. Our findings revealed significant differences, indicating that CuRGs may play a crucial role in tumor immunity mechanisms. Additionally, we have noticed a positive correlation between CuRGs and various crucial pathways that are linked to the occurrence, progression, and metastasis of tumors. CONCLUSIONS: Overall, our study systematically analyzes cuproptosis and its regulatory genes, emphasizing the potential of using cuproptosis as a basis for cancer therapy.

Colonic stent as a bridge to surgery versus emergency rection for malignant left-sided colorectal obstruction: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The role of self-expanding metal stent (SEMS) implantation as a bridge to surgery in malignant left-sided colorectal obstruction (MLCO) remains controversial. OBJECTIVE: To evaluate the safety of SEMS implantation versus emergency surgery (ER) in the treatment of MLCO. METHODS: Four major literature databases (Cochrane Library, Embase, PubMed, and Web of Science) were searched to collect articles published before April 20, 2023. After determining random or fixed-effect models based on heterogeneity tests, odds ratios (RR) or standardized mean differences (SMD) with their respective 95% confidence intervals (CI) were calculated. RESULTS: Nineteen randomized controlled studies were included. The main outcomes included overall tumor recurrence rate, 30-day mortality rate, and overall incidence of complications. Secondary outcomes included mortality-related indicators, tumor recurrence-related indicators, surgery-related indicators, and other relevant indicators. The study found that there was no significant difference in the 30-day mortality rate between the SEMS group and the er group. However, the SEMS group had a lower overall incidence of complications (RR = 0.787, P = .004), lower incision infection rate (RR = 0.472, P = .003), shorter operation time (SMD = -0.591, P = .000), lower intraoperative blood loss (SMD = -1.046, P = .000), lower intraoperative transfusion rate (RR = 0.624, P = .021), lower permanent stoma rate (RR = 0.499, P = .000), lower overall stoma rate (RR = 0.520,P = .000), shorter hospital stay (SMD = -0.643, P = .014), and more lymph node dissections during surgery (SMD = 0.222, 95% CI: 0.021-0.423, P = .031), as well as a higher primary anastomosis rate (RR = 0.472, 95% CI: 0.286-0.7 77, P = .003), among other advantages. However, the SEMS group had a higher overall tumor recurrence rate (RR = 1.339, P = .048). CONCLUSION: SEMS has significant advantages over er in relieving clinical symptoms and facilitating postoperative recovery in MLCO, but does not reduce the tumor recurrence rate. Neoadjuvant chemotherapy combined with SEMS may provide a new approach to the treatment of MLCO.

Exploring the relationship between urinary phthalate metabolites and Crohn's disease via oxidative stress, and the potential moderating role of gut microbiota: A conditional mediation model.

OBJECTIVE: Interactions between phthalic acid esters (PAEs) exposure and Crohn's disease (CD) were unknown. This study aims to examine the association between exposure to PAEs and CD activity and to explore the roles of oxidative stress and microbiota. METHODS: A cross-sectional study with 127 CD patients was conducted. The disease activity was evaluated based on symptoms (Harvey-Bradshaw index, HBI), endoscopy findings (Simple Endoscopic Score for CD, SES-CD), and computed tomography enterography (CTE-scores). Ten urinary PAEs metabolites (mPAEs), two urinary oxidative stress biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α), as well as 16S rRNA sequencing of stool samples were determined. Multiple linear regression models and Hayes's PROCESS macro for SPSS were used to evaluate the interplays between urinary PAEs metabolites, CD activities, oxidative stress, and microbiota diversity. RESULTS: There were positive associations between most mPAEs and HBI. Oxidative stress mediated 20.69-89.29% of the indirect associations between low molecular weight (LMW) mPAEs and HBI, while the majority of the high molecular weight (HMW) mPAEs were directly associated with HBI. In addition, microbiota diversity moderated the indirect associations of LMW mPAEs on HBI. CONCLUSIONS: PAEs exposure was related to CD activity, and the association could be mediated by oxidative stress and reversed or alleviated by rich gut microbiota.

Fundus image classification using Inception V3 and ResNet-50 for the early diagnostics of fundus diseases.

Purpose: We aim to present effective and computer aided diagnostics in the field of ophthalmology and improve eye health. This study aims to create an automated deep learning based system for categorizing fundus images into three classes: normal, macular degeneration and tessellated fundus for the timely recognition and treatment of diabetic retinopathy and other diseases. Methods: A total of 1,032 fundus images were collected from 516 patients using fundus camera from Health Management Center, Shenzhen University General Hospital Shenzhen University, Shenzhen 518055, Guangdong, China. Then, Inception V3 and ResNet-50 deep learning models are used to classify fundus images into three classes, Normal, Macular degeneration and tessellated fundus for the timely recognition and treatment of fundus diseases. Results: The experimental results show that the effect of model recognition is the best when the Adam is used as optimizer method, the number of iterations is 150, and 0.00 as the learning rate. According to our proposed approach we, achieved the highest accuracy of 93.81% and 91.76% by using ResNet-50 and Inception V3 after fine-tuned and adjusted hyper parameters according to our classification problem. Conclusion: Our research provides a reference to the clinical diagnosis or screening for diabetic retinopathy and other eye diseases. Our suggested computer aided diagnostics framework will prevent incorrect diagnoses caused by the low image quality and individual experience, and other factors. In future implementations, the ophthalmologists can implement more advanced learning algorithms to improve the accuracy of diagnosis.

How to reduce the exposure risk of medical staff from SARS-CoV-2 by reducing environmental contamination: Experience from designated hospitals in China.

Background: Using daily monitoring of environmental surfaces and personal protective equipment (PPE), we found an increase in environmental contamination since August 18, 2021, in a designated hospital for COVID-19 patients in China, which may lead to an increased risk of exposure to medical staff. Methods: To investigate the cause of increased environmental contamination and effect of our intervention, we obtained environmental samples at pre-intervention (August 18-21, 2021) and post-intervention (August 22-28, 2021) from six infection isolation rooms with windows for ventilation and other auxiliary areas at 105 and 129 sites before routine daily cleaning, respectively. In addition, we obtained PPE samples from 98 medical staff exiting the patient rooms/contaminated areas at 482 sites. Between August 22 and 24, 2021, we took measures to reduce environmental contamination based on sampling and inspection results. Findings: At pre-intervention, the positivity rates for contamination of environmental surfaces and PPE samples were significantly higher for critical patients (37.21 and 27.86%, respectively) than severely ill patients (25.00 and 12.50%, respectively) and moderately ill patients (0.00 and 0.00%, respectively) (Pearson's Chi-square: χ2 = 15.560, p = 0.000; Fisher's exact test: χ2 = 9.358, p = 0.007). Therefore, we inferred that the source of contamination of environmental surfaces and PPE was mainly the room of critically ill patients, likely through the hands of medical staff to the potentially contaminated areas. A critically ill patient had emergency tracheal intubation and rescue on August 18, 2021, due to worsened patient condition. The ventilator tube used for first aid did not match the ventilator, and the ventilator tube fell off multiple times on August 18-21, 2021, which may explain the increased contamination of environmental surfaces and PPE from critically ill patients, as well as lead to indirect contamination of potentially contaminated areas. The contamination positivity rates of environmental surfaces and PPE were reduced by replacing the appropriate ventilator catheter, limiting the number of people entering the isolation room simultaneously, increasing the frequency of environmental disinfection, standardizing the undressing process, setting up undressing monitoring posts to supervise the undressing process, and preventing the spread of virus infections in the hospital during an epidemic. Conclusions: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spread on object surfaces in isolation rooms mainly by touch, and the contamination of environmental surfaces and PPE was greater in rooms of patients with greater disease severity and higher surface touch frequency. Therefore, strict protective measures for medical staff, frequent environmental cleaning for isolation rooms, and compliance with mask wearing by patients when conditions permit should be advised to prevent SARS-CoV-2 spread in hospitals.

CF3SO2Na-Mediated Visible-Light-Induced Cross-Dehydrogenative Coupling of Heteroarenes with Aliphatic C(sp3)-H Bonds.

Minisci-type reaction is one of the important means to construct C(sp3)-H functionalization of heteroarenes. According to traditional methods, stoichiometric amounts of precious transition metal catalysts and chemical oxidants were required at high temperatures. Here, a green and gentle novel Minisci-type method was developed via visible-light-induced cross-dehydrogenative coupling of heteroarenes with aliphatic C(sp3)-H bonds under oxidant-free and transition-metal-catalyst-free conditions. Only the catalytic equivalent of CF3SO2Na and room temperature were required to maintain an efficient reaction.

Is It an Outbreak of Health Care-Associated Infection? An Investigation of Binocular Conjunctival Congestion After Laparoscopic Cholecystectomy Was Traced to Chitosan Derivatives.

Background: From May 6 to May 23, 2019, 24 (80.00%) patients who underwent laparoscopic cholecystectomy (LC) developed binocular conjunctival congestion within 4-8 h after their operation in the day ward of a teaching hospital. Methods: Nosocomial infection prevention and control staff undertook procedural and environmental investigations, performed a case-control retrospective study (including 24 cases and 48 controls), and reviewed all lot numbers of biological material products to investigate the suspected outbreak of health care-associated infection. Findings: Initially, an outbreak of health care-associated infection caused by bacteria was hypothesized. We first suspected the membranes that covered patients' eyes were cut using non-sterile scissors and thus contaminated, but they failed to yield bacteria. In addition, both corneal and conjunctival fluorescein staining results were negative in case-patients and isolated bacteria were ubiquitous in the environment or common skin commensals or normal flora of conjunctiva from 218 samples from day surgery and the day ward. Hence, we considered a non-infectious factor as the most likely cause of the binocular conjunctival congestion. Then, we found that case-patients were more likely than LC surgery patients without binocular conjunctival congestion to be exposed to biological materials in a retrospective case-control study. When we reviewed lot numbers, duration of use, and the number of patients who received four biological material products during LC in the day ward, we found that the BLK1821 lot of a modified chitosan medical membrance (the main ingredient is chitosan, a linear cationic polysaccharide) was used concurrently to when the case aggregation appeared. Finally, we surmised there was a correlation between this product and the outbreak of binocular conjunctival congestion. Relapse of the pseudo-outbreak has not been observed since stopping usage of the product for 6 months. Conclusion: A cluster of binocular non-infectious conjunctival congestion diagnosed after LC proved to be a pseudo-outbreak. We should pay more attention to adverse events caused by biomaterials in hospitals.

Resolvin D1 ameliorates hepatic steatosis by remodeling the gut microbiota and restoring the intestinal barrier integrity in DSS-induced chronic colitis.

BACKGROUND AND PURPOSE: The maintenance of intestinalmucosalbarrier function plays an important role in hepatic steatosis. Increasing evidence has shown that resolvin D1 (RVD1) exerts a potential effect on hepatic steatosis. The aims of this study were to explore the mechanisms of RVD1 on hepatic steatosis based on the gut-liver axis and intestinal barrier function. EXPERIMENTAL APPROACH: We established a DSS-induced chronic colitis model to evaluate hepatic steatosis. RVD1 was administered i.p. during the last 4 weeks. The colon and liver samples were stained with hematoxylin and eosin for histopathological analysis. The expression levels of intestinal tight junction genes and inflammatory genes were determined by quantitative PCR. The serum levels of glucose, cholesterol, triglycerides and LPS were measured, and the gut microbiota was analyzed by 16S rRNA gene sequencing. KEY RESULTS: RVD1 prevented weight loss, histopathological changes, and elevated levels of inflammatory cytokines. Moreover, RVD1 administration attenuated DSS-induced hepatic steatosis and inflammatory responses in mice. In addition, RVD1 improved intestinal barrier function by increasing levels of tight junction molecules and decreasing the plasma LPS levels. The RVD1-treated mice also showed a different gut microbiota composition compared with found in the mice belonging to the DSS group but similar to that in normal chow diet-fed mice. CONCLUSIONS AND IMPLICATIONS: RVD1 treatment ameliorates DSS-induced hepatic steatosis by ameliorating gut inflammation, improving intestinal barrier function and modulating intestinal dysbiosis.

Resolvin D1 Prevents Epithelial-to-Mesenchymal Transition and Reduces Collagen Deposition by Stimulating Autophagy in Intestinal Fibrosis.

BACKGROUND: Intestinal fibrosis is the most common complication of inflammatory bowel disease; nevertheless, specific therapies are still unavailable. Resolvin D1 (RvD1), a typical endogenous ω-3 fatty acid-derived lipid mediator, has attracted wide attention due to its remarkable anti-fibrosis effects. However, the efficacy and mechanisms of RvD1 in intestinal fibrosis remain unclear. AIM: To investigate the protective effect of RvD1 in a dextran sulfate sodium (DSS)-induced intestinal fibrosis model and explore the molecular mechanisms underlying its anti-fibrotic effect. METHODS: A DSS-induced intestinal fibrosis model and intestinal epithelial-to-mesenchymal transition (EMT) model were used to observe the efficacy of RvD1, and fibroblasts were stimulated with conditioned medium with or without TGF-ß1 to investigate the probable mechanisms of RvD1 in intestinal fibrosis disease. RESULTS: Intestinal fibrosis was effectively alleviated by RvD1 in a DSS-induced model, both preventively and therapeutically, and autophagy inhibition-induced EMT in intestinal epithelial cells was significantly suppressed in vivo and in vitro. Furthermore, RvD1 reduced epithelial cell EMT paracrine signaling, which promoted the differentiation of local fibroblasts into myofibroblasts. CONCLUSIONS: Our results suggested that RvD1 reduces autophagy-induced EMT in intestinal epithelial cells and ameliorates intestinal fibrosis by disrupting epithelial-fibroblast crosstalk.

Multi-center prospective study on central line-associated bloodstream infections in 79 ICUs of China.

BACKGROUND: China has not yet established a national surveillance network such as NHSN from America, so there is still no large-scale investigations on central line-associated bloodstream infection (CLABSI) incidence. Several retrospective studies in China reported that the incidence of CLABSI varied due to inconsistent diagnostic criteria. We performed a nationwide survey to investigate the utilization rate of central venous catheters (CVCs) and the incidence of CLABSI in ICUs of different areas of China. METHODS: This is a prospective multi-center study. Patients admitted to ICUs with the use of CVCs between January 1, 2014 and December 31, 2018 were enrolled in this study. Hospitals were given the definition of catheter-related bloodstream infection as: a laboratory-confirmed bloodstream infection where CVC was in place on the date of event or the day before. The characteristics of patients, information of catheterization, implementation rates of precautions, and CLABSIs were collected. The statistical analysis was performed by SPSS 25.0 software and website of Open Source Epidemiologic Statistics for Public Health. RESULTS: A total of 38,212 patients and 466,585 catheter days were involved in surveillance. The average CLABSI incidence in a thousand catheter days was 1.50, the lowest incidence unit was in pediatric ICU (0/1000 catheter days), and the lowest incidence area was in Northeast China (0.77/1000 catheter days), while the highest incidence unit was in cardiac ICU (2.48/1000 catheter days) and the highest incidence area was in Eastern China (1.62/1000 catheter days). The average utilization rate of CVC was 42.85%, the lowest utilization rate was in pediatric ICU (5.85%) and in Central China (38.05%), while the highest utilization rate was in surgical ICU (64.92%) and in Western China (51.57%). Among the 702 CLABSI cases reported, a total of 735 strains of pathogens were cultured. Staphylococcus spp. was the most common organism isolated (27.07%), followed by Enterobacteriaceae (22.31%). The implementation rates of all precautions showed an upward trend during the study period (P ≤ 0.001). CONCLUSION: The average incidence of CLABSI in ICUs in China is 1.5/1000 catheter days, similar to the rates reported in developed countries but lower than previous reports in China. CLABSI incidence showed regional differences in China. It is necessary to implement targeted surveillance of CLABSI cases by using standardized CLABSI surveillance definitions and methodologies.

Antibiotic Resistances and Molecular Characteristics of Clostridioides difficile in ICUs in a Teaching Hospital From Central South China.

Clostridioides (C.) difficile is a major healthcare-associated pathogen inducing infectious diarrhea. Approximately 25-33% of patients with antibiotic-associated diarrhea (AAD) and 90% of patients with pseudomembranous enteritis are caused by C. difficile infection (CDI). Stool samples were collected from hospitalized adults with presumptive AAD in four nonneonatal intensive care units (ICUs). Diagnosis of CDI was based on both clinical symptoms and laboratory results. The stool specimens were transferred onto CDIF (C. difficile agar), and C. difficile was finally confirmed by the latex agglutination test. Toxin-producing genes tcdA (A), tcdB (B), and cdt (CDT) were detected by PCR, and all isolates were performed multilocus sequence typing analysis. The antibiotic susceptibility of C. difficile isolates was assessed by the agar dilution method. A total of 184 C. difficile were isolated from 857 specimens in our study, the isolation rate of C. difficile was 21.5% (184/857). The 184 C. difficile were isolated from 179 patients, among these 115 patients were toxin-positive, giving the incidence of CDI being 58.0/10,000 patient days in the four ICUs. Among these 115 toxin-positive C. difficile isolates, 100 (87.0%) isolates produced two toxins (A+B+CDT-), three (2.6%) isolates were A+B+ with binary toxin-producing (A+B+CDT+), and 12 (10.4%) isolates only produced one toxin (A-B+CDT-). A total of 27 sequencing types (STs) were obtained. The most prevalent was ST3 (34 isolates), followed by ST39 (27 isolates), ST54 (19 isolates), ST26 (16 isolates), ST35 (15 isolates), and ST2 (13 isolates). All the ST26 isolates were nontoxigenic. Meanwhile, five STs were newly discovered. Although multidrug resistance was present in ≥50% of these C. difficile isolates, all of them were susceptible to tigecycline, fidaxomicin, metronidazole, and vancomycin. In conclusion, C. difficile isolates producing two toxins (A+B+CDT-) were dominant in our hospital. The most prevalent was ST3, and all ST26 isolates were NTCD. Although multidrug resistance was present in ≥50% of the C. difficile isolates, metronidazole, tigecycline, fidaxomicin, and vancomycin were still effective treatments for CDI in our hospital.

Gut Microbiota Composition Associated With Clostridium difficile-Positive Diarrhea and C. difficile Type in ICU Patients.

The gut microbiota composition of intensive care unit (ICU) patients suffering from Clostridium difficile-positive diarrhea (CDpD) is poorly understood. This prospective study aims to use 16S rDNA (and metagenome) sequencing to compare the microbiota composition of 58 (and 5) ICU patients with CDpD (CDpD group), 33 (and 4) ICU patients with C. difficile-negative diarrhea (CDnD group), and 21 (and 5) healthy control subjects (control group), as well as CDpD patients in the A+B+ (N = 34; A/B: C. difficile TcdA/B), A-B+ (N = 7), and A-B- (N = 17) subgroups. For 16S rDNA data, OTU clustering (tool: UPARSE), taxonomic assignment (tool: RDP classifier), α-diversity, and ß-diversity analyses (tool: QIIME) were conducted. For metagenome data, metagenome assembly (tool: SOAPdenovo), gene calling (tools: MetaGeneMark, CD-HIT, and SoapAligner), unigene alignment (tool: DIAMOND), taxon difference analysis (tool: Metastats), and gene annotation (tool: DIAMOND) were performed. The microbial diversity of the CDpD group was lower than that of the CDnD and control groups. The abundances of 10 taxa (e.g., Deferribacteres, Cryptomycota, Acetothermia) were significantly higher in the CDpD group than in the CDnD group. The abundances of Saccharomycetes and Clostridia were significantly lower in CDpD in comparison with control. Some taxa were significantly different between the A+B+ and A-B- subgroups. CDpD might relate to a decrease in beneficial taxa (i.e., Saccharomycetes and Clostridia) and an increase in harmful taxa (e.g., Deferribacteres, Cryptomycota, Acetothermia) in gut microbiota of ICU patients. C. difficile toxin type might be slightly associated with gut microbiota composition.

Estrogen receptor ß activation ameliorates DSS-induced chronic colitis by inhibiting inflammation and promoting Treg differentiation.

Estrogen receptor (ER) ß activation has anti-inflammatory activity. However, its effect on the development of inflammatory bowel disease (IBD) and the underlying mechanism have not been clarified. This study aimed to assess the clinical value of ERß+CD4+ T cells in IBD patients and examine the anti-inflammatory role of ERß activation in dextran sulfate sodium (DSS)-induced chronic colitis in mice. We investigated the effects of ERB041 (an ERß-specific agonist) on inflammatory cytokines and pro-inflammatory T-cell and regulatory T-cell (Treg) responses in murine colitis. We tested the role of ERß activation on Treg differentiation and its activity to suppress T-cell proliferation in vitro. We found that reduced frequency of circulating ERß+CD4+ T cells in IBD patients was negatively correlated with inflammation and disease severity. ERß and FoxP3 expression co-localized in the intestinal tissues of IBD patients. Treatment with ERB041 significantly mitigated colitis-induced weight loss, inflammation, and disease severity. It also restored the ERß+CD4+ T cell population in the spleen and colon lamina propria of these mice. ERB041 treatment inhibited CD4+CD25- and CD8+ T cell infiltration and restored Tregs and activated T-cell immunoreceptor with Ig and ITIM domains (TIGIT)+ Tregs in the colon lamina propria. In vitro, we found that ERß activation enhanced Treg differentiation, immunosuppression, and TGF-ß1/Smad signaling in CD4+ T cells. Our data suggest that ERß+CD4+ T cells represent a potential biomarker for evaluating IBD disease severity, and ERß activation may be valuable for the treatment of IBD by enhancing the Treg response.

[Impact Mechanisms of Carboxyl Group Modified Cathode on Acetate Production in Microbial Electrosynthesis Systems].

Microbial electrosynthesis systems (MESs) can convert carbon dioxide into added value compounds using microorganisms as catalyst, which is expected to help achieve conversion of greenhouse gases into resources. However, the synthetic efficiency of MESs is far behind the industry requirements. In this study, carbon cloth surfaces were bonded with carboxyl groups by electrochemical reduction of aryl diazonium salts and then used as a cathode in MESs reactors. The results showed that the hydrophilicity of the carbon cloth surfaces improved after the carboxyl groups were modified. However, weaker current of cyclic voltammetry was obtained in the modified cathode. Significant differences were observed between modified (CA-H, CA-M, CA-L) and non-modified cathode (CK) during the start-up period. After 48h, the hydrogen production rate of CA-H, CA-M, CA-L was 21.45, 28.60, and 22.75 times higher than CK. After 120h, the acetate accumulation concentration of CA-H, CA-M, CA-L was 2.01, 2.43, and 1.44 times higher than CK. After 324h, there was little difference in the electrochemical activity of cathodic biofilm and protein content (about 0.47 mg·cm-2) in all groups. The analysis of the community structure of cathodic biofilm showed that, in the genus level, Acetobacterium, Norank_p_Saccharibacteria, and Thioclava were the dominant species, accounting for 59.6% to 82.1%. There was little difference in the relative abundance of Acetobacterium in all groups (31.3% to 40.1%). However, the relative abundance of norank_p_Saccharibacteria in CA-H, CA-M, CA-L, and CK were 16.1%, 24.6%, 31.1%, and 37.5%, respectively. The carboxyl modified cathode had a great influence on the start-up stage of MESs, which could be a new idea for the rapid start-up of MESs.

[Sulfate Reduction and Microbial Community of Autotrophic Biocathode in Response to Externally Applied Voltage].

The removal efficiencies of environmental pollutants in a microbial electrolysis system (MES) with a biocathode are highly affected by the externally applied voltage. Although the cathode biofilm plays a key role in the pollution removal, its response to the applied voltage is still unknown. A two-chambered MES with a biocathode was constructed to study the impact of the different applied voltages (0.4, 0.5, 0.6, 0.7, and 0.8 V) on the sulfate reduction, extracellular polymer formation, and cathodic bacterial community. The results show that the current output and coulomb and COD removals of the MES are positively correlated with the applied voltage ranging from 0.4 to 0.8 V. The sulfate reduction rate first increases and then decreases with increasing voltage in the MES. The maximum sulfate reductive rate[78.9 g·(m3·d)-1] and maximum S2- production (31.9 mg·L-1±2.2 mg·L-1) were achieved at 0.7 V. The highest electron recovery efficiencies of the MES are 41.8%; hydrogen production may be a pathway leading to electron loss. The polysaccharide and protein contents of the cathode biofilm increase with increasing voltage. The cathode biomass at 0.8 V is 70% higher than that at 0.4 V. The high throughput sequencing results show that Proteobacteria and Dsulfovibrio are dominant in the cathodic microbial community at the phylum and genus levels, respectively. The relative abundance of Desulfovibrio shows little variation with the increasing voltage, indicating that Desulfovibrio is of advantage for using the cathode as electron donor for the respiratory metabolism. With the increasing voltage, the distribution of Desulfovibrio at species level indicates that the changes of Desulfovibriox magneticus RS-1 and s_unclassified_g_Desulfovibrio are contrary.

Epigenetic alterations of a novel antioxidant gene SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.

Esophageal squamous cell carcinoma (ESCC) occurs with the highest frequency in China, especially in the high-risk Northern Chinese. Recent studies have reported that SLC22A3 is significantly downregulated in non-tumor (NT) esophageal tissues from familial ESCC patients compared with those from sporadic ESCC. However, the mechanism of how SLC22A3 regulates familial ESCC remains unknown. In this study, post hoc genome-wide association studies (GWAS) in 496 cases with a family history of upper gastrointestinal tract cancers and 1056 controls were performed and the results revealed that SLC22A3 is a novel susceptibility gene for familial ESCC. Reduced expression of SLC22A3 in NT esophageal tissues from familial ESCC patients significantly correlates with its promoter hypermethylation. Moreover, case-control study of Chinese descendants from different risk areas of China revealed that the methylation of the SLC22A3 gene in peripheral blood leukocyte (PBL) DNA samples could be a risk factor for developing ESCC in this high-risk population. Functional studies showed that SLC22A3 is a novel antioxidant gene, and deregulation of SLC22A3 facilitates heat stress-induced oxidative DNA damage and formation of γ-H2AX foci in normal esophageal epithelial cells. Collectively, we show that epigenetic alterations of SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.

Hepatitis B virus upregulates GP73 expression by activating the HIF-2α signaling pathway.

Golgi Protein 73 (GP73) is a newly identified diagnostic and prognostic marker for liver cancer. GP73 is highly expressed in liver cancer tissues, however, the mechanism of its overexpression in tumors remains unknown. In the present study, the effect of hepatitis B virus (HBV) on GP73 expression was investigated in HepG2 cells, which are negative for HBV, and in HepG2.2.12 cells, which are integrated with HBV, using reverse transcription-quantitative polymerase chain reaction and western blot analysis. In addition, the cells were transfected with plasmid constructs overexpressing hepatitis B virus protein X (HBx), hypoxia-inducible factor (HIF)-1α, or HIF-2α in order to examine their roles in GP73 expression. The results demonstrated that HBV upregulated the expression of GP73 and HIF-2α in liver cancer cells. HIF-2α induced the expression of GP73 in HepG2 cells and was positively correlated with GP73 expression in liver cancer tissues. By contrast, HBx and HIF-1α did not induce GP73 expression in liver cancer cells. In summary, HBV may upregulate the expression of GP73 by activating the HIF-2α signaling pathway. The present results may illuminate the mechanism by which GP73 is overexpressed in liver cancer tissues.

Positive Expression of Programmed Death Ligand 1 in Peritumoral Liver Tissue is Associated with Poor Survival after Curative Resection of Hepatocellular Carcinoma.

BACKGROUND: Recurrence or metastasis of hepatocellular carcinoma (HCC) is mainly intrahepatic after curative resection, demonstrating that the peritumoral environment is important but often neglected. Programmed death ligand 1 (PD-L1) in intratumoral liver tissues is a poor prognosis factor whose impact is removed after curative resection. However, PD-L1 expression remains in the peritumoral liver tissues and its distribution and prognostic value are still not clear. METHODS: We assessed the expression of PD-L1 by immunohistochemistry in peritumoral liver tissues from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients. RESULTS: We found PD-L1 positive expression in 31.11% (28/90) of peritumoral tissues. Peritumoral PD-L1 expression was associated with a significantly worse overall survival (OS) (P=.000) and disease-free survival (DFS) (P=.001) compared to the negative expression group. Additionally, peritumoral PD-L1 positivity significantly correlated with vascular invasion and a lower albumin level (≤35 g/L). Univariate and multivariate Cox regression models both revealed peritumoral PD-L1 as an independent prognostic factor for OS (HR=2.853, P=.002) and DFS (HR=2.362, P=.003). The prognostic value of PD-L1 positivity was validated in the independent data set. CONCLUSIONS: Our data suggest PD-L1 expression in peritumoral hepatocytes is an independent prognostic factor for OS and DFS. This implies that future anti-cancer therapy should target not only residual tumor cells but also the "soil" for promoting tumor growth. Peritumoral PD-L1 could be a good target for adjuvant therapy after hepatectomy.

Assessing the risk and disease burden of Clostridium difficile infection among patients with hospital-acquired pneumonia at a University Hospital in Central China.

PURPOSE: Hospital-acquired pneumonia (HAP) remains one of the major hospital-acquired infections in China. Antibiotic treatment of HAP may lead to subsequent Clostridium difficile infection (CDI). Baseline data on the occurrence of CDI among HAP patients in China are currently unavailable. This study examines the risk and disease burden of CDI among HAP hospitalized patients (HAP-CDI). METHODS: We conducted a prospective study among ICU patients with HAP and hospital-onset diarrhea from January 2014 to December 2014 in a teaching hospital in China. All stool specimens were cultured for C. difficile which were typed by MLST. We used univariate and multivariable regression analyses to identify risk factors of HAP-CDI. FINDINGS: In total, 369 patients who met the inclusion criteria were enrolled. Thirty-two patients tested C. difficile positive. Among the isolated C. difficile strains, 90.63% (29/32) isolates were toxinogenic. Various MLST types were identified. The incidence of HAP-CDI was 11.67/10,000 patient days (95% CI, 7.97-16.55). Nineteen patients died from complications. The attributable mortality rate was 5.15% (19/369). The mortality rate of HAP-CDI group was 13.79% which was higher than HAP-non-CDI group. Univariate analyses demonstrated that old age, receiving antibiotics (OR = 8.70) and glucocorticoids (OR = 7.71) 1 month prior to hospitalization, respiratory failure (OR = 3.28) and receiving antimicrobials during hospitalization (OR = 1.15) were the risk factors associated with CDI. Multivariate conditional logistic regression analysis demonstrated the similar results. CONCLUSION: CDI was common among patients discharged from hospital for HAP at a university hospital. Prevention of the spreading of C. difficile among hospitalized patients is urgently needed.

Microtubule plus end-tracking proteins play critical roles in directional growth of hyphae by regulating the dynamics of cytoplasmic microtubules in Aspergillus nidulans.

Cytoplasmic microtubules (MTs) serve as a rate-limiting factor for hyphal tip growth in the filamentous fungus Aspergillus nidulans. We hypothesized that this function depended on the MT plus end-tracking proteins (+TIPs) including the EB1 family protein EBA that decorated the MT plus ends undergoing polymerization. The ebAΔ mutation reduced colony growth and the mutant hyphae appeared in an undulating pattern instead of exhibiting unidirectional growth in the control. These phenotypes were enhanced by a mutation in another +TIP gene clipA. EBA was required for plus end-tracking of CLIPA, the Kinesin-7 motor KipA, and the XMAP215 homologue AlpA. In addition, cytoplasmic dynein also depended on EBA to track on most polymerizing MT plus ends, but not for its conspicuous appearance at the MT ends near the hyphal apex. The loss of EBA reduced the number of cytoplasmic MTs and prolonged dwelling times for MTs after reaching the hyphal apex. Finally, we found that colonies were formed in the absence of EBA, CLIPA, and NUDA together, suggesting that they were dispensable for fundamental functions of MTs. This study provided a comprehensive delineation of the relationship among different +TIPs and their contributions to MT dynamics and unidirectional hyphal expansion in filamentous fungi.