Metagenomics of high-altitude groundwater reveal different health risks associated with antibiotic-resistant pathogens and bacterial resistome in the latitudinal gradient.

Groundwater on the Tibetan Plateau is a critical water resource to people in Asia. However, its prevalence of antibiotic-resistant pathogens (ARPs), bacterial resistome and their driving factors remain unknown. Using metagenomics analysis, a hotspot of antibiotic-resistance genes (ARGs) and last-resort ARGs (LARGs) with a total of 639 subtypes was identified in the groundwater. Importantly, 164 metagenome-assembled genomes (MAGs) which possessed both ARGs and virulence factors (VFs) were assigned as potential ARPs, with the most abundant species being Acinetobacter johnsonii and Acinetobacter pittii. A total of 157 potential ARPs, involving Escherichia coli, were predicted as "natural" ARGs supercarriers. Thirty-six ARPs dominated by the genus Acinetobacter and Pseudomonas were found to harbour LARGs. Co-localizations of the ARG-mobile genetic elements (MGEs) showed that MGEs were significantly associated with ARGs in the ARPs, which suggests ARPs play a prominent role in ARG dissemination. Notably, latitudinal gradient is a driving factor in the occurrence of ARGs and ARPs. The average abundances of ARGs and ARP decreased as the latitude increased, with the highest abundance occurring in the region between 28.6◦N and 29.5◦N. MetaCompare further revealed health risks associated with the resistome decreased as the latitudes increased. These findings indicated different health risks associated with ARPs and bacterial resistome in latitudinal gradient groundwater. They raise the concerns of mitigating ARPs risk in groundwater on the Tibetan Plateau.

CRISPR/Cas9-based engineered Escherichia coli biosensor for sensitive and specific detection of Cd(II) in drinking water.

Cadmium (Cd) is a ubiquitous pollutant that poses a potential threat to human health. Monitoring Cd(II) in drinking water has significant implications for preventing potential threats of Cd(II) to human. However, the weak signal output and response to nontarget interference limit the detection of Cd(II) using bacterial biosensors. In this study, to enable sensitive and specific detection of Cd(II) in water, a stable whole-cell biosensor, K12-PMP-luxCDABE-△cysI, was constructed in a dual-promoter mode by fusing the mercury promoter Pmer, regulatory gene merR(m), and luciferase gene luxCDABE into the E.coli chromosome based on CRISPR/Cas9 gene editing technology. By knocking out the cadmium-resistance-gene cysI, the sensitivity of the biosensor to Cd(II) was further enhanced. The constructed E. coli biosensor K12-PMP-luxCDABE-△cysI exhibited good nonlinear responses to 0.005-2 mg/L Cd(II). Notably, among the three constructed E. coli biosensor, it exhibited the strongest fluorescence intensity, with the limit of detection meeting the allowable limit for Cd(II) in drinking water. Simultaneously, it could specifically detect Cd(II). Nontarget metal ions, such as Zn(II), Hg(II), and Pb(II), did not affect its performance. Furthermore, it exhibited superior performance in detecting Cd(II) in real drinking water samples by avoiding background interference, and showed excellent stability with the relative standard deviation under 5%. Thus, K12-PMP-luxCDABE-△cysI holds promise as a potential tool for the detection of Cd(II) in drinking water.

Emergence of colistin-resistant Stenotrophomonas maltophilia with high virulence in natural aquatic environments.

The presence of Stenotrophomonas maltophilia in aquatic environments poses great health risks to immunocompromised individuals because of its multidrug resistance and resultant high mortality. However, a significant gap exists in the isolation and understanding of colistin-resistant S. maltophilia in aquatic environments. In this study, nine colistin-resistant S. maltophilia strains isolated from natural lakes were explored, and their phylogenetic relationship, biofilm formation, virulence, and antibiotic resistance profiles and underlying genetic determinants were assessed. After genome analysis, besides known multi-locus sequence typing (MLST) of ST532, new assigned ST965 and ST966 which phylogenetically clustered into soil isolates were found firstly. All the isolates exhibited resistance to multiple antibiotics, including aminoglycosides, beta-lactams, tetracyclines, and even colistin, with the highest minimum inhibitory concentration (MIC) against colistin reaching 640 mg/L. Comparative genomic analysis revealed aph(3')-Iic, blaL1, tetT, phoP, mcr-3, arnA, pmrE, and efflux pump genes as the genetic determinants underlying this multidrug resistance. Notably, the biofilm-forming capacities of the newly discovered ST965 and ST966 isolates were significant stronger than those of the known ST532 isolates (p < 0.01), resulting in the death of over 50 % of the Galleria mellonella population within 1 day of injection. The ST965 isolates demonstrated the highest virulence against G. mellonella, followed by the ST966 isolates and ST532 isolates which was phylogenetically clustered with clinical isolates, indicating that the novel S. maltophilia strains of ST965 and ST966 may pose considerable health risks to humans. Our findings provide insights into colistin-resistant S. maltophilia in aquatic environments and raise concerns about the health risks posed by the newly assigned sequence types of colistin-resistant S. maltophilia with potential high virulence in natural aquatic environments.

A mica filter enables bacterial enrichment from large volumes of natural water for sensitive monitoring of pathogens by nanopore sequencing.

Nanopore sequencing is extremely promising for the high-throughput detection of pathogenic bacteria in natural water; these bacteria may be transmitted to humans and cause waterborne infectious diseases. However, the concentration of pathogenic bacteria in natural water is too low to be detected directly by nanopore sequencing. Herein, we developed a mica filter to enrich over 85% of bacteria from > 10 L of natural water in 100 min, which led to a 102-fold improvement in the assay limits of the MinION sequencer for assessing pathogenic bacteria. Correspondingly, the sequencing time of S. Typhi detection at a concentration as low as 105 CFU/L was reduced from traditional 48 h to 3 h. The bacterial adsorption followed pseudo-first-order kinetics and the successful adsorption of bacteria to the mica filter was confirmed by scanning electron microscopy and Fourier infrared spectroscopy et al. The mica filter remained applicable to a range of water samples whose quality parameters were within the EPA standard limits for freshwater water. The mica filter is thus an effective tool for the sensitive and rapid monitoring of pathogenic bacteria by nanopore sequencing, which can provide timely alerts for waterborne transmission events.

Carbonaceous particulate matter promotes the horizontal transfer of antibiotic resistance genes.

There is growing concern about the transfer of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in airborne particulate matter. In this study, we investigated the effects of various types of carbonaceous particulate matter (CPM) on the transfer of ARGs in vitro. The results showed that CPM promoted the transfer of ARGs, which was related to the concentration and particle size. Compared with the control group, the transfer frequency was 95.5, 74.7, 65.4, 14.7, and 3.8 times higher in G (graphene), CB (carbon black), NGP (nanographite powder), GP1.6 (graphite powder 1.6 micron), and GP45 (graphite powder 45 micron) groups, respectively. Moreover, the transfer frequency gradually increased with the increase in CPM concentration, while there was a negative relationship between the CPM particle size and conjugative transfer frequency. In addition, the results showed that CPM could promote the transfer of ARGs by increasing ROS, as well as activating the SOS response and expression of conjugative transfer-related genes (trbBp, trfAp, korA, kroB, and trbA). These findings are indicative of the potential risk of CPM for the transfer of ARGs in the environment, enriching our understanding of environmental pollution and further raising awareness of environmental protection.

Comparative analysis of chlorine-resistant bacteria after chlorination and chloramination in drinking water treatment plants.

Chlorine-resistant bacteria (CRB) in drinking water treatment plants (DWTPs) jeopardize water quality and pose a potential risk to human health. However, the specific response of CRB to chlorination and chloramination remains uncharacterized. Therefore, we analyzed 16 S rRNA sequencing data from water samples before and after chlorination and chloramination taken between January and December 2020. Proteobacteria and Firmicutes dominated all finished water samples. After chloramination, Acinetobacter, Pseudomonas, Methylobacterium, Ralstonia, and Sphingomonas were the dominant CRB, whereas Ralstonia, Bacillus, Acinetobacter, Pseudomonas, and Enterococcus were prevalent after chlorination. Over 75% of the CRB e.g. Acinetobacter, Pseudomonas, Bacillus, and Enterococcus were shared between the chlorination and chloramination, involving potentially pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Notably, certain genera such as Faecalibacterium, Geobacter, and Megasphaera were enriched as strong CRB after chloramination, whereas Vogesella, Flavobacterium, Thalassolituus, Pseudoalteromonas, and others were enriched after chlorination according to LEfSe analysis. The shared CRB correlated with temperature, pH, and turbidity, displaying a seasonal pattern with varying sensitivity to chlorination and chloramination in cold and warm seasons. These findings enhance our knowledge of the drinking water microbiome and microbial health risks, thus enabling better infectious disease control through enhanced disinfection strategies in DWTPs.

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells.

Zhuo et al looked into the part of transmembrane 9 superfamily member 1 (TM9SF1) in bladder cancer (BC), and evaluated if it can be used as a therapeutic target. They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth, movement, invasion, and cell cycle advancement. Their results show that TM9SF1 can boost the growth, movement, and invasion of BC cells and their access into the G2/M stage of the cell cycle. This research gives a novel direction and concept for targeted therapy of BC.

Highly Active and Robust Catalyst: Co2B-Fe2B Heterostructural Nanosheets with Abundant Defects for Hydrogen Production.

A high-performance and reusable nonnoble metal catalyst for catalyzing sodium borohydride (NaBH4) hydrolysis to generate H2 is heralded as a nuclear material for the fast-growing hydrogen economy. Boron vacancy serves as a flexible defect site that can effectively regulate the catalytic hydrolysis performance. Herein, we construct a uniformly dispersed and boron vacancy-rich nonnoble metal Co2B-Fe2B catalyst via the hard template method. The optimized Co2B-Fe2B exhibits superior performance toward NaBH4 hydrolysis, with a high hydrogen generation rate (5315.8 mL min-1 gcatalyst-1), relatively low activation energy (35.4 kJ mol-1), and remarkable cycling stability, outperforming the majority of reported catalysts. Studies have shown that electron transfer from Fe2B to Co2B, as well as abundant boron defects, can effectively modulate the charge carrier concentration of Co2B-Fe2B catalysts. Density functional theory calculations confirm that the outer electron cloud density of Co2B is higher than that of Fe2B, among which Co2B with high electron cloud density can selectively adsorb BH4- ions, while the electron-deficient Fe2B is favorable for capturing H2O molecules, therefore synergistically promoting the catalytic NaBH4 hydrolysis to produce H2.

Using machine learning to explore the characteristics of eye movement patterns and relationship with cognition ability of Chinese children aged 1-6 years.

Researchers have begun to investigate the relationship between eye movement characteristics of gaze patterns and cognitive abilities, and have attempted to use eye-tracking technology as a new method to evaluate cognitive abilities. Traditional eye movement analysis methods typically separate spatial and temporal information of eye movements, mostly analyze averaged data, and consider individual differences as noise. In addition, current eye movement studies on gaze patterns mostly involve adults, while research on infants and toddlers is limited with small sample sizes and narrow age ranges. It is still unknown whether the conclusions drawn from adult-based research can be applied to children. Consequently, eye movement research on gaze patterns in children is necessary. To address the concerns stated above, this study used the Hidden Markov machine learning method to model gaze patterns of 330 children aged 1-6 years while observing faces freely, and analyzed characteristics of eye movement gaze patterns. Additionally, we analyzed the correlation between gaze patterns of 31 toddlers aged 1-3 years and 37 preschoolers aged 4-6 years, and the different dimensions of cognitive abilities. The findings indicated that children exhibited holistic and analytic gaze patterns while observing different faces freely. More children adopted a holistic gaze pattern, and there were age-specific gaze pattern characteristics and regularities. Gaze patterns of toddlers may be correlated with their adaptive abilities and gaze patterns of preschoolers may be correlated with their visual space abilities. Specifically, toddlers aged 1-3 years showed a moderate negative correlation between the H-A scale and the adaptive dimension, while preschoolers aged 4-6 years showed a low negative correlation between the H-A scale and the visual space dimension. This study may provide new insights into the characteristics of children's eye-movement gaze patterns during face observation, and potentially offer objective evidence for future research aimed at promoting the use of eye-tracking technology in the assessment of toddlers' adaptive abilities and preschoolers' visual space abilities in the field of face perception.

Landscape of antibiotic resistance genes and bacterial communities in groundwater on the Tibetan Plateau, and distinguishing their difference with low-altitude counterparts.

Groundwater is a vital source of drinking water for Tibetans. Antibiotic resistance genes (ARGs) and bacterial communities in groundwater on the Tibetan Plateau remain unclear. Furthermore, the characterization of their differences between high-altitude and low-altitude groundwater is still unrevealed. Herein, 32 groundwater samples were collected on the plateau, and intra- and extracellular ARGs (iARGs and eARGs), and bacterial communities were characterised through qPCR assays to 19 ARGs and 16S rRNA sequencing. It showed top four abundant intra- and extracellular last-resort ARGs (LARGs) were blaOXA-48, mcr-1, vanA, and vanB, whereas dominant common ARGs (CARGs) were tetA and ermB, respectively. CARGs had higher abundances than LARGs, and iARGs were more frequently detected than eARGs. Proteobacteria, an invasive resident phylum, and Firmicutes dominated eDNA release. Network analysis revealed all observed LARGs co-occurred with pathogenic and non-pathogenic bacteria. Community diversity was significantly associated with longitude and elevation, while nitrate correlated with ARGs. Comparative analysis demonstrated eARG frequencies and abundances were higher at high altitudes than at low altitudes. Additionally, Acinetobacter and Pseudomonas specifically dominated at high altitudes. This study reveals the widespread prevalence of ARGs, particularly LARGs, in groundwater on the less-disturbed Tibetan Plateau and underlines the potential risks associated with the LARG-carrying bacteria. ENVIRONMENTAL IMPLICATION: Antibiotic resistance genes (ARGs), which are defined as emerging environmental contaminants, are becoming a global concern due to their ability to confer antibiotic resistance to pathogens. Our findings highlight the prevalence of ARGs, particularly LARGs, in groundwater on the Tibetan Plateau, and the possibility that naturally-occurring pathogenic and non-pathogenic bacteria carry multiple LARGs. In addition, we further reveal differences in the distribution of ARGs and bacterial community between high-altitude and low-altitude groundwater. Collectively, our findings offer an important insight into the potential public risks related to groundwater on the Tibetan Plateau.

Spatial and temporal analysis of the seasonal dynamics of antibiotic resistance gene occurrence in recreational marine water.

People who engage in water sports in recreational marine water may be at high risk of exposure to hazardous antibiotic-resistant bacteria (ARB). However, information on the contribution of specific sources to ARB contamination in recreational marine water is still lacking. Here, we carried out monthly analyses of antibiotic resistance genes (ARGs), pathogenic bacteria and 16S rRNA sequencing data at the First Bathing Beach in Qingdao. The sampling sites were divided into four areas: swimming area, intermediate area, polluted area, and sewage outlet. Correlations between ARGs and bacterial communities among sampling sites were explored by spatial and temporal analysis. We found that all of 21 important ARG types were detected in the swimming area, with aadA (1.3 × 106 ± 2.7 × 106 genomic copies/L) and sul2 (4.3 × 105 ± 5.9 × 105 genomic copies/L) at the highest concentration. Most ARGs were detected at highest frequency and concentration in the sewage outlet and decreased from there to the swimming area. ARG correlation between these two areas was positive only in the cold season, suggesting that sewage was the main source of ARG pollution in the swimming area during that period. The ARGs ermA(1) and vanA were detected at highest frequency and concentration in the swimming area and were significantly correlated with the intestinal pathogen Enterococcus, which was more abundant here than in the surrounding areas during the warm season. Co-occurrence analysis of bacterial genera and ARGs showed that six genera were commonly correlated with ARGs in all sampling areas in the cold season, while none were found in the warm season. Our findings indicate that ARG pollution in the swimming area was also driven by sources other than sewage, especially in the warm season, which is the peak tourist season in Qingdao. These results provide a valuable basis for the implementation of effective strategies to control ARG risks in recreational waters.

Synergistic Regulation of Pt Clusters on Porous Support by Mo and P for Robust Bifunctional Hydrogen Electrocatalysis.

Developing efficient electrocatalysts toward hydrogen oxidation and evolution reactions (HER/HOR) in alkaline electrolytes is essential for realizing renewable hydrogen technologies. Herein, we demonstrate that the introduction of dual-active species such as Mo and P (Pt/Mo,P@NC) can effectively regulate the surface electronic structure of platinum (Pt) and significantly improve the HOR/HER performance. The optimized Pt/Mo,P@NC exhibits remarkable catalytic activity, achieving a normalized exchange current density of 2.89 mA cm-2 and a mass activity of 2.3 mA µgPt-1, which are approximately 2.2 and 13.5 times higher than those of the state-of-the-art Pt/C catalyst, respectively. Moreover, it performs an impressive HER performance with an overpotential of 23.4 mV at 10 mA cm-2, which is lower than most documented alkaline electrocatalysts. Experimental results reveal that the modifying effect of Mo and P optimizes the adsorption of H and OH on Pt/Mo,P@NC, resulting in an outstanding catalytic performance. This work has significant theoretical and practical significance for developing a novel and highly efficient catalyst for bifunctional hydrogen electrocatalysis.

Antidepressant exposure as a source of disinfectant resistance in waterborne bacteria.

The emergence of disinfectant-resistant pathogens in water is a major threat to public health. However, whether human-consumed pharmaceuticals can induce bacterial resistance to disinfectants remains unclear. Herein, Escherichia coli was exposed to 12 antidepressants, and susceptibility of antidepressant-induced chloramphenicol (CHL)-resistant mutants to disinfectants was tested. Whole genome sequencing, global transcriptomic sequencing, and real-time quantitative polymerase chain reaction were used to elucidate the underlying mechanisms. We observed that duloxetine, fluoxetine, amitriptyline, and sertraline significantly increased the mutation frequency of E. coli against CHL by 15- to 2948-fold. The resultant mutants increased the average MIC50 of sodium hypochlorite, benzalkonium bromide, and triclosan roughly 2- to 8-fold. Consistently, marRAB and acrAB-tolC genes, together with ABC transporter genes (e.g., yddA, yadG, yojI, and mdlA), were triggered to increase the efflux of disinfectants out of the cell, while ompF was inhibited, reducing disinfectant penetration into the cell. Additionally, the occurrence of DNA mutations in marR and acrR in the mutants was observed, potentially resulting in increased synthesis of the AcrAB-TolC pump. This study indicates that pharmaceutical exposure may create disinfectant-resistant bacteria, which may then be released into water systems, providing novel insights into the potential source of water-borne disinfectant-resistant pathogens.

Simulated Gastric Acid Promotes the Horizontal Transfer of Multidrug Resistance Genes across Bacteria in the Gastrointestinal Tract at Elevated pH Levels.

The assessment of factors that can promote the transmission of antibiotic resistance genes (ARGs) across bacteria in the gastrointestinal tract is in great demand to understand the occurrence of infections related to antibiotic-resistant bacteria (ARB) in humans. However, whether acid-resistant enteric bacteria can promote ARG transmission in gastric fluid under high-pH conditions remains unknown. This study assessed the effects of simulated gastric fluid (SGF) at different pH levels on the RP4 plasmid-mediated conjugative transfer of ARGs. Moreover, transcriptomic analysis, measurement of reactive oxygen species (ROS) levels, assessment of cell membrane permeability, and real-time quantitative assessment of the expression of key genes were performed to identify the underlying mechanisms. The frequency of conjugative transfer was the highest in SGF at pH 4.5. Antidepressant consumption and certain dietary factors further negatively impacted this situation, with 5.66-fold and 4.26-fold increases in the conjugative transfer frequency being noted upon the addition of sertraline and 10% glucose, respectively, compared with that in the control group without any additives. The induction of ROS generation, the activation of cellular antioxidant systems, increases in cell membrane permeability, and the promotion of adhesive pilus formation were factors potentially contributing to the increased transfer frequency. These findings indicate that conjugative transfer could be enhanced under certain circumstances in SGF at elevated pH levels, thereby facilitating ARG transmission in the gastrointestinal tract. IMPORTANCE The low pH of gastric acid kills unwanted microorganisms, in turn affecting their inhabitation in the intestine. Hence, studies on the factors that influence antibiotic resistance gene (ARG) propagation in the gastrointestinal tract and on the underlying mechanisms are limited. In this study, we constructed a conjugative transfer model in the presence of simulated gastric fluid (SGF) and found that SGF could promote the dissemination of ARGs under high-pH conditions. Furthermore, antidepressant consumption and certain dietary factors could negatively impact this situation. Transcriptomic analysis and a reactive oxygen species assay revealed the overproduction of reactive oxygen species as a potential mechanism by which SGF could promote conjugative transfer. This finding can help provide a comprehensive understanding of the bloom of antibiotic-resistant bacteria in the body and create awareness regarding the risk of ARG transmission due to certain diseases or an improper diet and the subsequent decrease in gastric acid levels.

Extended chloramination significantly enriched intracellular antibiotic resistance genes in drinking water treatment plants.

Chloramination and chlorination are both strong barriers that prevent the transmission of potential pathogens to humans through drinking water. However, the comparative effects of chloramination and chlorination on the occurrence of antibiotic resistance genes (ARGs) in drinking water treatment plants (DWTPs) remain unknown. Herein, the antibiotic resistome in water before and after chloramination or chlorination was analyzed through metagenomic sequencing and then verified through quantitative real-time polymerase chain reaction (qPCR). After the treatment of 90 min, chloramination led to higher enrichment of the total relative abundance of intracellular ARGs (iARGs) in water than chlorination, whereas chlorination facilitated the release of more extracellular ARGs (eARGs) than chloramination. According to redundancy and Pearson's analyses, the total concentration of the observed iARGs in the finished water exhibited a strong positive correlation with ammonium nitrogen (NH4+-N) concentration, presenting a linear upward trend with an increase in the NH4+-N concentration. This indicated that NH4+-N is a crucial driving factor for iARG accumulation during chloramination. iARG enrichment ceases if the duration of chloramination is shortened to 40 min, suggesting that shortening the duration would be a better strategy for controlling iARG enrichment in drinking water. These findings emphasized the potential risk of antibiotic resistance after extended chloramination, shedding light on the control of transmission of antibiotic-resistant bacteria through water by optimizing disinfection procedures in DWTPs.

How Do Team-Level and Individual-Level Linguistic Styles Affect Patients' Emotional Well-Being-Evidence from Online Doctor Teams.

BACKGROUND: In the post-epidemic era, online medical care is developing rapidly, and online doctor teams are attracting attention as a high-quality online medical service model that can provide more social support for patients. METHODS: Using online doctor teams on the Haodf.com platform as the research subject, this study investigates the key factors in the process of doctor-patient communication, which affects patients' emotional well-being. We also explore the different roles played by doctors as leaders and non-leaders in doctor-patient communication. From the perspective of language style, we select representative factors in the process of doctor-patient communication, namely the richness of health vocabulary, the expression of emotions, and the use of health-related terms (including perceptual words and biological words). We extract both team-level and individual-level linguistic communication styles through textual and sentiment analysis methods and empirically analyze their effects on patients' emotional well-being using multiple linear regression models. RESULTS: The results show that the expression of positive emotions by the team and attention to patients' perceptions and biological conditions benefit patients' emotional well-being. Leaders should focus on the emotional expression, whereas non-leaders should focus on the use of perceptual and biological words. CONCLUSIONS: This study expands the application of linguistic styles in the medical field and provides a practical basis for improving patients' emotional well-being.

Electronic Modulation and Mechanistic Study of Ru-Decorated Porous Cu-Rich Cuprous Oxide for Robust Alkaline Hydrogen Oxidation and Evolution Reactions.

Rational design of high-efficiency and viable electrocatalysts is essential in overcoming the bottleneck of sluggish alkaline hydrogen oxidation/evolution reaction (HOR/HER) kinetics. In this study, a metal-organic framework-derived strategy for constructing a Pt-free catalyst with Ru clusters anchored on porous Cu-Cu2 O@C is proposed. The designed Ru/Cu-Cu2 O@C exhibits superior HOR performance, with a mass activity of 2.7 mA µ g R u - 1 ${{{\rm \mu }{\rm g}}_{{\rm R}{\rm u}}^{-1}}$ at 50 mV, which is about 24 times higher than that of state-of-the-art Pt/C (0.11 mA µ g P t - 1 ${{{\rm \mu }{\rm g}}_{{\rm P}{\rm t}}^{-1}}$ ). Significantly, Ru/Cu-Cu2 O@C also displays impressive HER performance by generating 26 mV at 10 mA cm-2 , which exceeds the majority of documented Ru-based electrocatalysts. Systematic characterization and density functional theory (DFT) calculations reveal that efficient electron transfer between Ru and Cu species results in an attenuated hydrogen binding energy (HBE) of Ru and an enhanced hydroxy binding energy (OHBE) of Cu2 O, together with an optimized H2 O adsorption energy with Cu2 O as the H2 O*-capturing site, which jointly facilitates HOR and HER kinetics.

Femoral fixation methods for hamstring graft in anterior cruciate ligament reconstruction: A network meta-analysis of controlled clinical trials.

OBJECTIVE: To compare the clinical effectiveness of cortical button (CB), cross-pin (CP) and compression with interference screws (IS) fixation techniques in anterior cruciate ligament (ACL) reconstruction using hamstring graft. METHODS: Studies were systematically retrieved from PubMed, Embase, Cochrane Library and Web of Science up to May 20, 2021. Primary outcomes were KT-1000 assessment, International Knee Documentation Committee (IKDC) score A or B, Lachman's test, pivot-shift test, visual analogue scale (VAS) score, Lysholm score, Tegner score, and Cincinnati Knee Score. Secondary outcomes included reconstruction failures and synovitis. League tables, rank probabilities and forest plots were drawn for efficacy comparison. RESULTS: Twenty-six controlled clinical trials (CCTs) with 1,824 patients undergoing ACL reconstruction with hamstring graft were included. No significant differences were found among CB, CP and IS fixation methods regarding the 10 outcomes. For KT-1000 assessment, IKDC score A or B, Lachman's test, VAS score and pivot-shift test, CP had the greatest probability of becoming the best method, and IS may be the suboptimal method in 4 out of these 5 outcomes except pivot-shift test. CONCLUSIONS: CP, CB and IS fixations have comparable clinical performance, while CP fixation is most likely to be the optimum fixation technique for hamstring graft in ACL reconstruction. Future larger-sample studies of high quality comparing these techniques in more clinical outcomes are required.

Predicting the concentrations of enteric viruses in urban rivers running through the city center via an artificial neural network.

Viral waterborne diseases are widespread in cities due largely to the occurrence of enteric viruses in urban rivers, which pose a significant concern to human health. Yet, the application of rapid detection technology for enteric viruses in environmental water remains undeveloped globally. Here, multiple linear regression (MLR) modeling and artificial neural network (ANN) modeling, which used frequently measured physicochemical parameters in river water, were constructed to predict the concentration of enteric viruses including human enteroviruses (EnVs), rotaviruses (HRVs), astroviruses (AstVs), noroviruses GⅡ (HuNoVs GⅡ), and adenoviruses (HAdVs) in rivers. After training, testing, and validating, ANN models showed better performance than any MLR model for predicting the viral concentration in Jinhe River. All determined R-values for ANN models exceeded 0.89, suggesting a strong correlation between the predicted and measured outputs for target enteric viruses. Furthermore, ANN models provided a better congruence between the observed and predicted concentrations of each virus than MLR models did. Together, these findings strongly suggest that ANN modeling can provide more accurate and timely predictions of viral concentrations based on frequent (or routine) measurements of physicochemical parameters in river water, which would improve assessments of waterborne disease prevalence in cities.

Low concentration triphenyl phosphate fuels proliferation and migration of hepatocellular carcinoma cells.

Organophosphate flame retardants (OPFRs) have been widely used due to their unique properties. The OPFRs are mainly metabolized in the liver. However, whether the plasma level of OPFRs was involved in the progression of liver cancer remains unclear. Triphenyl phosphate (TPP) is one of the OPFRs that are mostly detected in environment. In this study, we performed CCK8, ATP, and EdU analyses to evaluate the effect of TPP at the concentrations at 0.025-12.8 µM on the proliferation, invasion, and migration of Hep3B, a hepatocellular carcinoma (HCC) cell line. Tumor-bearing mouse model was used for in vivo validation. The results showed that low concentrations of TPP at (0.025-0.1 µM), which are obtained in the plasma of patients with cancers, remarkably promoted cell invasion and migration of Hep3B cells. Animal experiments confirmed that TPP treatment significantly enhanced tumor growth in the xenograft HCC model. To explore the possible molecular mechanisms that might mediate the actions of TPP on Hep3B cells, we profiled gene expression in groups treated with or without TPP at the concentrations of 0.05 and 0.1 µM using transcriptional sequencing. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Protein-protein interaction (PPI) analyses demonstrated that pathways affected by differentially expressed genes (DEGs) were mainly in nuclear-transcribed mRNA catabolic processes, cytosolic ribosome, and ATPase activity. A 0.05 and 0.1 µM TPP led to up-regulation of a series of genes including EREG, DNPH1, SAMD9, DUSP5, PFN1, CKB, MICAL2, SCUBE3, and CXCL8, but suppressed the expression of MCC. These genes have been shown to be associated with proliferation and movement of cells. Taken together, our findings suggest that low concentration of TPP could fuel the proliferation, invasion, and migration of HCC cells. Thus, TPP is a risk factor in the progression of HCC in human beings.