Ligand recognition and G-protein coupling of trace amine receptor TAAR1.

Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis1. They recognize diverse endogenous trace amines and subsequently activate a range of G-protein-subtype signalling pathways2,3. Notably, TAAR1 has emerged as a promising therapeutic target for treating psychiatric disorders4,5. However, the molecular mechanisms underlying its ability to recognize different ligands remain largely unclear. Here we present nine cryo-electron microscopy structures, with eight showing human and mouse TAAR1 in a complex with an array of ligands, including the endogenous 3-iodothyronamine, two antipsychotic agents, the psychoactive drug amphetamine and two identified catecholamine agonists, and one showing 5-HT1AR in a complex with an antipsychotic agent. These structures reveal a rigid consensus binding motif in TAAR1 that binds to endogenous trace amine stimuli and two extended binding pockets that accommodate diverse chemotypes. Combined with mutational analysis, functional assays and molecular dynamic simulations, we elucidate the structural basis of drug polypharmacology and identify the species-specific differences between human and mouse TAAR1. Our study provides insights into the mechanism of ligand recognition and G-protein selectivity by TAAR1, which may help in the discovery of ligands or therapeutic strategies for neurological and metabolic disorders.

Regulate the Solvation Structure and Interface by Nitrate in Phosphate-Based Electrolytes for 4.5 V-Class Ni-Rich Batteries.

Phosphate-based electrolyte propels the advanced battery system with high safety. Unfortunately, restricted by poor electrochemical stability, it is difficult to be compatible with advanced lithium metal anodes and Ni-rich cathodes. To alleviate these issues, the study has developed a phosphate-based localized high-concentration electrolyte with a nitrate-driven solvation structure, and the nitrate-derived N-rich inorganic interface shows excellent performance in stabilizing the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode interface and modulating the lithium deposition morphology on the anode. The results show that the Li|| NCM811 cell has exceptional long-cycle stability of >80% capacity retention after 800 cycles at 4.3 V, 1 C. A more prominent capacity retention rate of 93.3% after 200 cycles can be reached with the high voltage of 4.5 V. While being compatible with the phosphate-based electrolyte with good flame retardancy and the good electrochemical stability of Ni-rich lithium metal battery (LMBs) systems, the present work expands the construction of anion-rich solvation structures, which is expected to promote the development of the high-performance LMBs with safety.

Localized High-Concentration Sulfone Electrolytes with High-Voltage Stability and Flame Retardancy for Ni-Rich Lithium Metal Batteries.

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes.

Transcriptome and open chromatin analysis reveals the process of myocardial cell development and key pathogenic target proteins in Long QT syndrome type 7.

OBJECTIVE: Long QT syndrome type 7 (Andersen-Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia, periodic paralysis and skeletal malformations. The development, differentiation and electrophysiological maturation of cardiomyocytes (CMs) changes promote the pathophysiology of Long QT syndrome type 7(LQT7). We aimed to specifically reproduce the ATS disease phenotype and study the pathogenic mechanism. METHODS AND RESULTS: We established a cardiac cell model derived from human induced pluripotent stem cells (hiPSCs) to the phenotypes and electrophysiological function, and the establishment of a human myocardial cell model that specifically reproduces the symptoms of ATS provides a reliable platform for exploring the mechanism of this disease or potential drugs. The spontaneous pulsation rate of myocardial cells in the mutation group was significantly lower than that in the repair CRISPR group, the action potential duration was prolonged, and the Kir2.1 current of the inward rectifier potassium ion channel was decreased, which is consistent with the clinical symptoms of ATS patients. Only ZNF528, a chromatin-accessible TF related to pathogenicity, was continuously regulated beginning from the cardiac mesodermal precursor cell stage (day 4), and continued to be expressed at low levels, which was identified by WGCNA method and verified with ATAC-seq data in the mutation group. Subsequently, it indicated that seven pathways were downregulated (all p < 0.05) by used single sample Gene Set Enrichment Analysis to evaluate the overall regulation of potassium-related pathways enriched in the transcriptome and proteome of late mature CMs. Among them, the three pathways (GO: 0008076, GO: 1990573 and GO: 0030007) containing the mutated gene KCNJ2 is involved that are related to the whole process by which a potassium ion enters the cell via the inward rectifier potassium channel to exert its effect were inhibited. The other four pathways are related to regulation of the potassium transmembrane pathway and sodium:potassium exchange ATPase (p < 0.05). ZNF528 small interfering (si)-RNA was applied to hiPSC-derived cardiomyocytes for CRISPR group to explore changes in potassium ion currents and growth and development related target protein levels that affect disease phenotype. Three consistently downregulated proteins (KCNJ2, CTTN and ATP1B1) associated with pathogenicity were verificated through correlation and intersection analysis. CONCLUSION: This study uncovers TFs and target proteins related to electrophysiology and developmental pathogenicity in ATS myocardial cells, obtaining novel targets for potential therapeutic candidate development that does not rely on gene editing.

Identification and validation of the association of Janus kinase 2 mutations with the response to immune checkpoint inhibitor therapy.

BACKGROUND: Janus kinase 2 (JAK2) mutation plays an important role in T cell immunity. However, the effect of JAK2 mutation on immunotherapy is largely uncharacterized. METHODS: In this study, we analyzed the effect of JAK2 mutation on the efficacy and outcomes of immune checkpoint inhibitor (ICI) therapy in the discovery cohort (n = 662) and the verification cohort (n = 1423). Furthermore, we explored the association of JAK2 mutation with the tumor immune microenvironment in a multiomics cohort. RESULTS: In the discovery cohort (n = 662), JAK2 mutant-type patients had a better objective response rate (58.8% vs. 26.7%, P = 0.010), durable clinical benefit (64.7% vs. 38.9%, P = 0.043), progression-free survival (hazard ratio [HR] = 0.431, P = 0.015), and overall survival (HR = 0.378, P = 0.025), relative to JAK2 wild-type patients. Moreover, we further verified the prognostic significance of JAK2 mutation in an independent ICI treatment cohort with a larger sample size (n = 1423). In addition, we discovered that the JAK2 mutation was remarkably related to increased immunogenicity, such as a higher TMB, higher expression of costimulatory molecules and stimulation of antigen processing mechanisms. In addition, JAK2 mutation was positively correlated with activated anticancer immunity, such as infiltration of various immune cells and higher expression of chemokines. CONCLUSION: Our study demonstrates that JAK2 mutation is a novel marker that can be used to effectively predict prognosis and response to ICI therapy.

Posterior circulation ischemic stroke: radiomics-based machine learning approach to identify onset time from magnetic resonance imaging.

PURPOSE: Posterior circulation ischemic stroke (PCIS) possesses unique features. However, previous studies have primarily or exclusively relied on anterior circulation stroke cases to build machine learning (ML) models for predicting onset time. To date, there is no research reporting the effectiveness and stability of ML in identifying PCIS onset time. We aimed to build diffusion-weighted imaging-based ML models to identify the onset time of PCIS patients. METHODS: Consecutive PCIS patients within 24 h of definite symptom onset were included (112 in the training set and 49 in the independent test set). Images were processed as follows: volume of interest segmentation, image feature extraction, and feature selection. Five ML models, naïve Bayes, logistic regression, tree ensemble, k-nearest neighbor, and random forest, were built based on the training set to estimate the stroke onset time (binary classification: ≤ 4.5 h or > 4.5 h). Relative standard deviations (RSD), receiver operating characteristic (ROC) curves, and the calibration plot was performed to evaluate the stability and performance of the five models. RESULTS: The random forest model had the best performance in the test set, with the highest area under the curve (AUC, 0.840; 95% CI: 0.706, 0.974). This model also achieved the highest accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (83.7%, 64.3%, 91.4%, 75.0%, and 86.5%, respectively). Furthermore, the model had high stability (RSD = 0.0094). CONCLUSION: The PCIS case-based ML model was effective for estimating the symptom onset time and achieved considerably high specificity and stability.

Acetyl-CoA synthetase 2 promotes diabetic renal tubular injury in mice by rewiring fatty acid metabolism through SIRT1/ChREBP pathway.

Diabetic nephropathy (DN) is characterized by chronic low-grade renal inflammatory responses, which greatly contribute to disease progression. Abnormal glucose metabolism disrupts renal lipid metabolism, leading to lipid accumulation, nephrotoxicity, and subsequent aseptic renal interstitial inflammation. In this study, we investigated the mechanisms underlying the renal inflammation in diabetes, driven by glucose-lipid metabolic rearrangement with a focus on the role of acetyl-CoA synthetase 2 (ACSS2) in lipid accumulation and renal tubular injury. Diabetic models were established in mice by the injection of streptozotocin and in human renal tubular epithelial HK-2 cells cultured under a high glucose (HG, 30 mmol/L) condition. We showed that the expression levels of ACSS2 were significantly increased in renal tubular epithelial cells (RTECs) from the diabetic mice and human diabetic kidney biopsy samples, and ACSS2 was co-localized with the pro-inflammatory cytokine IL-1ß in RTECs. Diabetic ACSS2-deficient mice exhibited reduced renal tubular injury and inflammatory responses. Similarly, ACSS2 knockdown or inhibition of ACSS2 by ACSS2i (10 µmol/L) in HK-2 cells significantly ameliorated HG-induced inflammation, mitochondrial stress, and fatty acid synthesis. Molecular docking revealed that ACSS2 interacted with Sirtuin 1 (SIRT1). In HG-treated HK-2 cells, we demonstrated that ACSS2 suppressed SIRT1 expression and activated fatty acid synthesis by modulating SIRT1-carbohydrate responsive element binding protein (ChREBP) activity, leading to mitochondrial oxidative stress and inflammation. We conclude that ACSS2 promotes mitochondrial oxidative stress and renal tubular inflammation in DN by regulating the SIRT1-ChREBP pathway. This highlights the potential therapeutic value of pharmacological inhibition of ACSS2 for alleviating renal inflammation and dysregulation of fatty acid metabolic homeostasis in DN. Metabolic inflammation in the renal region, driven by lipid metabolism disorder, is a key factor in renal injury in diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is abundantly expressed in renal tubular epithelial cells (RTECs) and highly upregulated in diabetic kidneys. Deleting ACSS2 reduces renal fatty acid accumulation and markers of renal tubular injury in diabetic mice. We demonstrate that ACSS2 deletion inhibits ChREBP-mediated fatty acid lipogenesis, mitochondrial oxidative stress, and inflammatory response in RTECs, which play a major role in the progression of diabetic renal tubular injury in the kidney. These findings support the potential use of ACSS2 inhibitors in treating patients with DN.

Microbial community succession and responses to internal environmental drivers throughout the operation of constructed wetlands.

Constructed wetlands (CWs) have been widely used to ensure effective domestic wastewater treatment. Microorganisms-derived CWs have received extensive attention as they play a crucial role. However, research on the succession patterns of microbial communities and the influencing mechanisms of internal environmental factors throughout entire CW operations remains limited. In this context, three parallel-operated CWs were established in this study to assess the microbial communities and their influencing environmental factors at different substrate depths throughout the operation process using 16S rRNA gene high-throughput sequencing and metagenomic sequencing. The results showed gradual reproduction and accumulation of the microbial communities throughout the CW operation. Although gradual increases in the richness and diversity of the microbial communities were found, there were decreases in the functional expression of the dominant microbial species. The excessive accumulation of microorganisms will decrease the oxidation-reduction potential (ORP) within CWs and attenuate their influence on effluent.. Dissolved oxygen (DO) was the major factor influencing the microbial community succession over the CW operation. The main identified functional bacterial genera responsible for the ammonium oxidation, nitrification, and denitrification processes in the CWs were Nitrosospira, Nitrobacter, Nitrospira, Rhodanobacter, and Nakamurella. The narG gene was identified as a key functional gene linking various components of nitrogen cycling, while pH, electrical conductivity (EC), and ORP were the major environmental factors affecting the metabolism characteristics of nitrogen functional microorganisms. This study provides a theoretical basis for the effective regulation of related microbial communities to achieve long-term, efficient, and stable CW operations.

The Impact of Empowerment Education on Discharge Readiness and Care Burden of Caregivers of Children with Congenital Heart Disease.

Context: Care burden refers to the physical burden that caregivers bear during the process of caring for children with congenital heart disease (CHD), and discharge readiness mainly refers to the confidence of the main caregivers in taking care of patients. Empowerment education's influence on the discharge readiness and caregivers' burden is unknown for children with CHD. Objective: The study intended to explore the impact of empowerment education on the discharge readiness and care burden of caregivers of children with CHD. Design: The research team conducted a prospective cohort study. Setting: The study took place at Anhui Provincial Children's Hospital in Hefei City, China. Participants: Participants were 163 caregivers of children who underwent surgery for CHD at the hospital between January 2019 and August 2021. Interventions: The research team divided participants into two groups using convenience sampling: (1) a control group, with 82 participants who received routine nursing education and intervention, and (2) an intervention group, with 81 participants who received empowered nursing education. Outcome Measures: Postintervention, the research team evaluated the caregivers': (1) readiness for the child's discharge and (2) burden level. Results: Postintervention, the intervention group's: (1) total score for discharge readiness and scores on the personal status and adaptability dimensions were significantly higher than those of the control group (all P < .05), and (2) care burden level was significantly lower than that of the control group (P < .05). Conclusions: Empowerment education can help caregivers of children with congenital defects of the heart to build awareness of the need to participate in disease management, improve disease-related knowledge and skills, reduce their negative emotions, and improve their level of preparation for their children's discharge and reduce their level of care burden. The therapy is worth further investigation and popularization.

Solution-Focused Group Counseling on Mental States in Hemodialysis Patients with Anxiety.

BACKGROUND: Hemodialysis patients usually suffer from anxiety due to physical and social factors, which belongs to a kind of psychological disorder, easily contributing to the decrease of patients' adherence to the treatment, and seriously affecting the patients' health status and quality of life. Solution-focused group counseling (SFGC) is a kind of psychotherapy proven to improve emotional problems in many fields. Still, the application of this therapy is rare in medical situations. This retrospective study aims to analyze the application of SFGC and probe into the effects on mental states in hemodialysis patients with anxiety. METHODS: From January 2022 to February 2023, 212 patients with hemodialysis and anxiety admitted to our hospital were selected, and 9 patients who did not meet the inclusion criteria were excluded. Finally, 203 patients were included in this retrospective study. According to different clinical management methods, 102 patients receiving routine management were classified as the control group (CG), and 101 patients receiving SFGC on the basis of routine management were included in the observation group (OG). The scores of the self-perceived burden scale (SPBS), medical coping modes questionnaire (MCMQ), and self-rating anxiety scale (SAS) of the two groups were collected. The data collected were calculated and processed by software SPSS 26.0, and the effects of different managements on the mental states of patients with hemodialysis and anxiety were compared. RESULTS: After management, the scores of SPBS in both groups were lower than those before management, and the score in OG was significantly lower than the CG (p < 0.001). After management, the confrontation scores increased, the avoidance and resignation scores decreased in the MCMQ of the two groups, and the scores in the OG changed significantly (p < 0.001). The SAS scores of the two groups after management were significantly lower than those before management, and the OG score was significantly lower than the CG (p < 0.001). CONCLUSION: SFGC has a positive effect on the mental states of patients with hemodialysis and anxiety, which is worthy of further clinical study.

Unique modulation effects on the performance of graphene-based ammonia sensors via ultrathin bimetallic Au/Pt layers and gate voltages.

Gas sensors with superior comprehensive performance at room temperature (RT) are always desired. Here, Au, Pt and Pt/Au-decorated graphene-based field effect transistor (FET) sensors for ammonia (denoted as Au/Gr, Pt/Gr and Pt/Au/Gr, respectively) are designed and fabricated. All these devices exhibited far better RT sensing performances for ammonia compared with graphene devices. Applying positive back gate voltages can further enhance their RT performance in which the Pt/Au/Gr devices show superior RT comprehensive performance such as a response of -16.2%, a recovery time of 4.6 min, and especially a much reduced response time of 54 s for 200 ppm NH3 with a detection limit of 103 ppb at a gate voltage of +60 V, and can be potentially tailored for further performance improvement by controlling the ratios of Pt and Au. The dependences of their performance on the gate voltage except for the response time could be reasonably explained by theoretical calculations in terms of the changes of the total density of states near the Fermi level, adsorption energies, transferred charges and adsorption distances. This study provides an effective solution for performance improvement of FET-based sensors via synergistic effects of ultrathin-layer multiple-metallic decoration and gate voltage, which would promote the exploration of novel sensors.

Prevalence of and factors associated with alexithymia among patients with chronic obstructive pulmonary disease in China: a cross-sectional study.

BACKGROUND: Alexithymia is a common psychological disorder. However, few studies have investigated its prevalence and predictors in patients with chronic obstructive pulmonary disease (COPD). Therefore, we aimed to determine the prevalence and predictors of alexithymia in Chinese patients. METHODS: This cross-sectional study included 842 COPD patients to assess the prevalence and predictors of alexithymia using the 20-item Toronto Alexithymia Scale (TAS-20). We used the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression, the modified British Medical Research Council dyspnea Rating Scale (mMRC) to assess dyspnea, St. George's Respiratory Questionnaire (SGRQ) to assess quality of life, and the age-adjusted Charlson comorbidity index (ACCI) to assess comorbidities. Alexithymia-related predictors were identified using univariate and multivariate logistic regression analyses. RESULTS: The prevalence of alexithymia in COPD patients was 23.6% (199/842). Multivariate analysis showed that age [odds ratio (OR) 0.886; 95% confidence interval (CI) 0.794-0.998], body mass index (OR 0.879; 95% CI 0.781-0.989), HADS-anxiety (OR 1.238; 95% CI 1.097-1.396), HADS-depression (OR 1.178; 95% CI 1.034-1.340), mMRC (OR 1.297; 95% CI 1.274-1.320), SGRQ (OR 1.627; 95% CI 1.401-1.890), ACCI (OR 1.165; 95% CI 1.051-1.280), and GOLD grade (OR 1.296; 95% CI 1.256-1.337) were independent predictors for alexithymia in patients with COPD. CONCLUSIONS: The prevalence of alexithymia was high in Chinese COPD patients. Anxiety, depression, dyspnea, quality of life, comorbidities, and disease severity are independent risk factors, and age and BMI are predictive factors for alexithymia in COPD patients.

A nomogram to predict hyperkalemia in patients with hemodialysis: a retrospective cohort study.

BACKGROUND: Hyperkalemia increases the risk of mortality and cardiovascular-related hospitalizations in patients with hemodialysis. Predictors of hyperkalemia are yet to be identified. We aimed at developing a nomogram able to predict hyperkalemia in patients with hemodialysis. METHODS: We retrospectively screened patients with end-stage renal disease (ESRD) who had regularly received hemodialysis between Jan 1, 2017, and Aug 31, 2021, at Lishui municipal central hospital in China. The outcome for the nomogram was hyperkalemia, defined as serum potassium [K+] ≥ 5.5 mmol/L. Data were collected from hemodialysis management system. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. A prediction model was constructed by multivariate logistic regression and presented as a nomogram. The performance of nomogram was measured by the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA). This model was validated internally by calculating the performance on a validation cohort. RESULTS: A total of 401 patients were enrolled in this study. 159 (39.65%) patients were hyperkalemia. All participants were divided into development (n = 256) and validation (n = 145) cohorts randomly. Predictors in this nomogram were the number of hemodialysis session, blood urea nitrogen (BUN), serum sodium, serum calcium, serum phosphorus, and diabetes. The ROC curve of the training set was 0.82 (95%CI 0.77, 0.88). Similar ROC curve was achieved at validation set 0.81 (0.74, 0.88). The calibration curve demonstrated that the prediction outcome was correlated with the observed outcome. CONCLUSION: This nomogram helps clinicians in predicting the risk of PEW and managing serum potassium in the patients with hemodialysis.

Predictors and outcomes of obstructive sleep apnea in patients with chronic obstructive pulmonary disease in China.

BACKGROUND: "Overlap syndrome" refers to obstructive sleep apnea (OSA) combined with chronic obstructive pulmonary disease (COPD), and has poorer outcomes than either condition alone. We aimed to evaluate the prevalence and possible predictors of overlap syndrome and its association with clinical outcomes in patients with COPD. METHODS: We assessed the modified Medical Research Council dyspnea scale (mMRC), Epworth sleepiness scale (ESS), COPD assessment test (CAT), Hospital Anxiety and Depression Scale (HADS), Charlson Comorbidity Index (CCI), and STOP-Bang questionnaire (SBQ) and performed spirometry and full overnight polysomnography in all patients. An apnea-hypopnea index (AHI) ≥ 5 events per hour was considered to indicate OSA. Risk factors for OSA in COPD patients were identified by univariate and multivariate logistic regression analyses. RESULTS: A total of 556 patients (66%) had an AHI ≥ 5 events per hour. There were no significant differences in age, sex ratio, mMRC score, smoking index, number of acute exacerbations and hospitalizations in the last year, and prevalence of cor pulmonale between the two groups (all p > 0.05). Body mass index (BMI), neck circumference, CAT score, CCI, ESS, HADS, and SBQ scores, forced expiratory volume (FEV)1, FEV1% pred, FEV1/forced vital capacity ratio, and prevalence of hypertension, coronary heart disease, and diabetes were all significantly higher and the prevalence of severe COPD was significantly lower in the COPD-OSA group compared with the COPD group (p < 0.05). BMI, neck circumference, ESS, CAT, CCI, HADS, hypertension, and diabetes were independent risk factors for OSA in COPD patients (p < 0.05). SBQ could be used for OSA screening in patients with COPD. Patients with severe COPD had a lower risk of OSA compared with patients with mild or moderate COPD (ß = - 0.459, odds ratio = 0.632, 95% confidence interval 0.401-0.997, p = 0.048). CONCLUSION: Patients with overlap syndrome had a poorer quality of life, more daytime sleepiness, and a higher prevalence of hypertension and diabetes than patients with COPD alone. BMI, neck circumference, ESS, CAT, CCI, HADS, hypertension, and diabetes were independent risk factors for OSA in patients with COPD. The risk of OSA was lower in patients with severe, compared with mild or moderate COPD.

Cometabolic degradation mechanism and microbial network response of methanotrophic consortia to chlorinated hydrocarbon solvents.

The cometabolism mechanism of chlorinated hydrocarbon solvents (CHSs) in mixed consortia remains largely unknown. CHS biodegradation characteristics and microbial networks in methanotrophic consortia were studied for the first time. The results showed that all CHSs can efficiently be degraded via cometabolism with a maximum degradation rate of 4.8 mg/(h·gcell). Chloroalkane and chloroethylene were more easily degraded than chlorobenzenes by methanotrophic consortia, especially nonfully chlorinated aliphatic hydrocarbons, which were converted to Cl- with a production rate of 0.29-0.36 mg/(h·gcell). In addition, the microecological response results indicated that Methylocystaceae (49.0%), Methylomonas (65.3%) and Methylosarcina (41.9%) may be the major functional degraders in methanotrophic consortia. Furthermore, the results of the microbial correlation network suggested that interactive relationships constructed by type I methanotrophs and heterotrophs determined biodegradability. Additionally, PICRUSt analysis showed that CHSs could increase the relative abundance of CHS degradation genes and reduce the relative abundance of methane oxidation genes, which was in good agreement with the experimental results.

LamB, OmpC, and the Core Lipopolysaccharide of Escherichia coli K-12 Function as Receptors of Bacteriophage Bp7.

Bp7 is a T-even phage with a broad host range specific to Escherichia coli, including E. coli K-12. The receptor binding protein (RBP) of bacteriophages plays an important role in the phage adsorption process and determines phage host range, but the molecular mechanism involved in host recognition of phage Bp7 remains unknown. In this study, the interaction between phage Bp7 and E. coli K-12 was investigated. Based on homology alignment, amino acid sequence analysis, and a competitive assay, gp38, located at the tip of the long tail fiber, was identified as the RBP of phage Bp7. Using a combination of in vivo and in vitro approaches, including affinity chromatography, gene knockout mutagenesis, a phage plaque assay, and phage adsorption kinetics analysis, we identified the LamB and OmpC proteins on the surface of E. coli K-12 as specific receptors involved in the first step of reversible phage adsorption. Genomic analysis of the phage-resistant mutant strain E. coli K-12-R and complementation tests indicated that HepI of the inner core of polysaccharide acts as the second receptor recognized by phage Bp7 and is essential for successful phage infection. This observation provides an explanation of the broad host range of phage Bp7 and provides insight into phage-host interactions.IMPORTANCE The RBPs of T4-like phages are gp37 and gp38. The interaction between phage T4 RBP gp37 and its receptors has been clarified by many reports. However, the interaction between gp38 and its receptors during phage adsorption is still not completely understood. Here, we identified phage Bp7, which uses gp38 as an RBP, and provided a good model to study the phage-host interaction mechanisms in an enterobacteriophage. Our study revealed that gp38 of phage Bp7 recognizes the outer membrane proteins (OMPs) LamB and OmpC of E. coli K-12 as specific receptors and binds with them reversibly. HepI of the inner-core oligosaccharide is the second receptor and binds with phage Bp7 irreversibly to begin the infection process. Determining the interaction between the phage and its receptors will help elucidate the mechanisms of phage with a broad host range and help increase understanding of the phage infection mechanism based on gp38.

In-depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis.

Cardiac remodelling following myocardial infarction (MI) is a maladaptive change associated with progressive heart failure and compromises long-term clinical outcome. A substantial proportion of patients afflicted by MI still develop adverse outcomes associated with cardiac remodelling. Therefore, it is crucial to identify biomarkers for the early prediction of cardiac remodelling. An in-depth proteomics approach, including both semi-quantitative and quantitative antibody arrays, was used to identify circulating biomarkers that may be associated with detrimental cardiac remodelling. Furthermore, statistical correlation analysis was performed between the candidate biomarkers and clinical cardiac remodelling data to demonstrate their clinical utility. A systematic proteomics approach revealed that sclerostin (SOST), growth differentiation factor-15 (GDF-15), urokinase-type plasminogen activator (uPA), and midkine (MK) were increased, while monocyte chemotactic protein-3 (MCP-3) was uniquely decreased in MI patients who developed cardiac remodelling, compared to MI patients who did not develop cardiac remodelling and healthy humen. Moreover, correlation analyses between serum proteomes and cardiac remodelling echocardiographic parameters demonstrated a moderate positive association between left ventricular end-diastolic volume index (LVEDVi) and the three serum proteins, uPA, MK and GDF-15 (P < .05, respectively), and a moderate negative correlation between LV ejection fraction (LVEF) and these serum proteins (P < .05, respectively). Importantly, uPA and MK were firstly identified to be associated with the development of cardiac remodelling. The present study contributes to a better understanding of the various cytokines expressed during adverse cardiac remodelling. The identified biomarkers may facilitate early identification of patients at high risk of ischaemic heart failure pending further confirmation through larger clinical trials.

Prolonged siRNA expression in mammalian cells using an Epstein-Barr virus-based plasmid expression system.

RNA interference (RNAi) is a powerful tool in gene function analysis and disease treatment, especially diseases that are 'undruggable' by classical small molecules. However, the RNAi applications are limited due to some defects, such as short duration and toxic side effects. New strategies are still needed to improve RNAi applications. Previous studies have illustrated that Epstein-Barr virus nuclear antigen 1 (EBNA-1) and the origin of plasmid replication (oriP) are critical factors for EBV latent gene expression, which can keep the replication of the EBV genome as an extrachromosomal element for a relatively long time. Here we report a plasmid expression system on the base of oriP and EBNA-1, which could produce protein as well as short interfering RNAs(siRNAs) for a long time in mammalian cells. siRNA expression mediated by this system causes efficient and specific down-regulation of gene expression. Except for analyzing gene function, this study also provided a new optional and practical way for protein and/or RNAi-based therapies that require enduring effect.

Cu/graphene interdigitated electrodes with various copper thicknesses for UV-illumination-enhanced gas sensors at room temperature.

Effective detection of NO2 and NH3 gases at room temperature (RT) is critical for environmental monitoring and protection. Here, graphene-based gas sensors (Cu/Gr device) of single layer graphene decorated by 6, 8 and 10 nm thick Cu layers with graphene instead of conventional metal as interdigital electrodes are designed and fabricated. The RT performance for both NO2 and NH3 detection can be greatly enhanced by UV light illumination which is closely related to the thickness of Cu layers in which the device with 8 nm thickness (8 nm Cu/Gr device) exhibits the best performances. Analysis of XPS reveals that Cu is partly oxidized to Cu+ and Cu2+ for 6 nm with extra Cuδ+ (1 < δ < 2) for 8 and 10 nm. The contents and distributions of copper oxides and copper in Cu layers influence the catalytic effects and the heterojunction barrier and thus the performances. The RT responses of -30.9% and -8.1% for 5 and 0.3 ppm NO2, and of +29.1% and +5.9% for 105 and 10 ppm NH3 are achieved for the 8 nm Cu/Gr device, respectively. The limits of detection (LODs) for NO2 and NH3 are 12 ppb and 17 ppb, respectively. The sensing mechanisms are discussed in terms of density functional theory (DFT) calculations and energy band diagrams. The study demonstrates an effective solution of improving the device performance by modifying the device configuration and incorporating combined oxides naturally oxidized, which provides the novel design alternatives for high performance sensors.

Simultaneous achievement of superior response and full recovery of titanium dioxide/graphene hybrid FET sensors for NH3 through p- to n-mode switch.

The switch in the sensing mode for better identification of donor/acceptor gases with simultaneous enhancement of the sensing performance at a fixed working temperature particularly room temperature (RT) is quite challenging for gas sensors. Herein, TiO2/graphene hybrid field effect transistor (FET) sensors (TiO2/GFET) with varied hybrid areas are presented. Superior sensing and recovery performances for NH3 are achieved through sensing mode switch via gate biasing. 16.40% response and full recovery for 25 ppm NH3 are achieved for TiO2/GFET sensors with 100% titanium dioxide coverage (D100) at RT (27 °C) with 15-20% humidity upon switching sensing mode from p- to n via gate biasing. Full recovery is attributed to the Coulomb interaction between charged polar donor molecules and positively polarized surface which is enhanced by the switch from p- to n-mode. The humidity can enhance response up to -35.48% for 25 ppm NH3 with full recovery in n-mode for D100. D100 shows superior selectivity towards NH3 against both electron-acceptor NO2 and several other electron-donor analytes. The sensing behaviors for NH3 are well elucidated using energy band diagrams based on the experimental results. This study proposes a novel idea for performance improvement of FET based sensors with p- and n-type hybrid sensing materials through p (n)- to n (p)-mode switch assisted by gate biasing by incorporating suitable electron (hole) rich materials to compensate holes (electrons) in p (n)-type materials for electron donor (acceptor) gas detection.