Design of internally integrated in-plane electrodes for superior flexible hybrid zinc-ion capacitor devices.

A unique configuration based on internally integrated electrodes is proposed for flexible hybrid zinc-ion capacitor (HZIC) devices. An in-depth charge storage process is studied, confirming the high electrochemical promise of HZICs for future practical applications.

Population pharmacokinetic analysis and dosing regimen optimization of teicoplanin in critically ill patients with sepsis.

Objectives: Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens. Methods: A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients' clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic/pharmacodynamic parameters, including trough concentration (Cmin), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC0-24/MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA. Results: A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03 L/h, 20.1 L, 3.12 L/h and 101 L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12/15 mg/kg every 12 h followed by a maintenance dose of 12/15 mg/kg every 24 h-72 h for patients with different renal functions were required to achieve a target Cmin of 15 mg/L and a target AUC0-24/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC0-24/MIC than reducing the unit dose for renal insufficient patients. Conclusion: A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic Cmin and AUC, and a single dose of at least 12 mg/kg may be needed. AUC0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin Cmin on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.

DLTKcat: deep learning-based prediction of temperature-dependent enzyme turnover rates.

The enzyme turnover rate, ${k}_{cat}$, quantifies enzyme kinetics by indicating the maximum efficiency of enzyme catalysis. Despite its importance, ${k}_{cat}$ values remain scarce in databases for most organisms, primarily because of the cost of experimental measurements. To predict ${k}_{cat}$ and account for its strong temperature dependence, DLTKcat was developed in this study and demonstrated superior performance (log10-scale root mean squared error = 0.88, R-squared = 0.66) than previously published models. Through two case studies, DLTKcat showed its ability to predict the effects of protein sequence mutations and temperature changes on ${k}_{cat}$ values. Although its quantitative accuracy is not high enough yet to model the responses of cellular metabolism to temperature changes, DLTKcat has the potential to eventually become a computational tool to describe the temperature dependence of biological systems.

Global Infection Rate of Rotavirus C during 1980-2022 and Analysis of Critical Factors in the Host Range Restriction of Virus VP4.

Information on rotavirus C (RVC) infection is lacking, partly because the prevalence of RVC among humans and animals worldwide is undefined. Data on the characteristics of the P genotype among RVC strains are also required. We performed systematic searches on the infection rates of RVC since 1980 based on the literature and gene sequences of the PubMed and GenBank databases. A phylogenetic tree of VP4 genes was constructed to evaluate the distribution of the P genotype of RVC from various hosts. The specific mutation motifs in VP8* with P [2]/P [4]/P [5] specificity were analyzed to elucidate their roles in host range restriction. The rate of RVC infection in humans has fallen from 3% before 2009 to 1%, whereas in animals it has risen from 10% to 25%. The P genotype of RVC showed strict host species specificity, and current human RVC infections are exclusively caused by genotype P [2]. In the VP8* hemagglutinin domain of the P [4]/P [5] genotype of swine RVC, specific insertion or deletion were found relative to the human P [2] genotype, and these motifs are a possible critical factor for host range restriction. Our findings highlight the need for further epidemiological surveillance, preventive strategies, and elucidation of the factors involved in the specific host range restriction of RVC-circulating strains.

Seroprevalence of pullorum disease in chicken across mainland China from 1982 to 2020: A systematic review and meta-analysis.

Pullorum disease (PD), caused by the bacterium Salmonella pullorum, severely threatens the health of chickens worldwide, especially in China, and generating concerns for public health safety. Greater awareness of the seroprevalence may facilitate the prevention and control of this disease. We conducted systematic review and meta-analysis on the seroprevalence of PD in chicken flocks across mainland China. The results show that the overall pooled estimates of PD seroprevalence in chicken flocks was 18.2%. Furthermore, during 38-year period the seroprevalence of PD was markedly high in all seven regions, being at least 14.9% in central China. Our results suggest PD was highly prevalent in autumn, followed by winter. Chickens older than 120 days (22.6%, CI95: 14.5%-31.9%) had a significantly higher positive rate of PD than those <120 days in age (9.4%, CI95: 3.7%-17.4%). Additionally, the rearing mode used is a risk factor associated with the seroprevalence of PD, it being considerably lower for caged chickens (13.7%, CI95: 7.1%-22.0%) than free-range chickens (30.4%, CI95: 17.3-45.4%). Our findings demonstrate that PD still poses a major threat to poultry industries in mainland China, and therefore comprehensive and stringent strategies are needed to prevent and control this disease.

Senecavirus A Enhances Its Adaptive Evolution via Synonymous Codon Bias Evolution.

Synonymous codon bias in the viral genome affects protein translation and gene expression, suggesting that the synonymous codon mutant plays an essential role in influencing virulence and evolution. However, how the recessive mutant form contributes to virus evolvability remains elusive. In this paper, we characterize how the Senecavirus A (SVA), a picornavirus, utilizes synonymous codon mutations to influence its evolution, resulting in the adaptive evolution of the virus to adverse environments. The phylogenetic tree and Median-joining (MJ)-Network of these SVA lineages worldwide were constructed to reveal SVA three-stage genetic development clusters. Furthermore, we analyzed the codon bias of the SVA genome of selected strains and found that SVA could increase the GC content of the third base of some amino acid synonymous codons to enhance the viral RNA adaptive evolution. Our results highlight the impact of recessive mutation of virus codon bias on the evolution of the SVA and uncover a previously underappreciated evolutionary strategy for SVA. They also underline the importance of understanding the genetic evolution of SVA and how SVA adapts to the adverse effects of external stress.

Nonsteroidal anti-inflammatory drugs associated acute kidney injury in hospitalized children: A systematic review and meta-analysis.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are regarded as nephrotoxins. Children commonly use NSAIDs and are susceptible to nephropathy, but the relationship between acute kidney injury (AKI) and use of NSAIDs is not well examined yet. OBJECTIVE: To evaluate the relationship between AKI and use of NSAIDs in hospitalized pediatric patients who are susceptible to nephropathy. METHODS: We conducted this systematic review and meta-analysis of observational studies by searching PubMed, Embase, and Cochrane Database for articles published up to June 1, 2020. Reports included involved children (age < 18 years) who used NSAIDs for various reasons and were admitted in the hospital. The main outcome measure was whether AKI occurred, and pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated using generic inverse variance methods. RESULTS: Seven studies reporting risk of AKI in the hospitalized pediatric patients receiving NSAIDs were included applying a random-effects model. In the hospitalized pediatric population, the pooled OR of AKI for present NSAID exposure was 1.55 (95%CI 1.26-1.92). CONCLUSIONS: NSAID exposure was associated with an approximate 1.6-fold rise in the odds of developing AKI in hospitalized pediatric patients. Avoidance, cautious use of NSAIDs and further evidence are needed. This study was registered with PROSPERO (identifier: CRD42021219779).