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ObjectivesThe present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China.MethodsA total of 219 new leprosy cases during two periods, 2018–2019 and 2020–2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods.ResultsThere was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January–March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K.ConclusionCOVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

Endothelial cells are the crucial inner lining of blood vessels, which are pivotal in vascular homeostasis and integrity. However, these cells are perpetually subjected to a myriad of mechanical, chemical, and biological stresses that can compromise their plasma membranes. A sophisticated repair system involving key molecules, such as calcium, annexins, dysferlin, and MG53, is essential for maintaining endothelial viability. These components orchestrate complex mechanisms, including exocytosis and endocytosis, to repair membrane disruptions. Dysfunctions in this repair machinery, often exacerbated by aging, are linked to endothelial cell death, subsequently contributing to the onset of atherosclerosis and the progression of cardiovascular diseases (CVD) and stroke, major causes of mortality in the United States. Thus, identifying the core machinery for endothelial cell membrane repair is critically important for understanding the pathogenesis of CVD and stroke and developing novel therapeutic strategies for combating CVD and stroke. This review summarizes the recent advances in understanding the mechanisms of endothelial cell membrane repair. The future directions of this research area are also highlighted.

Escherichia coli (E. coli) can cause diarrhoea in a wide range of hosts. Moreover, some trains with high virulence and drug resistance pose a serious threat to public health and livestock products. Diarrhoea caused by E. coli outbreaks in rabbitries result in serious economic losses. The aim of this study was to investigate the distribution of virulence genes and molecular genetic characteristics of E. coli from diarrhoeal rabbits in the main rearing areas of Sichuan province, China in 2015-2017. In total, 39 E. coli isolates were identified and undivided divided into 17 sequence types by multilocus sequence typing (MLST) and grouped in 22 clusters by pulsed-field gel electrophoresis. Polymerase chain reaction tests detected 6 virulence genes: eae (41.0%), ler (41.0%), ral (33.3%), afr2 (10.3%), irp2 (15.4%) and astA (7.7%) of the tested 17 virulence genes identifying 16 enteropathogenic E. coli (EPEC) isolates. The main sequence types U328, ST328 and ST20 carried rabbit EPEC associated virulence genes (eae, ler, ral and afr2). The results showed that the distribution of virulence genes varied by year and area; genotype had major types in local rearing areas but was of high diversity in Sichuan province.

Carbon emission constraints and trading policies in e-commerce environments have brought huge challenges to the operation of supply chain enterprises. In order to ensure the good operation of the e-commerce supply chain in a low-carbon environment, a supply chain scheduling optimization method based on integration of production and transportation with carbon emission constraints is proposed; we use it to analyze the impact of centralized decision-making mode and decentralized decision-making mode on supply chain scheduling and establish a scheduling optimization model that aims at optimal carbon emissions and costs. A multilevel genetic algorithm was designed according to the characteristics of the model, and numerical examples are used to verify the effectiveness of the model and algorithm. The results show that the centralized decision-making mode plays the role of the carbon emission constraints to the greatest extent; the carbon emissions and the cost are smallest in the centralized decision-making mode. The decentralized decision-making mode leads to the overall cost preference of the supply chain due to separate decisions made by enterprises, and the carbon emissions in the supply chain are greater. Transportation experts, business managers and government departments are interesting for integrated production and transportation scheduling in e-commerce supply chain with carbon emission constraints. Further research should address integrated production and transportation scheduling in dual-channel low supply chains.

Abstract Conformational change associated with allosteric regulation in a protein is ultimately driven by energy transformation. However, little is known about the latter process. In this work, we combined steered molecular dynamics simulations and sequence conservation analysis to investigate the conformational changes and energy transformation in the allosteric enzyme aspartokinase III (AK III) from Escherichia coli. Correlation analysis of energy change at residue level indicated significant transformation between electrostatic energy and dihedral angle energy during the allosteric regulation. Key amino acid residues located in the corresponding energy transduction pathways were identified by dynamic energy correlation analysis. To verify their functions, residues with a high energy correlation in the pathways were altered and their effects on allosteric regulation of AKIII were determined. This study sheds new insights into energy transformation during allosteric regulation of AK III and proposes a strategy to identify key residues that are involved in intramolecular energy transduction and thus in driving the allosteric process.

Myricaria elegans, an endemic species to the Himalayas, is a distinctive deciduous shrubbery plant-primarily distributed in the Qinghai-Tibet Plateau and adjacent regions in China. It is a kind of fuelwood, medicinal, and ecology-protecting woody plant species. In this study, the whole chloroplast (cp) genome sequence of M. elegans was assembled and characterized by high-throughput sequencing data. The complete cp genome of M. elegans was 155,245 bp in length with a GC content of 37.4%. It contained a large single-copy region (LSC) of 84,846 bp, and a small single-copy region (SSC) of 18,290 bp, which were separated by a pair of 26,053 bp inverted repeat regions (IRs). The cp genome of M. elegans was composed of 130 genes, including 85 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. Phylogenetic analysis revealed that M. elegans formed a clade with Myricaria, and it showed a close relationship with Myricaria prostrata.

Organic solvent tolerant oxidoreductases are significant for both scientific research and biomanufacturing. However, it is really challenging to obtain oxidoreductases due to the shortages of natural resources and the difficulty to obtained it via protein modification. This review summarizes the recent advances in gene mining and structure-functional study of oxidoreductases from extremophiles for non-aqueous reaction systems. First, new strategies combining genome mining with bioinformatics provide new insights to the discovery and identification of novel extreme oxidoreductases. Second, analysis from the perspectives of amino acid interaction networks explain the organic solvent tolerant mechanism, which regulate the discrete structure-functional properties of extreme oxidoreductases. Third, further study by conservation and co-evolution analysis of extreme oxidoreductases provides new perspectives and strategies for designing robust enzymes for an organic media reaction system. Furthermore, the challenges and opportunities in designing biocatalysis non-aqueous systems are highlighted.

Voltage-gated proton (Hv) channels are standalone voltage sensors without separate ion conductive pores. They are gated by both voltage and transmembrane proton gradient (i.e., ∆pH), serving as acid extruders in most cells. Like the canonical voltage sensors, Hv channels are a bundle of four helices (named S1 –S4), with the S4 segment carrying three positively charged Arg residues. Extensive structural and electrophysiological studies on voltage-gated ion channels, in general, agree on an outwards movement of the S4 segment upon activating voltage, but the real-time conformational transitions are still unattainable. With purified human voltage-gated proton (hHv1) channels reconstituted in liposomes, we have examined its conformational dynamics, including the S4 segment at different voltage and pHs using single-molecule fluorescence resonance energy transfer (smFRET). Here, we provide the first glimpse of real-time conformational trajectories of the hHv1 voltage sensor and show that both voltage and pH gradient shift the conformational dynamics of the S4 segment to control channel gating. Our results indicate that the S4 segment transits among three major conformational states and only the transitions between the inward and outward conformations are highly dependent on voltage and pH. Altogether, we propose a kinetic model that explains the mechanisms underlying voltage and pH gating in Hv channels, which may also serve as a general framework for understanding the voltage sensing and gating in other voltage-gated ion channels.

The current study investigates the association of various economic, non-economic, governance, and environmental indicators on human health for seven emerging economies. Covering the period from 2000Q1 to 2018Q1, this study uses various panel data approaches for empirical estimations. The data is found first-order stationary. Besides, the panel slope is heterogeneous and cross-sectional dependence is present. Further, the cointegration association is found valid among the variables. Therefore, panel quantile regression is used to determine the long-run impact of each explanatory variable on human health at four quantiles (Q25, Q50, Q75, and Q90). The estimated results asserted that economic growth, government health expenditure, and human capital significantly reduce human health disasters like malaria incidences and cases. At the same time, greenhouse gas emissions and regulatory quality are significantly and positively correlated to human health issues in emerging economies. Moreover, mixed (unidirectional and bidirectional) causal associations exist between the variables. This study also provides relevant policy implications based on the empirical results, providing a path for regulating various economic, environmental, and governance sectors. Effective policy implementation and preventive measures can reduce the spread of diseases and mortality rates due to Malaria.

Abstract Background There is limited knowledge on the mediating role of different health risk behavior on the relationship between social capital, socioeconomic status (SES), and health-related quality of life (HRQoL) in Chinese older adults. We conducted this study to (a) investigate the condition of health risk behaviors of the Chinese elderly, and (b) assess the relationship between SES, social capital, health risk behaviors, and HRQoL. Methods A sample of 4868 adults aged 60 years and older were included in this study, from the China’s Health-related Quality of Life Survey for Older Adults 2018. Participants’ demographic characteristics, SES (education level, family income), health risk behaviors (smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder) were collected. Social capital and HRQoL were assessed by the 16-item Personal Social Capital Scale (PSCS-16) and WHOQOL-Old, respectively. Structural equation modeling (SEM) was applied to examine the associations between variables. Results The proportion of smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder were 32.1, 36.3, 62.5, 45.7, 31.8, and 45.5%, respectively. Significant differences were observed in education level, family income, and social capital between elderly individuals with and without each of the six health risk behavior (all p-values

Abstract Background Diet-related knowledge, attitudes, and behaviors (KABs) are important for building healthier dietary patterns. We conducted this study to (a) investigate diet conditions of Chinese adult residents from the perspective of knowledge, attitudes, and behaviors, and (b) assess the association between diet-related KABs and self-rated health. Methods We analyzed the 2015 China Health and Nutrition Survey (CHNS) data. Individuals aged 18 years and older were included as study subjects (n = 12,814), assessing their diet-related knowledge, attitudes, behaviors, and self-rated health. Comparison of diet-related KABs in urban and rural residents was conducted using chi-square test. Ordinal logistic regression analysis was adopted to examine the association between diet-related KABs and self-rated health. Results The proportion of knowing about the Chinese Food Pagoda (CFP) or the Dietary Guidelines for Chinese Residents (DGCR) was 27.1%. 34.3% of the participants were assessed as having adequate dietary knowledge literacy. 24.3% reported a positive attitude towards healthy eating. 27.6 and 65.9% of the participants reported proactively looking for nutrition knowledge and preferring eating fruits & vegetables, respectively. Chi-square test indicated that rural people experienced poorer diet-related knowledge, attitudes, and behaviors than urban residents (all p-values

Metal–organic frames (MOFs) have recently been used to support redox enzymes for highly sensitive and selective chemical sensors for small biomolecules such as oxygen (O2), hydrogen peroxide (H2O2), etc. However, most MOFs are insulative and their three-dimensional (3D) porous structures hinder the electron transfer pathway between the current collector and the redox enzyme molecules. In order to facilitate electron transfer, here we adopt two-dimensional (2D) metal–organic layers (MOLs) to support the HRP molecules in the detection of H2O2. The correlation between the current response and the H2O2 concentration presents a linear range from 7.5 μM to 1500 μM with a detection limit of 0.87 μM (S/N = 3). The sensitivity, reproducibility, and stability of the enzyme sensor are promoted due to the facilitated electron transfer.

This study examines the impact of COVID-19 sentiment on office building rents and vacancy rates in China with a COVID-19 sentiment index constructed based on Baidu search queries on COVID-19-related keywords. We analyzed the data of office buildings and economic data from 2013 Q3 to 2022 Q2 in seven major Chinese cities with a two-stage Error Correction Model framework. We found that a heightened level of COVID-19 sentiment significantly and adversely affects the Chinese office buildings market. Specifically, office building rents decrease more than 8% if a city is exposed to an increase of one unit of COVID-19 sentiment for an entire quarter. The interaction terms model further reveals that the COVID-19 sentiment has a more substantial impact on office building rents where office vacancy is higher, reflecting an asymmetric effect. The findings here support the fear sentiment hypothesis. The findings suggest that a heightened level of investors’ COVID-19 sentiment resulted in a deterioration of office rents, reinforcing the role of investors’ sentiment in the pricing of office buildings. The findings suggest that investors should consider investor sentiment, particularly COVID-19 sentiment, in their decision-making.

Background: Cardiovascular disease (CVD) has become one of the leading causes of death and disability worldwide, and its incidence continues to increase because of an aging population. Studies have shown that the function of cardiomyocytes decreases during aging, leading to changes in the functional and structural integrity of the heart, ultimately resulting in CVD. The decrease in the number of functional cardiomyocytes has a negative impact on cardiac function; thus, myocardial aging is one of the main factors that causes heart-related diseases (such as CVD). Therefore, alleviating cardiac aging is one of the main ways of treating aging-related cardiac diseases. In this study, we evaluated the potential effect of taraxasterol on myocardial aging. Methods: The effect of taraxasterol on the aging of cardiomyocytes was analyzed in vivo and in vitro using a D-galactose treatment mouse model of cardiomyocyte senescence. Furthermore, the effect of taraxasterol on aging-induced desensitization of insulin signaling was also evaluated. Results: The experimental results indicated that taraxasterol could reduce cardiomyocyte senescence, which was evaluated using Sa-β-gal staining and senescence-related marker molecules (e.g., p16 and p21). We found that taraxasterol could significantly alleviate cardiomyocyte senescence in the in vitro cell model. Furthermore, we found that taraxasterol had the potential to alleviate cardiomyocyte senescence via the regulation of oxidative stress and inflammatory processes. Additionally, taraxasterol could relieve the desensitization of insulin signaling caused by aging. Finally, we showed that cardiovascular aging and fibrosis were alleviated by taraxasterol treatment in vivo. Conclusions: Taken together, this work illustrated that taraxasterol could reduce cardiac aging and fibrosis and enhance insulin signaling sensitivity, indicating that taraxasterol may be an effective drug or health food additive for treating cardiac aging and fibrosis.

L-Asparagine (Asn) has been regarded as one of the most economical molecules for nitrogen (N) storage and transport in plants due to its relatively high N-to-carbon (C) ratio (2:4) and stability. Although its internal function has been addressed, the biological role of exogenous Asn in plants remains elusive. In this study, different concentrations (0.5, 1, 2, or 5 mM) of Asn were added to the N-deficient hydroponic solution for poplar ‘Nanlin895’. Morphometric analyses showed that poplar height, biomass, and photosynthesis activities were significantly promoted by Asn treatment compared with the N-free control. Moreover, the amino acid content, total N and C content, and nitrate and ammonia content were dramatically altered by Asn treatment. Moreover, exogenous Asn elicited root growth inhibition, accompanied by complex changes in the transcriptional pattern of genes and activities of enzymes associated with N and C metabolism. Combined with the plant phenotype and the physiological and biochemical indexes, our data suggest that poplar is competent to take up and utilize exogenous Asn dose-dependently. It provides valuable information and insight on how different forms of N and concentrations of Asn influence poplar root and shoot growth and function, and roles of Asn engaged in protein homeostasis regulation.

Exogenous Gln as a single N source has been shown to exert similar roles to the inorganic N in poplar ‘Nanlin895′ in terms of growth performance, yet the underlying molecular mechanism remains unclear. Herein, transcriptome analyses of both shoots (L) and roots (R) of poplar ‘Nanlin895’ fertilized with Gln (G) or the inorganic N (control, C) were performed. Compared with the control, 3109 differentially expressed genes (DEGs) and 5071 DEGs were detected in the GL and GR libraries, respectively. In the shoots, Gln treatment resulted in downregulation of a large number of ribosomal genes but significant induction of many starch and sucrose metabolism genes, demonstrating that poplars tend to distribute more energy to sugar metabolism rather than ribosome biosynthesis when fertilized with Gln-N. By contrast, in the roots, most of the DEGs were annotated to carbon metabolism, glycolysis/gluconeogenesis and phenylpropanoid biosynthesis, suggesting that apart from N metabolism, exogenous Gln has an important role in regulating the redistribution of carbon resources and secondary metabolites. Therefore, it can be proposed that the promotion impact of Gln on poplar growth and photosynthesis may result from the improvement of both carbon and N allocation, accompanied by an efficient energy switch for growth and stress responses.

Chiral amines are key building blocks for pharmaceuticals. Economic assessment of commercial potential of bioprocesses is needed for guiding research. Biosynthesis of (S)-α-methylbenzylamine (MBA) was selected as case study. For transamination route, transaminase coupled with glucose dehydrogenase and lactate dehydrogenase catalyzed the reaction with NADH (Nicotinamide adenine dinucleotide) regeneration. Amine dehydrogenase coupled with NADH oxidase, which catalyzed the reductive amination process. Comparison of biosynthesis cost by reductive amination and transamination routes was carried out. Economic assessment based on the framework of cost analysis and preliminary process information revealed that cost is greatly dependent on enzyme price. The results indicated that enhancing the activity of amine dehydrogenase by 4–5 folds can drop the unit price of reductive amination to $0.5–0.6/g, which make it competitive with transamination route.

NADH oxidases (NOXs) play an important role in maintaining balance of NAD+/NADH by catalyzing cofactors regeneration. The expression of nox gene from Lactobacillus brevis in Escherichia coli BL21 (BL21 (DE3)) was studied. Two strategies, the high AT-content in the region adjacent to the initiation codon and codon usage of the whole gene sequence consistent with the host, obtained the NOX activity of 59.9 U/mg and 73.3 U/mg (crude enzyme), with enhanced expression level of 2.0 and 2.5-folds, respectively. Purified NOX activity was 213.8 U/mg. Gene fusion of glycerol dehydrogenase (GDH) and NOX formed bifuctional multi-enzymes for bioconversion of glycerol coupled with coenzyme regeneration. Kinetic parameters of the GDH-NOX for each substrate, glycerol and NADH, were calculated as Vmax(Glycerol) 20 μM/min, Km(Glycerol) 19.4 mM, Vmax (NADH) 12.5 μM/min and Km (NADH) 51.3 μM, respectively, which indicated the potential application of GDH-NOX for quick glycerol analysis and dioxyacetone biosynthesis.

1, 3-propanediol oxidoreductase (PDOR) is a key enzyme in glycerol bioconversion to 1,3-propanediol (1, 3-PD) which is a valuable chemical and one of the six new petrochemical products. We used error-prone PCR and activity screening to identify mutants of Klebsiella pneumoniae (K. pneumoniae) PDOR with improved activity. The activity of one of the identified mutants, PDOR'-24, which includes a single mutation, A199S, was 48 U/mg, 4.9 times that of the wild-type enzyme. Molecular docking was performed to analyze the identified mutants; and amino acids S103, H271, N366, D106, N262 and D364 were predicted to bond with NADH. The origins of the improved activity of PDOR'-24, as well as three other mutants were analyzed by simulating the interaction mechanism of the mutants with the substrate and coenzyme, respectively. This research provides useful information about the use of safranine O plate screening for the directed evolution of oxidoreductases, identifies interesting sites for improving PDOR activity, and demonstrates the utility of using molecular docking to analyze the interaction mechanism of the mutants with the substrate and coenzyme, respectively.

The objective of this study was to clarify the changes in the contents of endogenous carbohydrates and proline in the stolons and leaves of centipedegrass (Eremochloa ophiuroides (Munro) Hack.), during the natural cold acclimation (hardening) and de-acclimation (dehardening) in relation to freezing tolerance in the field at the transition zone between temperate and subtropical areas in China. The contents of carbohydrates and proline, and freezing tolerance estimated by LT50, which is the temperature at which 50% of the electrolytes in the organ was measured in the leachate, were determined at 10-day intervals from October 1, 2001 to April 18, 2002. It was indicated that the freezing tolerance of stolons increased (LT50 of stolons decreased) quickly, as temperature dropped before winter, but that of leaves which senesced along with the drop in temperature did not. The freezing tolerance of stolons decreased gradually along with the rise in temperature above 5 °C in spring, when the overwintered plants started to grow. The contents of proline and soluble carbohydrates, including sucrose, fructose and glucose, increased as LT50 decreased when temperature dropped below 5 °C before winter, and decreased as LT50 increased in early spring. Correlation analysis revealed that the freezing tolerance of stolons of centipedegrass significantly and positively correlated with the contents of proline and soluble carbohydrates, and the ratio of the soluble carbohydrates to starch. Thus, the freezing tolerance of stolons, which are critical organs that determine the winter surviving ability, largely depended on the content of soluble carbohydrates and the ratio of soluble carbohydrates to starch in centipedegrass. The possible relationship between freezing tolerance and carbohydrate metabolism was also discussed.

Mechanistic insights regarding the activity enhancement of dehydrogenase by metal ion substitution were investigated by a simple method using a kinetic and thermodynamic analysis. By profiling the binding energy of both the substrate and product, the metal ion's role in catalysis enhancement was revealed. Glycerol dehydrogenase (GDH) from Klebsiella pneumoniae sp., which demonstrated an improvement in activity by the substitution of a zinc ion with a manganese ion, was used as a model for the mechanistic study of metal ion substitution. A kinetic model based on an ordered Bi-Bi mechanism was proposed considering the noncompetitive product inhibition of dihydroxyacetone (DHA) and the competitive product inhibition of NADH. By obtaining preliminary kinetic parameters of substrate and product inhibition, the number of estimated parameters was reduced from 10 to 4 for a nonlinear regression-based kinetic parameter estimation. The simulated values of time-concentration curves fit the experimental values well, with an average relative error of 11.5% and 12.7% for Mn-GDH and GDH, respectively. A comparison of the binding energy of enzyme ternary complex for Mn-GDH and GDH derived from kinetic parameters indicated that metal ion substitution accelerated the release of dioxyacetone. The metal ion's role in catalysis enhancement was explicated.

Objective: This study sought to investigate brain responses to positive and negative events in individuals with internet gaming disorder (IGD) during real gaming as a direct assessment of the neural features of IGD. This investigation reflects the neural deficits in individuals with IGD while playing games, providing direct and effective targets for prevention and treatment of IGD. Methods: Thirty subjects with IGD and fifty-two matched recreational game use (RGU) subjects were scanned while playing an online game. Abnormal brain activities during positive and negative events were detected using a general linear model. Functional connectivity (FC) and correlation analyses between neural features and addiction severity were conducted to provide additional support for the underlying neural features. Results: Compared to the RGU subjects, the IGD subjects exhibited decreased activation in the dorsolateral prefrontal cortex (DLPFC) during positive events and decreased activation in the middle frontal gyrus (MFG), precentral gyrus and postcentral gyrus during negative events. Decreased FC between the DLPFC and putamen during positive events and between the MFG and amygdala during negative events were observed among the IGD subjects. Neural features and addiction severity were significantly correlated. Conclusions: Individuals with IGD exhibited deficits in regulating game craving, maladaptive habitual gaming behaviors and negative emotions when experiencing positive and negative events during real game-playing compared to RGU gamers. These abnormalities in neural substrates during real gaming provide direct evidence for explaining why individuals with IGD uncontrollably and continuously engage in game playing, despite negative consequences. [ABSTRACT FROM AUTHOR]