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Sediments are important heavy metal sinks in lakes, crucial for ensuring water environment safety. Existing studies mainly focused on well-studied lakes, leaving gaps in understanding pollution patterns in specific basins and influencing factors.We compiled comprehensive sediment contamination data from literature and public datasets, including hydro-geomorphological, climatic, soil, landscape, and anthropogenic factors. Using advanced machine learning, we analyzed typical pollution factors to infer potential sources and migration pathways of pollutants and predicted pollution levels in basins with limited data availability. Our analysis of pollutant distribution data revealed that Cd had the most extensive pollution range, with the most severe pollution occurring in the Huaihe and Yangtze River basins. Furthermore, we identified distinct groups of driving factors influencing various heavy metals. Cd, Cr, and Pb were primarily influenced by human activities, while Cu and Ni were affected by both anthropogenic and natural factors, and Zn tended more towards natural sources. Our predictions indicated that, in addition to the typical highly polluted areas, the potential risk of Cd, Cu and Ni is higher in Xinjiang, and in Tibet and Qinghai, the potential risk of Cd, Cr, Cu and Ni is higher. Pb and Zn presented lower risks, except in the Huaihe and Yangtze River Basins. Temperature, wind, precipitation, precipitation rate, and the cation exchange capacity of soil significantly impacted the predictions of heavy metal pollution in sediments, suggesting that particulate migration, rainfall runoff, and soil erosion are likely the main pathways for pollutant migration into sediments. Considering the migration, pathways, and sources of pollutants, we propose strategies such as low-impact development and promoting sustainable transportation to mitigate pollution. This study provides the latest insights into heavy metal pollution in Chinese lake sediments, offering references for policy-making and water resource management.
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Sinoatrial node (SAN) is the pacemaker of the heart in charge of initiating spontaneous electronical activity and controlling heart rate. Myocytes from SAN can generate spontaneous rhythmic action potentials, which propagate through the myocardium, thereby triggering cardiac myocyte contraction. Acutely, the method for isolating sinoatrial node myocytes (SAMs) is critical in studying the protein expression and function of myocytes in SAN. Currently, the SAMs were isolated by transferring SAN tissue directly into the digestion solution, but it is difficult to judge the degree of digestion, and the system was unstable. Here, we present a modified protocol for the isolation of SAMs in mice, based on the collagenase II and protease perfusion of the heart using a Langendorff apparatus and subsequent dissociation of SAMs. The appearance and droplet flow rate of the heart could be significantly changed during enzymatic digestion via perfusion, which allowed us to easily judge the degree of digestion and avoid incomplete or excessive digestion. The SAMs with stable yield and viability achieved from our optimized approach would facilitate the follow-up experiments.
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Separação Celular , Miócitos Cardíacos , Nó Sinoatrial , Animais , Nó Sinoatrial/citologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Separação Celular/métodos , Camundongos , Camundongos Endogâmicos C57BL , Masculino , PerfusãoRESUMO
Heavy metals interact with each other in a coexisting manner to produce complex combined toxicity to organisms. At present, the toxic effects of chronic co-exposure to heavy metals hexavalent chromium [Cr(VI)] and divalent nickel [Ni(II)] on organisms are seldom studied and the related mechanisms are poorly understood. In this study, we explored the mechanism of the colon injury in mice caused by chronic exposure to Cr or/and Ni. The results showed that, compared with the control group, Cr or/and Ni chronic exposure affected the body weight of mice, and led to infiltration of inflammatory cells in the colon, decreased the number of goblet cells, fusion of intracellular mucus particles and damaged cell structure of intestinal epithelial. In the Cr or/and Ni exposure group, the activity of nitric oxide synthase (iNOS) increased, the expression levels of MUC2 were significantly down-regulated, and those of ZO-1 and Occludin were significantly up-regulated. Interestingly, factorial analysis revealed an interaction between Cr and Ni, which was manifested as antagonistic effects on iNOS activity, ZO-1 and MUC2 mRNA expression levels. Transcriptome sequencing further revealed that the expression of genes-related to inflammation, intestinal mucus and tight junctions changed obviously. Moreover, the relative contents of Cr(VI) and Ni(II) in the Cr, Ni and Cr+Ni groups all changed with in-vitro gastrointestinal ï¼IVGï¼digestion, especially in the Cr+Ni group. Our results indicated that the chronic exposure to Cr or/and Ni can lead to damage to the mice colon, and the relative content changes of Cr(VI) and Ni(II) might be the main reason for the antagonistic effect of Cr+Ni exposure on the colon damage.
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Cromo , Colo , Mucina-2 , Níquel , Animais , Cromo/toxicidade , Níquel/toxicidade , Camundongos , Colo/efeitos dos fármacos , Colo/patologia , Mucina-2/genética , Mucina-2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Perfilação da Expressão Gênica , Masculino , Digestão/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-1/genética , Transcriptoma/efeitos dos fármacos , Ocludina/metabolismo , Ocludina/genética , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologiaRESUMO
A series of boron-promoted Ni-Co/Ca catalysts were synthesized by the sol-gel method to enhance syngas generation from biomass pyrolysis. The efficiency of these catalysts was evaluated during the pyrolysis of rice straw in a fixed-bed reactor, varying the Ni/Co ratio, boron addition, calcination temperature, and residence time. The catalysts underwent comprehensive characterization using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) analysis, scanning electron microscopy (SEM), and hydrogen temperature-programmed reduction (H2-TPR). The results indicated that the Ni-Co/Ca catalysts yielded superior syngas compared to singular Ni or Co catalysts, suggesting a synergistic interplay between nickel and cobalt. The incorporation of 4% boron significantly decreased the particle size of the active metals, enhancing both the catalytic activity and stability. Optimal syngas production was achieved under the following conditions: a biomass-to-catalyst mass ratio of 2:1, a Ni-Co ratio of 1:1, a calcination temperature of 400 °C, a pyrolysis temperature of 800 °C, and a 20 min residence time. These conditions led to a syngas yield of 431.8 mL/g, a 131.28% increase over the non-catalytic pyrolysis yield of 188.6 mL/g. This study not only demonstrates the potential of Ni-Co/Ca catalysts in biomass pyrolysis for syngas production but also provides a foundation for future catalyst performance optimization.
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Rational modulation of surface reconstruction in the oxygen evolution reaction (OER) utilizing defect engineering to form efficient catalytic activity centers is a topical interest in the field of catalysis. The introduction of point defects has been demonstrated to be an effective strategy to regulate the electronic configuration of electrocatalysts, but the influence of more complex planar defects (e.g., twins and stacking faults), on their intrinsic activity is still not fully understood. This study harnesses ultrasonic cavitation for rapid and controlled introduction of different types of defects in the FeCoNi/FeAl2O4 hybrid coating, optimizing OER catalytic activity. Theoretical calculations and experiments demonstrate that the different defects optimize the coordination environment and facilitate the activation of surface reconstruction into true catalytic activity centers at lower potentials. Moreover, it demonstrates exceptional durability, maintaining stable oxygen production at a high current density of 300â mA cm-2 for over 120â hours. This work not only presents a novel pathway for designing advanced electrocatalysts but also deepens our understanding of defect-engineered catalytic mechanisms, showcasing the potential for rapid and efficient enhancement of electrocatalytic performance.
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China has the world's longest high-speed rail (HSR) network, marked by dense transportation and complex operations. However, frequent train use coupled with extreme weather conditions has led to rising subgrade issues. Existing railway defect records suffer from inconsistency, hindering direct applicability. Currently, there is a lack of a relevant dataset dedicated to HSR subgrade defects. To bridge this gap, we developed a comprehensive georeferenced dataset that encompasses defect records extracted from peer-reviewed literature published between 1999 and 2023 in China. Rigorous quality control procedures were implemented to eliminate duplicate data and ensure the accuracy of the dataset. The dataset consists of georeferenced records for eight different defects, spanning across 661 locations and categorized at various scales, ranging from provinces to townships. The most commonly reported defect types include subgrade settlement, frost damage, uplift deformation, and mud pumping. This dataset provides a comprehensive map of historical subgrade defects affecting high-speed railways in China. It could facilitate operational risk assessments and the prediction of subgrade performance.
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This study addresses the escalating risk of high-speed railway (HSR) infrastructure in China, amplified by climate warming, increased rainfall, frequent extreme weather, and geohazard events. Leveraging a georeferenced dataset of recent HSR defects obtained through an extensive literature review, we employ machine learning techniques for a quantitative multi-defect risk assessment. Climatic, geomorphological, geohydrological, and anthropogenic variables influencing HSR subgrade safety are identified and ranked. Climatic factors significantly impact frost damage and mud pumping, while geomorphological variables exhibit greater influence on settlement and uplift deformation defects. Notably, frost damage is prevalent in the northeast and northwest, mud pumping along the southeast coast, and settlement and uplift deformation in the northwest and central areas. The generated comprehensive risk map underscores high-risk zones, particularly the Menyuan Hui Autonomous and Minle County sections of the Lanzhou-Urumqi HSR, emphasizing the need for focused attention and preventive actions to mitigate potential losses and ensure operational continuity.
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BACKGROUND: Improving people with disabilities' participation in sports and cultural activities benefits their physical and mental health. However, only a few studies have examined the factors that influence participation systematically. METHODS: Using the survey data gathered from 4,319 disabled people living in a district in Wuhan, China, this study explored the impacts of sports and cultural activity participation in terms of individual physiological characteristics, socioeconomic factors, and built environmental features. The sports and cultural facility supply and the walkability index of their community environment were calculated to assess built environment features. Binary logistic regression models were also used to investigate the influence of the aforementioned variables. RESULTS: There is a significant positive correlation between sports and cultural activity participation and education (OR = 3.44, p < 0.01), employment status (OR = 2.04, p < 0.01), as well as the number of cultural facilities (OR = 1.33, p < 0.01) in the neighborhood area. No significant association was found between the inclination to participate frequently and individual psychological factors. CONCLUSION: Regarding people with disabilities' participation in sports and cultural activities, socioeconomic and built environment factors are more influential than individual psychological ones. The findings can give ideas for identifying targeted and comprehensive interventions to promote a healthy lifestyle for people with disabilities.
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Pessoas com Deficiência , Esportes , Humanos , Esportes/psicologia , Pessoas com Deficiência/psicologia , Meio Social , Meio Ambiente , Inquéritos e QuestionáriosRESUMO
We explored the resource acquisition and growth strategies of plants adapting to different environments, focusing on the typical forest types of Sygera Mountain: Pinus armandii, Picea likiangensis var. Linzhiensis, Abies georgei var. Smithii, and Juniperus saltuaria. Then, we analyzed the nutrient content and stoichiometric ratios of C, N, P, and K in different plant organs (leaves, branches, trunks, and roots) to examine the stoichiometric characteristics and nutrient balance mechanisms in these forests. Results show that within the same forest type, different plant organs exhibit high C and low N, P, and K levels. N content in all organs followed the order leaves > branches > roots > trunks. During the growth phase, the concentrations of P and K in PLL and AGS follow the order branches > leaves > roots > trunks. In the dormant phase, the distribution in different organs had the order leaves > branches > roots > trunks. C content remained relatively stable over time. In the same organ across different forest types, increase in nitrogen content in plant leaves is an active adaptation of JS plants, indicating that JS has a conservative growth strategy and can adapt to environmental stress. Owing to the influence of seasons, the evolution process of N and P content fluctuates, allocating nutrients to supporting and transporting organs for resource optimization and allocation. The N and P content were lower in the growth phase than in the dormant phase. Seasonal variations in the C/N, C/P, and C/K ratios in different forests were inversely correlated with changes in N, P, and K content in plant organs, supporting the "growth rate hypothesis." Stoichiometric analysis suggests that different limiting elements exist in organs across various forest types. Principal component analysis indicates that the seasonal patterns of stoichiometric ratios in the organs of different forest types show species-specific characteristics, reflecting the evolutionary nutrient utilization strategies of plant genera. In summary, plant growth in different Sygera Mountain forest types is limited by N and P, with a high tendency toward nitrogen limitation. The nutrient utilization and distribution differences among various organs during different growth stages are primarily influenced by the limited availability of environmental nutrients and inherent physiological characteristics of the plants.
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Developing ruthenium-based heterogeneous catalysts with an efficient and stable interface is essential for enhanced acidic oxygen evolution reaction (OER). Herein, we report a defect-rich ultrathin boron nitride nanosheet support with relatively independent electron donor and acceptor sites, which serves as an electron reservoir and receiving station for RuO2, realizing the rapid supply and reception of electrons. Through precisely controlling the reaction interface, a low OER overpotential of only 180â mV (at 10â mA cm-2) and long-term operational stability (350â h) are achieved, suggesting potential practical applications. Inâ situ characterization and theoretical calculations have validated the existence of a localized electronic recycling between RuO2 and ultrathin BN nanosheets (BNNS). The electron-rich Ru sites accelerate the adsorption of water molecules and the dissociation of intermediates, while the interconnection between the O-terminal and B-terminal edge establishes electronic back-donation, effectively suppressing the over-oxidation of lattice oxygen. This study provides a new perspective for constructing a stable and highly active catalytic interface.
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Modulating the microenvironment of single-atom catalysts (SACs) is critical to optimizing catalytic activity. Herein, we innovatively propose a strategy to improve the local reaction environment of Ru single atoms by precisely switching the crystallinity of the support from high crystalline and low crystalline, which significantly improves the hydrogen evolution reaction (HER) activity. The Ru single-atom catalyst anchored on low-crystalline nickel hydroxide (Ru-LC-Ni(OH)2 ) reconstructs the distribution balance of the interfacial ions due to the activation effect of metal dangling bonds on the support. Single-site Ru with a low oxidation state induces the aggregation of hydronium ions (H3 O+ ), leading to the formation of a local acidic microenvironment in alkaline media, breaking the pH-dependent HER activity. As a comparison, the Ru single-atom catalyst anchored on high-crystalline nickel hydroxide (Ru-HC-Ni(OH)2 ) exhibits a sluggish Volmer step and a conventional local reaction environment. As expected, Ru-LC-Ni(OH)2 requires low overpotentials of 9 and 136â mV at 10 and 1000â mA cm-2 in alkaline conditions and operates stably at 500â mA cm-2 for 500â h in an alkaline seawater anion exchange membrane (AEM) electrolyzer. This study provides a new perspective for constructing highly active single-atom electrocatalysts.
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Designing stable single-atom electrocatalysts with lower energy barriers is urgent for the acidic oxygen evolution reaction. In particular, the atomic catalysts are highly dependent on the kinetically sluggish acid-base mechanism, limiting the reaction paths of intermediates. Herein, we successfully manipulate the steric localization of Ru single atoms at the Co3O4 surface to improve acidic oxygen evolution by precise control of the anchor sites. The delicate structure design can switch the reaction mechanism from the lattice oxygen mechanism (LOM) to the optimized adsorbate evolution mechanism (AEM). In particular, Ru atoms embedded into cation vacancies reveal an optimized mechanism that activates the proton donor-acceptor function (PDAM), demonstrating a new single-atom catalytic pathway to circumvent the classic scaling relationship. Steric interactions with intermediates at the anchored Ru-O-Co interface played a primary role in optimizing the intermediates' conformation and reducing the energy barrier. As a comparison, Ru atoms confined to the surface sites exhibit a lattice oxygen mechanism for the oxygen evolution process. As a result, the delicate atom control of the spatial position presents a 100-fold increase in mass activity from 36.96 A gRu(ads)-1 to 4012.11 A gRu(anc)-1 at 1.50 V. These findings offer new insights into the precise control of single-atom catalytic behavior.
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The emergence of green flexible aerogel electronics based on natural materials is expected to solve part of the global environmental and energy crisis. However, it is still challenging to achieve large-scale production and multifunctional stable applications of natural biomass fiber aerogel (BFA) materials. Herein, we exploit the interfacial bridging between the flower-type titanium dioxide nanoarray (FTNA) and natural fiber substrates to modulate the electronic structure and loss mechanism to achieve multifunctional properties. Specifically, the fibrous substrate with wrinkled features induces lattice strain in titania through precise interfacial bridging, effectively improving the intrinsic properties of the BFA materials. This interfacial bridging regulation strategy is also confirmed by X-ray absorption fine structure spectroscopy (XAS). More importantly, the construction of BFA products for different macroscopic and multifunctional applications through simple processing methods will facilitate the transition from natural materials to multifunctional flexible electronics. Therefore, the as-prepared blanket-type BFA (TCBFA) has good mechanical properties, electromagnetic protection properties, thermal stealth properties, high-temperature flame retardancy, and UV resistance. Meanwhile, the membrane-type (TCBFAM) multifunctional wearable fiber aerogel device exhibits superior flexibility, efficient Joule heating performance, and a smart response. This regulation strategy provides another concept for the design and innovation of green multifunctional fiber-integrated aerogels.
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[This corrects the article DOI: 10.1016/j.heliyon.2023.e15879.].
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Designing novel single-atom catalysts (SACs) supports to modulate the electronic structure is crucial to optimize the catalytic activity, but rather challenging. Herein, a general strategy is proposed to utilize the metalloid properties of supports to trap and stabilize single-atoms with low-valence states. A series of single-atoms supported on the surface of tungsten carbide (M-WCx , M=Ru, Ir, Pd) are rationally developed through a facile pyrolysis method. Benefiting from the metalloid properties of WCx , the single-atoms exhibit weak coordination with surface W and C atoms, resulting in the formation of low-valence active centers similar to metals. The unique metal-metal interaction effectively stabilizes the low-valence single atoms on the WCx surface and improves the electronic orbital energy level distribution of the active sites. As expected, the representative Ru-WCx exhibits superior mass activities of 7.84 and 62.52â A mgRu -1 for the hydrogen oxidation and evolution reactions (HOR/HER), respectively. In-depth mechanistic analysis demonstrates that an ideal dual-sites cooperative mechanism achieves a suitable adsorption balance of Had and OHad , resulting in an energetically favorable Volmer step. This work offers new guidance for the precise construction of highly active SACs.
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With the continuous improvement of living standards, the preferences of consumers are shifting to rice varieties with high eating and cooking quality (ECQ). Milled rice is mainly composed of starch, protein, and oil, which constitute the physicochemical basis of rice taste quality. This review summarizes the relationship between rice ECQ and its intrinsic ingredients, and also briefly introduces the effects of nitrogen fertilizer management on rice ECQ. Rice varieties with higher AC usually have more long branches of amylopectin, which leach less when cooking, leading to higher hardness, lower stickinesss, and less panelist preference. High PC impedes starch pasting, and it may be hard for heat and moisture to enter the rice interior, ultimately resulting in worse rice eating quality. Rice with higher lipid content had a brighter luster and better eating quality, and starch lipids in rice have a greater impact on rice eating quality than non-starch lipids. The application of nitrogen fertilizer can enhance rice yield, but it also decreases the ECQ of rice. CRNF has been widely used in cereal crops such as maize, wheat, and rice as a novel, environmentally friendly, and effective fertilizer, and could increase rice quality to a certain extent compared with conventional urea. This review shows a benefit to finding more reasonable nitrogen fertilizer management that can be used to regulate the physical and chemical indicators of rice grains in production and to improve the taste quality of rice without affecting yield.
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Electrocatalytic CO2 reduction via renewable electricity provides a sustainable way to produce valued chemicals, while it suffers from low activity and selectivity. Herein, we constructed a novel catalyst with unique Ti3 C2 Tx MXene-regulated Ag-ZnO interfaces, undercoordinated surface sites, as well as mesoporous nanostructures. The designed Ag-ZnO/Ti3 C2 Tx catalyst achieves an outstanding CO2 conversion performance of a nearly 100% CO Faraday efficiency with high partial current density of 22.59â mA cm-2 at -0.87â V versus reversible hydrogen electrode. The electronic donation of Ag and up-shifted d-band center relative to Fermi level within MXene-regulated Ag-ZnO interfaces contributes the high selectivity of CO. The CO2 conversion is highly correlated with the dominated linear-bonded CO intermediate confirmed by in situ infrared spectroscopy. This work enlightens the rational design of unique metal-oxide interfaces with the regulation of MXene for high-performance electrocatalysis beyond CO2 reduction.
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BACKGROUND: Lineage distribution of Mycobacterium tuberculosis (Mtb) isolates is strongly associated with geographically distinct human populations, and its transmission can be further impacted by the bacterial genome. However, the epidemic success of Mtb isolates at an individual level was unknown in eastern China. Knowledge regarding the emergence and transmission of Mtb isolates as well as relevant factors may offer a new solution to curb the spread of the disease. Thus, this study aims to reveal the evolution and epidemic success of Mtb isolates in eastern China. RESULTS: Of initial 1040 isolates, 997 were retained after removing duplicates and those with insufficient sequencing depth. Of the final samples, 733 (73.52%) were from Zhejiang Province, and 264 (26.48%) were from Shanghai City. Lineage 2 and lineage 4 accounted for 80.44% and 19.56%, with common ancestors dating around 7017 years ago and 6882 years ago, respectively. Sub-lineage L2.2 (80.34%) contributed the majority of total isolates, followed by L4.4 (8.93%) and L4.5 (8.43%). Additionally, 51 (5.12%) isolates were identified to be multidrug-resistant (MDR), of which 21 (29.17%) were pre-extensively drug-resistant (pre-XDR). One clade harboring katG S315T mutation may date back to 65 years ago and subsequently acquired mutations conferring resistance to another five antibiotic drugs. The prevalence of compensatory mutation was the highest in pre-XDR isolates (76.19%), followed by MDR isolates (47.06%) and other drug-resistant isolates (20.60%). Time-scaled haplotypic density analyses suggested comparable success indices between lineage 2 and lineage 4 (P = 0.306), and drug resistance did not significantly promote the transmission of Mtb isolates (P = 0.340). But for pre-XDR isolates, we found a higher success index in those with compensatory mutations (P = 0.025). Mutations under positive selection were found in genes associated with resistance to second-line injectables (whiB6) and drug tolerance (prpR) in both lineage 2 and lineage 4. CONCLUSIONS: Our study demonstrates the population expansion of lineage 2 and lineage 4 in eastern China, with comparable transmission capacity, while accumulation of resistance mutations does not necessarily facilitate the success of Mtb isolates. Compensatory mutations usually accompany drug resistance and significantly contribute to the epidemiological transmission of pre-XDR strains. Prospective molecular surveillance is required to further monitor the emergence and spread of pre-XDR/XDR strains in eastern China.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Estudos Prospectivos , China/epidemiologia , Mutação , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
Understanding the emergence and evolution of drug resistance can inform public health intervention to combat tuberculosis (TB). In this prospective molecular epidemiological surveillance study from 2015 to 2021 in eastern China, we prospectively collected whole-genome sequencing and epidemiological data on TB patients. We dissect the ordering of drug resistance mutation acquisition for nine commonly used anti-TB drugs, and we found that the katG S315T mutation first appeared around 1959, followed by rpoB S450L (1969), rpsL L43A (1972), embB M306V (1978), rrs 1401 (1981), fabG1 (1982), pncA (1985) and folC (1988) mutations. GyrA gene mutations appeared after the year of 2000. We observed that the first expansion of Mycobacterium tuberculosis (M.tb) resistance population among eastern China appeared after the introduction of isoniazid, streptomycin and para-amino salicylic acid, and the second expansion after the ethambutol, rifampicin, pyrazinamide, ethionamide and aminoglycosides. We speculate these two expansions are linked with population shift historically. By geospatial analysis, we found drug-resistant isolates migrated within eastern China. With epidemiological data of clonal strains, we observed some strains can evolve continuously in individuals and transmit readily in a population. In conclusion, this study mirrored the emergence and evolution of drug-resistant M.tb in eastern China were linked to the sequence and timing of introduction of anti-TB drugs, and multiple factors may contribute to the resistant population enlarged. To resolve the epidemic of drug-resistant TB, it requires applying anti-TB drugs carefully and/or identifying resistant patients timely to prevent them from developing high-level resistance and transmitting to others.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Estudos Prospectivos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , China , Mutação , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Bactérias/genéticaRESUMO
Background: Connexin 43 (Cx43), the predominant gap junction protein in hearts, is modified by specific (de)phosphorylation events under physiological and pathological states to affect myocardium function and structure. Previously we found that deficiency in Cx43 S282 phosphorylation could impair intercellular communication and contribute to cardiomyocyte apoptosis by activating p38 mitogen-activated protein kinase (p38 MAPK)/factor-associated suicide (Fas)/Fas-associating protein with a novel death domain (FADD) pathway, which is involved in myocardium injury in ischemia/reperfusion (I/R) heart. In addition, mutant at Cx43 S282 substituted with alanine heterozygous mice (S282A+/-) exhibited different degrees of ventricular arrhythmias and only some underwent myocardium apoptosis. In this study, we aimed to investigate the role of Cx43 pS282 in different cardiac pathological phenotypes. Methods: We examined cardiac function, structure, and relevant protein expression in S282A+/- mice (aged 2, 10 and 30 weeks) by electrocardiograph, echocardiography, histological staining, and co-immunoprecipitation followed by Western blot. Intraperitoneal isoprenaline injection and I/R surgery were applied in S282A+/- mice as external stimulus. 2,3,5-triphenyltetrazolium chloride staining was used for myocardium infarction evaluation. Results: Adult S282A+/- mice (aged 10 and 30 weeks) still exhibited spontaneous arrhythmia. Unlike neonatal stage (aged around 2 weeks), no apoptosis-related manifestations and the activation of p38 MAPK-Fas-FADD apoptotic pathway were observed in adult S282A+/- hearts. S282A+/- neonatal mice with cardiomyocytes apoptosis exhibited more than 60% dephosphorylation at Cx43 S282 than WT mice, while less than 40% S282 dephosphorylation were found in adult S282A+/- mice. In addition, although S282A+/- mice displayed normal cardiac function, they were highly susceptible to isoproterenol-induced ECG alternans and prone to cardiac injury and deaths upon I/R attack. Conclusions: These results reinforce that Cx43 S282 dephosphorylation acts as a susceptibility factor in regulating cardiomyocyte survival and cardiac electrical homeostasis in basal conditions and contributes to myocardium injury in the setting of I/R. Cx43 S282 phosphorylation was competent to induce spontaneous arrhythmias, cardiomyocyte apoptosis and deaths based on the degree of S282 dephosphorylation.