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Although cycloserine is a recommended drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) according to World Health Organization (WHO), few studies have reported on pharmacokinetics (PK) and/or pharmacodynamics (PD) data of cycloserine in patients with standardized MDR-TB treatment. This study aimed to estimate the population PK parameters for cycloserine and to identify clinically relevant PK/PD thresholds, as well as to evaluate the current recommended dosage.

Background This study aims to investigate the association between hemoglobin and major adverse cardiac events (MACE) in patients with stable coronary artery disease (CAD) who were treated with percutaneous coronary intervention (PCI). Methods This was a secondary analysis based on a retrospective cohort study involving 204 patients with stable CAD. Patients were divided into four groups according to hemoglobin levels (Q1: 6.90-12.30 g/dL; Q2: 12.40-13.80 g/dL; Q3: 13.90-14.90 g/dL; Q4: 15.00-19.00 g/dL). Lasso regression analysis was performed to select characteristic variables and reduce dimensions. Odds ratio (OR) and 95% confidence interval (CI) were used for comparing data among groups. Results After an average follow-up of 783 days, 28/204 (17.72%) patients with CAD occurred MACE. Univariate analysis data showed that hemoglobin level was negatively associated with the incidence of MACE in patients with CAD treated with PCI (Q2 vs Q1: OR=0.19, P=0.005; Q3 vs Q1: OR=0.25, P=0.013; Q4 vs Q1: OR=0.13, P=0.002). The negative correlation between hemoglobin and MACE still existed after adjusting selected variables obtained from multivariate regression analysis (Q2 vs Q1: OR= 0.18, P=0.007; Q3 vs Q1: OR=0.29, P=0.038; Q4 vs Q1: OR=0.19, P=0.016). Curve fitting illustrated that hemoglobin level presented a non-linear and negative association with MACE in patients with CAD treated with PCI. Conclusions Hemoglobin level can be utilized as a prognostic indicator of MACE in patients with CAD after PCI.

Reactive oxygen species (ROS) and the photoreceptor protein phytochrome B (phyB) play a key role in plant acclimation to stress. However, how phyB that primarily functions in the nuclei impacts ROS signaling mediated by respiratory burst oxidase homolog (RBOH) proteins that reside on the plasma membrane, during stress, is unknown. Arabidopsis thaliana and Oryza sativa mutants, RNA-Seq, bioinformatics, biochemistry, molecular biology, and whole-plant ROS imaging were used to address this question. Here, we reveal that phyB and RBOHs function as part of a key regulatory module that controls apoplastic ROS production, stress-response transcript expression, and plant acclimation in response to excess light stress. We further show that phyB can regulate ROS production during stress even if it is restricted to the cytosol and that phyB, respiratory burst oxidase protein D (RBOHD), and respiratory burst oxidase protein F (RBOHF) coregulate thousands of transcripts in response to light stress. Surprisingly, we found that phyB is also required for ROS accumulation in response to heat, wounding, cold, and bacterial infection. Our findings reveal that phyB plays a canonical role in plant responses to biotic and abiotic stresses, regulating apoplastic ROS production, possibly while at the cytosol, and that phyB and RBOHD/RBOHF function in the same regulatory pathway.

NAL1 (NARROW LEAF 1) is a breeding-valuable pleiotropic gene that affects multiple agronomic traits in rice, but the molecular mechanism is largely unclear. Here, we report that NAL1 is a serine protease and displays a novel hexameric structure whose formation is mediated by ATP-containing positively charged pocket at the N-terminal region. Moreover, we identified TOPLESS-related corepressor OsTPR2 involved in multiple growth and development processes as the substrate of NAL1. We found that NAL1 degraded OsTPR2, thus modulating the expression of downstream genes related to hormone signaling pathways, eventually achieving its pleiotropic physiological function. An elite allele NAL1A originated from wild rice could increase grain yield. Furthermore, the NAL1 homologs in different crops have a similar pleiotropic function to NAL1. Our study uncovers a NAL1-OsTPR2 regulatory module and provides gene resources for the design of high-yield crops.

Leaves comprise multiple cell types but our knowledge of the patterns of gene expression that underpin their functional specialization is fragmentary. Our understanding and ability to undertake rational redesign of these cells is therefore limited. We aimed to identify genes associated with the incompletely understood bundle sheath of C3plants, which represents a key target associated with engineering traits such as C4photosynthesis into rice. To better understand veins, bundle sheath and mesophyll cells of rice we used laser capture microdissection followed by deep sequencing. Gene expression of the mesophyll is conditioned to allow coenzyme metabolism and redox homeostasis as well as photosynthesis. In contrast, the bundle sheath is specialized in water transport, sulphur assimilation and jasmonic acid biosynthesis. Despite the small chloroplast compartment of bundle sheath cells, substantial photosynthesis gene expression was detected. These patterns of gene expression were not associated with presence/absence of particular transcription factors in each cell type, but rather gradients in expression across the leaf. Comparative analysis with C3Arabidopsisidentified a small gene-set preferentially expressed in bundle sheath cells of both species. This included genes encoding transcription factors from fourteen orthogroups, and proteins allowing water transport, sulphate assimilation and jasmonic acid synthesis. The most parsimonious explanation for our findings is that bundle sheath cells from the last common ancestor of rice and Arabidopsis was specialized in this manner, and since the species diverged these patterns of gene expression have been maintained.Significance statementThe role of bundle sheath cells in C4species have been studied intensively but this is not the case in leaves that use the ancestral C3pathway. Here, we show that gene expression in the bundle sheath of rice is specialized to allow sulphate and nitrate reduction, water transport and jasmonate synthesis, and comparative analysis with Arabidopsis indicates ancient roles for bundle sheath cells in water transport, sulphur and jasmonate synthesis.

Whole-genome sequencing (WGS) has shown tremendous potential in rapid diagnosis of drug-resistant tuberculosis (TB). In the current study, we performed WGS on drug-resistant Mycobacterium tuberculosis isolates obtained from Shanghai (n = 137) and Russia (n = 78). We aimed to characterise the underlying and high-frequency novel drug-resistance-conferring mutations, and also create valuable combinations of resistance mutations with high predictive sensitivity to predict multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB) phenotype using a bootstrap method. Most strains belonged to L2.2, L4.2, L4.4, L4.5 and L4.8 lineages. We found that WGS could predict 82.07% of phenotypically drug-resistant domestic strains. The prediction sensitivity for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), ofloxacin (OFL), amikacin (AMK) and capreomycin (CAP) was 79.71%, 86.30%, 76.47%, 88.37%, 83.33%, 70.00% and 70.00%, respectively. The mutation combination with the highest sensitivity for MDR prediction was rpoB S450L + rpoB H445A/P + katG S315T + inhA I21T + inhA S94A, with a sensitivity of 92.17% (0.8615, 0.9646), and the mutation combination with highest sensitivity for XDR prediction was rpoB S450L + katG S315T + gyrA D94G + rrs A1401G, with a sensitivity of 92.86% (0.8158, 0.9796). The molecular information presented here will be of particular value for the rapid clinical detection of MDR- and XDR-TB isolates through laboratory diagnosis.

Renewable sources planning is a planning method that considers the integration of renewable energy and buildings from the regional level, and matches and coordinates with energy demand, traditional energy supply system and different renewable energy sources. It is an important means to realize the microcirculation of regional energy system and is of great significance to realize the construction of low-carbon eco-city. Compared with the world advanced level, the unit energy consumption of China's major energy-consuming products is also very large. Therefore, developing new technologies and improving energy efficiency in China is one of the important ways to achieve energy conservation and consumption reduction. This paper introduces the connotation and planning methods of regional renewable sources planning, focusing on the evaluation of renewable sources, the prediction of regional building energy consumption, the matching method of energy demand and renewable resources, the feedback evaluation method of renewable sources planning and the safeguard measures for planning implementation. Considering that the optimization problem has obvious nonlinear and structural characteristics, ant colony algorithm is chosen to calculate the optimization results.

Plants are essential for life on Earth converting light into chemical energy in the form of sugars. To adjust for changes in light intensity and quality, and to become as efficient as possible in harnessing light, plants utilize multiple light receptors, signaling, and acclimation mechanisms. In addition to altering plant metabolism, development and growth, light cues sensed by some photoreceptors, such as phytochromes, impact on many plant responses to biotic and abiotic stresses. Central for plant responses to different stresses are reactive oxygen species (ROS) that function as key signaling molecules. Recent studies demonstrated that respiratory burst oxidase homolog (RBOH) proteins that reside at the plasma membrane and produce ROS at the apoplast play a key role in plant responses to different biotic and abiotic stresses. Here we reveal that phytochrome B (phyB) and RBOHs function as part of a key regulatory module that controls ROS production, transcript expression, and plant acclimation to excess light stress. We further show that phyB can regulate ROS production during stress even if it is restricted to the cytosol, and that phyB, RBOHD and RBOHF co-regulate thousands of transcripts in response to light stress. Surprisingly, we found that phyB is also required for ROS accumulation in response to heat, wounding, cold, and bacterial infection. Taken together, our findings reveal that phyB plays a canonical role in plant responses to biotic and abiotic stresses, regulating ROS production, and that phyB and RBOHs function in the same pathway.Significant StatementAbiotic and biotic stresses cause extensive losses to agricultural production and threaten global food security. Augmenting plant resilience to stressful conditions requires understanding of how plants sense stress. Here we report that the sensing of different abiotic and biotic stresses that result in the production of the key stress-response signaling molecules, reactive oxygen species, requires the plant photoreceptor protein phytochrome B. We further show that in contrast to its many nuclear functions, phytochrome B regulates reactive oxygen production by plasma membrane-localized respiratory burst oxidase homologs while localized to the cytosol. Our findings reveal the existence of a rapid stress response regulatory mechanism requiring phytochrome B and reactive oxygen species, essential for plant acclimation to stress.

Arsenic (As) can co-occur with zirconium dioxide nanoparticles (ZrO

Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of ≤ 2.5 µm (PM

The present study explores situational social support of drug abusers during compulsory rehabilitation and provides a preliminary estimation of relationship between social support and relapse. Links between social support and relapse are examined in a study of drug abusers accepting coercive detoxification and rehabilitation treatment, and self-reported relapse in the following 6 months ( N = 535). External and internal social support with abstinence-specific support inclusive are investigated. With certain demographic variables and risk-related variables controlled, greater special type of external social support (as measured by number of children) predicts a lower risk of relapse, which means better effect of compulsory rehabilitation. Participation into some of the institutional programs and experienced personal conflicts for abstinence show no statistically significant with relapse risk.

Upland rice is a distinct ecotype that grows in aerobic environments and tolerates drought stress. However, the genetic basis of its drought resistance is unclear. Here, using an integrative approach combining a genome-wide association study with analyses of introgression lines and transcriptomic profiles, we identify a gene, DROUGHT1 (DROT1), encoding a COBRA-like protein that confers drought resistance in rice. DROT1 is specifically expressed in vascular bundles and is directly repressed by ERF3 and activated by ERF71, both drought-responsive transcription factors. DROT1 improves drought resistance by adjusting cell wall structure by increasing cellulose content and maintaining cellulose crystallinity. A C-to-T single-nucleotide variation in the promoter increases DROT1 expression and drought resistance in upland rice. The potential elite haplotype of DROT1 in upland rice could originate in wild rice (O. rufipogon) and may be beneficial for breeding upland rice varieties.

As of October 5, 2020, China has reported 2,921 cases imported from overseas. Assessing the effectiveness of China's current policies on imported cases abroad is very important for China and other countries that are facing or will face overseas imported cases. In April, we used a susceptible-exposed-infectious-recovered metapopulation model to simulate the epidemic in seven foreign countries, China and the three Chinese key cities. Based on the model outside China, we estimated the proportion of people in incubation period and calculated the risk indexes for Chinese cities through analyzing aviation traffic data from these countries. Based on the model in China and the three key cities, we collected information on control measures and quantified the effectiveness of implementing the current policies at different times and intensities. Our model results showed that Shanghai, Beijing, Qingdao, Guangzhou, and Tianjin have the top five risk indexes. As of April 20, 2020, under current measures, the number of confirmed cases could be reduced by 99% compared with no air traffic restrictions and isolation measures; the reduction could be 93% with isolation of passengers only from key countries. If the current policy were postponed for 7, 10, or 20 days, the increase in the number of confirmed cases would be 1,329, 5,524, and 779,245 respectively, which is 2.1, 5.7, and 662.9 times the number of confirmed cases under current measures. Our research indicates that the importation control measures currently taken by China were implemented at an appropriate time to prevent the epidemic spreading and have achieved relatively good control results. However, it is necessary to remain vigilant; otherwise, another outbreak peak could occur., Author summary The epidemic of the COVID-19 has greatly affected the lives of people all over the world. Before the vaccine has been widely covered, we can only reduce the transmissibility of the virus through the implementation of strong non-pharmaceutical interventions. In response to air passengers who may be carrying the SARS-CoV-2, the Chinese plan is a comprehensive measure of reduction, centralized isolation, and completely testing. We conducted a retrospective assessment of the time and intensity of the implementation of China's policy in order to provide data support for the normal implementation of future measures. The model results indicate that the measures currently taken by China were implemented at an appropriate time to prevent the epidemic spreading and have achieved relatively good effect. This means that these measures need to be strictly implemented for a period of time as the global epidemic situation is still serious. Although our model refers to the seven countries with more severe epidemics in April, the assessment method can be applied to assess the importation risks brought by other countries.

Harmful algal blooms (HABs) in freshwater lakes and oceans date back to as early as the 19th century, which can cause the death of aquatic and terrestrial organisms. However, it was not until the end of the 20th century that researchers had started to pay attention to the hazards and causes of HABs. In this study, we analyzed 5720 published literatures on HABs studies in the past 30 years. Our review presents the emerging trends in the past 30 years on HABs studies, the environmental and human health risks, prevention and control strategies and future developments. Therefore, this review provides a global perspective of HABs and calls for immediate responses.

Arsenic (As) contamination in the sediments has received increasing attention, but its transfer and bioavailability to benthic infauna remain much less well known. In the present study, we deployed the diffusive gradients in thin films (DGT) to quantify the different As speciation in the overlying water and porewater, and assessed the exposure pathway, transfer and bioavailability of different As species in an infaunal clam Sinonovacula constricta. We demonstrated a very dynamic transformation and exposure of As in the sediment-water-clam microcosm. In such microcosm, arsenite [As(III)] in the overlying water, pore water and sediments was almost oxidized to arsenate [As(V)]. Conversely, the accumulated As(V) in the clams was reduced to As(III), followed by methylation to dimethylarsinic acid (DMA), whereas the overall conversion of toxic inorganic As species to less-toxic arsenobetaine (AsB) was much poor in the clams. Moreover, biotransformation depended on the As accumulation level. As(III) was the predominant As species in the control and the Low As treatment clam, whereas DMA was the predominant As species in the High As treatment clam. Significant and positive correlations were found between As(V) concentrations in the clams and those in DGT-labile As in overlying water/pore water, as well as between the DMA and As(V) concentrations in the clams and those in the sediment. DMA and As(V) in the sediments was much more bioavailable to the clams than inorganic As [As(III)] and AsB. Moreover, As(III) and As(V) in the overlying water and pore water, as well as DMA and As(V) in the sediments displayed high migration ability. Coupled DGT technology and biotransformation study therefore suggested that metabolism of ingested As species as well as ingestion and retention of DMA resulted in high DMA bioaccumulation in clams.

Arsenic (As) can co-occur with zirconium dioxide nanoparticles (ZrO2 NPs) in aquatic environments, but their combined influence along the aquatic food chain is barely explored. This study constructed water flea Daphnia magna – zebrafish Danio rerio to evaluate the impact of ZrO2 NPs on the accumulation, trophic transfer, transformation, and detoxification of arsenate (As(V)). The zebrafish were fed D. magna exposed to As(V), ZrO2 NPs, or As(V) + ZrO2 NPs for 20 d. Results demonstrated that ZrO2 NPs significantly facilitated total As and As(V) sorption in D. magna and in tissues of zebrafish. ZrO2 NPs enhanced the transformation of inorganic arsenic (iAs) to monomethylated acid (MMA), while decreased synthesis of arsenobetaine (AsB) in tissues, leading to iAs increased. Co-exposed As(V) and ZrO2 NPs facilitated upregulation of absorption-related genes (aqp7) and As biotransformation-related genes (gst, gss), and detoxification and oxidative stress-related genes (mt2, cat, sod1 and sod2). Therefore, genetic expression coupling with biotransformation for the first time demonstrated that As(V) combined with ZrO2 NPs led to increased harm to D. magna and zebrafish and amplified the ecological risks of As(V) along the aquatic food chain. Attention should be paid to the combined toxicity of As(V) and ZrO2 NPs in aquatic environment.

The role of muscle LIM protein (MLP), encoded by CSRP3, is not well understood in humans. CSRP3 knockout mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Using CRISPR/Cas9, we generated an MLP deficient human ESC line WAe009-A-41 carrying a compound heterozygous 13 bp deletion/1 bp insertion in the CSRP3 gene. The WAe009-A-41 line exhibited a normal female karyotype (46, XX), expressed pluripotency markers and exhibited capability to differentiate into the three germ layers in vitro. MLP expression was not detectable in WAe009-A-41 line. This cell line can be a useful tool for studying the role of CSRP3 in cardiomyopathy and heart failure.

When exposed to high light plants produce reactive oxygen species (ROS). InArabidopsis thalianalocal accumulation of ROS preferentially takes place in bundle sheath strands, but little is known about how this response takes place. Using rice and the ROS probes diaminobenzidine and 2’,7’-dichlorodihydrofluorescein diacetate, we found that after exposure to high light, ROS were produced more rapidly in bundle sheath strands than mesophyll cells. This response was not affected either by CO2supply or photorespiration. Consistent with these findings, deep sequencing of mRNA isolated from mesophyll or bundle sheath strands indicated balanced accumulation of transcripts encoding all major components of the photosynthetic apparatus. However, transcripts encoding several isoforms of the superoxide/H2O2-producing enzyme NADPH oxidase were more abundant in bundle sheath strands than mesophyll cells. ROS production in bundle sheath strands was reduced by blocking NADPH oxidase activity pharmacologically, but increased when the bundle sheath preferentialRBOHAisoform of NADPH oxidase was over-expressed. NADPH oxidase mediated accumulation of ROS in the rice bundle sheath was detected in etiolated leaves lacking chlorophyll indicating that high light and NADPH oxidase-dependent ROS production is not dependent on photosynthesis.

Background: Hydroxychloroquine (HCQ) and chloroquine (CQ) have been widely used for the treatment of the coronavirus disease 2019 (COVID-19), despite limited clinical evidence and controversial early reports. The aim of this report was to provide a systematic review of the literature and meta-analysis on the use of HCQ/CQ with respect to safety and clinical efficacy of these medications. Methods: We performed a systematic search of the medical databases and included studies if they focused on patients with COVID-19 who received HCQ or CQ alone, or in combination with other treatments, and were compared with a control group. We analyzed two important clinical objectives; viral clearance rate by reverse transcription-polymerase chain reaction (RT-PCR) negativity and all-cause mortality.Results: A total of 14 studies were included in the quantitative synthesis. The use of HCQ/CQ was associated with higher viral clearance rate compared with control group (OR: 3.12, 95% CI: 2.17-4.49 pI2 = 86%, p < 0.01), we performed a meta regression analysis. Both treatment within 24 hours (p=0.047) and comorbidities [hypertension (p=0.025), diabetes (p=0.049) and chronic lung disease (p=0.0064)] contributed to the heterogeneity. HCQ/CQ daily dose (p=0.61) and age (p=0.62) had no impact on effect size. Higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ. Overall, the use of HCQ/CQ resulted in longer QTc intervals.Conclusions: Our meta-analysis did not reveal a clinical benefit of HCQ/CQ on in-hospital outcomes for patients with COVID-19. The use of HCQ/CQ did not result in rapid viral clearance on RT-PCR. Moreover, our results showed that higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ.

Peripheral blood mononuclear cells (PBMCs) were isolated from a 57-year-old female who was clinically diagnosed as familial atrial fibrillation and were reprogrammed using non-integrative Sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and cMYC. The generated human induced pluripotent stem cell (hiPSC) line, ZZUSAHi001-A, exhibited a normal karyotype, showed robust expression of pluripotency markers and differentiated towards three germ layers in vivo.

Improving the performance of rice (Oryza sativa) under drought stress has the potential to significantly affect rice productivity. Here, we report that the ERF family transcription factor OsLG3 positively regulates drought tolerance in rice. In our previous work, we found that OsLG3 has a positive effect on rice grain length without affecting grain quality. In this study, we found that OsLG3 was more strongly expressed in upland rice than in lowland rice under drought stress conditions. By performing candidate gene association analysis, we found that natural variation in the promoter of OsLG3 is associated with tolerance to osmotic stress in germinating rice seeds. Overexpression of OsLG3 significantly improved the tolerance of rice plants to simulated drought, whereas suppression of OsLG3 resulted in greater susceptibility. Phylogenetic analysis indicated that the tolerant allele of OsLG3 may improve drought tolerance in cultivated japonica rice. Introgression lines and complementation transgenic lines containing the elite allele of OsLG3IRAT109 showed increased drought tolerance, demonstrating that natural variation in OsLG3 contributes to drought tolerance in rice. Further investigation suggested that OsLG3 plays a positive role in drought stress tolerance in rice by inducing reactive oxygen species scavenging. Collectively, our findings reveal that natural variation in OsLG3 contributes to rice drought tolerance and that the elite allele of OsLG3 is a promising genetic resource for the development of drought-tolerant rice varieties.

Summary Grain size, one of the important components determining grain yield in rice, is controlled by the multiple quantitative trait loci (QTLs). Intensive artificial selection for grain size during domestication is evidenced in modern cultivars compared to their wild relatives. Here, we report the molecular cloning and characterization of OsLG3b, a QTL for grain length in tropical japonica rice that encodes MADS‐box transcription factor 1 (OsMADS1). Six SNPs in the OsLG3b region led to alternative splicing, which were associated with grain length in an association analysis of candidate region. Quantitative PCR analysis indicated that OsLG3b expression was higher during the panicle and seed development stages. Analysis of haplotypes and introgression regions revealed that the long‐grain allele of OsLG3b might have arisen after domestication of tropical japonica and spread to subspecies indica or temperate japonica by natural crossing and artificial selection. OsLG3b is therefore a target of human selection for adaptation to tropical regions during domestication and/or improvement of rice. Phylogenetic analysis and pedigree records showed that OsLG3b had been employed by breeders, but the gene still has much breeding potential for increasing grain length in indica. These findings will not only aid efforts to elucidate the molecular basis of grain development and domestication, but also facilitate the genetic improvement of rice yield.

Arsenobetaine (AsB) is the major form of arsenic in marine fish; however, its biodynamics within the fish tissues is not well understood. This study simulated the biodynamics and biotransportation (absorption, distribution, and elimination) of dietary AsB and arsenate [As(V)] in the marine grouper Epinephelus fuscoguttatus, by constructing a physiologically based pharmacokinetic (PBPK) model. The transfer rates between different compartments (gill, intestine, liver, heart, kidney, and muscle) and blood were modeled during exposure (14 d) and depuration (20 d). The model showed that AsB had a weak ability to cross the intestinal membranes and circulated slowly in the blood. The newly AsB absorbed from the blood did not enter the hepatointestinal circulation for elimination, but was effectively distributed in liver. Thereafter, it was slowly absorbed and finally stored in the muscle, the most important organ for AsB deposition, at a constant rate of 63.5 d-1. In contrast, As(V) displayed a dynamic behavior, including rapid crossing through the intestinal membranes, quick circulation in the blood and transportation to other tissues, and elimination. Biodynamics coupled with biotransformation illustrated, for the first time, the unique strategies of dietary AsB that passed slowly through the fish intestine with the highest deposition rate in the muscle, thereby contributing to the high AsB bioaccumulation in the muscle tissue of marine fish. CAPSULE: AsB displayed a weaker ability to cross the intestine membranes, slowly absorbed and finally stored in muscle, whereas As(V) displayed rapid crossing the intestine membranes, quick transportation, and elimination.