Separation and Recovery of Valuable Carbon Components and Li/Ga Metals in Coal Gangue by Using a Flotation Flowsheet.

Coal gangue (CG), an industrial solid waste with high contents of Li and Ga, has attracted the attention of researchers. However, the utilization of CG remains an economic challenge. Pre-enrichment of Li and Ga by flotation was carried out with a view to improving the comprehensive utilization of CG. Mineral composition, time-of-flight secondary ion mass spectrometry (TOF-SIMS), and elemental composition were used to investigate the embeddedness of each mineral and the mode of elemental occurrence in the CG. The results showed that the main mineral compositions of the CG were kaolinite, quartz, and pyrite. Li and Ga were mainly associated with kaolinite and other clay minerals. Li and Ga had a high correlation with Al2O3 and SiO2, while Li and Ga were highly correlated with SiO2/Al2O3, indicating that Li and Ga may be associated with one or more high-alumina minerals. In addition, flotation tests proved that synergistic sorting of ash impurities and valuable components from the CG was a cost-effective method. The ash content of the final product was increased by 3% under the process of prediscarding concentrate-dissociation-secondary flotation, and the contents of Li and Ga in the final product were also slightly enriched, and the recovery rate of the carrier minerals of Li and Ga can reach 66.1%.

Ursolic acid targets secreted phosphoprotein 1 to regulate Th17 cells against non-alcoholic fatty liver disease.

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on NAFLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on NAFLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of NAFLD. In addition, this study revealed that in addition to the canonical TGF-ß/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in NAFLD progression. Conclusions: Ursolic acid could improve immune inflammation in NAFLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

Adsorption Behavior of NO and NO2 on Two-Dimensional As, Sb, and Bi Materials: First-Principles Insights.

To address the most significant environmental challenges, the quest for high-performance gas sensing materials is crucial. Among numerous two-dimensional materials, this study investigates the gas-sensitive capabilities of monolayer As, Sb, and Bi materials. To compare the gas detection abilities of these three materials, we employ first-principles calculations to comprehensively study the adsorption behavior of NO and NO2 gas molecules on the material surfaces. The results indicate that monolayer Bi material exhibits reasonable adsorption distances, substantial adsorption energies, and significant charge transfer for both NO and NO2 gases. Therefore, among the materials studied, it demonstrates the best gas detection capability. Furthermore, monolayer As and Sb materials exhibit remarkably high capacities for adsorbing NO and NO2 gas molecules, firmly interacting with the gas molecules. Gas adsorption induces changes in the material's work function, suggesting the potential application of these two materials as catalysts.

Efficacy and Safety in Early application of Ruxolinitib for high-risk: Acute lymphoblastic leukemia to prevent GVHD and recurrence after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been identified as the potentially curative treatment for high-risk acute lymphoblastic leukemia (ALL) in adult patients. However, relapse of the disease and/or development of graft-versus-host disease (GVHD) remain to be the most common barriers for successful allo-HSCT. Preclinical studies showed that ruxolitinib, a Janus tyrosine kinase (Jak)1 and Jak2 inhibitor, has a selective anti-GVHD effects while preserving a potent graft-versus-leukemia (GVL) effect. Our study aimed to investigate the efficacy and safety in early application of ruxolitinib for the high-risk ALL patients to prevent GVHD. METHODS: There were eight patients undergoing allo-HSCT at the Bone Marrow Transplantation Center of the Third Xiangya Hospital of Central South University between April 2020 and April 2021. Ruxolitinib (5-10 mg twice daily) was administered early (median time: 45 days) after stem cell infusion. RESULTS: After a median follow-up of 14 months (range from 8 to 18 months), the ALL disease relapse occurred in two cases. Among all eight patients, two of them developed grade I/II acute (a) GVHD, while no patient developed grade III/IV aGVHD, and one patient developed chronic (c) GVHD. As for the virus activation, no patient developed EBV activation or EBV related lymphoproliferative disease, and three patients developed CMV activation. Our results suggest that the early application of ruxolitinib could safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL patients. However, it may have a limited effect on preventing the recurrence of high-risk ALL and thus may require additional therapy with other anti-relapse drugs. CONCLUSIONS: Our preliminary observations suggest that an early application of ruxolitinib can safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL patients. However, ruxolitinib may have a limited effect on preventing the ALL recurrence of high-risk patients.

Research on personalized path recommendation of college physical education online teaching based on improved particle swarm optimization

In recent years, colleges and universities have paid great attention to the education of physical health has the characteristics of strong on-site interaction and high requirements for venues and equipment. The construction of online teaching mechanism of college physical education is not only an opportunity but also a challenge for College Physical Education in China. The construction of online physical education teaching mechanism in Colleges and universities not only helps to improve the physical education teaching system in Colleges and universities in China, but also helps to enhance the importance of college teachers and students on physical education network teaching and promote the diversification of college physical education teaching methods. However, in practice, due to the imperfect construction of their own teaching platform, the lack of online teaching ability of physical education teachers, and the lack of online teaching resources, some colleges and universities in China have affected the quality of online physical education teaching to a certain extent. So, this article presents a personalized path recommendation method mabpso based on the improved particle swarm optimization algorithm for college physical education online teaching. First of all, it combs the literature about personalized teaching path recommendation and intelligent optimization algorithm at home and abroad; Secondly, a feature model (Leet) is constructed for educators and teaching resources; Third, it mainly solves the disadvantage of bspo, that is, it is easy to be trapped in the local optimization. The solution is to get rid of this problem by continuously improving the algorithm to get a more accurate algorithm with strong inhibition, so as to maximize the accuracy of teaching path recommendation and have a more accurate probability in the final calculation (AU)

Effects of Ocimum basilicum essential oil and ginger extract on serum biochemistry, oxidative stress and gill tissue damage of pearl gentian grouper during simulated live transport.

This study explored the effects of the essential oil of Ocimum basilicum (EOOB) and ginger extract (GE) during the transportation of pearl gentian grouper from water quality, serum biochemistry, oxidative stress, meat flavor, and gill tissue morphology. Fish (450 ± 50 g) were allocated to the following 5 treatments: control group (fish transported in water only), 5 mg/LEOOB, 10 mg/LEOOB, 3 mg/LGE, and 6 mg/LGE and transported in insulation boxes (66 × 51 × 37.8 cm) for 72 h. Samples were taken at 0, 12, 36, 60, and 72 h immediately after transport. It was found that 10 mg/LEOOB and 6 mg/LGE could reduce the levels of total ammonia nitrogen (TAN), dissolved oxygen (DO), water pH, serum glucose (GLU), cortisol (COR), liver superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPX), increase the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), as well as significantly increase the total free amino acid (TFAA) content in muscle compared to the control group (P < 0.05). In addition, by observing the microstructure of gill tissue, it was found that compared with untreated grouper, the morphological damage of gill tissue in EOOB and GE treatment was alleviated. These results indicated that adding appropriate amounts of EOOB and GE to transport water could improve the water quality, relieve stress, and lower energy metabolism of grouper during transport. The results of this research will help to improve the survival rate of grouper after transportation and decrease economic losses to fishery.

Crosstalk-Free Position Mapping for One-Step Reconstruction of Surface Topological Information via Eigenfrequency-Registered Wearable Interface.

Exploring flexible tactile sensors capable of recognizing surface information is significant for the development of virtual reality, artificial intelligence, soft robotics, and human-machine interactions (HMI). However, it is still a challenge for current tactile sensors to efficiently recognize the surface pattern information while maintaining the simplicity of the overall system. In this study, cantilever beam-like magnetized micropillars (MMPs) with height gradients are assembled as a position-registered array for rapid recognition of surface pattern information. After crossing the surface location with convex patterns, the deformed MMPs undergo an intrinsic oscillating process to induce damped electrical signals, which can then be converted to a frequency domain for eigenfrequency extraction. Via precisely defining the specific eigenfrequencies of different MMPs, position mapping is realized in crosstalk-free behavior even though all signals are processed by one communication channel and a pair of electrodes. With a customized LabVIEW program, the surface information (e.g., letters, numbers, and Braille) can be accurately reconstructed by the frequency sequence produced in a single scanning procedure. We expect that the proposed interface can be a convenient and powerful platform for intelligent surface information perception and an HMI system in the future.

Effects of vitamin C combined with sodium alginate on serum biochemistry, oxidative stress, gill tissue morphology, and muscle quality of pearl gentian grouper during waterless transport.

This research examined the effects of sodium alginate (SA) and vitamin C (Vc) soaking of pearl gentian grouper before waterless transportation from the perspectives of serum parameters, oxidative stress, muscle quality, and gill tissue morphology. After the fish reached semi-dormancy with a cooling rate of 3 °C/h, fish (420 ± 25 g) were distributed to 4 treatments as follows: S1 group (50 mg/L Vc and 0.1% SA were added), S2 group (50 mg/L Vc and 0.3% SA were added), S3 group (50 mg/L Vc and 0.5% SA were added), and control group (without soaking in protective fluid). After oxygenated packaging, samples were taken at 0, 8, and 16 h of waterless transportation and 12 h after rehydration, respectively. It was found that after 16 h of waterless transport, compared with the control group, cortisol, glucose, blood urea nitrogen (BUN), uric acid (UA), creatinine (CREA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were significantly decreased (p < 0.05), while albumin, lysozyme (LZM), muscle pH, and total free amino acid (TFAA) contents were significantly elevated (p < 0.05) in the S3 group. Moreover, by gill tissue microscopy, it was found that the protective solution of group S3 did not cause serious deleterious morphological changes to the gill epithelium. The results showed that the grouper was soaked by protective fluid before waterless could maintain surface moisture, reduce gill and kidney function and oxidative stress damage, and maintain the stability of muscle quality. This study provides a novel transportation method for waterless preservation, which helps to reduce transportation costs and improve transportation efficiency.

Research on multi-target data association of the infrared fish-eye warning system.

The multi-target data association method is studied in order to realize multi-target tracking in infrared fish-eye warning system. The Neural Joint Probabilistic Data Association (NJPDA) algorithm is analyzed. It is found that the NJPDA algorithm only considers the distance information between the measurement and the target in the data association process, and its tracking accuracy needs to be further improved. Therefore, a new method fused with direction information is proposed based on the NJPDA algorithm. The proposed algorithm defines the concept of direction difference, introduces the direction information of target motion, and modifies the likelihood function by Gaussian weighting method, so as to fuse the direction information of target motion into the calculation of data interconnection probability. Experimental results demonstrate that the tracking success rate of the proposed algorithm is nearly 10 % higher than that of JPDA and NJPDA algorithms and its consuming time meets the real-time requirement of the infrared fish-eye warning system.

Comparison of the Immunogenicity and Efficacy of rBCG-EPCP009, BCG Prime-EPCP009 Booster, and EPCP009 Protein Regimens as Tuberculosis Vaccine Candidates.

Bacillus Calmette-Guérin (BCG) is the only widely used prophylactic tuberculosis (TB) vaccine that can prevent severe TB in infants. However, it provides poor protection in adults, and therefore, there is ongoing research into new TB vaccines and immunization strategies with more durable immune effects. The recombinant BCG and BCG prime-protein booster are two important vaccine strategies that have recently been developed based on BCG and could improve immune responses. In this study, three immune strategies based on four protective antigens, namely, ESAT-6, CFP-10, nPPE18, and nPstS1, were applied to construct recombinant rBCG-EPCP009, EPCP009 subunit protein, and BCG prime-EPCP009 booster vaccine candidates. The short- and long-term immune effects after vaccination in Balb/c mice were evaluated based on humoral immunity, cellular immunity, and the ability of spleen cells to inhibit in vitro mycobacterial growth. At 8 and 12 weeks after the initial immunization, splenocytes from mice inoculated with the BCG prime-EPCP009 protein booster secreted higher levels of PPD- and EPCP009-specific IFN-γ, IL-2, TNF-α, IL-17, GM-CSF, and IL-12 and had a higher IFN-γ+CD4+ TEM:IL-2+CD8+ TCM cell ratio than splenocytes from mice inoculated with the rBCG-EPCP009 and EPCP009 proteins. In addition, the EPCPE009-specific IgG2a/IgG1 ratio was slightly higher in the BCG prime-EPCP009 protein booster group than in the other two groups. The in vitro mycobacterial inhibition assay showed that the splenocytes of mice from the BCG prime-EPCP009 protein booster group exhibited stronger inhibition of Mycobacterium tuberculosis (M. tuberculosis) growth than the splenocytes of mice from the other two groups. These results indicate that the BCG prime-EPCP009 protein booster exhibited superior immunogenicity and M. tuberculosis growth inhibition to the parental BCG, rBCG-EPCP009, and EPCP009 proteins under in vitro conditions. Thus, the BCG prime-EPCP009 protein booster may be important for the development of a more effective adult TB vaccine.

A Dietary Source of High Level of Fluoroquinolone Tolerance in mcr-Carrying Gram-Negative Bacteria.

The emergence of antibiotic tolerance, characterized by the prolonged survival of bacteria following antibiotic exposure, in natural bacterial populations, especially in pathogens carrying antibiotic resistance genes, has been an increasing threat to public health. However, the major causes contributing to the formation of antibiotic tolerance and underlying molecular mechanisms are yet poorly understood. Herein, we show that potassium sorbate (PS), a widely used food additive, triggers a high level of fluoroquinolone tolerance in bacteria carrying mobile colistin resistance gene mcr. Mechanistic studies demonstrate that PS treatment results in the accumulation of intracellular fumarate, which activates bacterial two-component system and decreases the expression level of outer membrane protein OmpF, thereby reducing the uptake of ciprofloxacin. In addition, the supplementation of PS inhibits aerobic respiration, reduces reactive oxygen species production and alleviates DNA damage caused by bactericidal antibiotics. Furthermore, we demonstrate that succinate, an intermediate product of the tricarboxylic acid cycle, overcomes PS-mediated ciprofloxacin tolerance. In multiple animal models, ciprofloxacin treatment displays failure outcomes in PS preadministrated animals, including comparable survival and bacterial loads with the vehicle group. Taken together, our works offer novel mechanistic insights into the development of antibiotic tolerance and uncover potential risks associated with PS use.

Sustainable conversion of cottonseed hulls to valuable proanthocyanidins through ultrasound-assisted deep eutectic solvent extraction.

This study presents a novel approach for converting cottonseed hulls (CSHs) into valuable proanthocyanidins (PAs) through deep eutectic solvent (DES)-based ultrasound-assisted extraction (UAE-DES). Response surface methodology (RSM) was applied to optimize and model this process, resulting in maximum yields of 78.58 mg/g. The ideal PA extraction conditions were determined to be a liquid-to-material ratio of 36.25 mL/g, a water content of 33.21%, and an extraction period of 7.4 min. Molecular dynamic simulations (MDS) were performed to study the interactions between the solvent and target chemicals. Increased van der Waals forces and stronger interactions between DES and the target chemical catechin (CA) compared to those observed with methanol or water were observed. Furthermore, the optimized extract exhibited a higher PA content than can be obtained with conventional extraction methods and demonstrated antioxidant activity in vitro. The cottonseed hulls residues (CSRs) remaining after the extraction process can be used to produce activated carbon (ACCSR), which has some capacity to adsorb methylene blue (MB) contaminants. This study offers a reference for the fruitful transformation of waste biomass into high-value products.

An integrated quorum quenching biocatalytic nanoplatform for synergistic chemo-photothermal eradication of P. aeruginosa biofilm infections.

Decontamination of biofilm-associated infections presents a significant challenge due to the physical and chemical barrier created by the formation of extracellular matrices. This barrier restricts the access of antibiotics to the bacterial communities within the biofilm and provides protection to the persister cells, potentially leading to antibiotic resistance. In this study, we have developed an integrated quorum quenching biocatalytic nanoplatform for the synergistic chemo-photothermal eradication of P. aeruginosa biofilm infections. Ciprofloxacin (Cip), a model antibiotic, was absorbed onto PDA NPs through π-π stacking. Additionally, acylase (AC) was immobilized on PDA NPs through Schiff base reaction and Michael addition, resulting in the formation of the biocatalytic nanoplatform (PDA-Cip-AC NPs). This biocatalytic nanoplatform was able to enzymatically degrade AHL signaling molecules, thus achieving efficient quorum quenching activity to prevent biofilm formation. Furthermore, the NIR light-triggered on-demand Ciprofloxacin release further enhanced the eradication of P. aeruginosa biofilm infections with a synergy of local hyperthermia. We envision that this integrated quorum quenching nanoplatform provides a reliable tool for combating P. aeruginosa biofilm infections. STATEMENT OF SIGNIFICANCE: An integrated quorum quenching biocatalytic nanoplatform has been developed for the eradication of P. aeruginosa biofilm infections. Quorum-sensing signals play a crucial role in modulating bacterial cell-to-cell communication, biofilm formation, and secretion of virulence factors. This biocatalytic nanoplatform efficiently degrades AHL signaling molecules, thereby blocking cell-to-cell communication and preventing biofilm formation. Additionally, local hyperthermia and on-demand Ciprofloxacin release were achieved through NIR irradiation, working synergistically to eradicate P. aeruginosa biofilm infections.

Health-related quality of life among critically ill patients after discharge from the ICU-A systematic review protocol.

The impact of critical illness on patients is profound, resulting in physical, mental, and social consequences and poor health-related quality of life (HRQOL). Several studies investigated HRQOL among patients discharged from the intensive care unit (ICU). However, few systematic reviews cover studies conducted in the last decade or using valid instruments for measuring HRQOL in general ICU survivor populations. Herein, we conduct a systematic review of these studies that followed PRISMA guidelines. We will search PubMed, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Library, and Open Grey for papers. We will search for articles reporting the HRQOL of ICU survivors that were written in English and published from 01 January 2012 onward from the date of this protocol's publication. We will also extract HRQOL data and analyze associate factors. The risk of bias will be measured with a standard quality assessment tool. The strength of the results will depend on the number of studies and the consistency of their results. Trial registration number: PROSPERO CRD 42022304279.

LncRNAs associated with oxidative stress in diabetic wound healing: Regulatory mechanisms and application prospects.

Diabetes is a group of chronic diseases with blood glucose imbalance, and long-term hyperglycaemia causes sustained damage to various organs of the body, resulting in vascular lesions, neuropathy and impaired wound healing. Diabetic wound formation involves a variety of complex mechanisms, and they are characterized by a persistent chronic inflammatory response, degradation of angiogenesis and imbalance of extracellular matrix regulation, all of which are related to oxidative stress. Additionally, repair and healing of diabetic wounds require the participation of a variety of cells, cytokines, genes, and other factors, which together constitute a complex biological regulatory network. Recent studies have shown that long noncoding RNAs (lncRNAs) can be involved in the regulation of several key biological pathways and cellular functions demonstrating their critical role in diabetic wound healing. LncRNAs are a major family of RNAs with limited or no protein-coding function. Numerous studies have recently reported a strong link between oxidative stress and lncRNAs. Given that both lncRNAs and oxidative stress have been identified as potential drivers of diabetic wound healing, their link in diabetic wound healing can be inferred. However, the specific mechanism of oxidative stress related to lncRNAs in diabetic wound healing is still unclear, and elucidating the functions of lncRNAs in these processes remains a major challenge. This article reviews the mechanisms of lncRNAs related to oxidative stress in several stages of diabetic wound healing and discusses diagnostic and treatment potential of lncRNAs to treat diabetic wounds by improving oxidative stress, as well as the challenges of using lncRNAs for this purpose. It is hoped that these results will provide new targets and strategies for the diagnosis and treatment of impaired wound healing in diabetic patients.

Sleep Deprivation and Gut Microbiota Dysbiosis: Current Understandings and Implications.

Gut microbiota comprises the microbial communities inhabiting our gastrointestinal (GI) tracts. Accordingly, these complex communities play a fundamental role in many host processes and are closely implicated in human health and diseases. Sleep deprivation (SD) has become increasingly common in modern society, partly owing to the rising pressure of work and the diversification of entertainment. It is well documented that sleep loss is a significant cause of various adverse outcomes on human health including immune-related and metabolic diseases. Furthermore, accumulating evidence suggests that gut microbiota dysbiosis is associated with these SD-induced human diseases. In this review, we summarize the gut microbiota dysbiosis caused by SD and the succedent diseases ranging from the immune system and metabolic system to various organs and highlight the critical roles of gut microbiota in these diseases. The implications and possible strategies to alleviate SD-related human diseases are also provided.

MicroRNA regulation of phenotypic transformations in vascular smooth muscle: relevance to vascular remodeling.

Alterations in the vascular smooth muscle cells (VSMC) phenotype play a critical role in the pathogenesis of several cardiovascular diseases, including hypertension, atherosclerosis, and restenosis after angioplasty. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs (approximately 19-25 nucleotides in length) that function as regulators in various physiological and pathophysiological events. Recent studies have suggested that aberrant miRNAs' expression might underlie VSMC phenotypic transformation, appearing to regulate the phenotypic transformations of VSMCs by targeting specific genes that either participate in the maintenance of the contractile phenotype or contribute to the transformation to alternate phenotypes, and affecting atherosclerosis, hypertension, and coronary artery disease by altering VSMC proliferation, migration, differentiation, inflammation, calcification, oxidative stress, and apoptosis, suggesting an important regulatory role in vascular remodeling for maintaining vascular homeostasis. This review outlines recent progress in the discovery of miRNAs and elucidation of their mechanisms of action and functions in VSMC phenotypic regulation. Importantly, as the literature supports roles for miRNAs in modulating vascular remodeling and for maintaining vascular homeostasis, this area of research will likely provide new insights into clinical diagnosis and prognosis and ultimately facilitate the identification of novel therapeutic targets.

Characteristics of historical precipitation for winter wheat cropping in the semi-arid and semi-humid area.

Winter wheat (Triticum aestivum L.) is one of major crops in the area along Huai river, China where it is a semi-arid and semi-humid region with sufficient precipitation for an entire season, but with uneven distribution within various growth stages. The instability of precipitation is an important factor in limiting wheat production potential under climate change. Therefore, it is essential to characterise the precipitation associated with different crop developmental stages. Based on climate data from 1999 to 2020 in six representative meteorological stations, we characterised the historical precipitation relating to seven key growth stages in winter wheat. There is no clear trend of interannual variation of precipitation for wheat season, with an average of precipitation of 414.4 ± 121.2 mm. In terms of the distribution of precipitation grade within a season, light rain was dominant. Continuous rain occurred frequently during the pre-winter seedling and overwintering stages. The critical period of water demand, such as jointing and booting, has less precipitation. The fluctuation range of precipitation in sowing, heading-filling and maturation stages is large, which means that there is flood and drought at times. In conclusion, these findings provide a foundation for instructing winter wheat cropping in confronting with waterlogging and drought risk due to uneven precipitation in 'Yanhuai' region, China.

Genetic Characterization Conferred Co-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Isolates from Southern Xinjiang, China.

Background: Ethionamide (ETH), a structural analogue of isoniazid (INH), is used for treating multidrug-resistant tuberculosis (MDR-TB). Due to the common target InhA, INH and ETH showed cross-resistance in M. tuberculosis. This study aimed to explore the INH and ETH resistant profiles and genetic mutations conferring independent INH- or ETH-resistance and INH-ETH cross-resistance in M. tuberculosis circulating in south of Xinjiang, China. Methods: From Sep 2017 to Dec 2018, 312 isolates were included using drug susceptibility testing (DST), spoligotyping, and whole genome sequencing (WGS) to analyze the resistance characteristics for INH and/or ETH. Results: Among the 312 isolates, 185 (58.3%) and 127 (40.7%) belonged to the Beijing family and non-Beijing family, respectively; 90 (28.9%) were INH-resistant (INHR) with mutation rates of 74.4% in katG, 13.3% in inhA and its promoter, 11.1% in ahpC and its upstream region, 2.2% in ndh, 0.0% in mshA, whilst 34 (10.9%) were ETH-resistant (ETHR) with mutation rates of 38.2% in ethA, 26.2% in inhA and its promoter, and 5.9% in ndh, 0.0% in ethR or mshA; and 25 (8.0%) were INH-ETH co-resistant (INHRETHR) with mutation rates of 40.0% in inhA and its promoter, and 8% in ndh. katG mutants tended to display high-level resistant to INH; and more inhA and its promoter mutants showed low-level of INH and ETH resistance. The optimal gene combinations by WGS for the prediction of INHR, ETHR, and INHRETHR were, respectively, katG+inhA and its promoter (sensitivity: 81.11%, specificity: 90.54%), ethA+inhA and its promoter+ndh (sensitivity: 61.76%, specificity: 76.62%), and inhA and its promoter+ndh (sensitivity: 48.00%, specificity: 97.65%). Conclusion: This study revealed the high diversity of genetic mutations conferring INH and/or ETH resistance among M. tuberculosis isolates, which would facilitate the study on INHR and/or ETHR mechanisms and provide clues for choosing ETH for MDR treatment and molecular DST methods in south of Xinjiang, China.