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Abstract TBI-223, a novel oxazolidinone for tuberculosis, is designed to provide improved efficacy and safety compared to linezolid in combination with bedaquiline and pretomanid (BPaL). We aim to optimize the dosing of TBI-223 within the BPaL regimen for enhanced therapeutic outcomes. TBI-223 is investigated in preclinical monotherapy, multidrug therapy, and lesion penetration experiments to describe its efficacy and safety versus linezolid. A translational platform incorporating linezolid and BPaL data from preclinical experiments and 4 clinical trials (NCT00396084, NCT02333799, NCT03086486, NCT00816426) is developed, enabling validation of the framework. TBI-223 preclinical and Phase 1 data (NCT03758612) are applied to the translational framework to predict clinical outcomes and optimize TBI-223 dosing in combination with bedaquiline and pretomanid. Results indicate that daily doses of 1200–2400 mg TBI-223 may achieve efficacy comparable to the BPaL regimen, with >90% of patients predicted to reach culture conversion by two months.

Abstract The accuracy of target passive localization is influenced by the placement of signal receiving stations; therefore, many studies have been performed to optimize station placement. However, most of the present placement methods focus on the localization error of one target, and if the exact position of the target cannot be determined, but only the range of the target activity is known, how to study the localization station placement in a region is a problem that needs to be solved. This paper proposes a grey wolf optimization algorithm based on the regional target error model to solve the optimal station placement problem. Firstly, a regional target localization error model is established using the measured TDOA, and the overall error matrix within a region is derived. Then, by taking the trace of the error matrix as a criterion, the objective function is established to find the optimal location of the receiving station by grey wolf optimizer. The optimization parameters are also improved to increase the global search ability of the algorithm. Finally, the feasibility and reliability of the overall error model and the grey wolf algorithm proposed are verified by experiments from multiple perspectives. The station placement method proposed in this paper can effectively solve the localization problem of targets that are only known to be in a general activity region in advance, which is more realistic.

BackgroundLong-term heat stress (HS) severely restricts the growth performance of beef cattle and causes various health problems. The gut microbiota plays a crucial role in HS-associated inflammation and immune stress involving lymphocyte function. This study investigated the effects of dietary tea polysaccharide (TPS), a natural acidic glycoprotein, on HS-induced anorexia, inflammation, and gut microbiota dysbiosis in Simmental beef cattle.MethodsThe cattle were divided into two groups, receiving either normal chow or normal chow plus TPS (8 g/kg, 0.8%). Transcriptome sequencing analysis was used to analysis the differential signaling pathway of liver tissue. 16S rDNA sequencing was performed to analysis gut microbiota of beef cattle. Serum metabolite components were detected by untargeted metabolomics analysis.ResultsHepatic transcriptomics analysis revealed that differentially expressed genes in TPS-fed cattle were primarily enriched in immune processes and lymphocyte activation. TPS administration significantly reduced the expression of the TLR4/NF-κB inflammatory signaling pathway, alleviating HS-induced hepatic inflammation. Gut microbiota analysis revealed that TPS improved intestinal homeostasis in HS-affected cattle by increasing bacterial diversity and increasing the relative abundances of Akkermansia and Alistipes while decreasing the Firmicutes-to-Bacteroidetes ratio and the abundance of Agathobacter. Liquid chromatography-tandem mass spectrometry (LC‒MS/MS) analysis indicated that TPS significantly increased the levels of long-chain fatty acids, including stearic acid, linolenic acid, arachidonic acid, and adrenic acid, in the serum of cattle.ConclusionThese findings suggest that long-term consumption of tea polysaccharides can ameliorate heat stress-induced hepatic inflammation and gut microbiota dysbiosis in beef cattle, suggesting a possible liver-gut axis mechanism to mitigate heat stress.

BackgroundThis study assesses the impact of adverse childhood experiences (ACEs) on the cognitive function of older adults. Furthermore, it examines the potential underlying mechanism involving education level and the subjective “feeling of loneliness” (FOL).MethodsAnalyzing a population-based cohort sample from the China Health and Retirement Longitudinal Study database, 8,365 subjects aged 45 or older were interviewed in 2018. Ten ACEs indicators were measured using life history questionnaires assessed at 2014. FOL was assessed using a single item from 10-item Center for Epidemiological Studies Depression Scale (CESD-10). Cognitive function was assessed using a structured questionnaire comprising four dimensions: memory, orientation, computation, and visuospatial abilities.ResultsIn the fully adjusted model, which accounted for age, gender, marital status, smoke, drink, rural residence, and education levels of both mothers and fathers, the linear regression analysis indicated that ACEs were inversely associated the lower education level (B = −0.058, 95% CI = −0.090, −0.026, p

Niclosamide (NIC) is a commonly used insecticide and molluscicide in the prevention and treatment of parasitic diseases in fish. The utilization of NIC has the potential to disrupt the microbial community present on the mucosal tissue of fish, leading to localized inflammatory responses. The objective of this study was to evaluate the impact of NIC on the immune system and bacterial populations within the gill and gut of Mylopharyngodon piceus. Fish were subjected to varying concentrations of NIC, including a control group (0 μg/L), a low NIC group (15% 96 h LC50, LNG, 9.8 μg/L), and a high NIC group (80% 96 h LC50, HNG, 52.5 μg/L). Gill and gut samples were collected 28 days post-exposure for analysis. The findings revealed that the 96-h LC50 for NIC was determined to be 65.7 μg/L, and histopathological examination demonstrated that exposure to NIC resulted in gill filament subepithelial edema, exfoliation, degeneration, and a decrease in gill filament length. Furthermore, the gut exhibited apical enterocyte degeneration and leucocyte infiltration following NIC exposure. Additionally, NIC exposure led to a significant elevation in the levels of immunoglobulin M (IgM), complement component 3 (C3), and complement component 4 (C4) in both gill and gut tissues. Moreover, the activity of lysozyme (LYZ) was enhanced in the gill, while the activities of peroxidase (POD) and immunoglobulin T (IgT) were increased in gut tissue. The exposure to NIC resulted in enhanced mRNA expression of c3, c9, tnfα, il6, il8, and il11 in the gill tissue, while decreasing c3 and il8 expression in the gut tissue. Furthermore, the natural resistance-associated macrophage protein (nramp) mRNA increased, and liver-expressed antimicrobial peptide 2 (leap2) mRNA decreased in gill and gut tissues. And hepcidin (hepc) mRNA levels rose in gill but fell in gut tissue. NIC exposure also led to a decrease in gill bacterial richness and diversity, which significantly differed from the control group, although this separation was not significant in the gut tissue. In conclusion, the administration of NIC resulted in alterations in both the immune response and mucosal microbiota of fish. Furthermore, it was noted that gills displayed a heightened vulnerability to sublethal effects of NIC in comparison to gut tissues.

Abstract. Background:. Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US. Methods:. The deaths, and mortality rates of asthma in China and the US during 1990-2019 were obtained from the Global Burden of Disease Study 2019. The age-period-cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated. Results:. In 1990-2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively. Conclusions:. In 1990-2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

This study aimed to investigate the inhibitory effect of Zuojin Pill (ZJP) on KYSE 150 cells and xenograft tumours of the digestive tract cancer – esophageal cancer (EC) and its underlying mechanism. Initially, in vivo research demonstrated that oral administration of ZJP effectively inhibited the growth of EC tumours, and in vitro studies revealed that ZJP suppressed the proliferation, migration, and invasion of cells. Then, network pharmacology prediction identified the core target, active ingredient, and involvement of the PI3K-Akt signalling pathway in ZJP treatment of EC. Cell studies validated that ZJP affected the expression of core targets, and its active ingredients inhibited the proliferation of cells. Additionally, ZJP was shown to induce cell apoptosis, decrease mitochondrial membrane potential, and increase the level of intracellular oxidative stress. Further experimental verifications suggested that the inhibitory effects of ZJP on EC might be attributed to the modulation of PI3 K/Akt signalling pathways.

Background Miliary Tuberculosis (TB) remains an important infectious disease that threatens human health. The clinical characteristics and prognostic factors of miliary TB are summarized in this study.Methods The clinical information of miliary TB patients between 2010 and 2022 was retrospectively analyzed. Patients with miliary TB were characterized and compared to adverse outcomes cases. Factors independently associated with adverse outcomes were determined via multivariate logistic regression analysis.Results A total of 288 patients were analyzed, including 181 with adverse outcomes. The clinical manifestations are atypical. 88.54% Of them experienced systemic symptoms, whilst 69.79% manifested respiratory symptoms. 40.97% Presented with neurologic symptoms, while 35.07% reported gastrointestinal symptoms. The major comorbidities were pharmacological immunosuppression (21.53%), pneumoconiosis (15.28%), diabetes (10.76%), and pregnancy or postpartum (7.29%). Regarding microbiology, most patients were diagnosed via sputum or Bronchoalveolar Lavage Fluid (BALF), pleural effusion, ascites, cerebrospinal fluid, urine TB-DNA, and tuberculosis culture. Meanwhile, 2.43% of patients were diagnosed via cerebrospinal fluid NGS. Independent risk factors predictive of adverse outcomes were current smoking, leukocytosis, elevated alanine aminotransferase (ALT) levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis. The accuracy of the model was validated by an area under the ROC curve of 0.753 (95% IC 0.697–0.810).Conclusions The clinical manifestations of miliary TB are atypical, and early diagnosis is challenging. The major comorbidities in miliary TB patients were pharmacological immunosuppression, pneumoconiosis, diabetes, pregnancy, and postpartum. Regarding etiological detection, multi-site and multi-type specimens should be collected for a timely diagnosis. Cerebrospinal fluid mNGS test may be a viable choice in some cases. Finally, current smoking, leukocytosis, elevated ALT levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis were identified as independent risk factors for adverse outcomes.

ABSTRACTPreviously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain–Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016–2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1–34]; adults, 25 years [range, 0–183]) and intensive care unit (children, 16 years [range, 1–30]; adults, 17 years [range, 0–102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

IntroductionAn increasing body of research has demonstrated a correlation between pollutants from the environment and the development of cardiovascular diseases (CVD). However, the impact of volatile organic chemicals (VOC) on CVD remains unknown and needs further investigation.ObjectivesThis study assessed whether exposure to VOC was associated with CVD in the general population.MethodsA cross-sectional analysis was conducted utilizing data from five survey cycles (2005–2006, 2011–2012, 2013–2014, 2015–2016, and 2017–2018) of the National Health and Nutrition Examination Survey (NHANES) program. We analyzed the association between urinary VOC metabolites (VOCs) and participants by multiple logistic regression models, further Bayesian Kernel Machine Regression (BKMR) models and Weighted Quantile Sum (WQS) regression were performed for mixture exposure analysis.ResultsTotal VOCs were found to be positively linked with CVD in multivariable-adjusted models (p for trend = 0.025), independent of established CVD risk variables, such as hypertension, diabetes, drinking and smoking, and total cholesterol levels. Compared with the reference quartile of total VOCs levels, the multivariable-adjusted odds ratios in increasing quartiles were 1.01 [95% confidence interval (CI): 0.78–1.31], 1.26 (95% CI: 1.05–1.21) and 1.75 (95% CI: 1.36–1.64) for total CVD. Similar positive associations were found when considering individual VOCs, including AAMA, CEMA, CYMA, 2HPMA, 3HPMA, IPM3 and MHBMA3 (acrolein, acrylamide, acrylonitrile, propylene oxide, isoprene, and 1,3-butadiene). In BKMR analysis, the overall effect of a mixture is significantly related to VOCs when all chemicals reach or exceed the 75th percentile. Moreover, in the WQS models, the most influential VOCs were found to be CEMA (40.30%), DHBMA (21.00%), and AMCC (19.70%).ConclusionThe results of our study indicated that VOC was all found to have a significant association with CVD when comparing results from different models. These findings hold significant potential for public health implications and offer valuable insights for future research directions.

Abstract Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non‐invasive diagnosis method based on serum markers, such as α‐fetoprotein (AFP), and des‐γ‐carboxy‐prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere‐coated three‐dimensional (3D) hierarchical porous chip, named a SiO2‐chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non‐HCC and HCC subjects are enriched using an SiO2‐chip and performed RNA sequencing to identify HCC‐related long non‐coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT‐1 and EGFR‐AS‐1 are two HCC‐related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT‐PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy‐based approach for noninvasive and reliable HCC detection is developed.

Objective: To investigate the potential of CT-enhanced quantitative parameters for preoperative prediction of WHO/ISUP grading for renal clear cell carcinoma (ccRCC). Methods: The study involved collecting clinical and CT-enhanced data of 98 patients with ccRCC, who were then classified into low level group (76 cases) and high level group (22 cases) based on the WHO/ISUP classification. Differences in CT-enhanced quantitative parameters between the two groups were compared, and the diagnostic efficacy of each parameter for predicting ccRCC WHO/ISUP grading was evaluated. External verification was conducted to identify CT-enhanced quantitative parameters with the best generalization ability. Results: There were significant differences in the CT value, net increment, and enhancement rate in both cortical and substantive phases between the two groups. The AUC values were 0.834, 0.871, 0.900, 0.707, 0.678, and 0.762, respectively. The cut-off values were 123.5 HU, 71 HU, 0.73, 87.5 HU, 54 HU, 0.67, respectively. The diagnostic efficacy of cortical enhancement rate was the highest with an AUC of 0.900, a sensitivity of 0.842, and a specificity of 0.864. The external validation results revealed that the diagnostic efficacy of cortical phase enhancement rate (AUC=0.867) was better than that of cortical phase CT (AUC=0.735) and cortical phase net increment (AUC=0.709). The Z values were 2.134 and 2.417, respectively. Conclusion: The quantitative parameters of CT enhancement can be used to predict ccRCC WHO/ISUP grading. Cortical phase enhancement rate is the parameter with the highest diagnostic efficiency and the best generalization ability.

Abstract Dysregulation of pathogen-recognition pathways of the innate immune system is associated with multiple autoimmune disorders. Due to the intricacies of the molecular network involved, the identification of pathway- and disease-specific therapeutics has been challenging. Using a phenotypic assay monitoring the degradation of the immune adapter TASL, we identify feeblin, a chemical entity which inhibits the nucleic acid-sensing TLR7/8 pathway activating IRF5 by disrupting the SLC15A4-TASL adapter module. A high-resolution cryo-EM structure of feeblin with SLC15A4 reveals that the inhibitor binds a lysosomal outward-open conformation incompatible with TASL binding on the cytoplasmic side, leading to degradation of TASL. This mechanism of action exploits a conformational switch and converts a target-binding event into proteostatic regulation of the effector protein TASL, interrupting the TLR7/8-IRF5 signaling pathway and preventing downstream proinflammatory responses. Considering that all components involved have been genetically associated with systemic lupus erythematosus and that feeblin blocks responses in disease-relevant human immune cells from patients, the study represents a proof-of-concept for the development of therapeutics against this disease.

Abstract Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.

This study aimed to investigate the effects of applying arbuscular mycorrhizal fungi (AMF) on maize root growth and yield formation under different soil conditions. This study was conducted under sandy soil (S) and saline–alkali soil (Y), with treatments of AMF application (AM) and no AMF application (CK). The root characteristics, yield, and quality of maize were measured. High-throughput sequencing technology was employed to assess the impact of AMF on the soil microbial community structure, and the correlation between soil microbes and soil physicochemical properties was elucidated. The results show that under both sandy and saline–alkali soil conditions, AMF application significantly enhanced maize root growth, yield, grain quality, and soil available nitrogen (AN), available phosphorus (AP), and available potassium (AK) contents compared to the CK treatment. Soil microbial Alpha diversity analysis indicated that AMF application effectively increased soil microbial diversity and richness. Principal coordinate analysis (PCoA) and microbial community structure analysis revealed significant differences in bacterial communities between AM treatment in sandy soil (SAM) and CK in sandy soil (SCK), and significant differences in both bacterial and fungal communities between AM treatment in saline–alkali soil (YAM) and CK in saline–alkali soil (YCK). Furthermore, significant correlations between microbial communities and soil physicochemical properties were found, such as AN, AP, AK, soil salinity (SS), and organic matter (OM) content. AMF application had a greater impact on bacterial communities than on fungal communities. This study demonstrated that the use of AMF as a bio-fungal fertilizer was effective in improving spring maize yields, especially in terms of yield increase and quality stability in sandy and saline soils, thereby contributing to safe and sustainable cropping practices.

In a study aimed at developing a rapid and nondestructive method for testing the quality of strawberries, spectral data from four strawberry varieties at different ripening stages were collected using a geophysical spectrometer, primarily focusing on the 350–1800 nm band. The spectra were preprocessed using Savitzky–Golay (SG) filtering, and characteristic bands were extracted using Pearson correlation coefficient (PCC) analysis. Models for predicting strawberry quality were built using random forest (RF), support vector machine (SVM), partial least squares (PLS), and Gaussian regression (GPR). The results indicated that the SVM model exhibited relatively high accuracy in predicting anthocyanin, hardness, and soluble solids content in strawberries. For the test set, the SVM model achieved R2 and RMSE values of 0.81, 0.87, and 0.89, and 0.04 mg/g, 0.33 kg/cm2, and 0.72%, respectively. Additionally, the PLS model demonstrated relatively high accuracy in predicting the titratable acid content of strawberries, achieving R2 and RMSE values of 0.85 and 0.03%, respectively, for the test set. These findings provided a solid foundation for strawberry quality modeling and a veritable guide for non-destructive assessment of strawberry quality.

In recent years, with the increase in environmental awareness, people have become more and more concerned about the effectiveness with which coal burns. Laser-induced breakdown spectroscopy (LIBS) has become an important way of coal elemental analysis because of its uncomplicated sample handling, remote sensing capability, and superior sensitivity in identifying a wide range of elements, including both major and minor constituents, down to trace levels. However, the complexity of its mechanism of action, the experimental environmental factors, and the presence of matrix effects in its measurement spectrum have affected the measurement accuracy. In this paper, on the basis of introducing the experimental process and principle of LIBS, we summarize and analyze the influence of each factor on the LIBS detection medium, summarize the mainstream model analysis algorithms, and analyze the advantages and disadvantages of each model. While summarizing the LIBS in media detection in recent years, it aims to provide strong support and guidance for subsequent more in-depth exploration and research.

Abstract Background Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. Methods The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. Results Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. Conclusion Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear.ObjectivesThis study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms.MethodsIn this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention.ResultsThe VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV.ConclusionThe combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

ObjectiveTo evaluate the effects of behavioral intervention for polycystic ovary syndrome (PCOS).MethodsElectronic databases were searched, including Pubmed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to 1 April 2023. Inclusion criteria for this study required a diagnosis of PCOS. Interventions of interest included behavioral intervention and routine treatment compared with routine treatment. The studies included in the analysis were designed as randomized controlled trials (RCTs). We conducted meta-analyses following the recommended guidelines. The data was analyzed using either the random effects model or fixed effects model. The results of the studies were expressed as either mean differences (MD) or standardized mean differences (SMD) along with their corresponding 95% confidence intervals (CIs).ResultsEight RCTs were identified, including data from 744 patients (415 in the intervention group and 329 in the control group). The results indicate an improvement in the effectiveness of behavioral interventions for weight loss (MD: -1.07; 95% CI: -2.1 to 0.03; I2 = 0%; P=0.04), body mass index (BMI) (MD: -1.12; 95% CI: -1.92 to -0.33; I2 = 73%; P=0.006), waist circumference (MD: -3.97; 95% CI: -5.64 to -2.29; I2 = 0%; P

Diabetic encephalopathy (DE) is a common central nervous system complication of diabetes mellitus without effective therapy currently. Recent studies have highlighted synaptic mitochondrial damages as a possible pathological basis for DE, but the underlying mechanisms remain unclear. Our previous work has revealed that phosphatidate phosphatase Lipin1, a critical enzyme involved with phospholipid synthesis, is closely related to the pathogenesis of DE. Here, we demonstrate that Lipin1 is significantly down-regulated in rat hippocampus of DE. Knock-down of Lipin1 within hippocampus of normal rats induces dysregulation of homeostasis in synaptic mitochondrial dynamics with an increase of mitochondrial fission and a decrease of fusion, then causes synaptic mitochondrial dysfunction, synaptic plasticity deficits as well as cognitive impairments, similar to that observed in response to chronic hyperglycemia exposure. In contrast, an up-regulation of Lipin1 within hippocampus in the DE model ameliorates this cascade of dysfunction. We also find that the effect of Lipin1 that regulating mitochondrial dynamics results from maintaining appropriate phospholipid components in the mitochondrial membrane. In conclusion, alterations in hippocampal Lipin1 contribute to hippocampal synaptic mitochondrial dysfunction and cognitive deficits observed in DE. Targeting Lipin1 might be a potential therapeutic strategy for the clinical treatment of DE.

Through the incorporation of phosphorus (P) as a third component, an in-situ formation of a magnetic phase with a nanotwin structure was achieved. The utilization of selective laser melting (SLM) enabled the synthesis of a Cu–Fe–P immiscible alloy that exhibits an integrated structure and function. The microstructure predominantly consists of a magnetic heterogeneous Fe–P-rich phase, comprising a mixture of Fe2P and a small quantity of Fe3P, which is distributed within the ε-Cu Cu-rich matrix in alternating “fiber-layer” and “particle-shape” forms. Additionally, the fibrous Fe2P phase exhibited precipitation of α-Fe, while the Fe–P-rich phase experienced the precipitation of high-density nanotwinned Cu (nt-Cu) particles. The microstructure density and structural characteristics of Cu–Fe–P immiscible alloys were enhanced through the adjustment of laser energy density, leading to improvements in their mechanical and magnetic properties. It was observed that the microstructure density initially increased and then decreased with increasing laser energy density. The highest relative density of the Cu–Fe–P immiscible alloy microstructure (98%) was achieved at a laser energy density of 53 J/mm3. Furthermore, the influence of laser energy density on the mechanical and soft magnetic properties of Cu–Fe–P immiscible alloys was examined. The findings indicate that the mechanical and soft magnetic properties of these alloys are affected by the laser energy density. The findings indicate that the compact Cu–Fe–P immiscible alloys exhibit favorable compression mechanical properties and soft magnetic properties. Specifically, the ultimate compressive stress can reach 890.5 ± 20 MPa, while the failure strain can reach 20.5 ± 2%. Additionally, the coercivity is observed to be as low as 20.0 Oe, the magnetic saturation strength as high as 93.5 emu/g, and the residual magnetization at 1.1 emu/g.

[Introduction] In the context of the new power system, low-carbon maintenance of wind turbines and coordinated maintenance with conventional wind turbine generator systems (WTGS) need to be solved urgently. In this paper, taking into account the impact of multi-attribute meteorological factors and low carbon and economic needs, an optimization model for wind power, hydropower and thermal power combined low-carbon maintenance based on continuous hidden Markov model is established. [Method] Firstly, dynamic tracking of wind farm maintenance capacity was realized by taking rainfall, wind speed and lightning hazard degree as the observation sequence, taking maintenance capacity as hidden state sequence, and using continuous hidden Markov model (CHMM) process. Then, an optimization model for wind power, hydropower and thermal power combined low-carbon maintenance was constructed by taking the optimal maintenance capacity as the decision-making basis, taking the minimum total cost as the optimization objective, and taking the maintenance constraints and system control constraints into consideration. Finally, took the IEEE30-node system as an example. [Result] The results show that the proposed model has more significant economic benefits and low carbon characteristics. [Conclusion] The research in this paper has high theoretical value for the operation and maintenance of WTGS, and has strong engineering applicability.

Abstract With the widespread use of radars, different types of radar emitters are being used in the real electromagnetic environment. Radar emitter identification (REI) is an important technique in spectrum management. Methods based on deep learning have been successful in REI. However, they are difficult to be updated with signals from newly available categories. Additionally, two issues that must be considered in a real REI task. First, signals from new unknown radar emitters may appear in the identification stage. Hence the model used in REI must have an open‐set recognition capability. Second, obtaining numerous labelled samples in time are difficult in the incremental stage of the model. Thus, it is important to keep the model performance stable under conditions of small samples. To solve these problems, a one‐dimensional neural network is designed combined with ArcFace loss in the initial training stage to reserve more embedding space for future new classes, thereby facilitating the update of the model and open‐set recognition. An unbiased cosine similarity classifier was adopted, and the historical categories were memorised by their prototypes. When a new category is added, the prototype was calculated and the classifier weights were updated. The proposed method can identify unknown classes and add them to the model when given new labels, thereby resulting in an increase of the model's identifiable types. Extensive experiments were performed. The results show that the proposed model is highly efficient and requires small sample sizes, thereby making it suitable for REI.

(1) Background: One method of eradicating brucellosis is to cull cattle that test positive for antibodies 12 months after being vaccinated with the 19-strain vaccine. Variations in immunization regimens and feeding practices may contribute to differences in the rate of persistent antibodies. We conducted this study to investigate the real positive rate of Brucella antibody in field strains of Brucella spp. after immunization over 12 months in dairy cows. This research aims to provide data to support the development of strategies for preventing, controlling, and eradicating brucellosis. (2) Method: We employed the baseline sampling method to collect samples from cows immunized with the A19 vaccine for over 12 months in Lingwu City from 2021 to 2023. Serological detection was conducted using the RBPT method. An established PCR method that could distinguish between 19 and non-19 strains of Brucella was utilized to investigate the field strains of Brucella on 10 dairy farms based on six samples mixed into one using the Mathematical Expectation strategy. (3) Results: We analyzed the rates of individual seropositivity and herd seropositive rates in dairy cattle in Lingwu City from 2021 to 2023 and revealed that antibodies induced by the Brucella abortus strain A19 vaccine persist in dairy herds for more than 12 months. We established a PCR method for identifying both Brucella A19 and non-A19 strains, resulting in the detection of 10 field strains of Brucella abortus from 1537 dairy cows. By employing a Mathematical Expectation strategy, we completed testing of 1537 samples after conducting only 306 tests, thereby reducing the workload by 80.1%. (4) Conclusions: There was a certain proportion of cows with a persistent antibody titer, but there was no evidence that all of these cattle were naturally infected with Brucella. The established PCR method for distinguishing between Brucella abortus strain 19 and non-19 strains can be specifically utilized for detecting natural Brucella infection in immunized cattle. We propose that relying solely on the detection of antibodies in cattle immunized with the A19 vaccine more than 12 months previously should not be solely relied upon as a diagnostic basis for brucellosis, and it is essential to complement this approach with PCR analysis to specifically identify field Brucella spp. Brucella abortus was the predominant strain identified in the field during this study. Detection based on the Mathematical Expectation strategy can significantly enhance detection efficiency.

The timely and accurate mapping of crop types is crucial for agricultural insurance, futures, and assessments of food security risks. However, crop mapping is currently focused on the post-harvest period, and less attention has been paid to early crop mapping. In this study, the feasibility of using Sentinel-1 (S1) and Sentinel-2 (S2) data for the earliest identifiable time (EIT) for major crops (sunflower, maize, spring wheat, and melon) was explored in the Hetao Irrigation District (HID) of China, based on the Google Earth Engine (GEE) platform. An early crop identification strategy based on the Random Forest (RF) model for HID was proposed, and the performance of the model transfer was evaluated. First, the median synthesis, linear shift interpolation, and the Savitzky–Golay (SG) filter methods were used to reconstruct the time series of S1 and S2. Subsequently, the sensitivity of different input features, time intervals, and data integration to different early crop identifications was evaluated based on the RF model. Finally, the model with optimal parameters was evaluated in terms of its transfer capacity and used for the early mapping of crops in the HID area. The results showed that the features extracted from S2 images synthesized at 10-day intervals performed well in obtaining crop EITs. Sunflower, maize, spring wheat, and melon could be identified 90, 90, 70, and 40 days earlier than the harvest date. The identification accuracy, measured by the F1-score, could reach 0.97, 0.95, 0.98, and 0.90, respectively. The performance of the model transfer is good, with the F1-score decreasing from 0 to 0.04 and no change in EIT for different crops. It was also found that the EIT of crops obtained using S1 data alone was 50–90 days later than that obtained using S2 data alone. Additionally, when S1 and S2 were used jointly, S1 data contributed little to early crop identification. This study highlights the potential of early crop mapping using satellite data, which provides a feasible solution for the early identification of crops in the HID area and valuable information for food security assurance in the region.

The laying of power cables is a crucial aspect of developing and maintaining modern electrical infrastructure, which is vital for transmitting electricity reliably and efficiently. This review discusses the challenges and advancements in cable laying technologies, emphasizing the critical role of these techniques in meeting the increasing demands for power transmission in the backdrop of the global shift to renewable energy. Three main traditional cable laying methods are explored, including underground, overhead, and submarine, each suited to specific environmental and operational conditions. Then, the cable faults due to the impropriate laying process are discussed. Subsequently, the challenges and advancements encountered in cable laying processes are investigated, especially the difficulties of the cable laying of underground cable, submarine cable, and high-temperature superconductivity cable. This review also considers the impact of technological innovations on improving efficiency in cable laying processes, highlighting the advances driven by digitalization and automation.

Calmodulin (Calm), a crucial Ca2+ sensor, plays an important role in calcium-dependent signal transduction cascades. However, the expression and the relevance of Calm in stress and immune response have not been characterized in Megalobrama amblycephala. In this study, we identified the full-length cDNA of Calm (termed MaCalm) in blunt snout bream M. amblycephala, and analyzed MaCalm expression patterns in response to cadmium and Aeromonas hydrophila challenges. MaCalm was 1603 bp long, including a 5′-terminal untranslated region (UTR) of 97 bp, a 3′-terminal UTR of 1056 bp and an open reading frame (ORF) of 450 bp encoding a polypeptide of 149 amino acids with a calculated molecular weight (MW) of 16.84 kDa and an isoelectric point (pI) of 4.09. Usually, MaCalm contains four conservative EF hand motifs. The phylogenetic tree analysis indicated that the nucleotide sequence of MaCalm specifically clustered with Ctenopharyngodon idella with high identity (98.33%). Tissue distribution analysis demonstrated that the ubiquitous expression of MaCalm mRNA was found in all tested tissues, with the highest expression in the brain and the lowest expression in muscle. MaCalm showed significant upregulation at 14 d and 28 d post exposure to varying concentrations of cadmium in the liver; HSP70 transcripts in the liver significantly upregulated at 14 d post exposure to different concentrations of cadmium. Moreover, in response to the A. hydrophila challenge in vivo, MaCalm transcripts in the liver first increased and then decreased, but MaCalm transcripts in the kidney declined gradually with prolonged infection. After the A. hydrophila challenge, the expression level of HSP70 was significantly downregulated at 24 h in the liver and its expression level was notably downregulated at 12 h and at 24 h in the kidney. Collectively, our results suggest that MaCalm possesses vital roles in stress and immune response in M. amblycephala.

Niclosamide (NIC) is a potent salicylanilide molluscicide/helminthicide commonly utilized for parasite and mollusc control in aquatic environments. Due to its persistent presence in water bodies, there is growing concern regarding its impact on aquatic organisms, yet this remains inadequately elucidated. Consequently, this study aims to assess the hepatotoxic effects and detoxification capacity of black carp (Mylopharyngodon piceus) in a semi-static system, employing various parameters for analysis. NIC was applied to juvenile black carp at three different concentrations (0, 10 and 50 μg/L) for 28 days in an environmentally realistic manner. Exposure to 50 μg/L NIC resulted in an increase in hepatic lysozyme (LYZ), alkaline phosphatase (ALP), and complement 4 (C4) levels while simultaneously causing a decrease in peroxidase (POD) activity. Additionally, NIC exposure exhibited a dose-dependent effect on elevating serum levels of LYZ, ALP, complement 3 (C3), C4, and immunoglobulin T (IgT). Notably, the mRNA levels of immune-related genes tnfα, il8, and il6, as well as nramp and leap2, were upregulated in fish exposed to NIC. RNA-Seq analysis identified 219 differentially expressed genes (DEGs) in M. piceus after NIC exposure, with 94 upregulated and 125 downregulated genes. KEGG and GO analyses showed enrichment in drug metabolism pathways and activities related to oxidoreductase, lip oprotein particles, and cholesterol transport at 50 μg/L NIC. Additionally, numerous genes associated with lipid metabolism, oxidative stress, and innate immunity were upregulated in NIC-exposed M. piceus. Taken together, these findings indicate that NIC has the potential to cause hepatotoxicity and immunotoxicity in M. piceus. This research offers important insights for further understanding the impact of molluscicide/helminthicide aquatic toxicity in ecosystems.

To investigate whether Mandarin fish developed oxidative stress after being domesticated with artificial feed, we conducted a series of experiments. Oxidative stress is an important factor leading to diseases and aging in the body. The liver integrates functions such as digestion, metabolism, detoxification, coagulation, and immune regulation, while the gills are important respiratory organs that are sensitive to changes in the water environment. Therefore, we used the liver and gills of Mandarin fish as research materials. The aim of this study was to investigate the effects of short-term artificial feed domestication on the expression of oxidative stress genes and the changes in oxidative-stress-related enzyme activity in the liver and gills of Mandarin fish. We divided the Mandarin fish into two groups for treatment. The control group was fed with live bait continuously for 14 days, while the experimental group was fed with half artificial feed and half live bait from 0 to 7 days (T-7 d), followed by solely artificial feed from 7 to 14 days (T-14 d). The experimental results showed that there was no difference in the body weight, length, and standard growth rate of the Mandarin fish between the two groups of treatments; after two treatments, there were differences in the expression of genes related to oxidative stress in the gills (keap1, kappa, gsta, gstt1, gstk1, SOD, and CAT) and in the liver (GPx, keap1, kappa, gsta, gstt1, gr, and SOD). In the liver, GPx activity and the content of MDA were significantly upregulated after 7 days of domestication, while in the gills, SOD activity was significantly upregulated after 7 days of domestication and GPx activity was significantly downregulated after 14 days of domestication. These results suggest that artificial feed domestication is associated with oxidative stress. Moreover, these results provide experimental basic data for increasing the production of aquaculture feed for Mandarin fish.

Abstract Background Catheter-related bladder discomfort (CRBD is a painful complication of intraoperative urinary catheterization after anaesthesia. We conducted this study to compare the effect of tramadol and lornoxicam for the prevention of postoperative CRBD. Methods One-hundred twenty patients (aged 18–60 years, ASA physical status 1–2, undergoing elective uterine surgery requiring intraoperative urinary catheterization were randomly divided into three groups with 40 patients in each group. Group T received 1.5 mg/kg tramadol, group L received 8-mg lornoxicam, and group C received normal saline. The study drugs were administered intravenously at the end of the surgery. The incidence and severity of CRBD were reported at 0, 1, 2, and 6 h after arrival at the postanaesthesia care unit (PACU). Results The incidence of CRBD was significantly lower in groups T and L than in group C at 1, 2, and 6 h after surgery. The incidence of moderate to severe CRBD was also significantly lower in groups T and L than in group C at 0, 1, and 2 h after surgery. The severity of CRBD reported as mild, moderate, and severe was reduced in groups T and L compared with group C at most times after surgery. Group T had a higher incidence of nausea than group C, and there were no differences in dizziness, drowsiness, or vomit among the three groups. Conclusions Tramadol and lornoxicam administered intravenously at the end of the surgery were both effective in preventing the incidence and severity of CRBD after uterine surgery. However, tramadol increased the incidence of nausea compared with saline, but there was no difference between tramadol and lornoxicam. Trial registration ChiCTR2100052003. Registered on 12/10/2021.

Abstract Interface degradation between mandrel and sheath can cause a decrease in insulation performance and mechanical strength of composite insulators. In this study, the interface ageing properties of cycloaliphatic epoxy resin and silicone rubber composite insulator were compared. A water diffusion test was adopted to simulate the composite insulator ageing in a hot and humid environment. A four‐electrode system was built to detect leakage current at different locations (mandrel, sheath and interface), which is an important basis for evaluating insulator performance. The ageing degree of insulator could be quantitatively characterised by leakage current change. It was found that the infiltrated moisture had a great effect on insulation performance. Based on the water absorption test result, the interface performance of two insulators was mainly influenced by their sheath sealing quality. As an auxiliary evaluation method, temperature rise during the test was recorded using an infrared camera. The experiment results showed that interface degradation was the main factor for the insulation performance decrease of silicone rubber composite insulators. However, insulation level reduction of the cycloaliphatic epoxy resin was caused by the wet sheath. In addition, a model for temperature rise of cycloaliphatic epoxy resin insulators was proposed based on good correspondence between sheath material and insulation. The model incorporated multiple processes such as ageing and heating of insulators, and it can predict the early temperature rise well.

Abstract The pea enation mosaic disease (PEMD) causes significant yield losses worldwide. PEMD is caused by two taxonomically unrelated but symbiotic viruses, pea enation mosaic virus 1 (PEMV-1) and pea enation mosaic virus 2 (PEMV-2). In this study, the complete genomes of four isolates of PEMV-1 and PEMV-2 from Yunnan Province of China were determined and analyzed. The four isolates of PEMV-1 or PEMV-2 shared ≥ 98.7% nucleotide sequence identities at whole genome level. The four Chinese PEMV-1 isolates were most closely related to PEMV-1-Ramsey-1 with nucleotide sequence identities of 97.8–98.0%, while the four Chinese PEMV-2 isolates were most closely related to PEMV-2-DSMZ PV-0088, with nucleotide sequence identities of 94.3–94.5%. The two full-length infectious cDNA clones of the Yunnan-Dali isolates of the two viruses (PEMV-1-YDL and PEMV-2-YDL) were constructed. Co-inoculation of PEMV-1-YDL and PEMV-2-YDL in pea seedlings caused systemic infection, with typical enation and mosaic symptoms on new leaves after inoculation, while the inoculated Nicotiana benthamiana plants showed curling symptoms. Inoculation of pea seedlings with either PEMV-1-YDL or PEMV-2-YDL did not cause obvious symptoms on the new leaves. It has been known that PEMV-2 helps the systemic infection of PEMV-1. However, our results showed that PEMV-1-YDL alone could cause a systemic infection. The pathogenicity of the two infectious clones was tested on different pea cultivars, and some cultivars were PEMD-tolerant. This is the first report of the infectious clones constructed from the Chinese isolates of PEMV-1 and PEMV-2. The current approach will facilitate determination of the synergistic relationship between PEMV-1 and PEMV-2 and their interactions with the host plant by reverse genetic analysis.

Abstract Postoperative nausea and vomiting (PONV) can lead to various postoperative complications. The risk assessment model of PONV is helpful in guiding treatment and reducing the incidence of PONV, whereas the published models of PONV do not have a high accuracy rate. This study aimed to collect data from patients in Sichuan Provincial People’s Hospital to develop models for predicting PONV based on machine learning algorithms, and to evaluate the predictive performance of the models using the area under the receiver characteristic curve (AUC), accuracy, precision, recall rate, F1 value and area under the precision-recall curve (AUPRC). The AUC (0.947) of our best machine learning model was significantly higher than that of the past models. The best of these models was used for external validation on patients from Chengdu First People’s Hospital, and the AUC was 0.821. The contributions of variables were also interpreted using SHapley Additive ExPlanation (SHAP). A history of motion sickness and/or PONV, sex, weight, history of surgery, infusion volume, intraoperative urine volume, age, BMI, height, and PCA_3.0 were the top ten most important variables for the model. The machine learning models of PONV provided a good preoperative prediction of PONV for intravenous patient-controlled analgesia.

ObjectivesThis study aims to explore the relationship between the severity of asthma and neutrophils and related oxidative stress-associated molecules in peripheral blood and induced sputum.MethodsA total of 67 subjects were included in this study, namely, 25 patients with severe asthma and 42 patients with non-severe asthma. Clinical data, induced sputum and peripheral blood were collected. Lung function and molecules related to oxidative stress in induced sputum and peripheral blood of asthma patients were detected. The relationship between neutrophils and asthma severity was analyzed. HDAC2 mRNA and protein expression levels and HDAC2 activity were also analyzed. Multivariate logistic regression was performed to select statistically significant variables.ResultsThe absolute value of neutrophils and percentage of neutrophils were higher in the severe asthma patients. These two values were used to predict the severity of asthma by ROC analysis, with the best cutoff values being 4.55 × 109/L (sensitivity 83.3%, specificity 64.0%) and 55.15% (sensitivity 54.8%, specificity 88.0%). The ROS concentration of neutrophils in the induced sputum samples and the 8-iso-PGF2α concentration in the peripheral blood samples were higher in the severe asthma group (P = 0.012; P = 0.044), whereas there was reduced HDAC2 protein activity in PBMCs (P < 0.001). A logistic equation and a nomogram were created to give a precise prediction of disease severity.ConclusionOxidative stress is increased in severe asthma patients. Peripheral blood neutrophils and 8-iso-PGF2α can be used as biomarkers to predict the severity of asthma. A prediction model was created for evaluating asthma severity.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. At present, the mechanism of non-coding RNA in renal injury in SLE patients is still unclear. A total of 64 DEcircRNAs, 75 DEmiRNAs, and 249 DEmRNAs were identified. We integrated 10 circRNAs, 10 miRNAs, and 88 target mRNAs into a circRNA-miRNA-mRNA network and obtained 9 hub genes (circ-0000006, miR-766-3p, miR-409-3p, miR-339-3p, miR-331-3p, miR-140-3p, miR-186-5p, miR-149-5p, PSME3). The ROC curve results showed that the diagnostic efficiency of 6 hub miRNA was higher than that of has_circ_0000006 and PSEME3. SsGSEA analysis revealed immune cell composition in SLE and control renal tissues, including 3 types of immune cells up-regulated (gamma delta T cell, effector memory CD4 T cell, central memory CD8 T cell) and 4 types down-regulated (memory B cell, mast cell, macrophage, immature dendritic cell, eosinophil) in SLE patients. In addition, PSME3 was negatively correlated with 3 up-regulated immune cells and positively correlated with 4 down-regulated immune cells in SLE patients. Our study provides a deeper understanding of the circRNA-related competing endogenous RNA regulatory mechanism in the renal injury of systemic lupus erythematosus.

AbstractBoron (B) deficiency is detrimental to Glycine max (L.) Merr., which is one of the leading oil crops. In this study, physiological analysis of soybean seedlings under B deficiency and control after 12 h, 24 h, 72 h and 8 days was carried out, and the roots were subjected to transcriptome sequencing analysis. The results showed that under B deficiency, the plant height, SPAD and chlorophyll fluorescence value of soybean seedlings decreased significantly, indicating that B stress significantly inhibited plant growth and photosynthesis. RNA-seq revealed a total of 5126 DEGs (Differentially Expressed Genes), and nine DEGs co-existed at the four-time points, among which GLYMA_03G130600 regulates transcription factor ORG3, which is related to plant growth. GO analysis revealed a total of annotated 4018 DEGs, among which the terms plasma membrane, extracellular, enzyme activity, ion transport metabolic process and oxidoreductase activity were significantly enriched at the four time points, which might hinder the growth of soybean and accelerate senescence. KEGG analysis showed that at level 1, the DEGs were mainly enriched in photosynthesis-related, phenylpropanoid biosynthesis, nitrogen metabolism and plant hormone signal transduction. At level 2 of secondary metabolism, the DEGs were mainly enriched in energy metabolism and amino acid metabolism pathways, which indicates that B stresses mainly affect photosynthesis, hormone regulation and amino acid metabolism of soybean, thus affecting plant growth. The above results give deeper insight into the soybean response to B deficiency and lay the foundation for further studies of the molecular mechanism of soybean response to boron deficiency.

Background Lifestyle and metabolic diseases influence the severity and pathogenesis of cardiovascular disease through numerous mechanisms, including regulation via posttranslational modifications. A specific posttranslational modification, the addition of O‐linked β‐N acetylglucosamine (O‐GlcNAcylation), has been implicated in molecular mechanisms of both physiological and pathologic adaptations. The current study aimed to test the hypothesis that in cardiomyocytes, sustained protein O‐GlcNAcylation contributes to cardiac adaptations, and its progression to pathophysiology. Methods and Results Using a naturally occurring dominant‐negative O‐GlcNAcase (dnOGA) inducible cardiomyocyte‐specific overexpression transgenic mouse model, we induced dnOGA in 8‐ to 10‐week‐old mouse hearts. We examined the effects of 2‐week and 24‐week dnOGA overexpression, which progressed to a 1.8‐fold increase in protein O‐GlcNAcylation. Two‐week increases in protein O‐GlcNAc levels did not alter heart weight or function; however, 24‐week increases in protein O‐GlcNAcylation led to cardiac hypertrophy, mitochondrial dysfunction, fibrosis, and diastolic dysfunction. Interestingly, systolic function was maintained in 24‐week dnOGA overexpression, despite several changes in gene expression associated with cardiovascular disease. Specifically, mRNA‐sequencing analysis revealed several gene signatures, including reduction of mitochondrial oxidative phosphorylation, fatty acid, and glucose metabolism pathways, and antioxidant response pathways after 24‐week dnOGA overexpression. Conclusions This study indicates that moderate increases in cardiomyocyte protein O‐GlcNAcylation leads to a differential response with an initial reduction of metabolic pathways (2‐week), which leads to cardiac remodeling (24‐week). Moreover, the mouse model showed evidence of diastolic dysfunction consistent with a heart failure with preserved ejection fraction. These findings provide insight into the adaptive versus maladaptive responses to increased O‐GlcNAcylation in heart.

Fragile karst areas of Guangxi are the key areas of vegetation protection and restoration work of the government. It is of great significance to study the effects of meteorological disasters on vegetation change for disaster prevention and reduction and ecological protection in the karst areas. The Normalized Differential Vegetation Index (NDVI), as a tool for monitoring vegetation growth, has a strong responsiveness to vegetation and can qualitatively and quantitatively evaluate the vegetation cover and its growth vitality. Therefore, in this study, we analyzed the trend of vegetation change and the impacts of multiple meteorological hazards, such as drought, torrential rainfall, high temperature, and low temperature, on the vegetation of the karst region in Guangxi by using the linear trend method, GIS spatial analysis, and correlation analysis, using the MODIS NDVI and temperature and precipitation information from 2000 to 2020 in the karst region of Guangxi. The results show that: (1) NDVI increased significantly in the karst areas, and 32.2% of the areas had significant improvement in vegetation. The improvement was the most obvious mainly in the central part of the study area, while the vegetation degradation trend was obvious in partial scattered areas in northeast and southwest. (2) On the interannual scale, NDVI was negatively correlated with some meteorological disaster indexes, such as relative humidity index, the number of drought days, the amount of extremely heavy rainstorm, the amount of heavy rainstorm, the number of days with high temperature of ≥35 °C, the number of days with high temperature of 35–37 °C, the number of days with high temperature of ≥37 °C, the minimum temperature, and the effective accumulated temperature of ≤0 °C. The obvious negative effect area of drought on vegetation was mainly concentrated in the middle of the study area, and that of rainfall was mainly distributed in the southwest, northeast and northwest; that of high temperature was mainly distributed in the northwest and northeast, and that of low temperature was mainly concentrated in the southwest and north. (3) On the multi-year monthly scale, the responses of NDVI to drought, high temperature and low temperature disaster indexes had a lag effect, but had no lag effect on rainfall disaster indexes. The lag time of vegetation to drought was 1 month, and the lag time to high temperature and low temperature was 3 months.

Abstract Background Acanthocephala is a clade of obligate endoparasites whose mitochondrial genomes (mitogenomes) and evolution remain relatively poorly understood. Previous studies reported that atp8 is lacking from acanthocephalan mitogenomes, and that tRNA genes often have nonstandard structures. Heterosentis pseudobagri (Arhythmacanthidae) is an acanthocephalan fish endoparasite for which no molecular data are currently available, and biological information is unavailable in the English language. Furthermore, there are currently no mitogenomes available for Arhythmacanthidae. Methods We sequenced its mitogenome and transcriptome, and conducted comparative mitogenomic analyses with almost all available acanthocephalan mitogenomes. Results The mitogenome had all genes encoded on the same strand and unique gene order in the dataset. Among the 12 protein-coding genes, several genes were highly divergent and annotated with difficulty. Moreover, several tRNA genes could not be identified automatically, so we had to identify them manually via a detailed comparison with orthologues. As common in acanthocephalans, some tRNAs lacked either the TWC arm or the DHU arm, but in several cases, we annotated tRNA genes only on the basis of the conserved narrow central segment comprising the anticodon, while the flanking 5’ and 3’ ends did not exhibit any resemblance to orthologues and they could not be folded into a tRNA secondary structure. We corroborated that these are not sequencing artefacts by assembling the mitogenome from transcriptomic data. Although this phenomenon was not observed in previous studies, our comparative analyses revealed the existence of highly divergent tRNAs in multiple acanthocephalan lineages. Conclusions These findings indicate either that multiple tRNA genes are non-functional or that (some) tRNA genes in (some) acanthocephalans might undergo extensive posttranscriptional tRNA processing which restores them to more conventional structures. It is necessary to sequence mitogenomes from yet unrepresented lineages and further explore the unusual patterns of tRNA evolution in Acanthocephala.

Abstract Background Perioperative hypotension increases postoperative complication rates and prolongs postoperative recovery time. Whether Passive Leg Raising test (PLR) and Subclavian Vein Diameter (DSCV) can effectively predict post-anesthesia hypotension remains to be tested. This study aimed to identify specific predictors of General Anesthesia (GA)induced hypotension by measuring DSCV in the supine versus PLR position. Methods A total of 110 patients who underwent elective gynecological laparoscopic surgery under general anesthesia, were enrolled in this study. Before anesthesia, DSCV and theCollapsibility Index of DSCV(DSCV-CI) were measured by ultrasound, and the difference in maximal values of DSCV between supine and PLR positions was calculated, expressed as ΔDSCV. Hypotension was defined as Mean Blood Pressure (MBP) below 60mmhg or more than 30% below the baseline. Patients were divided into two groups according to the presence (Group H) or absence (Group N) of postanesthesia hypotension. The area under the receiver operating characteristic curve (ROC) and logistic regression analyses were used to evaluate the predictability of DSCV and other parameters for predicting preincision hypotension. Results Three patients were excluded due to unclear ultrasound scans, resulting in a total of 107 patients studied. Twenty-seven (25.2%) patients experienced hypotension. Area under the ROC curve of ΔDSCV was 0.75 (P

To accurately and non-destructively monitor the growth of spring wheat in the Hetao irrigation area, UAV remote sensing was employed during various fertility stages. Digital image indices from diverse fertilization treatments were calculated and compared with physiological indices to identify the most sensitive digital image indices corresponding to these indices. The study underscored the critical importance of the flowering stage in the growth of spring wheat, thus highlighting the necessity of focusing on this stage. This finding reiterated that the flowering stage was pivotal for spring wheat development in the Hetao Irrigation Area. Several digital image indices, such as GLA, R, G, INT, g, GRVI, MGRVI, RGBVI, EXG, and GRRI, exhibited a high frequency of significant correlations with physiological indices during the four primary reproductive stages of wheat. Consequently, these sensitive digital image indices during the flowering stage can more effectively characterize the physiological indices of spring wheat.

To clarify the allometric growth pattern and hunger tolerance of Hemibarbus maculatus Bleeker larvae, the morphological lengths of their functional organs were measured continuously and their primary feeding rates under a state of starvation were studied. A control group and starvation group were set up for this study, and 10 larvae were sampled from each group every day in order to study their allometric growth pattern and starvation tolerance. The results indicated that the Hemibarbus maculatus larvae opened their mouths for feeding at 4 days after hatching, and that the yolk sac disappeared completely at 11 days after hatching. The Hemibarbus maculatus larvae preferentially developed their heads, fins, and eyes, related to the functions of feeding, balancing, and swimming, in order to cope with complex environments. The growth inflection points for the head length, pectoral fin length, dorsal fin length, eye diameter, eye spacing, snout length, and body height were characterized by total lengths of 10.93 mm, 11.67 mm, 11.67 mm, 13.17 mm, 16.53 mm, 15.13 mm, and 15.13 mm, respectively. Prior to and following the inflection point, positive allometric growth was observed in all organs. After the inflection point, the dorsal fin continued to maintain positive allometric growth, while the others changed to isometric allometric growth. A growth inflection point was not observed for trunk length or the lengths of the tail and anal fins. The trunk length always maintained negative allometry, while the tail and anal fin lengths were reversed. The growth inflection point of the tail length was at a total length of 13.68 mm. Before and after the growth inflection point, negative and isometric allometric growths were observed, respectively. According to the relationship between the total length and number of days after hatching, the growth inflection point of the Hemibarbus maculatus larvae was concentrated at TL = 10.93–16.53 mm, which was observed 14–20 days after hatching. The point of no return for the Hemibarbus maculatus larvae was 12–13 days after hatching, and the ratio of days after hatching in the mixed trophic period to the endotrophic period was 1.75, indicating that the larvae had strong hunger tolerance. Therefore, when considering a water temperature of 22.66 ± 1.56 °C, 4–5 days after hatching is the best time to cultivate in the pond, and it should not be carried out later than 12 days after hatching.

Wine grape quality is influenced by the variety and growing environment, and the quality of the grapes has a significant impact on the quality of the wine. Tannins are a crucial indicator of wine grape quality, and, therefore, rapid and non-destructive methods for detecting tannin content are necessary. This study collected spectral data of Pinot Noir and Chardonnay using a geophysical spectrometer, with a focus on the 500–1800 nm spectrum. The spectra were preprocessed using Savitzky–Golay (SG), first-order differential (1D), standard normal transform (SNV), and their respective combinations. Characteristic bands were extracted through correlation analysis (PCC). Models such as partial least squares (PLS), support vector machine (SVM), random forest (RF), and one-dimensional neural network (1DCNN) were used to model tannin content. The study found that preprocessing the raw spectra improved the models’ predictive capacity. The SVM–RF model was the most effective in predicting grape tannin content, with a test set R2 of 0.78, an RMSE of 0.31, and an RE of 10.71%. These results provide a theoretical basis for non-destructive testing of wine grape tannin content.