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Background: Dyslipidemia is increasingly common in people living with HIV (PLHIV), thereby increasing the risk of cardiovascular events and diminishing the quality of life for these individuals. The study of blood lipid metabolism of PLHIV has great clinical significance in predicting the risk of cardiovascular disease. Therefore, this study aims to examine the blood lipid metabolism status of HIV-infected patients in Huzhou before and after receiving highly active antiretroviral therapy (HAART) and to explore the impact of different HAART regimens on dyslipidemia. Method: PLHIV confirmed in Huzhou from June 2010 to June 2022 was included. The baseline characteristics and clinical data during the follow-up period were collected, including some blood lipid indicators (total cholesterol and triglycerides) and HAART regimens. A multivariate logistic regression model and the generalized estimating equation model were used to analyze the independent effects of treatment regimens on the risk of dyslipidemia. Result: The overall prevalence of dyslipidemia among PLHIV after HAART was 70.11%. PLHIV receiving lamivudine (3TC) + efavirenz (EFV) + zidovudine (AZT) had a higher prevalence of dyslipidemia compared to those receiving 3TC+EFV+tenofovir disoproxil fumarate (TDF). In a logistic analysis adjusted for important covariates such as BMI, age, diabetes status, etc., we found that the risks of dyslipidemia were higher with 3TC+EFV+AZT (dyslipidemia: odds ratio [OR] = 2.09, 95% confidence interval [Cl]: 1.28–3.41; TG ≥1.7: OR = 2.40, 95%Cl:1.50–3.84) than with 3TC+EFV+TDF. Furthermore, on PLHIV that was matched 1:1 by the HAART regimens, the results of the generalized estimation equation again showed that 3TC+EFV+AZT (TG ≥1.7: OR = 1.84, 95%Cl: 1.10–3.07) is higher for the risk of marginal elevations of TG than 3TC+EFV+TDF. Conclusion: The prevalence of dyslipidemia varies according to different antiretroviral regimens. Using both horizontal and longitudinal data, we have repeatedly demonstrated that AZT has a more adverse effect on blood lipids than TDF from two perspectives. Therefore, we recommend caution in using the 3TC+EFV+AZT regimen for people at clinical risk of co-occurring cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: From 2004 onwards, the Chinese government has freely offered complimentary Chinese herbal medicine (CHM) to Chinese HIV/AIDS patients, alongside the prescribed first line therapy of highly active antiretroviral therapy (HAART). Thus, we aimed to explore the effectiveness and safety of CHM for patients with HIV/AIDS. Methods: The data from the Guangxi pilot database and antiviral treatment sites database have been respectively developed into two datasets in this prospective cohort real-world study, the CHM combined HAART group (the integrated group) and the HAART group. A 1:1 propensity score matching (PSM) was performed and the longitudinal data were analyzed using a generalized estimating equation (GEE) model with an autocorrelation matrix and log link function attached to the Gamma distribution. Results: A final sample of 629 patients, 455 and 174 in the integrated group and HAART group respectively, were obtained from the full dataset. As covariates for PSM, gender, age, baseline CD4+ and CD4+/ CD8+ were assessed based on the results of the logistic regression analyses. Following PSM, 166 pairs from the full dataset were matched successfully, with 98 pairs in the baseline CD4+ > 200 subgroup, and 55 pairs in the baseline CD4+ ≤ 200 subgroup. In the full dataset, HAART group achieved higher CD4+ count (OR = 1.119, 95%CI [1.018, 1.230]) and CD4+/CD8+ ratio (OR = 1.168, 95%CI [1.045, 1.305]) than the integrated group, so did in the CD4+ > 200 subgroup. For the CD4+ ≤ 200 subgroup, the CD4+ (OR = 0.825, 95%CI [0.694, 0.980]) and CD4+/CD8+ (OR = 0.826, 95%CI [0.684, 0.997]) of the integrated group were higher than those of the HAART group. The safety outcomes showed that there were no significant differences in BUN, ALT and AST levels between the groups but Cr showed significantly higher levels in HAART groups of all three datasets. Conclusions: Compared to HAART alone, CHMs combined with HAART had better effects in improving the immune function of HIV/AIDS in patients with baseline CD4+ count ≤ 200. The results of the two subgroups are in opposite directions, and chance does not explain the apparent subgroup effect. A study with larger sample size and longer follow-up period is warranted in order to increase study credibility. [ABSTRACT FROM AUTHOR]

Raspberry ketone accounts for the characteristic aroma of the raspberry fruit. In order to explore the genes involved in raspberry ketone synthesis, the transcriptome in fruit tissues of two red raspberry varieties "Polka" and "Orange legend", were sequenced and 24213 single genes were obtained. As the red raspberry fruit ripening, genes involved in flavonoid and anthocyanin synthesis were up-regulated, while those associated with lignin synthesis were down-regulated. A gene (RinPKS4) highly related to raspberry ketone synthesis was identified by transcriptome analysis, and RinPKS4 gene was over-expressed in raspberry in order to further understand the function of RinPKS4 gene in raspberry ketone synthesis. The results showed that the gene expression level of RinPKS4 in the leaf tissues of a transgenic lines increased by about 4-fold and the content of raspberry ketone increased by 42.64% compared with the wide type. This study lays a theoretical foundation for further study on the synthesis and regulation of raspberry ketone in red raspberry. [ABSTRACT FROM AUTHOR]

Background: Postoperative nausea and vomiting are common complications after surgery, and female patients are more likely to experience these adverse events. The goal of this study was to explore the relationship between the CHRM3 rs2165870 polymorphism and postoperative vomiting incidence in female patients who underwent laparoscopic surgery. Methods: Two hundred female patients who underwent elective laparoscopic surgery with subsequent patient-controlled intravenous analgesia using dexmedetomidine and sufentanil were prospectively enrolled. The CHRM3 rs2165870 and KCNB2 rs349358 polymorphisms were genotyped using MassARRAY SNP typing technology. Demographic data and preoperative laboratory results of all patients were recorded. Postoperative analgesia-related information, incidence of postoperative nausea and vomiting, and other adverse events were followed up and recorded for analysis. Results: No significant differences were observed in any of the demographic characteristics of these patients among the different genotype carriers (P>0.05). The percentages of patients with each genotype of CHRM3 were 67% (GG), 28.5% (GA) and 4.5% (AA). We found that the AA or A allele of the CHRM3 rs2165870 polymorphism elevated the risk of postoperative vomiting (AA versus GG; OR, 6.94; 95% CI, 1.49–32.46; P = 0.014; A versus G; OR, 2.52; 95% CI, 1.22–5.19; P = 0.012). The percentages of patients with each genotype of KCNB2 were 84.5% (TT), 15.5% (CT) and 0% (CC). There were no significant differences in the postoperative nausea or vomiting rate across the KCNB2 rs349358 polymorphisms (P>0.05). Conclusion: The CHRM3 rs2165870 polymorphism is associated with the occurrence of postoperative vomiting in female patients who have undergone laparoscopic surgery. The AA genotype or A allele of the CHRM3 rs2165870 polymorphism elevates the risk of postoperative vomiting. Trial registration: www.chictr.org.cn, registration number: ChiCTR2200062425. [ABSTRACT FROM AUTHOR]

Background: In recent years, increasing attention has been focused on the impact of red blood cell indices (RCIs) on disease prognosis. We aimed to investigate the association of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV) with mortality. Methods: The study used cohort data from U.S. adults who participated in the 1999–2008 National Health and Nutrition Examination Survey. All-cause mortality was the primary outcome during follow-up, with secondary cardiovascular mortality outcomes. COX regression was applied to analyze the connection between RCIs and mortality. We adopted three models to minimize potential bias. Smooth-fit curves and threshold effect analyses were utilized to observe the dose-response relationship between RCIs and all-cause and cardiovascular mortality. In addition, we performed sensitivity analyses. Results: 21,203 individuals were enrolled in our research. During an average 166.2 ± 54.4 months follow-up, 24.4% of the population died. Curve fitting indicated a U-shaped relationship between MCV and MCH with all-cause mortality, and the relationship of MCHC to all-cause mortality is L-shaped. We identified inflection points in the relationship between MCV, MCH, and MCHC and all-cause mortality as 88.56732 fl, 30.22054 pg, 34.34624 g/dl (MCV <88.56732 fl, adjusted HR 0.99, 95 CI% 0.97–1.00; MCV >88.56732 fl, adjusted HR 1.05, 95 CI% 1.04–1.06. MCH <30.22054 pg, adjusted HR 0.95, 95 CI% 0.92–0.98; MCH >30.22054 pg, adjusted HR 1.08, 95 CI% 1.04–1.12. MCHC <34.34624 g/dl, adjusted HR 0.88, 95 CI% 0.83–0.93). Besides, the MCV curve was U-shaped in cardiovascular mortality (MCV <88.56732 fl, adjusted HR 0.97, 95 CI% 0.94–1.00; MCV >88.56732 fl, adjusted HR 1.04, 95 CI% 1.01–1.06). Conclusion: This cohort study demonstrated that RCIs (MCH, MCHC, and MCV) were correlated with mortality in the general population. Three RCIs were nonlinearly correlated with all-cause mortality. In addition, there were nonlinear relationships between MCH and MCV and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to validate the performance of six available scoring models for predicting hospital mortality in children with suspected or confirmed infections. Methods: This single-center retrospective cohort study included pediatric patients admitted to the PICU for infection. The primary outcome was hospital mortality. The six scores included the age-adapted pSOFA score, SIRS score, PELOD2 score, Sepsis-2 score, qSOFA score, and PMODS. Results: Of the 5,356 children admitted to the PICU, 9.1% (488) died, and 25.1% (1,342) had basic disease with a mortality rate of 12.7% (171); 65.3% (3,499) of the patients were younger than 2 years, and 59.4% (3,183) were male. The discrimination abilities of the pSOFA and PELOD2 scores were superior to those of the other models. The calibration curves of the pSOFA and PELOD2 scores were consistent between the predictions and observations. Elevated lactate levels were a risk factor for mortality. Conclusion: The pSOFA and PELOD2 scores had superior predictive performance for mortality. Given the relative unavailability of items and clinical operability, the pSOFA score should be recommended as an optimal tool for acute organ dysfunction in pediatric sepsis patients. Elevated lactate levels are related to a greater risk of death from infection in children in the PICU. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. Methods: The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. Results: This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). Conclusions: Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. Trial registration: Prospero Registration NumberCRD42021243185. [ABSTRACT FROM AUTHOR]

Mule duck is vitally important to the production of global duck meat. Here, we present two high-quality haplotypes of a female mule duck (haplotype 1 (H1):1.28 Gb, haplotype 2 (H2): 1.40 Gb). The continuity (H1: contig N50 = 14.90 Mb, H2: contig N50 = 15.70 Mb) and completeness (BUSCO: H1 = 96.9%, H2 = 97.3%) are substantially better than those of other duck genomes. We detected the structural variations (SVs) in H1 and H2. We observed a positive correlation between autosome length and the number of SVs. Z chromosome was some deficient in deletions and insertions, but W chromosome was some excessive. A total of 1,451 genes were haplotype specific expression (HSEs). Among them, 737 specifically expressed in H1, and 714 specifically expressed in H2. We found that H1 and H2 HSEs tended to be involved in similar biological processes, such as myometrial relaxation and contraction pathways, muscle structure development and phosphorylation. Our haplotype-resolved genome assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in mule duck. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) represents a significant worldwide health issue, experiencing an increasing incidence rate. Effective dietary strategies are vital for T2DM management, but the optimal dietary patterns remain debated due to inconsistent research outcomes and single-outcome reporting. Network Meta-Analysis (NMA) provides a powerful approach for integrating data from randomized controlled trials (RCTs), enabling a detailed evaluation of the impact of different dietary patterns. This document presents our strategy for a systematic review and network meta-analysis, aimed at assessing the influence of key dietary patterns on glycemic control, lipid profiles, and weight management in individuals with Type 2 Diabetes Mellitus (T2DM). Materials and methods: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and network meta-analyses guidelines, we conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library, without language or date restrictions. Our objective is to assess the efficacy of various dietary interventions in managing Type 2 Diabetes Mellitus (T2DM). We used standardized mean differences for pairwise comparisons and a Bayesian framework for ranking interventions via Surface Under the Cumulative Ranking Curve (SUCRA). Key analyses include heterogeneity, transitivity, and sensitivity assessments, along with quality and risk evaluations using the Cochrane Collaboration's tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Ethics and dissemination: This systematic review and network meta-analysis involve aggregate data from previous trials, obviating the need for additional ethical approval. The search strategy will be executed starting October 2023, with all searches completed by December 2023, to encompass the most current studies available. Findings will be shared through academic conferences and peer-reviewed journals focused on diabetes care and nutrition. Trial registration: PROSPERO registration number CRD42023465791. [ABSTRACT FROM AUTHOR]

In experiments, the distributions of mRNA or protein numbers in single cells are often fitted to the random telegraph model which includes synthesis and decay of mRNA or protein, and switching of the gene between active and inactive states. While commonly used, this model does not describe how fluctuations are influenced by crucial biological mechanisms such as feedback regulation, non-exponential gene inactivation durations, and multiple gene activation pathways. Here we investigate the dynamical properties of four relatively complex gene expression models by fitting their steady-state mRNA or protein number distributions to the simple telegraph model. We show that despite the underlying complex biological mechanisms, the telegraph model with three effective parameters can accurately capture the steady-state gene product distributions, as well as the conditional distributions in the active gene state, of the complex models. Some effective parameters are reliable and can reflect realistic dynamic behaviors of the complex models, while others may deviate significantly from their real values in the complex models. The effective parameters can also be applied to characterize the capability for a complex model to exhibit multimodality. Using additional information such as single-cell data at multiple time points, we provide an effective method of distinguishing the complex models from the telegraph model. Furthermore, using measurements under varying experimental conditions, we show that fitting the mRNA or protein number distributions to the telegraph model may even reveal the underlying gene regulation mechanisms of the complex models. The effectiveness of these methods is confirmed by analysis of single-cell data for E. coli and mammalian cells. All these results are robust with respect to cooperative transcriptional regulation and extrinsic noise. In particular, we find that faster relaxation speed to the steady state results in more precise parameter inference under large extrinsic noise. Author summary: Over the past decade, significant progress has been made in the theory and experiments of single-cell stochastic gene expression dynamics. The most well studied and widely used stochastic gene expression model is the two-state telegraph model. However, the conventional telegraph model is too simple and limited in its predictive power because it lacks a description of some important biological mechanisms, such as feedback regulation, multiple gene activation steps, and multiple gene activation pathways. This raises a important question: what can we learn when fitting a complex gene expression model to a simple telegraph model? In this paper, we investigate four complex gene expression models by fitting their steady-state mRNA or protein number distributions to the telegraph model and then obtain estimates of the effective parameters. We show that while the estimated values of the parameters in the "artificial" telegraph model are not always accurate, they are still sometimes reliable and can also reveal important dynamical properties of the complex models such as the ability for a complex model to produce bimodality. Moreover, we provide an effective method of distinguishing the complex models from the telegraph model by using additional information such as gene expression data at multiple time points. Finally, we show that fitting the mRNA or protein number distributions to the telegraph model may even reveal the underlying gene regulation mechanism of a complex model by using measurements under varying experimental conditions. The effectiveness of these methods is well confirmed by analysis of single-cell gene expression data for E. coli and mammalian cells. [ABSTRACT FROM AUTHOR]

Purpose: Investigating the association between red cell distribution width (RDW) and all-cause mortality in patients with breast cancer, to evaluate the potential clinical prognostic value of RDW. Methods: Based on the RDW index, patients with breast cancer in the Medical Information Mart for Intensive Care (MIMIC-IV) database were categorized into quartiles. The primary outcomes included in-hospital mortality from all causes during the first six months, the first year, and the first three years. Cox hazards regression and restricted cubic spline (RCS) models were developed to investigate the effects of RDW on primary outcomes. Results: The study included 939 patients (female). The 6-month, 1-year, and 3-year mortality rates were 14.0%, 21.4%, and 28.4%, respectively. Multivariate Cox proportional hazards analyses demonstrated that RDW exhibited an autonomous association with an increased risk of all-cause mortality. After adjusting for confounders, higher RDW quartiles were significantly associated with 6-month mortality (adjusted hazard ratio (HR), 3.197; 95% confidence interval (CI), 1.745–5.762; P < 0.001), 1-year mortality (adjusted HR, 2.978; 95% CI, 1.867–4.748; P < 0.001), and 3-year mortality (adjusted HR, 2.526; 95% CI, 1.701–3.750; P < 0.001). The RCS curves demonstrated that high RDW (> 14.6) was associated with a greater risk of all-cause mortality. Subgroup analyses revealed no statistically significant differences in the interactions between the subgroups. Conclusion: The study revealed a highly pronounced relationship between RDW and overall mortality, indicating its potential as an autonomous prognostic factor for increased mortality among patients with breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Hematology is an essential field for investigating the prognostic outcomes of cardiovascular diseases (CVDs). Recent research has suggested that mean corpuscular hemoglobin concentration (MCHC) is associated with a poor prognosis in several CVDs. There is no evidence of a correlation between MCHC and hypertension. Therefore, our study aimed to analyze the association of MCHC with all-cause and cardiovascular mortality in hypertensive patients. Methods: We used cohort data from U.S. adults who participated in the National Health and Nutrition Examination Survey from 1999–2014. COX regression was applied to analyze the relationship between MCHC and all-cause and cardiovascular mortality. In addition, three models were adjusted to reduce confounding factors. We reanalyzed the data after propensity score matching (PSM) to inspect the stability of the results. Stratified analysis was additionally adopted to investigate the results of each subgroup. Results: Our research included 15,154 individuals. During a mean follow-up period of 129 months, 30.6% of the hypertensive population succumbed to mortality. Based on previous studies, we categorized patients with MCHC ≤33mg/dl as the hypochromia group and those with >33mg/dl as the non-hypochromia group. After PSM, the hypochromia group had higher all-cause mortality (adjusted hazard ratio [HR]:1.26, 95% confidence interval [95%CI]:1.11–1.43) and cardiovascular mortality (adjusted HR:1.42, 95%CI:1.12–1.80) than the non-hypochromia group. The results of the COX regression remain stable after matching. Stratified analyses before PSM revealed an interaction of anemia in the relationship between MCHC and mortality, whereas there was no significant interaction after matching. Conclusion: In hypertensive individuals, low MCHC was correlated with a poor prognosis. Further studies on MCHC are necessary to analyze the potential mechanisms of its poor prognosis in hypertensive populations. [ABSTRACT FROM AUTHOR]

Post-transcriptional regulation by small RNAs and post-translational modifications (PTM) such as lysine acetylation play fundamental roles in physiological circuits, offering rapid responses to environmental signals with low energy consumption. Yet, the interplay between these regulatory systems remains underexplored. Here, we unveil the cross-talk between sRNAs and lysine acetylation in Streptococcus mutans, a primary cariogenic pathogen known for its potent acidogenic virulence. Through systematic overexpression of sRNAs in S. mutans, we identified sRNA SmsR1 as a critical player in modulating acidogenicity, a key cariogenic virulence feature in S. mutans. Furthermore, combined with the analysis of predicted target mRNA and transcriptome results, potential target genes were identified and experimentally verified. A direct interaction between SmsR1 and 5'-UTR region of pdhC gene was determined by in vitro binding assays. Importantly, we found that overexpression of SmsR1 reduced the expression of pdhC mRNA and increased the intracellular concentration of acetyl-CoA, resulting in global changes in protein acetylation levels. This was verified by acetyl-proteomics in S. mutans, along with an increase in acetylation level and decreased activity of LDH. Our study unravels a novel regulatory paradigm where sRNA bridges post-transcriptional regulation with post-translational modification, underscoring bacterial adeptness in fine-tuning responses to environmental stress. Author summary: Post-transcriptional regulation and post-translational modification are widely present in physiological circuits due to their low energy consumption and rapid response to the environment. sRNA is an important post-transcriptional regulatory factor in bacterial response to environmental stress, and bacteria also use sRNA as a key signal to control multicellular behaviors such as biofilm formation and quorum sensing to regulate virulence. S. mutans is an intractable cariogenic pathogen, but the role of sRNA in S. mutans is poorly understood. Here, we elucidated the virulence regulation and mechanism of sRNA SmsR1 in S. mutans by means of transcriptomics, acetyl-proteomics and animal models, and found its relationship with protein acetylation (post-translational modification), and a new role of sRNA physiological regulatory network was shown. This study presents an innovative perspective that a sRNA in S. mutans is involved in the correlation between post-transcriptional regulation and post-translational modification. [ABSTRACT FROM AUTHOR]

Background: The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia. Methods: By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors. Results: The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082–2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169–2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results. Conclusions: This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) are the most common systemic autoimmune diseases, and they are increasingly being recognized as occurring in the same patient population. These two diseases share several clinical features and laboratory parameters, but the exact mechanism of their co-pathogenesis remains unclear. The intention of this study was to investigate the common molecular mechanisms involved in RA and pSS using integrated bioinformatic analysis. RNA-seq data for RA and pSS were picked up from the Gene Expression Omnibus (GEO) database. Co-expression genes linked with RA and pSS were recognized using weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. Then, we screened two public disease–gene interaction databases (GeneCards and Comparative Toxicogenomics Database) for common targets associated with RA and pSS. The DGIdb database was used to predict therapeutic drugs for RA and pSS. The Human microRNA Disease Database (HMDD) was used to screen out the common microRNAs associated with RA and pSS. Finally, a common miRNA–gene network was created using Cytoscape. Four hub genes (CXCL10, GZMA, ITGA4, and PSMB9) were obtained from the intersection of common genes from WGCNA, differential gene analysis and public databases. Twenty-four drugs corresponding to hub gene targets were predicted in the DGIdb database. Among the 24 drugs, five drugs had already been reported for the treatment of RA and pSS. Other drugs, such as bortezomib, carfilzomib, oprozomib, cyclosporine and zidovudine, may be ideal drugs for the future treatment of RA patients with pSS. According to the miRNA–gene network, hsa-mir-21 may play a significant role in the mechanisms shared by RA and pSS. In conclusion, we identified commom targets as potential biomarkers in RA and pSS from publicly available databases and predicted potential drugs based on the targets. A new understanding of the molecular mechanisms associated with RA and pSS is provided according to the miRNA–gene network. [ABSTRACT FROM AUTHOR]

Phosphorus (P) deficiency is one of the most critical factors for plant growth and productivity, including its inhibition of lateral root initiation. Auxin response factors (ARFs) play crucial roles in root development via auxin signaling mediated by genetic pathways. In this study, we found that the transcription factor ZmARF1 was associated with low inorganic phosphate (Pi) stress-related traits in maize. This superior root morphology and greater phosphate stress tolerance could be ascribed to the overexpression of ZmARF1. The knock out mutant zmarf1 had shorter primary roots, fewer root tip number, and lower root volume and surface area. Transcriptomic data indicate that ZmLBD1, a direct downstream target gene, is involved in lateral root development, which enhances phosphate starvation tolerance. A transcriptional activation assay revealed that ZmARF1 specifically binds to the GC-box motif in the promoter of ZmLBD1 and activates its expression. Moreover, ZmARF1 positively regulates the expression of ZmPHR1, ZmPHT1;2, and ZmPHO2, which are key transporters of Pi in maize. We propose that ZmARF1 promotes the transcription of ZmLBD1 to modulate lateral root development and Pi-starvation induced (PSI) genes to regulate phosphate mobilization and homeostasis under phosphorus starvation. In addition, ZmERF2 specifically binds to the ABRE motif of the promoter of ZmARF1 and represses its expression. Collectively, the findings of this study revealed that ZmARF1 is a pivotal factor that modulates root development and confers low-Pi stress tolerance through the transcriptional regulation of the biological function of ZmLBD1 and the expression of key Pi transport proteins. Author summary: Phosphorus (P) is a critical macronutrient for plant growth and development. Root system architecture (RSA) affects the ability of plants to obtain water and mineral nutrients from soil. Several auxin response factors (ARFs) are involved in auxin signaling and lateral root (LR) formation in P-deficient plants, but the molecular mechanisms underlying P deficiency-induced changes in the RSA of maize is not well understood. We found that ZmARF1 positively regulates root development and confers tolerance to low inorganic phosphate (Pi) stress in maize. ZmARF1 regulates root development by interacting with the promoter of ZmLBD1 and positively regulating its expression. Furthermore, we empirically revealed that ZmARF1 enhanced Pi mobilization under low Pi stress by positively regulating the expression of ZmPHR1, ZmPHT1;2, and ZmPHO2, which are key Pi transporters in the Pi transport machinery of maize. Overall, enhanced root development and expression of key Pi transporter proteins have been suggested as key nexuses mediating the biological function of ZmARF1 in conferring low-Pi stress tolerance in maize. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and cause chronic infections, commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we performed assays for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To identify the pivotal factors that are involved in host immune defense, we integrated chromatin accessibility and gene expression to investigate molecular changes in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics. Our multi-omics investigation discovered a significant concordance for innate immunological and inflammatory responses following P. aeruginosa infection between hosts and alveolar macrophages. Furthermore, we discovered that multi-omics changes in pioneer factors Stat1 and Stat3 play a crucial role in the immunological regulation of P. aeruginosa infection and that their downstream molecules (e.g., Fas) may be implicated in both immunosuppressive and inflammation-promoting processes. Taken together, these findings indicate that transcription factors and their downstream signaling molecules play a critical role in the mobilization and rebalancing of the host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, providing insights and resources for omics analyses. Author summary: Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative aerobic pathogenic bacterium that is widespread in the environment, can undergo anaerobic metabolic activity under certain conditions, is particularly pathogenic and is often associated with lung infections and high mortality rates. In recent years, molecular studies of the mechanisms of the host immune response to bacterial infection have been well interpreted, but the multi-omics changes of multiple molecules in P. aeruginosa systematic analysis of the relationship between them has never been uncovered in detail. In this study, we integrated bioinformatics analysis of ATAC-seq, RNA-seq, proteomics and ubiquitinated proteomics to reveal the landscape of molecular and functional changes of P. aeruginosa infected lung tissues in multiple dimensions. Moreover, we reveal a host defense mechanism by which the crucially important transcription factors Stat1 and Stat3 may co-operatively regulate the expression of the downstream inflammatory genes. [ABSTRACT FROM AUTHOR]

Sisal is a leaf fiber crop with a high integrated value and a wide range of uses in the application of soil remediation of heavy metal contamination. This study provides a preliminary understanding of how sisal responds to Cd stress and presents a theoretical basis for exploring the potential of sisal in the remediation of Cd-contaminated soils. In this work, the activities of the antioxidant enzymes (SOD, POD, and CAT) of sisal were measured by hydroponics with the addition of CdCl2·2.5H2O and different concentrations of Cd stress. Whole transcriptome sequencing (RNA-Seq) analysis was performed with lllumina sequencing technology, and qRT-PCR was conducted to verify the differential genes. The results obtained were as follows: (1) Short-term low concentration of Cd stress (20 mg/kg) had a transient promotion effect on the growth of sisal roots, but Cd showed a significant inhibitory effect on the growth of sisal roots over time. (2) Under different concentrations of Cd stress, the Cd content in sisal root was greater than that in sisal leaf, and Cd accumulated mainly in sisal roots. (3) With the increase of Cd stress concentration, the antioxidant enzyme catalase activity increased, peroxidase activity showed a decreasing trend, and superoxide dismutase showed a trend of increasing and then decreasing. (4) Transcriptome sequencing analysis detected 123 differentially expressed genes (DEGs), among which 85 genes were up-regulated and 38 genes were down-regulated. The DEGs were mainly concentrated in flavonoid biosynthesis and glutathione metabolism, and both processes had some regulatory effects on the Cd tolerance characteristics of sisal. This study elucidated the physiological, biochemical and transcriptomic responses of sisal under cadmium stress, and provided a theoretical basis for the ecological restoration function of sisal. [ABSTRACT FROM AUTHOR]

Nitrogen (N), phosphorus (P), and potassium (K) exert various effects on strawberry (Fragaria ananassa Duchesne) yields. In this study, we employed an orthogonal experimental design (T1-T9) with three fertilization treatments (N, P, and K) at three levels to identify an optimal fertilization scheme for strawberry cultivation. The effects of fertilizer combinations the rhizosphere soil microbial community were also explored by using bacterial full-length 16S rRNA and fungal ITS (internal transcribed spacer) sequencing (30 samples for each analysis). The results showed that the average plant height and leaf area of the fertilized groups were 24.6% and 41.6% higher than those of the non-fertilized group (T0). After 60 d of planting, the sucrase activity in the T6 group increased by 76.67% compared to the T0 group, with phosphate fertilizer exerting a more significant impact on sucrase activity. The T6 treatment group had the highest alpha diversity index among bacterial and fungal microorganisms, and had a different microbial community structure compared with the control group. The most abundant bacterial taxa in the strawberry rhizosphere soil were Proteobacteria, Bacteroidota, and Acidobacteriota, and the most abundant fungal phyla were Monoblepharomycota, Glomeromycota, and Mucoromycota. Application of the optimal combined fertilizer treatment (T6) significantly increased the abundance of Proteobacteria and altered the abundance of Gemmatimonas compared to other treatment groups. Notably, Gemmatimonas abundance positively correlated with strawberry plant height and soil N, P, and K levels. These findings indicated that the relative abundance of beneficial bacteria could be enhanced by the application of an optimal fertilizer ratio, ultimately improving strawberry agronomic traits. [ABSTRACT FROM AUTHOR]

The mutational processes dictating the accumulation of mutations in genomes are shaped by genetic background, environment and their interactions. Accurate quantification of mutation rates and spectra under drugs has important implications in disease treatment. Here, we used whole-genome sequencing and time-resolved growth phenotyping of yeast mutation accumulation lines to give a detailed view of the mutagenic effects of rapamycin and hydroxyurea on the genome and cell growth. Mutation rates depended on the genetic backgrounds but were only marginally affected by rapamycin. As a remarkable exception, rapamycin treatment was associated with frequent chromosome XII amplifications, which compensated for rapamycin induced rDNA repeat contraction on this chromosome and served to maintain rDNA content homeostasis and fitness. In hydroxyurea, a wide range of mutation rates were elevated regardless of the genetic backgrounds, with a particularly high occurrence of aneuploidy that associated with dramatic fitness loss. Hydroxyurea also induced a high T-to-G and low C-to-A transversion rate that reversed the common G/C-to-A/T bias in yeast and gave rise to a broad range of structural variants, including mtDNA deletions. The hydroxyurea mutation footprint was consistent with the activation of error-prone DNA polymerase activities and non-homologues end joining repair pathways. Taken together, our study provides an in-depth view of mutation rates and signatures in rapamycin and hydroxyurea and their impact on cell fitness, which brings insights for assessing their chronic effects on genome integrity. Author summary: As the ultimate source of genetic variation, mutation plays critical roles in evolution. An accurate depiction of its intrinsic rate and signature can help us understand the genetic basis of biodiversity and diseases. However, the ubiquitous existence of natural selection often leads to bias for the observable mutations in natural populations. To minimize such confounding effect introduced by selection, we applied evolution experiment by random single-cell bottlenecks, which allows almost all kinds of mutations to accumulate in an unbiased way. With this setup, we examined the mutation rates and signatures of yeast cells in two commonly used chemotherapy drugs that impairs essential cellular functions such as DNA and protein synthesis. We found elevated mutation rates for a wide range of genetic variants, accompanied by dramatic fitness loss in hydroxyurea. The mutational signatures suggest the involvement of low fidelity DNA replication and repair processes. The mutagenic effects of rapamycin are marginal but with frequent chromosome XII amplifications that compensate for rapamycin-induced rDNA contraction on this chromosome. Our findings provide an example of how such experiments on model organisms can help us better understand the chronic mutagenic effects of drugs and their underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis (CE) is a worldwide neglected zoonotic disease caused by infection with the larval stage of the tapeworm Echinococcus granulosus sensu lato (E. granulosus s.l.), which predominantly resides in the liver accompanied by mild inflammation. Macrophages constitute the main cellular component of the liver and play a central role in controlling the progression of inflammation and liver fibrosis. However, the role of hepatic macrophages in the establishment and growth of hydatid cysts in the liver during E. granulosus sensu stricto (E. granulosus s.s.) infection has not been fully elucidated. Here, we showed that CD68+ macrophages accumulated in pericystic areas of the liver and that the expression of CD163, a marker of anti-inflammatory macrophages, was more evident in active CE patients than in inactive CE patients. Moreover, in a mouse model of E. granulosus s.s. infection, the pool of hepatic macrophages expanded dramatically through the attraction of massive amounts of monocyte-derived macrophages (MoMFs) to the infection site. These infiltrating macrophages preferentially polarized toward an iNOS+ proinflammatory phenotype at the early stage and then toward a CD206+ anti-inflammatory phenotype at the late stage. Notably, the resident Kupffer cells (KCs) predominantly maintained an anti-inflammatory phenotype to favor persistent E. granulosus s.s. infection. In addition, depletion of hepatic macrophages promoted E. granulosus s.s. larval establishment and growth partially by inhibiting CD4+ T-cell recruitment and liver fibrosis. The above findings demonstrated that hepatic macrophages play a vital role in the progression of CE, contributing to a better understanding of the local inflammatory responses surrounding hydatid cysts and possibly facilitating the design of novel therapeutic approaches for CE. Author summary: Cystic echinococcosis (CE) is one of the neglected zoonoses caused by Echinococcus granulosus s.l. larvae and is a worldwide public health problem. Previous study showed that CE is usually characterized by mild local inflammation, indicating that E. granulosus s.l. can control liver inflammation to shape an 'immunosuppressive' microenvironment, a balance between pro- and anti-inflammatory responses to maintain immune homoeostasis during persistent infection. Here, by combining data from human CE samples and animal models, we found that hepatic macrophages are involved in the control of liver inflammation to favor persistent E. granulosus s.s. infection. The pool of hepatic macrophages expanded dramatically at the early stage through the attraction of massive amounts of MoMFs that preferentially initially polarized toward a proinflammatory phenotype and then toward an anti-inflammatory phenotype to favor persistent infection at the late stage after infection. Depletion of hepatic macrophages accelerated hydatid cyst establishment and growth by inhibiting CD4+ T-cell infiltration and liver fibrosis during E. granulosus s.s. infection. Our findings contribute to a better understanding of the local microenvironment in CE and possibly facilitate the design of novel therapeutic approaches for CE that target hepatic macrophages. [ABSTRACT FROM AUTHOR]

Text pre-processing is an important component of a Chinese text classification. At present, however, most of the studies on this topic focus on exploring the influence of preprocessing methods on a few text classification algorithms using English text. In this paper we experimentally compared fifteen commonly used classifiers on two Chinese datasets using three widely used Chinese preprocessing methods that include word segmentation, Chinese specific stop word removal, and Chinese specific symbol removal. We then explored the influence of the preprocessing methods on the final classifications according to various conditions such as classification evaluation, combination style, and classifier selection. Finally, we conducted a battery of various additional experiments, and found that most of the classifiers improved in performance after proper preprocessing was applied. Our general conclusion is that the systematic use of preprocessing methods can have a positive impact on the classification of Chinese short text, using classification evaluation such as macro-F1, combination of preprocessing methods such as word segmentation, Chinese specific stop word and symbol removal, and classifier selection such as machine and deep learning models. We find that the best macro-f1s for categorizing text for the two datasets are 92.13% and 91.99%, which represent improvements of 0.3% and 2%, respectively over the compared baselines. [ABSTRACT FROM AUTHOR]

Metabolic suppression in the ischemic heart is characterized by reduced levels of NAD+ and ATP. Since NAD+ is required for most metabolic processes that generate ATP, we hypothesized that nicotinamide restores ischemic tissue NAD+ and improves cardiac function in cardiomyocytes and isolated hearts, and enhances survival in a mouse model of cardiac arrest. Mouse cardiomyocytes were exposed to 30 min simulated ischemia and 90 min reperfusion. NAD+ content dropped 40% by the end of ischemia compared to pre-ischemia. Treatment with 100 μM nicotinamide (NAM) at the start of reperfusion completely restored the cellular level of NAD+ at 15 min of reperfusion. This rescue of NAD+ depletion was associated with improved contractile recovery as early as 10 min post-reperfusion. In a mouse model of cardiac arrest, 100 mg/kg NAM administered IV immediately after cardiopulmonary resuscitation resulted in 100% survival at 4 h as compared to 50% in the saline group. In an isolated rat heart model, the effect of NAM on cardiac function was measured for 20 min following 18 min global ischemia. Rate pressure product was reduced by 26% in the control group following arrest. Cardiac contractile function was completely recovered with NAM treatment given at the start of reperfusion. NAM restored tissue NAD+ and enhanced production of lactate and ATP, while reducing glucose diversion to sorbitol in the heart. We conclude that NAM can rapidly restore cardiac NAD+ following ischemia and enhance glycolysis and contractile recovery, with improved survival in a mouse model of cardiac arrest. [ABSTRACT FROM AUTHOR]

This paper aims to examine the impact of executive compensation incentive on corporate innovation capability by dividing executive compensation incentive into short-term monetary incentive and long-term equity incentive. We also investigate the interaction between the two types of executive compensation incentive. Data are collected from China's agro-based companies during 2012–2019, and multiple regression analysis is utilized. The empirical results show that short-term monetary incentive has no impact on innovation capability, while long-term equity incentive stimulates innovation capability. Regarding company ownership, the impact of long-term equity incentive in state-owned enterprises is greater than that in private-owned enterprises. In addition, the complementary effect between short-term and long-term compensation incentive has a positive impact on innovation capability regardless of company ownership. The findings of this paper could help agribusiness managers to design the reasonable incentive system to incentivize corporate executives and enhance the capability of independent innovation. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are involved in various biological roles, including viral infection and antiviral immune responses. To identify influenza A virus (IAV) infection-related circRNAs, we compared the circRNA profiles of A549 cells upon IAV infection. We found that circVAMP3 is substantially upregulated after IAV infection or interferon (IFN) stimulation. Furthermore, IAV and IFN-β induced the expression of QKI-5, which promoted the biogenesis of circVAMP3. Overexpression of circVAMP3 inhibited IAV replication, while circVAMP3 knockdown promoted viral replication, suggesting that circVAMP3 restricts IAV replication. We verified the effect of circVAMP3 on viral infection in mice and found that circVAMP3 restricted IAV replication and pathogenesis in vivo. We also found that circVAMP3 functions as a decoy to the viral proteins nucleoprotein (NP) and nonstructural protein 1 (NS1). Mechanistically, circVAMP3 interfered with viral ribonucleoprotein complex activity by reducing the interaction of NP with polymerase basic 1, polymerase basic 2, or vRNA and restored the activation of IFN-β by alleviating the inhibitory effect of NS1 to RIG-I or TRIM25. Our study provides new insights into the roles of circRNAs, both in directly inhibiting virus replication and in restoring innate immunity against IAV infection. Author summary: Influenza A virus (IAV) poses a serious public health and socio-economic threat as a result of pandemic and seasonal epidemics. IAV utilizes host cell mechanisms to promote its replication, while the host innate immune system can induce a variety of antiviral agents to fight IAV infection. Recent studies have found that more and more noncoding RNAs (ncRNAs) are involved in antiviral immune response. Circular RNAs (circRNAs), a new member of ncRNAs, are involved in a variety of biological roles, and most studies have focused on their function in cancer. Recently, several research groups have found that circRNAs have significantly changed upon IAV infection and they also take part in viral infection and antiviral immune responses. However, the biogenetic processes, potential functions, and underlying mechanisms of most circRNAs in IAV infection remain unclear. Here, we screened the circRNA transcription profiles of three IAV strains to identify circRNAs involved in viral replication. We found that circVAMP3 was also induced by IFN-β during IAV infection, with the largest increase. We further found that circVAMP3 formation is mediated by QKI-5, which acts as a decoy for viral proteins to inhibit IAV replication. Our study provides new insights into the role of circRNAs against IAV infection. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) comprises a continuum of symptoms and associated problems that has led AUD to be a leading cause of morbidity and mortality across the globe. Given the heterogeneity of AUD from mild to severe, consideration is being given to providing a spectrum of interventions that offer goal choice to match this heterogeneity, including helping individuals with AUD to moderate or control their drinking at low-risk levels. Because so much remains unknown about the factors that contribute to successful moderated drinking, we use dynamical systems modeling to identify mechanisms of behavior change. Daily alcohol consumption and daily desire (i.e., craving) are modeled using a system of delayed difference equations. Employing a mixed effects implementation of this system allows us to garner information about these mechanisms at both the population and individual levels. Use of this mixed effects framework first requires a parameter set reduction via identifiability analysis. The model calibration is then performed using Bayesian parameter estimation techniques. Finally, we demonstrate how conducting a parameter sensitivity analysis can assist in identifying optimal targets of intervention at the patient-specific level. This proof-of-concept analysis provides a foundation for future modeling to describe mechanisms of behavior change and determine potential treatment strategies in patients with AUD. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbances are highly prevalent in patients with age-related neurodegenerative diseases, which severely affect cognition and even lead to accumulated β-amyloid. Encouraging results from recent studies on transcranial direct current stimulation (tDCS) showed moderate positive effects on sleep quality in preclinical Alzheimer's disease (AD). Compared to tDCS, transcranial alternating current stimulation (tACS) enables the entrainment of neuronal activity with optimized focality through injecting electric current with a specific frequency and has significant enhancement effects on slow wave activities. Methods and design: This is a randomized, double-blind, sham-controlled clinical trial comparing 40 Hz tACS with tDCS in mild neurocognitive disorders due to AD with sleep disturbances. Magnetic resonance imaging (MRI) data is used to construct personalized realistic head model. Treatment outcomes, including sleep quality, cognitive performance and saliva Aβ levels will be conducted at baseline, 4th week, 8th week, 12th week and 24th week. Conclusions: It is expected that the repeated gamma-band tACS will show significant improvements in sleep quality and cognitive functions compared to tDCS and sham tDCS. The findings will provide high-level evidence and guide further advanced studies in the field of neurodegenerative diseases and sleep medicine. Trial registration: ClinicalTrials.gov Identifier: NCT05544201. [ABSTRACT FROM AUTHOR]

Infection with the cestode Echinococcus multilocularis (E. multilocularis) causes alveolar echinococcosis (AE), a tumor-like disease predominantly affecting the liver but able to spread to any organ. T cells develop functional defects during chronic E. multilocularis infection, mostly due to upregulation of inhibitory receptors such as T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) and programmed death-1 (PD-1). However, the role of lymphocyte activation gene-3 (LAG3), an inhibitory receptor, in AE infection remains to be determined. Here, we discovered that high expression of LAG3 was mainly found in CD4+ T cells and induced regulatory T cells (iTregs) in close liver tissue (CLT) from AE patients. In a mouse model of E. multilocularis infection, LAG3 expression was predominantly found in T helper 2 (Th2) and Treg subsets, which secreted significantly more IL-4 and IL-10, resulting in host immune tolerance and disease progression at a late stage. Furthermore, LAG3 deficiency was found to drive the development of effector memory CD4+ T cells and enhance the type 1 CD4+ T-cell immune response, thus inhibiting metacestode growth in vivo. In addition, CD4+ T cells from LAG3-deficient mice produced more IFN-γ and less IL-4 when stimulated by E. multilocularis protoscoleces (EmP) antigen in vitro. Finally, adoptive transfer experiments showed that LAG3-knockout (KO) CD4+ T cells were more likely to develop into Th1 cells and less likely to develop into Tregs in recipient mice. Our work reveals that high expression of LAG3 accelerates AE disease progression by modulating the immune imbalance of CD4+ T-cell subsets. These findings may provide a novel immunotherapeutic strategy against E. multilocularis infection. Author summary: Alveolar echinococcosis (AE) is a parasitic disease with high mortality caused by E. multilocularis infection. Our previous studies confirmed that T-cell-mediated cellular immunity, especially that mediated by CD4+ T cells, plays a key role in limiting metacestode growth. Here, we report that high LAG3 expression in liver-infiltrating CD4+ T cells is associated with their immune imbalance in AE patients and a mouse model of later-stage disease. High expression of LAG3 promotes the formation of Th2 cells and Tregs, and LAG3 deficiency induces a shift in the immune response to the Th1 type to delay the growth of metacestodes in chronic E. multilocularis infection. These findings suggest that LAG3 blockade may be an effective immune strategy for the treatment of AE patients. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the association of blepharitis and ischemic stroke. Methods: This nationwide retrospective cohort study used population-based data in Taiwan. Individuals aged 20 and above with diagnosis of blepharitis was included based on electrical medical records. After exclusion of ineligible cases, 424,161 patients were identified between 2008 and 2018. The blepharitis and non-blepharitis cohorts were matched based on sex, age, and comorbidities. Multivariable-adjusted Cox proportional hazards model was adopted to calculate the hazard ratio and 95% confidence interval (CI) between blepharitis and non-blepharitis cohorts. The incidence of ischemic stroke was estimated by Kaplan–Meier analysis. Results: 424,161 pairs of blepharitis cohort and non-blepharitis cohort were 1:1 propensity score matched for statistical analysis. Patients with blepharitis had significantly increased risk of ischemic stroke compared with the individuals without blepharitis (adjusted hazard ratio 1.32, 95% CI 1.29–1.34, P < 0.001). A significantly higher risk of ischemic stroke was observed in blepharitis cohort with a previous diagnosis of cancer than in those without cancer (P for interaction < 0.0001). Kaplan–Meier survival analysis revealed the cumulative incidence of ischemic stroke increased in the blepharitis cohort compared with that in the non-blepharitis cohort in 10 years (log-rank P < 0.001). The follow-up period analysis further indicated 1.41-fold adjusted hazard (95% CI 1.35−1.46, P < 0.001) of ischemic stroke within a year after blepharitis diagnosis. Conclusions: Patients with blepharitis had an elevated risk of developing ischemic stroke. Early treatment and active surveillance are suggested for patients with chronic blepharitis. Further research is required to determine the casual relationship between blepharitis and ischemic stroke, as well as the underlying mechanism. [ABSTRACT FROM AUTHOR]

For a long time, one of the important safety problems in open-pit mines is the stability of a large number of high slopes with gently inclined soft interlayer. Rock masses formed after long geological processes generally have some initial damage. Mining works also cause varying degrees of disturbance and damage to rock masses in the mining area during the mining process. This phenomenon means that accurate characterization of the time-dependent creep damage for rock masses under shear load is necessary. The damage variable D is defined based on the spatial and temporal evolution laws of shear modulus and initial level of damage for the rock mass. In addition, a coupling damage equation between the initial damage of the rock mass and shear creep damage is established based on Lemaitre's strain equivalence assumption. Kachanov's damage theory is also incorporated to describe the entire process of time-dependent creep damage evolution for rock masses. A creep damage constitutive model that can reasonably reflect the actual mechanical properties of rock masses under multi-stage shear creep loading conditions is established. This takes into account multi-stage shear creep loading conditions, instantaneous creep damage during the shear load phase, staged creep damage and factors influencing the initial damage of rock masses. The reasonableness, reliability and applicability of this model are verified by comparing the results of the multi-stage shear creep test with calculated values from the proposed model. As opposed to the traditional creep damage model, the shear creep model established in this present study takes into account the initial damage of rock masses and can describe the multi-stage shear creep damage characteristics of rock masses more convincingly. [ABSTRACT FROM AUTHOR]

Based on the Peircean semiotic theory, this study aims to explore the semiotic construction of a festival tourist attraction using the Guangfu Temple Fair in China as a case. A qualitative research method of grounded theory was used to analyze the organizers' planning scheme, conference materials, 7 interviews, and 45 tourists' interviews. We found that festival organizers produce festivalscape based on social values and tourists' expectations, including safety assurance, cultural activity, personnel service, facilities, creative interaction, food, a trade show, and the festival atmosphere. Tourists in the festivalscape, through cultural, novel, social, and emotional experience and collateral observations, assign meaning to the festival's attractiveness in terms of cultural diversity, vibrant activities, distinctive features, and a sense of ceremony. These findings indicate that organizers' sign production and tourists' sign interpretation constitute the conceptual model of the semiotic construction of festivals as tourist attractions. Furthermore, the study extends the understanding of tourist attractions and will help organizers to create successful festival attractions. [ABSTRACT FROM AUTHOR]

Background: The hospital environment, particularly the intensive care unit (ICU), contributes to the transmission of several nosocomial pathogens, which can survive in this setting for a longer period of time and, in turn, contaminate the surfaces or the medical tools. Thus, appropriate disinfection of these areas and devices are crucial for controlling and preventing further infection. In this study, we examined the effect of different concentrations of chlorine-containing disinfectants (500mg/L, 1000mg/L, and 2000mg/L) on the ICU environment. Methods: This quasi-experimental study was based on a convenient sampling method. In this study, High-frequency objects were selected as subjects in ICU, with a total sample of 216.A hall including 6 beds was examined,selecting 4 high-frequency surfaces per bed unit:a bed gear, infusion system, bed end table, and monitor were disinfected with 500, 1000, and 2000 mg/L of chlorine (as Cl2), respectively.The surface dissection was performed at 21:00 o'clock daily, after which ATP fluorescence monitoring and bacterial count detection were performed. Results: There was no significant difference in ATP bioluminescence (F = 2.03, P > 0.05) and bacterial counting (χ2 = 2.03, P > 0.05) when using different concentrations of chlorine-containing disinfectant in the ICU. Yet, compared with high concentration (2000mg/L), a low concentration disinfectant reduced the hospital cost. Conclusion: By reducing the concentration of ICU high-frequency contact table disinfectants, it is possible to reduce the risk of long-term contamination with chlorine-containing disinfectants and reduce the cost of using ICU chlorine-containing disinfectants. [ABSTRACT FROM AUTHOR]

Although cellulose derivatives are widely applied in high-tech materials, the relation between their force responses and their surface chemical properties in a biological environment as a function of pH is unknown. Here, interaction forces of surface modified cellulose nanocrystals (CNCs), lignin residual cellulose nanocrystals (LCNCs), and 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized cellulose nanofibres (TCNFs) with OSO3−, COO− and lignin chemical groups were measured using in situ peak force quantitative nanomechanical mapping and force spectroscopy in salt solution at two pH values. We found that the forces acting between the tip and CNC or LCNC are steric dominated showing long range and slow decay as a result of their low surface charge density. High Mw lignin contributed to the increased repulsion range for LCNCs compared to CNCs. The repulsion measured for TCNFs at the very short range was electrostatic force dominating showing a steep decay attributed to its high surface charge density. In the case of TCNFs, electrostatic double layer force was also evidenced by the attraction measured at secondary minima. In all the three cases the electro steric interactions are pH dependent. Dissipation maps verified that the force behavior for each material was related to structural conformation restriction of the groups at compression. The slow decayed repulsion of CNCs or LCNCs is related to a weak restriction of conformational change due to small surface groups or high molecular weight bound polymers forming flat layers, whereas the steep repulsion of TCNFs is attributed to a strong conformation restriction of carboxylic groups occurred by forming extended structure. Our results suggest that the force responses of the materials were dominated by surface charges and structural differences. TCNFs showed superior nanomechanical and repulsion properties over CNCs or LCNCs at neutral pH. [ABSTRACT FROM AUTHOR]

With the development of medical science, long noncoding RNA (lncRNA), originally considered as a noise gene, has been found to participate in a variety of biological activities. Several recent studies have shown the involvement of lncRNA in various human diseases, such as gastric cancer, prostate cancer, lung cancer, and so forth. However, obtaining lncRNA-disease relationship only through biological experiments not only costs manpower and material resources but also gains little. Therefore, developing effective computational models for predicting lncRNA-disease association relationship is extremely important. This study aimed to propose an lncRNA-disease association prediction model based on the weight matrix and projection score (LDAP-WMPS). The model used the relatively perfect lncRNA-miRNA relationship data and miRNA-disease relationship data to predict the lncRNA-disease relationship. The integrated lncRNA similarity matrix and the integrated disease similarity matrix were established by fusing various methods to calculate the similarity between lncRNA and disease. This study improved the existing weight algorithm, applied it to the lncRNA-miRNA-disease triple network, and thus proposed a new lncRNA-disease weight matrix calculation method. Combined with the improved projection algorithm, the lncRNA-miRNA relationship and miRNA-disease relationship were used to predict the lncRNA-disease relationship. The simulation results showed that under the Leave-One-Out-Cross-Validation framework, the area under the receiver operating characteristic curve of LDAP-WMPS could reach 0.8822, which was better than the latest result. Taking adenocarcinoma and colorectal cancer as examples, the LDAP-WMPS model was found to effectively infer the lncRNA-disease relationship. The simulation results showed good prediction performance of the LDAP-WMPS model, which was an important supplement to the research of lncRNA-disease association prediction without lncRNA-disease relationship data. [ABSTRACT FROM AUTHOR]

Osteoclasts are the only multinucleated cells in vivo responsible for bone resorption and are vital for regulating bone remodeling and maintaining bone mass. The RAW264.7 cell line is widely used to study osteoclastic differentiation and biological molecular mechanism. However, protocols for inducing osteoclast formation in RAW264.7 cells vary considerably between laboratories, hindering the replication of results. Therefore, we tested the influence of culture conditions on osteoclast differentiation, including cell density and receptor activator of nuclear factor kappa-B ligand (RANKL) concentrations with or without macrophage colony-stimulating factors (M-CSF). Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the morphology of osteoclasts. qPCR was used to detect gene expression of osteoclast-specific gene marker cathepsin K (CTSK), osteoclast transcription factors c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). The bone resorption function was evaluated by a scanning electron microscope (SEM). RANKL treatment increased multinucleated osteoclasts formation and increased CTSK, c-Fos and NFATc1 gene expression. Compared with RANKL treatment, M-CSF significantly decreased multinucleated osteoclasts formation, reduced CTSK gene expression and had little effect on c-Fos and NFATc1 gene expression. Concerning bone resorption activity, RANKL treatment increased bone resorption pits on bovine bone slices. Significantly higher levels of osteoclastogenesis were observed with RAW264.7-cell density of 2×104 cells/well in 24-well plates. Our results suggest that the addition of 50 ng/ml M-CSF has no positive effect on osteoclastogenesis. RANKL treatment and cell density contribute to osteoclast formation, and the optimal conditions are beneficial when exploring osteoclast function and mechanism. [ABSTRACT FROM AUTHOR]

Soil salinization is one of the current global environmental problems. Current research on crops in saline-alkali land focuses on salt tolerance, but less on its ecological benefits. However, plants and the environment can interact and influence each other, which is the theory used to carry out Nature-based Solutions (NbS). Therefore, the research on crop plants with both ecological and economic benefits is novel and valuable work. Then three widely planted cash crops (Solanum melongena, Momordica charantia, Capsicum annuum) were selected for salt stress treatment (NaCl, 150mmol/L), some physiological indicators (chlorophyll, soluble protein, Proline (Pro), malondialdehyde (MDA)) of plant and the soil properties (electrical conductivity, pH, the soil salt content) were measured. The results showed that the salinity content of the three plant cultivation soils was significantly different (P<0.05) after the salt stress; all three crops had some desalination capacity, but Capsicum annuum had the strongest salt resistance and desalination capacity. [ABSTRACT FROM AUTHOR]

Revegetation of exposed sub-soil, while a desirable recovery strategy, often fails due to extreme soil chemical properties, such as low organic matter and pH levels. Microalgae play a key role in maintaining water quality in the lakes and rivers on the Qinghai-Tibet plateau. Plateau microalgae have extensive application prospects in environmental purification, biotechnology, medicine and cosmetics, food industry, and renewable energy. To identify the high biomass of microalgae present in nature, microalgae with the greatest biomass were screened from natural water samples through filtration, pre-culture, and plate scribing separation. Following identification via 18S rRNA sequencing as for the Desmodesmus sp., we constructed a neighbor-joining phylogenetic tree. The novel Desmodesmus sp. from the Tibetan Yamdrok Lake were identified through polyphasic taxonomy. Simultaneously, the sequence of the experimental samples and the target species were shown different following the identification and analysis of SNP and InDel loci. The light-absorbing properties of plateau Desmodesmus sp. have been investigated previously. The characteristic absorption peak of Desmodesmus sp. on the plateau was measured at 689 nm in the visible spectrum using full wavelength scanning with a UV-Vis spectrophotometer. For Desmodesmus sp. which is prone to settling in the process of amplification culture. By monitoring the change trend of total nitrogen, total phosphorus, pH and electrical conductivity in algae solution system, we determined that the logarithmic growth phase and the best transfer window of Desmodesmus sp. were at 15–20 days. This study can provide basic research methods for the study of microalgae in high altitude areas, and lay a foundation for the later study and application of microalgae. [ABSTRACT FROM AUTHOR]

The ZIP protein (ZRT, the IRT-like protein) is an important metal transporter that transports Zn, Fe, and other divalent metal ions in plants. In this study, we identified 20 ZIP genes in lettuce (Lactuca sativa L.). We used bioinformatics methods and renamed them according to their E value in hmmsearch. We also analyzed their gene structure, chromosomal location, constructed a phylogenetic tree, conserved motifs, performed synonymous analysis and responses to abiotic stresses. The results show that these LsZIP genes have 3–11 exons and were distributed unequally on 8 of the 9 chromosomes in lettuce. Based on phylogenetic analyses, the LsZIP gene family can be divided into three subfamilies, and the LsZIP genes within the same subfamily shared similar gene structure. The LsZIP genes contain 12 Motifs, of which Motif1 to Motif8 are widely distributed in group Ⅰ. Furthermore, the LsZIP gene contains numerous hormones and anti-stress response elements. Real-time quantitative PCR demonstrated that most LsZIP genes is up-regulated under the elemental stress in this experiment, indicating that they are positively regulated. But different elemental stressors can induce the expression of LsZIP gene to varying degrees. The LsZIP genes also change in response to different elemental stresses. The present study serves as a basic foundation for future functional studies on the lettuce ZIP family. [ABSTRACT FROM AUTHOR]

Using data from China Family Panel Studies (CFPS) and based on the Probit and Tobit models, this study investigates the impact of air pollution on residents' outdoor exercise behaviour from the microscopic level. Specifically, this study examined the effects of PM2.5 index changes on residents' decision to participate in outdoor exercise and the duration of outdoor exercise participation. The empirical results show that the increase of PM2.5 index has a significant inhibitory effect on residents' participation in outdoor exercise, and has passed the robustness test and endogeneity test. Further testing found that the inhibitory effect was significantly different between urban and rural areas, and in the central, north-eastern and western regions where economic development was relatively backward, the conclusion that air pollution inhibited residents' outdoor exercise behaviour still holds true. However, the level of air pollution had no significant effect on the outdoor exercise behaviour of residents in the eastern region. So, while air pollution discourages residents from participating in outdoor exercise, the results are more applicable to less economically developed areas. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis, with 250 million people affected, is characterized by its serious hepatic inflammatory response and fibrosis formation, which could lead to dangerous complications, such as portal hypertension, splenomegaly and even ascites. But until now, the pathogenesis of schistosomiasis remains largely unknown. Farnesoid X Receptor (FXR), a bile acid-activated nuclear transcription factor mainly expresses in hepatocytes in the liver, can regulate liver diseases by controlling bile acid metabolism. Methodology/Principal findings: In this study, we found that the expression of FXR was decreased in the liver of infected mice as shown by western blot and RT-qPCR assays. Furthermore, hepatocyte-specific FXR-deficient mice (FXRflox/floxAlbCre, FXR-HKO) were generated and infected with ~16 cercariae of S. japonicum for five weeks. We found that FXR deficiency in hepatocytes promoted the progression of liver injury, aggravated weight loss and death caused by infection, and promoted inflammatory cytokines production, such as IL-6, IL-1β, TNF-α, IL-4, IL-10, and IL-13. Surprisingly, hepatic granulomas and fibrosis were not affected. In addition, using UPLC-MS/MS spectrometry, it was found that S. japonicum infection resulted in elevated bile acids in the liver of mice, which was more obvious in FXR-deficient mice. Meanwhile, autophagy was induced in littermate control mice due to the infection, but it was significantly decreased in FXR-HKO mice. Conclusions/Significance: All these findings suggest that FXR deficiency in hepatocytes disrupts bile acid homeostasis and inhibits autophagy, which may aggravate the damages of hepatocytes caused by S. japonicum infection. It highlights that FXR in hepatocytes plays a regulatory role in the progression of schistosomiasis. Author summary: The liver, a critical metabolic organ, consists of approximately 80% parenchymal hepatocytes. Hepatic schistosomiasis results in inflammatory granulomas response and fibrosis formation that inevitably affects hepatocytes. However, whether and how hepatocytes involved in the progression of liver injury caused by S. japonicum is not clear. Here, we found that, the level of FXR, a key regulator of bile acid metabolism in hepatocytes, was clearly decreased in the liver of mice with this worm infection. Further, we found that FXR specifically deficient in hepatocytes increased bile acids toxicity and inhibited hepatocellular autophagy induced by worm infection, which therefore accelerated the progression of schistosomiasis by promoting hepatocyte injuries but not the formation of egg granulomas and hepatic fibrosis. Our work provides a regulatory loop of FXR/bile acids-autophagy in schistosomiasis, which suggests a role of hepatic FXR in the protection from hepatic damages caused by infection with S. japonicum. [ABSTRACT FROM AUTHOR]

Background: Postoperative ileus (POI) is an important complication of gastrointestinal (GI) surgery. Acupuncture has been increasingly used in treating POI. This study aimed to assess the effectiveness and safety of acupuncture for POI following GI surgery. Methods: Seven databases (PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wan fang Data, VIP Database for Chinese Technical Periodicals, and Chinese Biomedical Literature Database) and related resources were searched from inception to May 30, 2021. Randomized controlled trials (RCTs) reporting the acupuncture for POI in GI were included. The quality of RCTs was assessed by the Cochrane Collaboration Risk of Bias tool, and the certainty of the evidence was evaluated by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. A meta-analysis was performed by using RevMan 5.4 software. Results: Eighteen RCTs involving 1413 participants were included. The meta-analysis showed that acupuncture could reduce the time to first flatus (TFF) (standardized mean difference [SMD] = −1.14, 95% confidence interval [CI]: −1.54 to −0.73, P < 0.00001), time to first defecation (TFD) (SMD = −1.31, 95% CI: −1.88 to −0.74, P < 0.00001), time to bowel sounds recovery (TBSR) (SMD = −1.57, 95% CI: −2.14 to −1.01, P < 0.00001), and length of hospital stay (LOS) (mean difference [MD] = −1.68, 95% CI: −2.55 to −0.80, P = 0.0002) compared with usual care. A subgroup analysis found that acupuncture at distal acupoints once daily after surgery had superior effects on reducing TFF and TFD. A sensitivity analysis supported the validity of the finding. Acupuncture also manifested an effect of reducing TFF, TFD and TBSR compared with sham acupuncture but the result was not stable. Relatively few trials have reported whether adverse events have occurred. Conclusions: Acupuncture showed a certain effect in reducing POI following GI surgery with very low-to-moderate quality of evidence. The overall safety of acupuncture should be further validated. More high-quality, large-scale, and multicenter original trials are needed in the future. [ABSTRACT FROM AUTHOR]

Over the past four decades, China's economy has experienced tremendous economic growth but also a widening urban-rural income gap. Given the dilemma of the urban-rural income gap in China explained by neoclassical equilibrium theory, this paper attempts to provide a new theoretical explanation for the large-income gap between urban and rural areas in China. We select data from 30 provinces(cities) in China over the period from 2006 to 2017 as a sample to investigate whether and how the degree of farmland financial innovation narrows the urban-rural income gap. The results show that the coefficient for farmland financial innovation is significantly negative at the 1% level, signifying that financial innovation can narrow the urban-rural income gap in China. The mediation effect test provides evidence that farmland financial innovation narrows the urban-rural income gap by promoting the permanent migration of the labor force and upgrading the industrial structure. Our results indicate that the government should promote various forms of farmland financial innovation, establish rural property rights transaction system and free farmers from deep farmer-land attachment to realize permanent labor migration. [ABSTRACT FROM AUTHOR]

To perform a mental health evaluation and an early psychological intervention for healthcare workers (HCWs) during the coronavirus disease 2019 (COVID-19) epidemic, an online survey was conducted among 3055 HCWs in the paediatric intensive care units (PICUs) of 62 hospitals in China on March 26, 2020, by the Neurology and Sedation Professional Group, Emergency Department, Paediatrics Branch, Chinese Medical Association. The questionnaire was divided into three parts, including general information, the Impact of Event Scale-Revised (IES-R), and the Depression Anxiety Stress Scale-21 (DASS-21). The results show that a total of 970 HCWs (45.99%) were considered to meet the clinical cut-off scores for posttraumatic stress (PTS), and the proportions of participants with mild to extremely severe symptoms of depression, anxiety and stress were 39.69%, 36.46% and 17.12%, respectively. There was no significant difference in the psychological impact among HCWs of different genders. Married HCWs were 1.48 times more likely to have PTS than unmarried HCWs (95% Cl: 1.20–1.82, p <0.001). Compared with junior professional title participants, the PTS-positive rate of HCWs with intermediate professional titles was 1.91 times higher (90% Cl: 1.35–2.70, p<0.01). Those who had been in contact with confirmed COVID-19 cases were 1.40 times (95% Cl: 1.02–1.92, p <0.05) more likely to have PTS than those who did not have contact with COVID-19 cases or did not know the relevant conditions. For depression, the proportion of HCWs with intermediate professional titles was significantly higher, at 1.65 times (90% Cl: 1.17–2.33, p <0.01) that of those with junior professional titles. The depression of HCWs at work during the epidemic was 1.56 times that of HCWs on vacation (95% Cl: 1.03–2.37, p <0.05), and their anxiety was 1.70 times greater (95% Cl: 1.10–2.63, p <0.05). Participants who had been in contact with confirmed COVID-19 cases had more pronounced anxiety, 1.40 times that of those who did not have contact with COVID-19 cases or did not know the relevant conditions (95% Cl: 1.02–1.92, p <0.05). There was no significant correlation between the variables and the positive results of stress symptoms. In total, 45.99%, 39.69%, 36.46% and 17.12% of PICU HCWs were affected by PTS, depression, anxiety and stress, respectively, to varying degree. Married status, intermediate professional titles and exposure history were independent risk factors for PTS. Intermediate professional titles and going to work during the epidemic were independent risk factors for depression, and going to work and exposure history during the epidemic were independent risk factors for anxiety. In the face of public health emergencies, HCWs not only specialize in paediatric intensive care but also, as a high-risk group, must actively take preventive measures and use mitigation strategies. [ABSTRACT FROM AUTHOR]

Meiotic recombination is an essential biological process that ensures faithful chromosome segregation and promotes parental allele shuffling. Tetrad analysis is a powerful approach to quantify the genetic makeups and recombination landscapes of meiotic products. Here we present RecombineX (https://github.com/yjx1217/RecombineX), a generalized computational framework that automates the full workflow of marker identification, gamete genotyping, and tetrad-based recombination profiling based on any organism or genetic background with batch processing capability. Aside from conventional reference-based analysis, RecombineX can also perform analysis based on parental genome assemblies, which facilitates analyzing meiotic recombination landscapes in their native genomic contexts. Additional features such as copy number variation profiling and missing genotype inference further enhance downstream analysis. RecombineX also includes a dedicate module for simulating the genomes and reads of recombinant tetrads, which enables fine-tuned simulation-based hypothesis testing. This simulation module revealed the power and accuracy of RecombineX even when analyzing tetrads with very low sequencing depths (e.g., 1-2X). Tetrad sequencing data from the budding yeast Saccharomyces cerevisiae and green alga Chlamydomonas reinhardtii were further used to demonstrate the accuracy and robustness of RecombineX for organisms with both small and large genomes, manifesting RecombineX as an all-around one stop solution for future tetrad analysis. Interestingly, our re-analysis of the budding yeast tetrad sequencing data with RecombineX and Oxford Nanopore sequencing revealed two unusual structural rearrangement events that were not noticed before, which exemplify the occasional genome instability triggered by meiosis. Author summary: Meiosis is a fundamental cellular process that ensures faithful chromosome segregation and promotes allele shuffling. Tetrad analysis, which isolates and genotypes all four meiotic products (i.e., tetrad) derived from a single meiosis, remains the most straightforward and powerful way of studying meiotic recombination and its modulators at fine scales. The wide application of tetrad analysis in yeasts, filamentous fungi, green algae, and land plants have substantially expanded our understanding of meiotic recombination in terms of both genome-wide landscapes and molecular mechanisms. Here we described the first generalized computational framework named RecombineX that automates the full workflow of tetrad analysis based on any organism or genetic background. In addition, aside from conventional reference-based analysis, RecombineX can also perform analysis based on parental genome assemblies, which enables analyzing meiotic recombination landscapes in their native genomic contexts. Using both simulated and real tetrad-sequencing data, we further demonstrated RecombineX's trustable performance, versatile usage, and batch-processing capability, manifesting RecombineX as an all-around one stop solution for tetrad analysis. Especially considering that meiotic gamete genome sequencing from different natural and mutant backgrounds can now be acquired, we expect RecombineX to become a popular tool that empowers future tetrad analysis across different genetic backgrounds and species. [ABSTRACT FROM AUTHOR]

Foodborne diseases have become a serious havoc, where antimicrobial resistance is throwing significant challenges on daily basis. With the increase of drug-resistant bacteria and food-borne infection associated with Vibrio parahaemolyticus, new and effective strategies were needed to control the emergence of vibriosis. Lytic bacteriophages come up as a promising way to resist the pathogenic population in various applications. In this study, a V. parahaemolyticus specific phage vB_VpS_PG28 was isolated from sewage in the seafood market. Results showed vB_VpS_PG28, is strictly a lytic bacteriophage and has a relatively large burst size of 103 plaque-forming units per infected cell. Comparative genomic and bioinformatic analyses proved that vB_VpS_PG28 is a new bacteriophage that had a homologous relation with Vibrio phages of family Siphoviridae, especially with phage VH2_2019, but transmission electron microscopy of vB_VpS_PG28 morphology characterized its morphology is similar to that of Myoviridae family. In silico analysis indicated that the vB_VpS_PG28 genome consists of 82712 bp (48.08% GC content) encoding 114 putative ORFs without tRNA,and any gene associated with resistance or virulence factors has not been found. The bacteriophage in the present study has shown significant outcomes in order to control bacterial growth under in vitro conditions. Thus, we are suggesting a beneficiary agent against foodborne pathogens. Further, to ensure the safe usage of phage oral toxicity testing is recommended. [ABSTRACT FROM AUTHOR]

Background: A range of helminth species involve the migration of developing larvae through the lung and establish chronic infections in the host that include potent immune regulatory effects. Trichinella spiralis is one of the most successful parasitic symbiotes. After released by intestinal female adult worms, newborn larvae of T. spiralis travel through the circulatory system to the lung and finally reach skeletal muscle cells. As unique inflammation modulator of intracellular parasitism, T. spiralis shows improved responses to autoimmune disease and viral pulmonary inflammation by exerting immunomodulatory effects on innate and adaptive immune cells. Methodology/Principal findings: C57BL/6 mice were divided into four groups: uninfected; helminth- T. spiralis infected; P. aeruginosa infected; and co-infected. Mice infected with T. spiralis were incubated for 6 weeks, followed by P. aeruginosa intranasal inoculation. Bronchial alveolar lavage fluid, blood and lung samples were analyzed. We found that T. spiralis induced Th2 response in the mouse lung tissue, increased lung CD4+ T cells, GATA3, IL-4, IL-5 and IL-13 expression. Pre-existing T. spiralis infection decreased lung neutrophil recruitment, inflammatory mediator IL-1β and IL-6 expression and chemokine CXCL1 and CXCL2 release during P. aeruginosa- pneumonia. Furthermore, T. spiralis co-infected mice exhibited significantly more eosinophils at 6 hours following P. aeruginosa infection, ameliorated pulmonary inflammation and improved survival in P. aeruginosa pneumonia. Conclusions: These findings indicate that a prior infection with T. spiralis ameliorates experimental pulmonary inflammation and improves survival in P. aeruginosa pneumonia through a Th2-type response with eosinophils. Author summary: Helminth infections elicit type 2 immunity, which influences host immune responses to additional threats, such as allergens, metabolic disease and other pathogens. Pseudomonas aeruginosa is one of the most common gram-negative pathogens causing pneumonia in immunocompromised patients. The mortality rate of ventilator associated pneumonia caused by P. aeruginosa is higher than that due to other pathogens. Trichinella spiralis is a zoonotic nematode of intracellular parasitism that infects a wide range of vertebrate hosts, including humans. There is a lung migratory phase in the life cycle of T. spiralis. In this study, we found that T. spiralis induced Th2 response in the mouse lung tissue. T. spiralis co-infected mice exhibited significantly more eosinophils and less neutrophils at 6 hours following P. aeruginosa infection, ameliorated pulmonary inflammation and improved survival in P. aeruginosa pneumonia. These findings suggest a pre-existing chronic helminth with a lung migration phase infection promotes the survival of bacterial airway co-infected host. [ABSTRACT FROM AUTHOR]

With the tendency toward economic and strategy decoupling between China and the United States and amidst the anti-globalization trend, enterprises are facing unprecedented challenges and opportunities. In this study, we reveal how the agile intuition (AI) of top managers with respect to the external environment affects enterprise innovation behavior (IB) based on the cognition–behavior framework. Strategic learning (SL) is considered a moderator, and knowledge sharing (KS) is considered a mediator. The survey sample consists of 305 managers from 47 enterprises in China during the COVID-19 period. The empirical results show that top management agile intuition significantly promotes enterprise IB; knowledge sharing (KS) partially mediates the relationship between top manager AI and enterprise IB; and SL suppresses the promotion effect of top manager AI on enterprise IB to a certain extent, hindering blind innovation. In a surprising result, we find that strategic guidance by an external consultant does not significantly affect the enterprise IB in China. [ABSTRACT FROM AUTHOR]

Background: The incineration and burying of the soiled bedding of laboratory animals, as well as using detergents to treat their feces, is hazardous to the environment. This highlights the need for an alternative, environmentally friendly solution for the treatment of the waste of laboratory animal facilities. This study aims to evaluate the efficacy of ozone disinfection of the soiled bedding and feces of laboratory animals. Methods: Two grams of soiled beddings were randomly sampled from the cages of mice and rats. These samples were mixed in a beaker with 40ml saline. Ozone was piped into the beaker at a concentration of 500mg/h. Samples were taken from the beaker at time 0min, 30min, 45min and 60min after ozone treatment for microbiological culturing in an incubator for 48h. Colony form unit of each plate (CFU/plate) at each time point were counted, the mean CFU/plate at each time point after ozone treatment were compared with that present at time zero. Feces of rabbits and dogs were treated and pathogens were counted the similar way as that of bedding of the mice and rats; samples being taken at 0min, 15min, 30min, 45min and 60min. Results: Pathogens were observed in beddings of both mice and rats as well as in feces of rabbits and dogs. Ozone treatment for 30min killed more than 93% of pathogens in the bedding of the two rodent species and 60min of treatment killed over 99% of pathogens. Treatment of rabbit and dog feces for 30min killed over 96% pathogens present, and 60min's treatment killed nearly all the pathogens. Both Gram positive and Gram negative pathogens were sensitive to ozone treatment. Conclusion: Ozone treatment of bedding and feces is an effective and environment friendly way to deal with the waste of animal facilities, saving energy and potentially enabling their reuse as fertilizer. [ABSTRACT FROM AUTHOR]

Administrative division adjustments, such as agglomerations, upgrading, and revocation, introduce a series of uncertain impacts on the social and economic development in administrative regions. Previous studies have focused more on the economic effects of administrative division adjustments, but in this paper, we also consider the environmental effects of such adjustments. In 2011, with the approval of the State Council, the prefecture-level Chaohu city was officially revoked, resulting in a county-level Chaohu city. One district and four counties under the jurisdiction of the original Chaohu city were placed under the jurisdiction of Hefei, Wuhu, and Ma'anshan. This adjustment made Chaohu Lake an inner lake of Hefei city. The administrative division adjustment of Chaohu Lake, China, is used as a quasi-natural experiment to explore the influence of such an adjustment on pollution control. The synthetic control method (SCM) is used in this study to evaluate the effect of the administrative division adjustment on the water quality indicators of Chaohu Lake. The following conclusions are drawn. First, after the administrative division adjustment, some water quality indicators, such as ammonia nitrogen, improved; however, other major pollution indicators, such as chemical oxygen demand (COD) and dissolved oxygen (DO), worsened to varying degrees. Second, the results reveal that improper development ideas, excessive industrial expansion, and the shift in economic growth and environmental goals were problems after the adjustment. Returning to the original intention of the administrative division adjustment, rationalizing the Chaohu Lake management system and designing a sound and feasible accountability mechanism are fundamental measures for reducing pollution. [ABSTRACT FROM AUTHOR]