ABSTRACT
We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.
Subject(s)
Antigens, Viral , Evolution, Molecular , Hemagglutinin Glycoproteins, Influenza Virus , Influenza A Virus, H7N9 Subtype , Influenza in Birds , Influenza, Human , Phylogeny , Influenza A Virus, H7N9 Subtype/genetics , Influenza A Virus, H7N9 Subtype/immunology , China/epidemiology , Animals , Influenza in Birds/virology , Influenza in Birds/epidemiology , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Influenza, Human/epidemiology , Influenza, Human/virology , Influenza, Human/immunology , Antigens, Viral/immunology , Antigens, Viral/genetics , Birds/virology , Antigenic VariationABSTRACT
Rice tillering is an important agronomic trait that influences plant architecture and ultimately affects yield. This can be genetically improved by mining favourable variations in genes associated with tillering. Based on a previous study on dynamic tiller number, we cloned the gene Tiller number 1a (Tn1a), which encodes a membrane-localised protein containing the C2 domain that negatively regulates tillering in rice. A 272 bp insertion/deletion at 387 bp upstream of the start codon in the Tn1a promoter confers a differential transcriptional response and results in a change in tiller number. Moreover, the TCP family transcription factors Tb2 and TCP21 repress the Tn1a promoter activity by binding to the TCP recognition site within the 272 bp indel. In addition, we identified that Tn1a may affect the intracellular K+ content by interacting with a cation-chloride cotransporter (OsCCC1), thereby affecting the expression of downstream tillering-related genes. The Tn1a+272 bp allele, associated with high tillering, might have been preferably preserved in rice varieties in potassium-poor regions during domestication. The discovery of Tn1a is of great significance for further elucidating the genetic basis of tillering characteristics in rice and provides a new and favourable allele for promoting the geographic adaptation of rice to soil potassium.
ABSTRACT
In this paper, we introduce a novel technique that utilizes randomly rotated elements (RREs) for the cross-polarization and axial ratio (AR) control of a circularly polarized programmable metasurface (CPPMS). We evaluate the CPPMS performance by comparing RREs layout with uniform elements (UEs) layout, and analyze far-field radiation parameters for 50 groups of CPPMS with different RREs layouts. Simulation results demonstrate consistent and improved performance across various RREs layouts, showcasing reduced cross-polarization and enhanced AR beamwidth. To validate these findings, we design a 1-bit CPPMS in Ku-band comprising 20 × 20 elements with the optimal RREs layout, and conduct measurements in an anechoic chamber. The CPPMS prototype achieves high gain (22.34 dBi), low cross-polarization (-20.5â dB), and a narrow 3â dB AR beamwidth (8.93°). Notably, it offers wide-angle beam scanning capabilities of up to ±60°. The gain bandwidth at -3â dB ranges from 14.54 to 16.65â GHz, with a relative bandwidth of 7.3%, while the 3â dB AR bandwidth extends from 14.24 to 16.07â GHz. Consequently, the proposed 1-bit CPPMS exhibits high-performance two-dimensional AR beam scanning, presenting promising applications in satellite communications.
ABSTRACT
INTRODUCTION: T cells play a critical role in inflammatory diseases. The aim of the present study was to investigate the effects of Majie cataplasm (MJC) on asthma and to propose a possible mechanism involved in this process. METHODS: Airway inflammation, infiltration of inflammatory cells, levels of interleukin (IL)-4, IL-10, IL-17, and interferon (IFN)-γ, levels of Th2, Treg, Th17, and Th1 cells, and the expressions of IL-4, IL-10, IL-17, IFN-γ, GATA binding protein 3 (GATA-3), Foxp3, RAR-related orphan receptor gamma (RORγt), and T-bet were detected. RESULT: MJC treatment reduced lung airway resistance and inflammatory infiltration in lung tissues. MJC treatment also reduced the numbers of eosinophils and neutrophils in the blood and bronchoalveolar lavage fluid (BALF). The levels of IL-4 and IL-17 in the blood, BALF, and lungs were suppressed by MJC, and IFN-γ and IL-10 were increased. Furthermore, MJC suppressed the percentage of Th2 and Th17 and increased the percentage of Th1 and Treg in spleen cells. In addition, MJC can inhibit asthma by increasing expressions of IFN-γ, IL-10, T-bet, and Foxp3, as well as decreasing expressions of IL-4, IL-17, GATA-3, and RORγt. CONCLUSION: MJC may improve airway hyperresponsiveness and inflammation by regulating Th1/Th2/Treg/Th17 balance in ovalbumin-induced rats. And MJC may be a new source of anti-asthma drugs.
Subject(s)
Asthma , Cytokines , Animals , Asthma/immunology , Asthma/metabolism , Asthma/drug therapy , Rats , Cytokines/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Th2 Cells/immunology , Male , Th17 Cells/immunology , Th17 Cells/metabolism , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/cytology , Lung/immunology , Lung/pathology , Th1 Cells/immunology , Rats, Sprague-Dawley , Disease Models, Animal , Ovalbumin/immunology , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Forkhead Transcription Factors/metabolism , T-Box Domain Proteins/metabolismABSTRACT
OBJECTIVE: Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology. METHODS: U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF). RESULTS: OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1ß and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results. CONCLUSIONS: KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA.
Subject(s)
Cell Membrane , Chondrocytes , Osteoarthritis , Receptors, Opioid, kappa , STAT3 Transcription Factor , Animals , Male , Mice , 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology , Cell Membrane/metabolism , Cell Membrane/drug effects , Chondrocytes/metabolism , Chondrocytes/pathology , Chondrocytes/drug effects , Mice, Inbred C57BL , Osteoarthritis/pathology , Osteoarthritis/metabolism , Receptors, Opioid, kappa/metabolism , Receptors, Opioid, kappa/genetics , Signal Transduction/drug effects , STAT3 Transcription Factor/metabolismABSTRACT
AIM: To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) in people with suboptimally controlled type 2 diabetes (T2D) in China. METHODS: INITIATION (NCT05002933) was a prospective, interventional, multicentre, single-arm, phase IV study conducted in China. Individuals with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin (insulin experienced) were included. The primary endpoint was the change in HbA1c from baseline to week 24. Safety assessments included hypoglycaemia and adverse events (AEs). RESULTS: In total, 568 participants were enrolled and 562 initiated Gla-300 treatment (189 in the insulin-naïve subgroup; 373 in the insulin-experienced subgroup). At week 24, the mean ± standard error (SE) change in HbA1c from baseline was -0.91% ± 0.05% (-9.9 ± 0.5 mmol/mol; P < .0001). Significant HbA1c reductions were also observed in the insulin-naïve (mean ± SE change: -1.38% ± 0.09% [-15.1 ± 1.0 mmol/mol]) and insulin-experienced (-0.68% ± 0.05% [-7.4 ± 0.5 mmol/mol]) subgroups (both P < .0001). During the 24-week treatment period, the incidence of confirmed hypoglycaemia (plasma glucose ≤ 3.9 mmol/L) was 39.7% for all hypoglycaemia and 13.3% for nocturnal hypoglycaemia; the incidence of severe hypoglycaemia was low (0.5%). Overall, treatment-emergent AEs (TEAEs) were reported in 126 participants (22.4%), with no serious treatment-related TEAEs. CONCLUSIONS: Gla-300 was effective in improving glycaemic control and had a relatively low risk of hypoglycaemia in people with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin in China.
ABSTRACT
The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC.
Subject(s)
Antineoplastic Agents , Cell Proliferation , Drug Discovery , Protein-Tyrosine Kinases , Proto-Oncogene Proteins , Humans , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Proliferation/drug effects , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Animals , Molecular Structure , Mice , Structure-Activity Relationship , Apoptosis/drug effects , Drug Screening Assays, Antitumor , Dose-Response Relationship, Drug , Proteolysis/drug effects , Molecular Docking Simulation , Cell Line, Tumor , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Mice, NudeABSTRACT
Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by synovitis and cartilage destruction. The active compound, icariin (ICA), derived from the herb Epimedium, exhibits potent anti-inflammatory properties. However, its clinical utility is limited by its water insolubility, poor permeability, and low bioavailability. To address these challenges, we developed a multifunctional drug delivery system-adipose-derived stem cells-exosomes (ADSCs-EXO)-ICA to target active macrophages in synovial tissue and modulate macrophage polarization from M1 to M2. High-performance liquid chromatography analysis confirmed a 92.4 ± 0.008% loading efficiency for ADSCs-EXO-ICA. In vitro studies utilizing cellular immunofluorescence (IF) and flow cytometry demonstrated significant inhibition of M1 macrophage proliferation by ADSCs-EXO-ICA. Enzyme-linked immunosorbent assay, cellular transcriptomics, and real-time quantitative PCR indicated that ADSCs-EXO-ICA promotes an M1-to-M2 phenotypic transition by reducing glycolysis through the inhibition of the ERK/HIF-1α/GLUT1 pathway. In vivo, ADSCs-EXO-ICA effectively accumulated in the joints. Pharmacodynamic assessments revealed that ADSCs-EXO-ICA decreased cytokine levels and mitigated arthritis symptoms in collagen-induced arthritis (CIA) rats. Histological analysis and micro computed tomography confirmed that ADSCs-EXO-ICA markedly ameliorated synovitis and preserved cartilage. Further in vivo studies indicated that ADSCs-EXO-ICA suppresses arthritis by promoting an M1-to-M2 switch and suppressing glycolysis. Western blotting supported the therapeutic efficacy of ADSCs-EXO-ICA in RA, confirming its role in modulating macrophage function through energy metabolism regulation. Thus, this study not only introduces a drug delivery system that significantly enhances the anti-RA efficacy of ADSCs-EXO-ICA but also elucidates its mechanism of action in macrophage function inhibition.
Subject(s)
Adipose Tissue , Arthritis, Rheumatoid , Exosomes , Flavonoids , Macrophages , Animals , Flavonoids/pharmacology , Flavonoids/chemistry , Exosomes/metabolism , Rats , Macrophages/drug effects , Macrophages/metabolism , Adipose Tissue/cytology , Male , Arthritis, Experimental/drug therapy , Rats, Sprague-Dawley , Drug Delivery Systems/methods , Stem Cells/metabolism , Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effectsABSTRACT
PURPOSE: The relationship between varicella zoster virus (VZV) infection and the risk of dementia has not been previously studied specifically. Therefore, this study sought to determine the relationship between studying VZV infection and dementia occurring in the general population by conducting an extensive meta-analysis of published cases. METHOD: A systematic literature search was conducted in seven online databases by October 31, 2022. Heterogeneity was tested by the I2 index. Pooled HR and 95% CI were used to estimate the effect of VZV infection on dementia. Sensitivity analyses and publication bias were also performed. RESULT: Nine studies involving 3,326,673 subjects were included. VZV infection was associated with an increased risk of dementia (HR = 1.11, 95% CI: 1.02-1.21). The risk of dementia was reduced in those who received antiviral therapy compared to those who did not (HR = 0.84, 95% CI: 0.71-0.99). In addition, VZV infection was found to be associated with an increased risk of developing dementia in the pooled results of the moderate quality study (HR = 1.81,95% CI: 1.27-2.59), and this association persisted when subgroup analyses were performed based on region (Asia: HR = 1.18,95% CI: 1.04-1.33). CONCLUSIONS: Our results suggest that VZV infection might increase the risk of developing dementia, but there is no clear mechanism about the true relationship, and since there is no effective treatment for dementia, and our results suggest that some populations can benefit from antiviral therapy, it is at least arguable that patients who develop VZV infection should be treated with appropriate antiviral medications.
Subject(s)
Dementia , Herpes Zoster , Humans , Antiviral Agents/therapeutic use , Dementia/epidemiology , Dementia/etiology , Dementia/drug therapy , Herpes Zoster/complications , Herpes Zoster/epidemiology , Herpesvirus 3, HumanABSTRACT
Objective: The primary aim of this study is to explore the effects of enteral nutrition support with ultrasound-guided three-lumen gastrojejunal tube insertion on nutritional status in patients with severe neurological diseases. Additionally, we aim to assess the impact of this intervention on the success rate of catheterization and the aspiration rate, to comprehensively evaluate its benefits and optimize patient care. Methods: Between March 2022 and March 2023, 60 patients were recruited and randomly divided into ultrasound-guided and control groups of 30 patients each using the Simple Randomisation method. In the control group, a triple-lumen feeding tube was blindly inserted at the bedside for enteral nutritional therapy, and in the ultrasound-guided group, ultrasound-guided identification of gastric structures for placement of a triple-lumen feeding tube for enteral nutritional support, and both treatments were continued for 2 weeks. The success rate of catheterization, nutritional status, aspiration rate, patient satisfaction, and incidence of complications were compared between the two groups before and after treatment. Results: The difference in the success rate of catheterization between the ultrasound guidance group and control group was not statistically significant (93.33% vs 96.67%, P>0.05). After treatment, TP (70.84±3.54 vs 67.15±4.23), ALB (41.23±3.65 vs 38.22±3.47), and Hb (11.54±0.62 vs 9.35±0.28) levels in the ultrasound guidance group were higher than in the control group (P < .05). The difference in aspiration rate between the ultrasound guidance group and control group was not statistically significant [0.00% (0/30) vs 3.33% (1/30), P > .05]. The patient satisfaction in the ultrasound guidance group was higher than that in the control group (P < .05). The difference in the incidence of complications (stomachache, headache, nausea, and vomiting) between the ultrasound guidance group and control group was not statistically significant (6.67% vs 20.00%, P > .05). Conclusion: Enteral nutrition support with ultrasound-guided three-lumen gastrojejunal tube insertion can improve the success rate of catheterization and nutritional status, reduce aspiration rate, and improve satisfaction in patients with severe neurological diseases. In the future, we need to further investigate the incorporation of ultrasound guidance into standard care protocols for patients with severe neurological disorders requiring enteral nutrition. The indications for ultrasound guidance in nursing should also be expanded. In conclusion, ultrasound-guided insertion should be considered the technique of choice for improving nutritional status in the population of patients with severe neurological disease.
ABSTRACT
Increasing studies have investigated inflammatory burden of adults with childhood adversity, but less is known about how childhood maltreatment affects the inflammation level of adolescents. Baseline data of a school cohort of physical and mental health status and life experience survey on primary and secondary school students in Anhui Province, China was used. Childhood maltreatment of children and adolescents was assessed by Chinese version of Childhood Trauma Questionnaire-Short Form (CTQ-SF). Urine samples were collected to assess levels of soluble urokinase Plasminogen Activator Receptor (suPAR), C-reactive protein (CRP) and cytokines interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA). Logistic regression was conducted to examine the association between childhood maltreatment exposure and risk of high inflammation burden. A total of 844 students were included with mean age 11.41 ± 1.57 years old. Adolescents with emotional abuse were significantly more likely to have high level of IL-6 (OR = 3.59, 95% CI 1.16-11.14). In addition, adolescents with emotional abuse were more likely to show high IL-6 and high suPAR combination (OR = 33.41, 95% CI 1.69-659.22), and high IL-6 and low CRP combination (OR = 4.34, 95% CI 1.29-14.55). Subgroup analyses showed that emotional abuse was associated with high IL-6 burden among boys or adolescents with depression. Childhood emotional abuse was positively associated with higher burden of IL-6. Early detection and prevention of emotional abuse for children and adolescents, especially for boys or adolescents with depression status, may be helpful for preventing elevated inflammatory burden and related health problems.
Subject(s)
Child Abuse , Interleukin-6 , Psychological Tests , Self Report , Male , Adult , Child , Humans , Adolescent , Child Abuse/psychology , Receptors, Urokinase Plasminogen Activator , Surveys and Questionnaires , Schools , InflammationABSTRACT
The impact of adverse childhood experiences (ACEs) on adult health has been extensively examined, but the association between ACEs and sleep, emotion, behavior and academic outcomes of children and adolescents is not well known. A total of 6363 primary and middle school students were included to examine the effect of ACEs on sleep quality, emotional and behavioral problems and academic achievement and further explore the mediation role of sleep quality and emotional and behavioral problems. Children and adolescents with ACE exposure had 1.37 times risk of poor sleep quality (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI]: 1.21-1.55), 1.91 times risk of emotional and behavioral problems (adjusted OR = 1.91, 95%CI: 1.69-2.15) and 1.21 times risk of self-reported lower academic achievement (adjusted OR = 1.21, 95%CI: 1.08-1.36). Most types of ACEs were significantly associated with poor sleep quality, emotional and behavioral problems and lower academic achievement. There were dose-response relationships between cumulative ACE exposure and risk of poor sleep quality, emotional and behavioral problems, and lower academic achievement. Sleep quality and emotional and behavioral performance mediated 45.9% of the effect of ACEs exposure on math scores and 15.2% of the effect of ACEs exposure on English scores. Early detection and prevention of ACEs among children and adolescents are urgent and essential, and targeted interventions for sleep and emotional and behavioral performance as well as early educational interventions are recommended for children with ACEs exposure.
Subject(s)
Academic Success , Adverse Childhood Experiences , Problem Behavior , Child , Adult , Humans , Adolescent , Sleep Quality , EmotionsABSTRACT
This study aimed to examine the association between nighttime sleep duration and emotional and behavioral problems (EBPs) among rural preschool children. This longitudinal study including 1595 preschool children aged 3-6 years from 26 kindergartens in four counties was conducted in Anhui Province rural areas. Cross-lagged panel models and multivariable logistic regressions were performed to examine the bidirectional association between nighttime sleep duration and EBPs and further explore the predictive effect of nighttime sleep duration on EBPs. Compared to baseline, preschool children at follow-up had significantly more nighttime sleep duration (10.01 ± 0.68 vs. 10.15 ± 0.69) and lower EBPs (total difficulties: 15.8% vs. 11.2%; prosocial behavior problems: 12.4% vs. 7.0%). Results of cross-lagged panel models indicated that nighttime sleep duration was a predictor for EBPs, but not vice versa. Results of logistic regression analysis showed that each 1-h increase in nighttime sleep duration at T1 was associated with a 0.77-fold reduction in the risk of total difficulties at T2 (the most adjusted OR = 0.774, 95% CI 0.607-0.988, P = 0.040), but not with the prosocial behavior. Interestingly, the predictive effect of nighttime sleep duration at T1 on EBPs at T2 was only found in girls, children aged 3 years and children with lower maternal education. The decreased nighttime sleep duration may predict future EBPs, especially in girls, younger preschool children and children with lower maternal education. Extending sleep duration may improve EBPs in preschool children.
Subject(s)
Problem Behavior , Female , Humans , Child, Preschool , Problem Behavior/psychology , Longitudinal Studies , Sleep Duration , Surveys and Questionnaires , Emotions , SleepABSTRACT
Broad-spectrum antibiotics are frequently used to treat bacteria-induced infections, but the overuse of antibiotics may induce the gut microbiota dysbiosis and disrupt gastrointestinal tract function. Probiotics can be applied to restore disturbed gut microbiota and repair abnormal intestinal metabolism. In the present study, two strains of Enterococcus faecium (named DC-K7 and DC-K9) were isolated and characterized from the fecal samples of infant dogs. The genomic features of E. faecium DC-K7 and DC-K9 were analyzed, the carbohydrate-active enzyme (CAZyme)-encoding genes were predicted, and their abilities to produce short-chain fatty acids (SCFAs) were investigated. The bacteriocin-encoding genes in the genome sequences of E. faecium DC-K7 and DC-K9 were analyzed, and the gene cluster of Enterolysin-A, which encoded a 401-amino-acid peptide, was predicted. Moreover, the modulating effects of E. faecium DC-K7 and DC-K9 on the gut microbiota dysbiosis induced by antibiotics were analyzed. The current results demonstrated that oral administrations of E. faecium DC-K7 and DC-K9 could enhance the relative abundances of beneficial microbes and decrease the relative abundances of harmful microbes. Therefore, the isolated E. faecium DC-K7 and DC-K9 were proven to be able to alter the gut microbiota dysbiosis induced by antibiotic treatment.
Subject(s)
Anti-Bacterial Agents , Dysbiosis , Enterococcus faecium , Gastrointestinal Microbiome , Animals , Dysbiosis/microbiology , Gastrointestinal Microbiome/drug effects , Anti-Bacterial Agents/pharmacology , Mice , Feces/microbiology , Fatty Acids, Volatile/metabolism , Probiotics/pharmacology , Dogs , Bacteriocins/pharmacologyABSTRACT
Wheat culms, comprising four to six internodes, are critically involved in determining plant height and lodging resistance, essential factors for field performance and regional adaptability. This study revealed the regulatory function of miR319 in common wheat plant height. Repression of tae-miR319 through short tandem target mimics (STTM) caused an increased plant height, while overexpression (OE) of tae-miR319 had the opposite effect. Overexpressing a miR319-resistant target gene TaPCF8 (rTaPCF8), increased plant height. TaPCF8 acted as a transcription repressor of downstream genes TaIAAs, which interact physically with TaSPL14. The significant differences of indole-3-acetic acid (IAA) contents indicate the involvement of auxin pathway in miR319-mediated plant height regulation. Finally, we identified two TaPCF8 haplotypes in global wheat collections. TaPCF8-5A-Hap2, as per association and evolution examinations, was subjected to strong substantial selection throughout wheat breeding. This haplotype, associated with shorter plant height, aligns with global breeding requirements. Consequently, in high-yield wheat breeding, we proposed a potential molecular marker for marker-assisted selection (MAS). Our findings offer fresh perspectives into the molecular mechanisms that underlie the miR319-TaPCF8 module's regulation of plant height by orchestrating auxin signaling and biosynthesis in wheat.
ABSTRACT
PURPOSE: Physical activity (PA) has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between PA and the risk of developing gastric cancer (GC). The purpose of this study was to evaluate the impact of PA on the incidence and mortality risk of GC through a meta-analysis, as well as investigate potential dose-response relationships. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of PA on the risk of GC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The results showed that PA correlated with lower incidence of GC (RR: 0.83, 95% CI: 0.77-0.90), decreased risk of GC mortality (RR: 0.76, 95% CI: 0.66-0.89). The results of the subgroup analysis showed that PA was associated with reduced incidence of GC across gender, different regions, study designs, different sites of GC and different types of PA. A linear relationship was found for frequency of PA. CONCLUSIONS: This meta-analysis found that PA was associated with a reduced risk of GC incidence and mortality. The correlation between PA and GC occurrence was in a dose-response relationship.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/epidemiology , Incidence , Risk , Exercise , Research DesignABSTRACT
AIM: The current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC). METHODS: Relevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs). RESULTS: Six SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled data showed no significant difference in serious adverse events between patients receiving FMT and those receiving placebo (OR 1.53 [0.74, 3.19]). Evidence quality of the outcomes derived from re-meta-analysis was significantly higher after overcoming the limitations of previous SRs/MAs. CONCLUSION: In conclusion, moderate- to high-quality evidence supported a promising use of FMT to safely induce remission in UC. However, further trials with larger sample size are still required to comprehensively analyze the delivery route, total dosage, frequency, and donor selection in FMT.
Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/therapy , Fecal Microbiota Transplantation/adverse effects , Systematic Reviews as TopicABSTRACT
In this paper, a dual-band metasurface (MS) generating multiple orbital angular momentum (OAM) beams independently in full polarizations is proposed. First, the design principle of controlling full polarizations independently is analyzed. Second, the frequency selective surface is introduced to the meta-atom design that ensures the meta-atom operates at Ku- and Ka-band independently, while, at each band, sixteen optimized meta-atoms realize the high reflection amplitude and enough phase coverage. Next, the optimized dual-band meta-atom controlling full polarizations independently is utilized to design the MS, which could generate eight independent OAM beams including the x-polarized, y-polarized, left hand circularly polarized, and right hand circularly polarized OAM beams at dual-band. Finally, the MS is designed, fabricated, and measured. Both simulated and measured results verify that the proposed MS could generate multiple OAM beams in full polarizations at dual-band, showing the perspective in the OAM-based area, such as the wireless communication, target detection, and security encryption.
ABSTRACT
The incidence of postoperative gastrointestinal dysfunction among neurosurgical patients is as high as 80%. Probiotics help to maintain gastrointestinal barrier defense, provide competitive adherence to mucus and epithelial cells, and regulate gastrointestinal motility. Therefore, the purpose of this study was to investigate whether probiotics enhance gastrointestinal health after craniotomy in patients with brain tumors. This study was a 15-day, prospective, randomized, double-blind, placebo-controlled trial for patients being treated with elective craniotomy for brain tumors. Participants were randomly divided into the probiotics group (4 g probiotics, twice daily) and placebo group. The primary outcome was the time of first stool after surgery. The secondary outcomes included assessments of the gastrointestinal function, changes in gastrointestinal permeability and clinical outcomes. We enrolled a total of 200 participants (probiotics: 100; placebo: 100) and followed the principles of intention-to-treat analysis. The time of first stool and flatus were significantly shorter in the probiotics group compared to the placebo group (P < 0.001, respectively). No significant trends were observed for any other of the secondary outcome variables. Our findings suggest that probiotics can improve the gastrointestinal mobility of patients received craniotomy, and this improvement cannot be explained by changes in gastrointestinal permeability.
Subject(s)
Brain Neoplasms , Gastrointestinal Diseases , Probiotics , Humans , Prospective Studies , Feces , Probiotics/therapeutic use , Brain Neoplasms/surgery , Double-Blind Method , Treatment OutcomeABSTRACT
Hepcidin, as an antimicrobial peptide, is associated with innate immunity and is considered a potential antibiotic substitute. In the present study, the hepcidin gene from the cavefish - Onychostoma macrolepis was identified and analyzed. The recombinant hepcidin protein (rOmhepc) was obtained by prokaryotic expression, evaluating the inhibitory effect of 5 pathogenic bacteria in vitro. Sixty O. macrolepis injected with 100 µL A. hydrophila (1.5 × 108 CFU/mL) were randomly divided into the therapeutic group and infection group, and therapeutic group was injected with 100 µL rOmhepc (100 µg/mL) at 6 and 18 h. The survival rates of O. macrolepis and bacterial load in liver were measured at 24 h. The liver tissues were collected at 0, 6, 12, and 24 h after A. hydrophila injection for investigating expression levels of immune-related, inflammatory factor genes and FPN1 gene. The results demonstrated that the hepcidin CDS contained 279 bp and encoded 93 aa. Hepcidin protein has a hydrophobic surface formed by multiple hydrophobic residues (CCGCCYC), and the theoretical pI was 7.53. Omhepc gene was expressed at varying levels in tested tissues, with the liver showing the highest expression, followed by the spleen. The expression of hepcidin gene following A. hydrophila infection was up-regulated and then down-regulated in liver, and the highest expression level was found at 12 h with a 10.93-fold. The rOmhepc remarkably inhibited the growth of A. hydrophila, Staphylococcus aureus, and Streptococcus agalactiae, with inhibition rates reaching 69.67 %, 42.97 %, and 65.74 % at 100 µg/mL. The mortality rates of O. macrolepis and bacterial load in liver were significantly decreased in the therapeutic group than that of infection group (p < 0.05). After the rOmhepc therapeutic, interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were significantly down-regulated with 14.4-fold and 106.07-fold at 24 h. Furthermore, the expression of immune-related genes (C3, TNF-α, IFN-γ) and Ferroportin gene (FPN1) significantly decreased (p < 0.05). The integrated analyses indicated that the rOmhepc could significantly inhibit the growth of A. hydrophila both in vitro and in vivo, attenuating the over-expression of inflammatory factor, FPN1 and immune-related genes.