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Abstract Chronic kidney disease (CKD) is a global health challenge associated with lifestyle factors such as diet, alcohol, BMI, smoking, sleep, and physical activity. Metabolomics, especially nuclear magnetic resonance(NMR), offers insights into metabolic profiles’ role in diseases, but more research is needed on its connection to CKD and lifestyle factors. Therefore, we utilized the latest metabolomics data from the UK Biobank to explore the relationship between plasma metabolites and lifestyle factors, as well as to investigate the associations between various factors, including lifestyle-related metabolites, and the latent phase of CKD onset. The study enrolled approximately 500,000 participants from the UK Biobank (UKB) between 2006 and 2010, excluding 447,163 individuals with missing data for any metabolite in the NMR metabolomics, any biomarker in the blood chemistry (including eGFR, albumin, or cystatin C), any factor required for constructing the lifestyle score, or a baseline diagnosis of CKD. Lifestyle scores (LS) were calculated based on several factors, including diet, alcohol consumption, smoking, BMI, physical activity, and sleep. Each healthy lifestyle component contributed to the overall score, which ranged from 0 to 6. A total of 249 biological metabolites covering multiple categories were determined by the NMR Metabolomics Platform. Random forest algorithms and LASSO regression were employed to identify lifestyle-related metabolites. Subsequently, accelerated failure time models(AFT) were used to assess the relationship between multiple factors, including traditional CKD-related biomarkers (such as eGFR, cystatin C, and albumin) and lifestyle-related metabolites, with the latent phase of incident CKD. Finally, we performed Kaplan–Meier survival curve analysis on the significant variables identified in the AFT model. Over a mean follow-up period of 13.86 years, 2,279 incident chronic kidney disease (CKD) cases were diagnosed. Among the 249 metabolites analyzed, 15 were identified as lifestyle-related, primarily lipid metabolites. Notably, among these metabolites, each 1 mmol/L increase in triglycerides in large LDL particles accelerated the onset of CKD by 24%. Diabetes, hypertension, and smoking were associated with a 56.6%, 31.5% and 22.3% faster onset of CKD, respectively. Additionally, each unit increase in age, BMI, TDI, and cystatin C was linked to a 3.2%, 1.4%, 1.6% and 32.3% faster onset of CKD. In contrast, higher levels of albumin and eGFR slowed the onset of CKD, reducing the speed of progression by 3.0% and 3.9% per unit increase, respectively. Nuclear magnetic resonance metabolomics offers new insights into renal health, though further validation studies are needed in the future.

Abstract Peritoneal fibrosis has been linked to hypoxia-inducible factor 1-alpha (HIF-1α) as well as O-linked-N-acetylglucosaminylation (O-GlcNAcylation) in peritoneal dialysis (PD). Genistein, recognized for its HIF-1α inhibitory and antifibrotic effects, presents a potential intervention against peritoneal mesothelial-mesenchymal transition (MMT) as well as fibrosis in PD. This study employed human peritoneal mesothelial cells (HPMCs) together with adenine-induced chronic kidney disease (CKD) rats undergoing peritoneal dialysis to explore Genistein’s role in high glucose-induced peritoneal MMT and fibrosis. Our findings reveal that Genistein exerts anti-MMT and anti-fibrotic effects by inhibiting HIF-1α in HPMCs under high glucose conditions. Genistein inhibited O-GlcNAcylation status of HIF-1α through the mTOR/O-GlcNAc transferase (OGT) pathway, promoting its ubiquitination as well as the subsequent proteasomal degradation. In adenine-induced CKD rats undergoing peritoneal dialysis, Genistein suppressed the mTOR/OGT expression and reduced the abundance of O-GlcNAcylation along with HIF-1α in the peritoneum. Additionally, Genistein protected against increased peritoneal thickness, fibrosis, and angiogenesis, while improving peritoneal function. Based on our results, it could be inferred that Genistein might inhibit the abundance of HIF-1α via the mTOR/OGT pathway, thereby ameliorating MMT as well as fibrosis in PD.

Abstract Background Vital pulp therapy (VPT) has recently been reported as an effective approach for preventing and treating carious pulp injury in permanent teeth. Compared with root canal treatment (RCT), which involves complete removal of the pulp tissue, VPT effectively maintains pulp vitality and retains the physiological functions of the pulp. In the research pool, large-scale randomized controlled trials evaluating the treatment outcome of VPT using calcium silicate cements and RCT in cariously exposed permanent teeth are lacking. Here, we present a monocentric clinical protocol to compare the effects of VPT using iRoot BP Plus (Innovative Bioceramix, Vancouver, BC, Canada) as a pulp-capping material with RCT. Methods The proposed trial is an open-label, single-centre, randomized, controlled, noninferiority trial. In total, 462 patients will be included in this trial according to the following criteria: adult patients (18–50 years old), pulp exposure during the treatment of deep caries in mature permanent teeth, a diagnosis of reversible or partially irreversible pulpitis without apical translucency on X-ray, without periodontitis or systemic disease. Patients with signed informed consent forms will be enrolled and randomly divided into two groups (VPT and RCT) with a balanced treatment allocation (1:1). Clinical evaluations will be conducted at baseline and at 3, 6, 12, and 24 months after treatment, with the potential for extension. The primary outcome measure will be the duration of success. The secondary outcomes will include the success rate at the 1-year follow-up and any adverse reactions. The Kaplan‒Meier method and log-rank test will be used to compare the duration of success of both treatments. For other outcomes, the χ 2 test or Fisher’s exact test will be used for categorical variables, and the t test or Mann‒Whitney U test will be used for continuous variables to assess the differences between groups. Discussion The results of this trial will provide a clinical reference for selecting treatments for carious pulp injuries in permanent teeth. Trial registration ClinicalTrials.gov ChiCTR2100051369. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ). Registered on 21 September 2021

Abstract Coix lacryma-jobi L. is a traditional medicinal plant in east Asia and is an important crop in Guizhou province, southwest China, where there are elevated levels of soil mercury and arsenic (As). Exposure to multiple potentially toxic elements (PTEs) may affect plant accumulation of metal(loid)s and food safety in regions with high geological metal concentrations. Field experiments were conducted to study the effects of PTEs on metal(loid) accumulation and physiological response of C. lacryma in different plant parts at three pollution levels. Total root length, number of root tips, number of branches, and number of root crosses increased with increasing pollution level, with increases in highly polluted areas of 44.2, 57.0, 79.6, and 97.2%, respectively, compared to lightly polluted areas. Under multi-element stress the activity of C. lacryma antioxidant oxidase showed an increase at low and medium PTE concentrations and inhibition at high concentrations. The As contents were all below the maximum limit of cereal food contaminants in China (GB 2762-2022, As

The Han River, a key water source for China’s South-to-North Water Diversion Project, faces ecological challenges due to urbanization-driven heavy metal pollution and eutrophication. This study analyzed microbial communities in sediment samples from 15 sites using 16S rDNA sequencing. Our findings revealed a significant decrease in α-diversity with increasing copper (Cu) concentration, with the downstream region (group L) exhibiting higher diversity compared to the upstream region (group U). Group U was dominated by Alphaproteobacteria, while Clostridia prevailed in groups M and L. Analysis of β-nearest taxon index (βNTI) indicated that stochastic processes primarily shaped community assembly. Redundancy analysis (RDA) identified Cu, Fe, and Cr as key environmental factors influencing bacterial community composition in group U, while COD, Chl_a, pH, TN, and TP affected groups M and L. The study emphasizes the importance of addressing heavy metal pollution in eutrophic waters to protect microbial community diversity.

BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, mostly resulting from impaired insulin production and diminished glucose metabolism regulation. Qiwei Baizhu San (QWBZS) is a classic formula used in traditional Chinese medicine for the treatment of T2DM. A comprehensive analysis of the efficacy and safety of QWBZS in the treatment of T2DM is essential.MethodsThis study’s protocol was registered with PROSPERO (CRD42024576129). As of August 2024, we searched eight databases to screen and include randomized controlled trials of QWBZS for T2DM. Heterogeneity sources were examined via subgroup analyses, the robustness of the results was determined by sensitivity analyses, publication bias was evaluated using funnel plots and Egger’s test, evidence quality was appraised with GRADEpro, and possible mechanisms of QWBZS for T2DM were categorized and summarized.ResultsThis analysis encompassed 14 qualifying trials with a total of 1,169 subjects. The analytical results suggested that QWBZS, when combined with conventional treatment, was more effective than conventional treatment alone in improving FBG, 2hPG, HbA1c, HOMA-IR, TC, TG, LDL-C, and HDL-C. When QWBZS was used alone, it was more effective than conventional therapy in FBG, 2hPG, and HbA1c. And QWBZS could improve the overall effectiveness of clinical treatment in T2DM patients. The impact of QWBZS therapy alone on HOMA-IR and lipid metabolism remained unclear due to the limited number of trials included. Analysis of adverse events suggested that QWBZS was relatively safe.ConclusionThis study suggested that QWBZS, when combined with conventional treatment, was more effective in improving glucose metabolism, insulin resistance, and lipid metabolism compared to conventional treatment alone in individuals with T2DM. QWBZS alone also contributed to the regulation of blood glucose levels. Meanwhile, QWBZS could improve the overall effective rate of clinical treatment with a relatively high safety profile. Nevertheless, owing to the inferior quality and significant heterogeneity of the existing evidence, additional high-quality studies are requisite to furnish more dependable evidence for the future clinical application of QWBZS.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=576129, identifier [CRD42024576129].

Summary: Inflammatory cells infiltration in the cerebrospinal fluid is a hallmark of severe enterovirus 71 (EV71) infection, but which type of immune cells are critical for severe EV71 infection remains unclear. Here, we observe that both neutrophils and macrophages are increased in the brains of patients and mice with severe EV71 infection, and the depletion of neutrophils but not macrophages results in a marked enhancement of survival of EV71-infected mice. Furthermore, CCR1/3 may play an important role in CCL3 facilitating the accumulation of neutrophils in the brains of patients. Inhibition of CCL3 by anti-CCL3 antibodies or selected miRNAs significantly reduces the neutrophils infiltration in brains and the mortality of EV71-infected mice. Collectively, CCL3-mediated neutrophils recruitment into the brain contributes to the severe immunopathology of EV71 infection, which provides a potential diagnostic and therapeutic target for EV71 infection.

ObjectiveRetroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibroinflammatory tissue that surrounds the abdominal aorta and the iliac arteries and often entraps the ureters. Hydronephrosis is a common complication of RPF, however, its clinical features and outcomes have not been well elucidated.MethodsA total of 115 RPF-related hydronephrosis patients have been recruited from 9 clinical centers in China since March 2010. They were followed up until death or September 2021, whichever came first.ResultsThe mean age at diagnosis was 58.83 ± 12.13 years, and 80 patients (69.57%) were men. The median disease duration was 3.00 (1.00, 9.00) months. Renal impairment was observed in 88.35% of the patients, and 49.57% showed bilateral ureteral involvement. Elevated ESR and CRP were presented in 80.28 and 62.02% of the patients, respectively. Overall, 28.21% (11/39) of the patients had increased IgG4 levels, and 41.38% (12/29) showed positive pathological IgG4 staining (IgG4+/IgG+ ≥ 40% or IgG4+ ≥ 10/HPF). Among them, three patients were diagnosed as IgG4RD. After 60.43 ± 34.53 months of follow-up, 36 patients had poor prognosis, which was associated with severe kidney impairment, bilateral hydronephrosis and inflammation status (elevated ESR and IgG) at diagnosis by case–control study. eGFR and creatinine were independent risk factors after adjusting for all other significant associations (p = 0.002 and p = 0.067, respectively). Glucocorticoid-based therapy could reduce the time of stenting, decrease the need for long-term ureteral stenting/percutaneous nephrostomy (PNS)/ureterolysis, increase the rate of mass shrinkage, and reduce the new requirement of hemodialysis compared to surgery-only strategy for RPF-related hydronephrosis patients in need of renal drainage, but did not reduce new-onset renal atrophy.ConclusionSeverity of kidney dysfunction and inflammation status were related to the poor prognosis of hydronephrosis induced by RPF. More efficient interventions and strategies are needed to further improve outcomes.

Health concerns have arisen worldwide as a result of contaminated food and water. This study was aimed to determine the levels of selected heavy metals i.e. cadmium (Cd), chromium (Cr), copper (Cu) manganese (Mn), and nickel (Ni) in various sources such as drinking water, vegetables, and soil in districts Ghizer and Gilgit, Pakistan. Human health risks were assessed using deterministic indices, a probabilistic approach, and multivariate analysis. The determinations were carried out by spectrophotometrically (AAS-700, Perkin Elmer, USA) following the standard procedures for heavy metal levels. The mean concentration was recorded as Cd 0.036 mg/L, Cr 0.076 mg/L, and Ni 0.394 mg/L, respectively. It revealed an exceeded level for Cd (0.03 mg/L) and Cr (0.07 mg/L) against the safe limits in drinking water of Gilgit and Ghizer. The highest hazard quotient (HQ) was recorded as Cd 3000, Cr 3863.33, Cu 21.7, Mn 45.71, and Ni 22.35 for children regarding the consumption of vegetables from district Ghizer. Whereas higher HQ values were recorded for adults regarding consumption of vegetables from district Gilgit. A hazard index (HI) indicates significant non-carcinogenic health risks (HI > 1) in Ghizer and Gilgit drinking water and vegetables. Gilgit soil HI values exceeded more than one due to dermal contact, while HI > 1 due to oral and dermal exposure in Ghizer. Furthermore, drinking water samples and vegetables from both districts showed cancer risk (CR) > 1 × 10–4. The cumulative lifetime cancer risk (CR) was observed as 88.61 and 65.61 for adults whereas 2. 98 and 0.38 for children pertaining to vegetable consumption from Ghizer and Gilgit. It was found that the lifetime cancer risk (LCR) for Ghizer was higher than that for Gilgit, based on soil dermal and oral contact. Monte Carlo Simulation revealed adverse health risks in children as compared to adults. As a result of exposure to toxic metals, drinking water and vegetable consumption have higher cancer-causing risks. Therefore, we recommend that both districts implement strict monitoring regulations for drinking water and vegetables.

Compound flash drought and heatwave (FDHW) events have garnered increasing amounts of attention due to their substantial impacts on agriculture, water resources, and public health. However, studies on their intensity and classification in China are limited. In this study, we classified FDHW events in China from 1980 to 2022 using a classification framework designed to address regional patterns and explore their characteristics further. The results showed that FDHW events in northern China mostly occurred in early to mid-summer, whereas in southern China, excluding the Southwest River Basin, they occurred predominantly in mid to late summer. Furthermore, the spatial coverage of FDHW events across China significantly expanded. From 1980 to 2022, FDHW events in China evolved toward higher intensities and longer durations. This trend was especially notable in the Jiang-Huai River Basin, the main grain-producing region and a densely populated area of China. From the perspective of land‒atmosphere coupling, the amplifying effect of flash droughts and high temperatures increased with their intensity. When high temperatures reached the extreme level, the amplification effect on flash droughts was evident: 35.76% from the water deficit perspective and 38.82% from the soil moisture perspective. During extreme flash droughts, the amplification effect on high temperatures intensified: 41.51% from the water deficit perspective and 45.06% from the soil moisture perspective. The Southwest River Basin became a hotspot for the interaction between flash droughts and high temperatures. This study has implications for developing science-based policies to tackle risks in the water, energy and food sectors in China.

Background Podocyte injury plays an important role in the occurrence and progression of diabetic kidney disease (DKD), which leads to albuminuria. Cytoskeletal remodeling is an early manifestation of podocyte injury in DKD. However, the underlying mechanism of cytoskeletal remodeling has not been clarified. Histone deacetylase sirtuin6 (Sirt6) has been found to play a key role in DKD progression, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) pathway directly regulates the cytoskeletal structure of podocytes. Whereas, the relationship between Sirt6, the PI3K/AKT pathway and DKD progression remains unclear.Methods Renal injury of db/db mice was observed by PAS staining and transmission electron microscope. Expression of Sirt6 in the glomeruli of db/db mice was detected by immunofluorescence. UBCS039, a Sirt6 activator, was used to explore the renal effects of Sirt6 activation on diabetic mouse kidneys. We also downregulating Sirt6 expression in podocytes using the Sirt6 inhibitor, OSS_128167, and induced upregulation of Sirt6 using a recombinant plasmid, after which the effects of Sirt6 on high glucose (HG)-induced podocyte damage were assessed in vitro. Podocyte cytoskeletal structures were observed by phalloidin staining. The podocyte apoptotic rate was assessed by flow cytometry, and PI3K/AKT signaling activation was measured by Western blotting.Results Db/db mice exhibited renal damage including elevated urine albumin-to-creatinine ratio (ACR), increased mesangial matrix, fused podocyte foot processes, and thickened glomerular basement membrane. The expression of Sirt6 and PI3K/AKT pathway components was decreased in db/db mice. UBCS039 increased the expressions of Sirt6 and PI3K/AKT pathway components and ameliorated renal damage in db/db mice. We also observed consistent Sirt6 expression was in HG-induced podocytes in vitro. Activation of the PI3K/AKT pathway via a Sirt6 recombinant plasmid ameliorated podocyte cytoskeletal remodeling and apoptosis in HG-treated immortalized human podocytes in vitro, whereas Sirt6 inhibition by OSS_128167 accelerated HG-induced podocyte damage in vitro.Conclusions Sirt6 protects podocytes against HG-induced cytoskeletal remodeling and apoptosis through activation of the PI3K/AKT signaling pathway. These findings provide evidence supporting the potential efficacy of Sirt6 activation as a promising therapeutic strategy for addressing podocyte injury in DKD.

Global concerns over harmful cyanobacterial blooms brought on by eutrophication are now widespread. Aquatic ecological restoration techniques that use algicidal bacteria to control toxic algae show promise. A Bacillus subtilis S4 (S4) strain with strong Microcystis aeruginosa algicidal activity and the capacity to degrade microcystins (MCs) were successfully isolated and evaluated in this study. The dynamics of internal and extracellular MC concentration as well as the physiological response and morphological properties of M. aeruginosa were investigated in the M. aeruginosa/bacteria co-culture system. The findings demonstrated that when S4 density grew from 1 × 106 cells/ml to 1 × 108 cells/ml, the release of M. aeruginosa lysis and MCs was boosted; however, MCs dropped by approximately 90% within 18 h, regardless of bacterial density. Comparing the bacterial cell incubation system to the control and bacterial cell-free filtrate systems, the assessment of extracellular and intracellular MCs revealed a 95% reduction in MCs. The findings showed that 89% of MCs were decreased by bacterial cells, while 98% of M. aeruginosa cells were algaecided by bacterial metabolites. Sustainable eradication of M. aeruginosa and MCs has been accomplished by the combined efforts of the S4 strain and its metabolites. By secreting algicidal chemicals that are resistant to proteases, acid, base, and heat, the S4 strain indirectly acts as an algaecide. The S4 strain possesses a strong ability to break down MCs and a very effective and stable algaecide function, indicating that it can potentially treat eutrophic water with hazardous algae.

ObjectiveThe aim of this study was to assess the predictive capabilities of a radiomics signature obtained from arterial spin labeling (ASL) imaging in forecasting and detecting stages of kidney damage in patients with diabetes mellitus (DM), as well as to analyze the correlation between texture feature parameters and biological clinical indicators. Additionally, this study seeks to identify the imaging risk factors associated with early renal injury in diabetic patients, with the ultimate goal of offering novel insights for predicting and diagnosing early renal injury and its progression in patients with DM.Materials and methodsIn total, 42 healthy volunteers (Group A); 68 individuals with diabetes (Group B) who exhibited microalbuminuria, defined by a urinary albumin-to-creatinine ratio (ACR)< 30 mg/g and an estimated glomerular filtration rate (eGFR) within the range of 60–120 mL/min/1.73m²; and 53 patients with diabetic nephropathy (Group C) were included in the study. ASL using magnetic resonance imaging (MRI) at 3.0T was conducted. The radiologist manually delineated regions of interest (ROIs) on the ASL maps of both the right and left kidney cortex. Texture features from the ROIs were extracted utilizing MaZda software. Feature selection was performed utilizing a range of methods, such as the Fisher coefficient, mutual information (MI), probability of classification error, and average correlation coefficient (POE + ACC). A radiomics model was developed to detect early diabetic renal injury, extract imaging risk factors associated with early diabetic renal injury, and examine the relationship between significant texture feature parameters and biological clinical indicators. Patients with DM and kidney injury were followed prospectively. The study utilized seven machine learning algorithms to develop a detective radiomics model and a comprehensive predictive model for assessing the progression of kidney damage in patients with DM. The diagnostic efficacy of the models in detecting variations in diabetic kidney damage over time was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Empower (R) was used to establish a correlation between clinical biological indicators and texture feature metrics. Statistical analysis was conducted using R, Python, MedCalc 15.8, and GraphPad Prism 8.ResultsA total of 367 texture features were extracted from the ROIs in the kidneys and refined based on selection criteria using MaZda software across groups A, B, and C. The renal blood flow (RBF) values of the renal cortex in groups A, B, and C exhibited a decreasing trend, with values of 256.458 ± 54.256 mL/100g/min, 213.846 ± 52.109 mL/100g/min, and 170.204 ± 34.992 mL/100g/min, respectively. There was a positive correlation between kidney RBF and eGFR (r = 0.439, P

Abstract The current research focuses on the effects of nutritional supplementation and exercise on dialysis patients, but whether physical activity (PA) can reduce the risk of adverse outcomes for patients with different nutritional status is not clear. The maintenance hemodialysis (MHD) patients were recruited from April 2021 to April 2022. The information of PA was obtained from the international physical activity questionnaire (IPAQ). The outcomes were cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death. We used COX proportional risk model to estimate the association between PA and the outcomes of MHD patients. Patients are classified into two groups based on geriatric nutritional risk index (GNRI) and classified by age, and we used COX proportional risk model to estimate the association of PA and outcomes in subgroups. The isotemporal substitution model (ISM) was used to estimate the effects of replacing light physical activity (LPA) with moderate physical activity (MPA) or vigorous physical activity (VPA) on risk of cardiovascular events, tumors, and all-cause death in different subgroups. The effects of PA on ankle-brachial index (ABI) and body fat content were analyzed in different IPAQ groups. A total of 241 maintenance hemodialysis patients were included, 105 peoples developed cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death (43.6%). The median follow-up time was 12 months. MPA reduced the risk of outcome in MHD patients or high GNRI patients (40% vs 39%).In MHD patients who was under 65 years with high GNRI, MPA reduced cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death by 55%.PA reduced the risk of cardiovascular event by 65%, but did not reduce the risk of tumor or all-cause death. Replacing LPA with VPA did not improve clinical outcomes. It actually increases the risk of heart failure 0.4%. MPA reduced the risk of cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor, all-cause death in MHD patients under 65 years, while VPA had no health benefit. Trial registration: ChiCTR210050998.

Abstract Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 μg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.

Abstract The aim of this study was to investigate the fertility of "Huajin 6" and the effect of exogenous methyl jasmonate on its fertility. In this study, "Huajin 6", "Huajin 6" treated with methyl jasmonate and "Damaohua" were used as the research objects, the stamen phenotypes and the shape of pollen grains were observed, pollen viability and stigma receptivity were measured. The results showed that the pistil structure and function were normal, and although the stamen anthers did not dehisce, they were still capable of producing pollen with a certain amount of vigor. Methyl jasmonate could promote the opening of the flowers of "Huajin 6" and improve the development of pollen grains to a certain extent, but it could not promote anthers dehiscence of "Huajin 6". This study can provide theoretical guidance for the cultivation of new honeysuckle varieties using "Huajin 6".

This study performed rational feeding of fermented feed to channel catfish and determined its effects on growth, the intestinal bacterial community, and metabolomics of channel catfish. There were three groups: continuous feeding (A, continuous addition of fermented feed to the puffed feed), interval feeding involving weekly intervals addition of fermented feed added to the puffed feed (B), and the control group only fed the puffed feed (C). The experiment lasted 6 months. Channel catfish were weighed and the intestinal flora and metabolomics were detected by 16S rRNA sequencing technology and liquid chromatography-based metabolomics technology, respectively after the experiment. The final body weight (FBW) of channel catfish was significantly higher in the interval feeding group than that in the control group and the continuous feeding group (P < 0.05). The richness and microbial diversity of the intestine was the highest in the interval feeding group, while the richness of the continuous feeding group was the lowest (P > 0.05). Firmicutes, Actinobacteriota, Cyanobacteria, Proteobacteria, Fusobacteriota, Chloroflexi, and Deinococcota were the dominant bacterial phyla among the intestinal flora. The dominant intestinal genera included norank_f_norank_o_Chloroplast, Mycobacterium, Cetobacterium, Romboutsia, Exiguobacterium and Clostridium_sensu_stricto_1. Metabolomic analysis showed that the continuous feeding group mainly affected galactose metabolism and the phosphotransferase system of the intestinal flora in channel catfish through the significant upregulation of N-acetyl-D-galactosamine (P < 0.05) that affected the digestion and absorption of carbohydrates by fish. The differential metabolites L-serine and L-phenylalanine were significantly upregulated (P < 0.05) in the interval feeding group. This affected sulfur metabolism and amino acid metabolism of the intestinal flora, and affected energy absorption, anti-inflammation, and immunity of the channel catfish. This study provided a theoretical basis for the exploration of feeding methods using fermentation feed and healthy green breeding of channel catfish.

Abstract Background Chronic kidney disease (CKD) is a progressive disease for which there is no effective cure. We aimed to identify potential drug targets for CKD and kidney function by integrating plasma proteome and transcriptome. Methods We designed a comprehensive analysis pipeline involving two-sample Mendelian randomization (MR) (for proteins), summary-based MR (SMR) (for mRNA), and colocalization (for coding genes) to identify potential multi-omics biomarkers for CKD and combined the protein–protein interaction, Gene Ontology (GO), and single-cell annotation to explore the potential biological roles. The outcomes included CKD, extensive kidney function phenotypes, and different CKD clinical types (IgA nephropathy, chronic glomerulonephritis, chronic tubulointerstitial nephritis, membranous nephropathy, nephrotic syndrome, and diabetic nephropathy). Results Leveraging pQTLs of 3032 proteins from 3 large-scale GWASs and corresponding blood- and tissue-specific eQTLs, we identified 32 proteins associated with CKD, which were validated across diverse CKD datasets, kidney function indicators, and clinical types. Notably, 12 proteins with prior MR support, including fibroblast growth factor 5 (FGF5), isopentenyl-diphosphate delta-isomerase 2 (IDI2), inhibin beta C chain (INHBC), butyrophilin subfamily 3 member A2 (BTN3A2), BTN3A3, uromodulin (UMOD), complement component 4A (C4a), C4b, centrosomal protein of 170 kDa (CEP170), serologically defined colon cancer antigen 8 (SDCCAG8), MHC class I polypeptide-related sequence B (MICB), and liver-expressed antimicrobial peptide 2 (LEAP2), were confirmed. To our knowledge, 20 novel causal proteins have not been previously reported. Five novel proteins, namely, GCKR (OR 1.17, 95% CI 1.10–1.24), IGFBP-5 (OR 0.43, 95% CI 0.29–0.62), sRAGE (OR 1.14, 95% CI 1.07–1.22), GNPTG (OR 0.90, 95% CI 0.86–0.95), and YOD1 (OR 1.39, 95% CI 1.18–1.64,) passed the MR, SMR, and colocalization analysis. The other 15 proteins were also candidate targets (GATM, AIF1L, DQA2, PFKFB2, NFATC1, activin AC, Apo A-IV, MFAP4, DJC10, C2CD2L, TCEA2, HLA-E, PLD3, AIF1, and GMPR1). These proteins interact with each other, and their coding genes were mainly enrichment in immunity-related pathways or presented specificity across tissues, kidney-related tissue cells, and kidney single cells. Conclusions Our integrated analysis of plasma proteome and transcriptome data identifies 32 potential therapeutic targets for CKD, kidney function, and specific CKD clinical types, offering potential targets for the development of novel immunotherapies, combination therapies, or targeted interventions.

Abstract Background The worldwide occurrence of triplet pregnancy is estimated to be 0.093%, with a natural incidence of approximately 1 in 8000. This study aims to analyze the neonatal health status and birth weight discordance (BWD) of triplets based on chorionicity from birth until discharge. Methods This was a retrospective study. We reviewed a total of 136 triplet pregnancies at our tertiary hospital between January 1, 2001, and December 31, 2021. Maternal and neonatal outcomes, inter-triplet BWD, neonatal morbidity, and mortality were analyzed. Results Among all cases, the rates of intrauterine death, neonatal death, and perinatal death were 10.29, 13.07, and 24.26%, respectively. Thirty-seven of the cases resulted in fetal loss, including 13 with fetal anomalies. The maternal complications and neonatal outcomes of the 99 triplet pregnancies without fetal loss were compared across different chorionicities, including a dichorionic (DC) group (41 cases), trichorionic (TC) group (37 cases), and monochorionic (MC) group (21 cases). Neonatal hypoproteinemia (P 25% increased the risk of neonatal anemia (AOR = 10.135) and need for blood transfusion after birth (AOR = 7.127). TC pregnancy, MCDA or MCTA, and BWD > 25% increased neonatal hypoproteinemia, with AORs of 4.629, 5.123, and 5.343, respectively. Conclusions The BWD differed significantly according to chorionicity. Additionally, TC pregnancies reduced the risk of neonatal anemia and need for blood transfusion, but increased the risk of neonatal hypoproteinemia. In contrast, the BWD between the largest and smallest triplets increased the risk of neonatal anemia and the need for blood transfusion. TC pregnancy, MCDA or MCTA, and BWD > 25% increased the risks of neonatal hypoproteinemia. However, due to the limited number of triplet pregnancies, further exploration of the underlying mechanism is warranted.

Litter decomposition is significantly influenced by soil fauna, litter quality, and climate. Effects of soil fauna on litter decomposition are largely dependent on the size classes of the fauna. However, the understanding of how different soil fauna groups affect litter decomposition remains elusive. In this study, we conducted a global meta-analysis of experiments using litterbags with varying mesh sizes to quantify the contributions of mesofauna and macrofauna to litter decomposition by calculating log response ratios. Additionally, we quantitatively assessed how climatic conditions and litter quality influence the effect of these two faunal size classes on litter decomposition. Our findings demonstrated that mesofauna and macrofauna increased litter decomposition by an average of 12.25% and 22.14%, respectively. Furthermore, the relative increase in litter decomposition induced by mesofauna and macrofauna exhibited a significant statistical difference on a global scale. Specifically, in dry and temperate climatics, the effect of soil macrofauna on litter decomposition was significantly greater than that of mesofauna. Climatic conditions, particularly temperature and precipitation, were the primary factors influencing litter decomposition by both mesofauna and macrofauna. In contrast, litter quality significantly influenced decomposition only by macrofauna in dry and tropical climatic conditions. Our findings underscore that the relative increase in litter decomposition rates to mesofauna and macrofauna differed significantly on a global scale and that the climate and litter quality differentially regulate litter decomposition across faunal size classes.

Pharyngoesophageal diverticulum (PED) is a rare disease of the esophagus that is usually asymptomatic and often found incidentally during a thyroid ultrasound examination. Due to its anatomical location close to the thyroid, it is easily misdiagnosed as a thyroid nodule, which leads to unnecessary thyroid biopsies and surgical treatment. The occurrence of a single esophageal diverticula is common, while the existence of multiple diverticula is rare. Left side diverticula are more common than right sided ones, while bilateral occurrences are rarely reported. We report an extremely rare case of bilateral pharyngeal esophageal diverticula. The patient was a 55-year-old asymptomatic man who came to our hospital after thyroid nodules were identified in another hospital. Due to the extensive clinical experience of the ultrasound physician at our facility, the patient was suspected to have bilateral esophageal diverticula, which was confirmed by using swallow contrast-enhanced ultrasound (CEUS). Consequently, unnecessary thyroid treatments were avoided in this patient. This study shows that although bilateral pharyngeal diverticula are unusual, the possibility of their existence should be considered if nodules are located posterior to the bilateral thyroid glands and have suspicious imaging characteristics. Particular attention should be given to nodules located on the right side of the thyroid, which are sometimes overlooked easily due to their very low incidence. If real-time ultrasound cannot be used in making the diagnosis, PED can be further identified using swallowing CEUS to avoid unnecessary thyroid fine needle aspiration (FNA) and surgical treatment.

Introduction Osteoporotic vertebral compression fracture (OVCF) is a common complication in elderly patients with osteoporosis. Despite undergoing percutaneous kyphoplasty (PKP) treatment, a significant percentage of OVCF patients (1.8% to 31.9%) continue to experience residual low back pain. While acupuncture has shown promise in relieving this pain, there is currently no systematic review on its efficacy specifically for residual low back pain after PKP in OVCF patients. This project aims to evaluate the effectiveness and safety of acupuncture as a treatment for this condition.Methods and analysis A comprehensive search will be conducted, including manual and electronic searches of literature published. Various databases such as MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Library, International Clinical Trial Registration Platform, China National Knowledge Network, China Biomedical Literature Database, China Scientific Journal Database and Wan-fang Database will be explored. Additional sources like bibliographies and meeting minutes will also be searched. All randomised controlled clinical trials related to acupuncture for treating residual low back pain after PKP in OVCF patients will be included. Two researchers will independently perform study selection, data extraction and quality assessment. The primary outcome measure will be pain relief assessed using a visual analogue scale (VAS) or other validated scales. Secondary outcomes include effectiveness, Oswestry dysfunction index (ODI), quality of life questionnaire (QUALEFFO-41), follow-up relapse rate and adverse events. If feasible, a meta-analysis using RevMan V.5.3 software will be conducted. Otherwise, descriptive or subgroup analyses will be performed. Database searches will commence after the publication of this agreement, with an estimated commencement date of 1 August 2024.Ethics and dissemination Ethical approval is not required since this review does not involve individual patient data. The findings will be disseminated through peer-reviewed journals or relevant conferences.PROSPERO registration number CRD42023478838.

Abstract Gastric cancer is a highly prevalent disease that poses a serious threat to public health. In clinical practice, gastroscopy is frequently used by medical practitioners to screen for gastric cancer. However, the symptoms of gastric cancer at different stages of advancement vary significantly, particularly in the case of early gastric cancer (EGC). The manifestations of EGC are often indistinct, leading to a detection rate of less than 10%. In recent years, researchers have focused on leveraging deep learning algorithms to assist medical professionals in detecting EGC and thereby improve detection rates. To enhance the ability of deep learning to detect EGC and segment lesions in gastroscopic images, an Improved Mask R-CNN (IMR-CNN) model was proposed. This model incorporates a “Bi-directional feature extraction and fusion module” and a “Purification module for feature channel and space” based on the Mask R-CNN (MR-CNN). Our study includes a dataset of 1120 images of EGC for training and validation of the models. The experimental results indicate that the IMR-CNN model outperforms the original MR-CNN model, with Precision, Recall, Accuracy, Specificity and F1-Score values of 92.9%, 95.3%, 93.9%, 92.5% and 94.1%, respectively. Therefore, our proposed IMR-CNN model has superior detection and lesion segmentation capabilities and can effectively aid doctors in diagnosing EGC from gastroscopic images.

Abstract Background pOsNAR2.1:OsNAR2.1 expression could significantly increase nitrogen uptake efficiency and grain yield of rice. Result This study reported the effects of overexpression of OsNAR2.1 by OsNAR2.1 promoter on physiological and agronomic traits associated with drought tolerance. In comparison to the wild-type (WT), the pOsNAR2.1:OsNAR2.1 transgenic lines exhibited a significant improvement in survival rate when subjected to drought stress and then irrigation. Under limited water supply conditions, compared with WT, the photosynthesis and water use efficiency (WUE) of transgenic lines were increased by 39.2% and 28.8%, respectively. Finally, the transgenic lines had 25.5% and 66.4% higher grain yield than the WT under full watering and limited water supply conditions, respectively. Compared with the WT, the agronomic nitrogen use efficiency (NUE) of transgenic lines increased by 25.5% and 66.4% under full watering and limited water supply conditions, and the N recovery efficiency of transgenic lines increased by 29.3% and 50.2%, respectively. The interaction between OsNAR2.1 protein and OsPLDα1 protein was verified by yeast hybrids. After drought treatment, PLDα activity on the plasma membrane of the transgenic line increased 85.0% compared with WT. Conclusion These results indicated that pOsNAR2.1:OsNAR2.1 expression could improve the drought resistance of rice by increasing nitrogen uptake and regulating the expression of OsPLDα1.

Introduction: Stuck tunneled central venous catheters (CVCs) have been increasingly reported. In rare cases, the impossibility of extracting the CVC from the central vein after regular traction is the result of rigid adhesions to the surrounding fibrin sheath. Forced traction during catheter removal can cause serious complications, including cardiac tamponade, hemothorax, and hemorrhagic shock. Knowledge and experience on how to properly manage the stuck catheter are still limited. Case Presentation: Here, we present two cases that highlight the successful removal of the stuck tunneled CVC via thoracotomy through the close collaboration of multidisciplinary specialists in the best possible way. Both patients underwent an unsuccessful attempt at thrombolytic therapy with urokinase, catheter traction under the guidance of digital subtraction angiography and intraluminal balloon dilation. And we reviewed the literature on stuck catheters in the hope of providing knowledge and effective approaches to attempted removal of stuck catheters. Conclusion: There is no standardized procedure for dealing with stuck catheters. Intraluminal percutaneous transluminal angioplasty should be considered as the first-line treatment, while open surgery represents a second option only in the event of failure. Care must be taken that forced extubation can cause patients life-threatening.

Abstract Physical activity (PA) is linked to a decreased risk of type 2 diabetes mellitus (T2DM). However, the influence of circadian PA trajectories remains uncertain. This study aims to explore the optimal circadian PA trajectory pattern for reducing the risk of T2DM. Methods: A total of 502,400 participants were recruited from the UK Biobank between 2006 and 2010, and 102,323 participants provided valid accelerometer-captured acceleration data. After excluding individuals with prior T2DM, 99,532 participants were included in the final analysis. We initially investigated the association between PA intensity at 24 hourly time points and T2DM. Subsequently, PA trajectories were identified using K-means cluster analysis. Cox proportional hazard models were employed to estimate hazard ratios (HR). Four distinct PA trajectories were identified: consistently low, single peak, double peak, and intense trajectories. Compared to consistently low, single peak, double peak and intense PA trajectory reduced the risk of T2DM progressively. Sensitivity analyses, further excluding individuals with glycated hemoglobin (HbA1c) ≥ 6.5% or random glucose ≥ 11.1 mmol/L and adjusted for daily average acceleration, yielded consistent results. This confirms that the ideal circadian PA trajectory serves as a protective factor, independently of PA intensity. Subgroup analyses indicated that these effects were more pronounced in men and individuals with eGFR

Abstract Background The accumulation of heavy metals, including cadmium (Cd), in soil endangers the quality of agricultural products and can harm human health. At present, the application of passivators is a relatively efficient, quick, and economical way to address this problem. In the experimental site of the present study, the effects of different composite passivators (red mud + lime + phosphorite powder, red mud + lime + biochar, lime + humic acid + seafoam, seafoam + biochar + red mud, seafoam + biochar + phosphorite powder) on the physiology and biochemistry of Chinese cabbage were investigated. Results After passivator application, the soil’s effective state Cd content was reduced, and the Cd content, bioconcentration factor (BCF), transfer coefficient (TF), oxidative stress, and antioxidant enzyme activity levels of Chinese cabbage leaves and stalks were reduced to different degrees. The reduction of reactive oxygen species content was mainly owing to passivator application, which reduced the degree of oxidative stress and increased the content of osmotic substances, the activity of antioxidant enzymes, and the ability to scavenge hydroxyl radicals. The soluble protein content of Chinese cabbage was mainly increased by an increase in the content of osmotic substances and non-enzymatic antioxidant substances and a reduction in the inhibition of protein synthesis. Conclusions Our findings suggest that the reduction of reactive oxygen species was the main cause of the reduction of Cd accumulation, transport, and toxicity in leaves. The increase in soluble protein was the main cause of the reduction of Cd accumulation, transport, and toxicity in petioles. Graphical Abstract

Abstract Background There is a lack of relevant studies evaluating the long-term impact of cardiovascular health factor (CVH) metrics on chronic kidney disease (CKD). Objective This study investigates the long-term change in CVH metrics in older people and explores the relationship between CVH metrics trajectory and CKD. Methods In total, 27,635 older people aged over 60 from the community-based Tianjin Chronic Kidney Disease Cohort study were enrolled. The participants completed five annual physical examinations between January 01, 2014, and December 31, 2018, and a subsequent follow-up between January 01, 2019, and December 31, 2021. CVH metrics trajectories were established by the group-based trajectory model to predict CKD risk. The relationships between baseline CVH, CVH change (ΔCVH), and CKD risk were also explored by logistic regression and restricted cubic spline regression model. In addition, likelihood ratio tests were used to compare the goodness of fit of the different models. Results Six distinct CVH metrics trajectories were identified among the participants: low-stable (11.19%), low-medium-stable (30.58%), medium-stable (30.54%), medium-high-decreased (5.46%), medium-high-stable (18.93%), and high-stable (3.25%). After adjustment for potential confounders, higher CVH metrics trajectory was associated with decreased risk of CKD (P for trend

Abstract Background Hypoxia contributes to cancer progression through various molecular mechanisms and hepatocellular carcinoma (HCC) is one of the most hypoxic malignancies. Hypoxia-inducible gene domain protein-1a (HIGD1A) is typically induced via epigenetic regulation and promotes tumor cell survival during hypoxia. However, the role of HIGD1A in HCC remains unknown. Methods HIGD1A expression was determined in 24 pairs of human HCC samples and para-tumorous tissues. Loss-of-function experiments were conducted both in vivo and in vitro to explore the role of HIGD1A in HCC proliferation and metastasis. Results Increased HIGD1A expression was found in HCC tissues and cell lines, which was induced by hypoxia or low-glucose condition. Moreover, HIGD1A knockdown in HCC cells arrested the cell cycle at the G2/M phase and promoted hypoxia-induced cell apoptosis, resulting in great inhibition of cell proliferation, migration, and invasion, as well as tumor xenograft formation. Interestingly, these anti-tumor effects were not observed in normal hepatocyte cell line L02. Further, HIGD1A knockdown suppressed the expression of ornithine decarboxylase 1 (ODC1), a rate-limiting enzyme of polyamine metabolism under c-Myc regulation. HIGD1A was found to bind with the c-Myc promoter region, and its knockdown decreased the levels of polyamine metabolites. Consistently, the inhibitory effect on HCC phenotype by HIGD1A silencing could be reversed by overexpression of c-Myc or supplementation of polyamines. Conclusions Our results demonstrated that HIGD1A activated c-Myc–ODC1 nexus to regulate polyamine synthesis and to promote HCC survival and malignant phenotype, implying that HIGD1A might represent a novel therapeutic target for HCC.

The lower limbs play an important role in daily human activities. Therefore, a 3D tibial model is constructed, and finite element analysis is performed to investigate the biomechanical characteristics and injury tolerance of lower limb flexion movement. The maximum equivalent stress at 30° flexion was 19.1 MPa and 31.2 MPa in the normal and dynamic eversion positions, respectively, of the knee joint, 1.4 MPa and 1.1 MPa in the medial tibial plateau, and 1.8 MPa and 1.2 MPa in the lateral tibial plateau. The peak contact force was generally approximately 4000 N when different positions of the tibia were impacted. The maximum contact force of the frontal impact was larger than that of the external impact at 4109 N and 3927 N, respectively. The dynamic knee valgus posture and lateral impacts are more likely to cause tibial injury. The findings of this study provide information for the prevention of sports injuries and rehabilitation treatment.

Selenium, as an essential trace element, is intricately linked to the onset and progression of numerous diseases due to deficiencies in selenium intake. Selenium compounds exhibit tumor specificity and can efficiently inhibit the growth of tumor cells, making them potential candidates for cancer treatment. Nevertheless, given its status as one of the most widely consumed crops globally, increasing the selenium content in rice could prove advantageous in alleviating the prevailing issue of selenium intake deficiency, particularly in China. This review explored the regulatory role of selenium in rice growth, the regional distribution characteristics of soil selenium content in various rice-growing regions in China, and the impact of cultivation practices on selenium fortification in rice, aiming to suggest improved rice cultivation management strategies to enhance the capacity for rice selenium biofortification. The findings revealed that: (1) In Northeast and North China, characterized by alkaline soils and severe selenium deficiency, it is advisable to moderately decrease the duration of flooding, elevate the soil redox potential, and apply organic and nitrogen fertilizers in a judicious manner. (2) In Southwest China, which is characterized by acidic soils, alternating wet and dry irrigation should be employed, and the biofortification of selenium can be facilitated by applying lime and foliar spraying of selenium fertilizer. (3) In the south-central region of China, distinguished by acidic soils and double-cropped rice, it is recommended that intermittent or alternating wet and dry irrigation be employed, and the reasonable application of organic, silica, and selenium fertilizers is advocated. (4) In the northwest region, characterized by slightly alkaline soil and mild selenium deficiency, it is recommended to implement various water management practices, including shallow water during the seedling stage, deep water during the booting stage, and wet grain filling. Additionally, a rational application of nitrogen, phosphorus, and potassium fertilizers, along with foliar application of selenium fertilizer, should be employed. (5) Cultivating selenium-enriched, high-yielding, and high-quality rice varieties proves to be an effective strategy in addressing selenium deficiency. In conclusion, the unique characteristics of diverse rice-growing regions in China indicate that suitable water management, fertilization techniques, and varietal selection practices can effectively enhance the selenium content in rice, thereby maximizing the nutritional requirements for selenium.

In this paper, an effective numerical approach that combines the fast L1 formula and barycentric Lagrange interpolation is proposed for solving a kind of time-fractional evolution equations. This type of equation contains a nonlocal term involving the time variable, resulting in extremely high computational complexity of numerical discrete formats in general. To reduce the computational burden, the fast L1 technique based on the L1 formula and sum-of-exponentials approximation is employed to evaluate the Caputo time-fractional derivative. Meanwhile, a fast and unconditionally stable time semi-discrete format is obtained. Subsequently, we utilize the barycentric Lagrange interpolation and its differential matrices to achieve spatial discretizations so as to deduce fully discrete formats. Then error estimates of related fully discrete formats are explored. Eventually, some numerical experiments are simulated to testify to the effective and fast behavior of the presented method.