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Diquat (DQ) is a potent, non-selective herbicide which can result in severe poisoning and a high mortality if ingested accidentally or intentionally. Diquat poisoning can cause extensive damage to multiple organs, including the intestines, liver, kidneys, brain, and other organs. As there are no specific antidotes available for DQ poisoning, the current therapeutic strategies are essentially restricted to blood purification therapy and supportive care. Numerous studies on the molecular mechanisms and potential therapeutic agents have been conducted over the past few decades. However, there has been no comprehensive summary or analysis of these findings. This review extensively investigates the molecular mechanisms underlying DQ-induced organ injury, with a particular focus on the major signaling pathways. In addition, searches were conducted in PubMed and Web of Science using the following search terms: \"diquat\"[tiab] OR \"diquat\"[MeSH Terms]. A total of 166 eligible papers published over the past 35 years were selected. Consequently, more than seventy potential therapeutic agents with protective effects against DQ-induced toxicity are summarized and analyzed. In the future, it will be essential to conduct preclinical research and clinical trials to extrapolate these findings to humans. Graphical Abstract

Abstract Background Blinded independent central review (BICR) mitigates assessment bias in oncology trials but imposes significant operational burdens. Its value in hematologic malignancies—where multimodal response criteria reduce reliance on subjective imaging assessments compared to solid tumors—remains unestablished. This meta-analysis evaluates BICR-investigator concordance specifically in hematology trials. Methods We systematically identified Phase II/III hematology trials (2014-2024) reporting progression-free survival (PFS) and/or objective response rate (ORR) assessments by both investigators and BICR from PubMed. Agreement was quantified using Pearson/Spearman correlation, pooled hazard ratio ratio (HRR, HRINV/HRBICR) for PFS, and odds ratio ratio for ORR (OddsRR, ORINV/ORBICR). We also analyzed the odds ratio for ORR for single arms (OddsINV/OddsBICR). Subgroup analyses assessed the impact of masking, cancer type based on imaging dependence, and sample size. Results Data from 70 studies (37 PFS comparisons; 23 ORR comparisons; 29 single-arm ORR) were analyzed. For PFS, the pooled HRR was 0.96 (95% CI: 0.89, 1.03), with perfect agreement in statistical significance (Cohen’s kappa = 1). For ORR, the pooled OddsRR was 0.99 (95% CI: 0.85, 1.14). Single-arm trials showed minimal odds difference between assessors (OR = 1.02, 95% CI: 0.90, 1.17). Subgroup analyses (masking, cancer type, sample size) consistently showed high agreement. Conclusions Investigator and BICR assessments demonstrated substantial concordance in hematology trials. The common applications of BICR in registration trials provide minimal added value for primary endpoint validation in this setting. We recommend prioritizing investigator training and standardized criteria to optimize resource allocation.

Objective: To explore the composition of the intestinal microbiota in ulcerative colitis (UC) patients and to identify differences in the microbiota between patients with active disease and those in remission.Methods: Between September 2020 and June 2021, we enrolled into our study, and collected stool samples from, patients with active UC or in remission and healthy control subjects. The diagnosis of UC was based on clinical, endoscopic, radiological, and histological findings. The composition of the intestinal microbiota was determined by sequencing of the 16S rRNA V3–V4 region and by bioinformatic methods. The functional composition of the intestinal microbiota was predicted using PICRUSt 2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) software.Results: We found that the intestinal flora was significantly less rich and diverse in UC patients than in healthy control subjects. Beta diversity analysis revealed notable differences in the intestinal flora compositions among the three groups, but there was no statistical difference in alpha diversity between UC patients with active disease and those in remission. At the phylum level, the relative abundances of Proteobacteria and Patescibacteria were significantly higher, and the relative abundances of Desulfobacterota and Verrucomicrobiota were lower, in UC patients with active disease than in the healthy control group. Higher levels of potential pathogens and lower levels of butyrate-producing bacteria were also detected in UC patients with active disease. Linear discriminant analysis Effect Size (LefSe) revealed that 71 bacterial taxa could serve as biomarkers, with 26 biomarkers at the genus level. In addition, network analysis showed that there was a positive correlation between Roseburia and Lachnospira. Functional predictions indicated that gene functions involving the metabolism of some substances, such as methane, lipopolysaccharide, geraniol, and ansamycins, were significantly different among the three groups.Conclusion: The richness and diversity of the intestinal microbiota differed significantly among the three groups. Richness describes the state of being rich in number of intestinal bacteria, whereas diversity is the number of different species of intestinal bacteria. Different bacterial taxa could be used as biomarkers, expanding our understanding of the relationship between the intestinal microbiota microenvironment and UC in the future.

Osteoporosis, one of the most common non-communicable human diseases worldwide, is one of the most prevalent disease of the adult skeleton. Glucocorticoid-induced osteoporosis(GIOP) is the foremost form of secondary osteoporosis, extensively researched due to its prevalence.Probiotics constitute a primary bioactive component within numerous foods, offering promise as a potential biological intervention for preventing and treating osteoporosis. This study aimed to evaluate the beneficial effects of the probiotic on bone health and its underlying mechanisms in a rat model of glucocorticoid dexamethasone-induced osteoporosis, using the osteoporosis treatment drug alendronate as a reference. We examined the bone microstructure (Micro-CT and HE staining) and analyzed the gut microbiome and serum metabolome in rats. The results revealed that treatment significantly restored parameters of bone microstructure, with elevated bone density, increased number and thickness of trabeculae, and decreased Tb.Sp. Gut microbiota sequencing results showed that probiotic treatment increased gut microbial diversity and the ratio of Firmicutes to Bacteroidota decreased. Beneficial bacteria abundance was significantly increased ( _NK4A136_group, , , , and _R_7_group), and harmful bacteria abundance was significantly decreased ( ). According to the results of serum metabolomics, significant changes in serum metabolites occurred in different groups. These differential metabolites were predominantly enriched within the pathways of Pentose and Glucuronate Interconversions, as well as Propanoate Metabolism. Furthermore, treatment of significantly increased serum levels of Pyrazine and gamma-Glutamylcysteine, which were associated with inhibition of osteoclast formation and promoting osteoblast formation. can protect rats from DEX-induced GIOP by mediating the \"gut microbial-bone axis\" promoting the production of beneficial bacteria and metabolites. Therefore is a potential candidate for the treatment of GIOP.

Fasting and especially intermittent fasting have been shown to be an effective intervention in many diseases, such as obesity and diabetes. The fasting-mimicking diet (FMD) has recently been found to ameliorate metabolic disorders. To investigate the effect of a new type of low-protein low-carbohydrate FMD on diabetes, we tested an FMD in db/db mice, a genetic model of type 2 diabetes. The diet was administered every other week for a total of 8 weeks. The intermittent FMD normalized blood glucose levels in db/db mice, with significant improvements in insulin sensitivity and β cell function. The FMD also reduced hepatic steatosis in the mice. Deterioration of pancreatic islets and the loss of β cells in the diabetic mice were prevented by the FMD. The expression of β cell progenitor marker Ngn3 was increased by the FMD. In addition, the FMD led to the reconstruction of gut microbiota. Intermittent application of the FMD increased the genera of Parabacteroides and Blautia while reducing Prevotellaceae, Alistipes and Ruminococcaceae. The changes in these bacteria were also correlated with the fasting blood glucose levels of the mice. Furthermore, intermittent FMD was able to reduce fasting blood glucose level and increase β cells in STZ-induced type 1 diabetic mouse model. In conclusion, our study provides evidence that the intermittent application of an FMD is able to effectively intervene in the progression of diabetes in mice.

The combined index of hemoglobin, albumin, lymphocyte, and platelet (HALP) is a novel indicator reflecting systemic inflammation and nutritional status. To explore the relationship between HALP score and ICU mortality risk in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A total of 1533 AECOPD patients from the eICU Collaborative Research Database (eICU-CRD) between 2014 and 2015 were included in this retrospective cohort study. Univariate and multivariate Cox proportional hazards models were utilized to investigate the association of HALP score, platelet-to-lymphocyte ratio (PLR) score, and lymphocyte-to-monocyte ratio (LMR) score with the ICU mortality risk in patients with AECOPD. Stratified analyses were performed based on patients’ ICU admission type, body mass index (BMI), and Acute Physiology, Age and Chronic Health Evaluation IV (APACHE IV) score. Of these 1533 AECOPD patients, 123 (8.00%) patients died in the ICU. Low HALP score [hazard ratio (HR) = 1.69; 95% confidence interval (CI) 1.14–2.53] and low LMR score (HR = 1.60; 95% CI 1.07–2.39) were associated with an increased ICU mortality risk in patients with AECOPD after adjusting for all confounders. Stratified analyses indicated that low HALP score were still associated with a higher ICU mortality risk in patients admitted to ICU by emergency (HR = 1.81; 95% CI 1.11–2.96), obese patients (HR = 2.81; 95% CI 1.29–6.10), and patients with low APACHE scores (HR = 2.87; 95% CI 1.75–4.69). Low HALP score was associated with an increased risk of ICU mortality in patients with AECOPD, suggesting that the HALP score may be a novel prognostic predictor in patients with AECOPD.

Tooth decay is prevalent, and secondary caries causes restoration failures, both of which are related to demineralization. There is an urgent need to develop new therapeutic materials with remineralization functions. This article represents the first review on the cutting edge research of poly(amido amine) (PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP). PAMAM was excellent nucleation template, and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization. NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities. PAMAM+NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates, superior acid-neutralization, and ions release. Therefore, the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone. PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions. Besides, the long-term remineralization capability of PAMAM+NACP was established. After prolonged fluid challenge, the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration. Furthermore, the hardness of pre-demineralized dentin was increased back to that of healthy dentin, indicating a complete remineralization. Therefore, the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization, hardness increase, and caries-inhibition capabilities.

Background Inducing embryogenic callus with regenerative potential is a pivotal step in barley transformation. Our previous research suggests that epigenetic regulatory factors might influence barley callus formation and regeneration capacity, though the exact mechanisms remain unclear. Results In this study, we utilized RNA sequencing (RNA-seq) and whole-genome bisulfite sequencing (WGBS) to examine transcriptional and DNA methylome alterations during callus induction from immature embryos of the barley cultivar Golden Promise. Our findings revealed a slight decline in overall DNA methylation content and distinct 5-methylcytosine (5mC) enrichment patterns in CG, CHG, and CHH sequence contexts within genes and transposable elements. By integrating DNA methylation and transcriptome data, we identified differentially expressed genes (DEGs) associated with differentially methylated regions (DMRs) in the CG (879 DEGs), CHG (229 DEGs), and CHH (2020 DEGs) contexts. Notably, DMRs linked to 210, 94, and 1,214 DEGs were located in the 2 kb upstream regions in the CG, CHG, and CHH contexts, respectively. A negative correlation was observed between promoter methylation levels and transcript abundances of key regeneration-associated genes, such as HvKRP4 , HvCYCD1;1 , HvSCR , HvRAP2.6L/ERF113 , HvWIND4 , HvWOX5 , HvE2Fa , HvPHV , and HvLBD16 . This indicates a regulatory function of DNA methylation in transcriptional regulation during callus induction. Furthermore, treatment with the DNA methylation inhibitor 5-Aza-2′-deoxycytidine (5-Aza-dC) suppressed callus formation. Comparative RNA sequencing analysis between control and treated groups revealed 2,628 and 1,224 DEGs potentially regulated by DNA methylation, at 2- and 9-days post-induction, respectively. These genes were primarily associated with cell cycle and abscisic acid signalling pathways, influenced directly and indirectly by the global reduction in DNA methylation induced by 5-Aza-dC treatment. Conclusions This study provides insights into the intricate relationship between DNA methylation and gene expression during barley callus formation. It could inform future efforts to enhance regeneration and transformation in this significant crop species. Clinical trial number Not applicable.

Using data on China’s A-share listed enterprises from 2012 to 2019, we investigate the impact of China’s green finance reform and innovation pilot (GFRIP) policy on green innovation by the difference-in-difference (DID) method. The results show that the GFRIP policy has a significant role in promoting enterprises’ green innovation. Heterogeneity analysis shows that the positive effect of the GFRIP policy on green innovation is only significant for heavily polluting enterprises, large enterprises, state-owned enterprises, and enterprises headquartered in regions with a low level of marketization. Debt financing is an important mechanism for the GFRIP policy to promote corporate green innovation; that is, the GFRIP policy alleviates corporate debt financing constraints and then promotes corporate green innovation. Our study provides theoretical and practical enlightenment for developing countries such as China to deepen reform of the green financial system and promote green innovation.