SEARCH · Search PubMed

Results for “Citric acid supplementation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

337 records · Page 12Linked to original sources

PubMed2026

A profile of suspected female homicide cases at the Johannesburg and Diepkloof Forensic Pathology Service Medico-legal Mortuaries for 2020-2022.

This study profiles suspected female homicide victims in Johannesburg, South Africa, during the COVID-19 period marked by socio-environmental changes from lockdown restrictions. Guided by the Socio-Ecological Model, a retrospective case series of 369 victims was reviewed using medico-legal mortuary records from Johannesburg and Diepkloof Forensic Pathology Service facilities. Descriptive analyses were conducted, supplemented by a chi-square test to assess whether distributions of causes of death among women differed between COVID-19 and non-COVID-19 periods. No statistically significant association was found, χ2 (6, N = 339) = 6.68, p = 0.35. Key findings highlight that Black, unemployed, unmarried women aged 21-40 were at greatest risk. Cause of death was established in 97.0% (358/369) of cases, with firearm injuries predominating (43.9%), followed by sharp‑force (24.5%) and blunt‑force trauma (13.1%). Approximately 90% of victims were suspected to have been killed by males, with half of deaths attributed to intimate partner violence. Homicide frequency decreased during strict lockdowns but rose as restrictions eased, suggesting that movement and alcohol controls may reduce risk. Despite temporary disturbance caused by COVID‑19 restrictions, the underlying risk profile of female homicide victims remained unchanged. These findings inform multi-level prevention and intervention strategies in South Africa.

Humans↗

PubMed2026

Chinese herbal medicine Xiangsu Hewei Granules in treating non-erosive gastroesophageal reflux disease with liver stomach stagnation heat syndrome: A multicentre, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsu Hewei Granules are an herbal preparation that has shown potential for controlling symptoms of nonerosive gastroesophageal reflux disease (NERD) in preliminary studies. However, high-quality randomized controlled evidence for its use in NERD remains lacking. AIM: To verify the efficacy and safety of Xiangsu Hewei Granules in treating NERD with liver stomach stagnation heat syndrome. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, multicentre phase III trial included 480 patients (aged 18-65 years) with confirmed NERD (GerdQ≥8; negative H. pylori) and traditional Chinese medicine (TCM) liver stomach stagnation heat syndrome. Patients were randomized 3:1 to receive either Xiangsu Hewei Granules or placebo, thrice daily for 8 weeks. The primary outcomes were the effective rate of the response based on visual analog scale (VAS) scores for heartburn and acid regurgitation at week 8. The secondary outcomes included reductions in the TCM syndrome score, etc. RESULTS: 479 participants (mean age 48.5 years, SD10.2; 54.3% female) entered the full analysis set and safety set (360 tests group; 119 control group, 1 participant in the control group withdrawing before medication). At week 8, compared with the control group, the test group demonstrated significantly better effective rate of VAS score response for heartburn(76.39% vs 21.01%, 95% CI 55.38 (45.98, 62.94) %, p < 0.01),acid regurgitation (79.72% vs 23.53%, 95% CI56.39 (46.90, 64.12) %, p < 0.01), and TCM syndrome score (69.23% vs 30.13%, p < 0.01) at week 8. CONCLUSION: In this selected population of NERD patients with liver-stomach stagnation heat syndrome (e.g., negative H. pylori, no pH-impedance phenotype, and low anxiety/depression scores), Xiangsu Hewei Granules demonstrated efficacy and safety in improving heartburn, acid regurgitation, and TCM syndrome scores. However, generalizability to the broader NERD population and its comparative effectiveness against standard proton pump inhibitor therapy require further investigation.

Humans↗

PubMed2026

Effectiveness of grief interventions in underrepresented regions: a systematic review and exploratory meta-analysis.

Background: Most evidence on grief and bereavement interventions originates from Western, Educated, Industrialized, Rich, and Democratic (WEIRD) populations, raising concerns about the generalizability and cultural relevance of existing findings in diverse global contexts. Individuals confronted with the death of a close person, particularly in cases of sudden or potentially traumatic loss, may be at increased risk of adverse psychological and physical health outcomes, highlighting the importance of effective interventions. This study aimed to synthesize evidence on the effectiveness of grief interventions in underrepresented regions.Method: A systematic search of Web of Science, APA PsycInfo, and Scopus, supplemented by manual reference checks, identified randomized controlled trials (RCTs) targeting bereaved individuals in underrepresented regions. Meta-analyses were conducted to estimate overall and subgroup effects based on control type, loss type, and intervention characteristics.Results: Fourteen RCTs comprising 1122 participants were included. Grief interventions demonstrated a significant moderate-to-large effect compared to control conditions (SMD = -0.74, 95% CI [-1.01, -0.47]). Substantial heterogeneity was observed (I² = 77%). No significant subgroup differences were identified.Conclusion: Grief interventions show promising effectiveness across diverse cultural and geographical contexts. However, the limited and heterogeneous evidence base highlights the need for more high-quality RCTs and for the development of culturally sensitive and contextually grounded approaches to mental health care in underrepresented regions.

Humans↗

PubMed2026

Comparing Traditional Motor Speech Practice to Contextualized Speech Practice in Preschoolers With Childhood Apraxia of Speech.

PURPOSE: The aim of this study was to compare retention of real-word targets across practice conditions (contextualized vs. motor-only) within a modified integral stimulation treatment for preschoolers with childhood apraxia of speech (CAS). METHOD: A single-subject experimental design with alternating treatments was used with matched target sets randomly assigned to contextualized practice, motor-only practice, or no treatment. Three preschoolers with CAS completed 18 therapy sessions, each consisting of two 25-min blocks: one contextualized practice and one motor-only practice. Order of practice was randomized each visit. Changes in percent phonemes correct (PPC) and lexical stress accuracy, derived from blinded transcription, were explored with visual analysis and effect sizes (standardized mean difference, d statistic). RESULTS: Meaningful improvements (d > 1) were observed in PPC across words treated in contextualized practice for all three children immediately posttreatment and for two of three children at the 1-month follow-up. Meaningful improvements in the motor-only condition were observed in two of three children immediately posttreatment and at follow-up. No meaningful changes were observed in lexical stress across any conditions in any participant. CONCLUSIONS: This study provides preliminary support for the feasibility of a modified integral stimulation therapy that incorporates elements of linguistically grounded therapies (linguistic retrieval, recasts, expansions) that may facilitate target retention in some preschoolers with CAS. However, other elements should be explored in conjunction with integral stimulation to maximize clinical outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.33228981.

Humans↗

PubMed2026

Chalcone-indole hybrid scaffolds as promising anticancer drug candidates: a mini-review.

Cancer treatment is hampered by severe systemic side effects, poor tumor selectivity, and multidrug resistance (MDR). Molecular hybridization integrates chalcone and indole, two privileged antitumor pharmacophores, into one scaffold to generate chalcone-indole hybrids that synergistically enhance antitumor potency, improve tumor targeting, and reverse MDR. This mini-review analyzes literature from 2020 to 2026 on chalcone-indole anticancer hybrids. Based on structural modification patterns, the reported hybrids are categorized into four subgroups: simple substituted, α/β-position modified, N-1 fatty acid-substituted, and multi-pharmacophore fused hybrids. For each category, we summarize structure-activity relationships (SARs), antiproliferative activity, selective toxicity, molecular mechanisms, and in vivo xenograft performance. Most lead compounds exert tumor-suppressive effects via tubulin polymerization inhibition, G2/M cell cycle arrest, ROS overaccumulation, and mitochondrial-dependent apoptosis. Representative hybrids 10a, 12a, 21a, and 25a exhibit remarkable efficacy against drug-resistant colorectal, lung, and breast tumors with favorable in vivo safety. We highlight the application potential of different subtypes for specific malignancies, including α/β-modified analogues for resistant colorectal cancer, N-1 fatty acid-platinum conjugates for platinum-resistant lung cancer, NLRP3 inhibitor 7a for oral cancer, and multi-pharmacophore fused derivatives for broad-spectrum activity. Current bottlenecks limiting clinical transformation are discussed. This review provides structural design rules for developing novel chalcone-indole targeted anticancer agents.

Humans↗

PubMed2026

Systematic modular engineering of genome-integrated Escherichia coli MG1655 for high-level 2'-fucosyllactose production.

2'-Fucosyllactose (2'-FL), the most abundant human milk oligosaccharide (HMO), has attracted considerable interest for its prebiotic and immunomodulatory functions, with broad applications in infant nutrition. In this study, we report the development of a high-yield, genome-integrated 2'-FL-producing strain based on Escherichia coli MG1655 through systematic modular optimization. Starting from a single-copy BKHT strain (MGC06), we first optimized the copy number of the α-1,2-fucosyltransferase (α-1,2-FT) gene BKHT. Subsequently, the GDP-L-fucose supply was enhanced through coordinated genomic integration of the gene clusters cpsG-cpsB and gmd-fcl, while the multidrug efflux transporter gene mdfA was integrated to improve product export and strain robustness. BKHT copy number was then re-evaluated in the optimized background, with four copies yielding the highest production. The final engineered strain, harboring all genetic modifications stably integrated into the chromosome, produced 17.18 g/L 2'-FL in shake-flask culture. In fed-batch fermentation using a 5-L bioreactor, this strain achieved a titer of 154.12 g/L after 60 h, with a productivity of 2.57 g/L/h. Notably, throughout the entire fermentation process, no antibiotics or inducers were supplemented, underscoring the genetic stability and regulatory compliance of this plasmid-free system. To our knowledge, this represents the highest 2'-FL titer reported to date, positioning our engineered strain as a promising candidate for commercial 2'-FL production.

Escherichia coli↗

PubMed2026

Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.

BACKGROUND: The gut microbiome has emerged as a potential contributor to cardiovascular diseases (CVDs), including atherosclerosis, acute coronary syndrome (ACS), and peripheral arterial disease (PAD). While observational studies link dysbiosis to CVD, causal relationships remain uncertain. METHODS: This narrative review synthesizes evidence from human observational studies, clinical interventions, and experimental models to distinguish association from mechanistic plausibility and clinical causality. Literature was searched through July 2026 in PubMed/MEDLINE, Web of Science, and Scopus. RESULTS: Microbial metabolites-including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)-modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor-mediated signaling and epigenetic regulation. SCFAs demonstrate potentially protective effects via GPCR and HDAC pathways, while TMAO is associated with atherothrombotic risk. However, much mechanistic evidence derives from preclinical studies. Heterogeneity from diet, geography, host characteristics, renal function, and medications substantially influences microbiota-CVD associations. CONCLUSION: The gut-vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome-directed therapies (dietary modulation, pre/pro/synbiotics, targeted metabolite inhibition) are investigational. Prospective, standardized, adequately powered human studies with clinically meaningful outcomes are essential before routine cardiovascular application.

Gastrointestinal Microbiome↗

PubMed2026

Functional Reading Activities to Motivate and Empower: Maintenance of Reading Outcomes for Young Adults With Intellectual and Developmental Disabilities Following a Randomized Controlled Trial.

PURPOSE: This study examined whether the effects of Functional Reading Activities to Motivate and Empower (FRAME), a functional, strategy-based reading comprehension intervention for young adults with intellectual and developmental disabilities (IDDs), were maintained 6 months following the completion of the intervention and explored participants' perceptions of the intervention's feasibility, relevance, and perceived impact. METHOD: Participants were 44 young adults with IDDs (ages 18-26 years) who participated in a previously reported randomized controlled trial (FRAME participants: n = 23; controls: n = 21). Trial outcomes were assessed via telepractice at pretest, posttest, and 6-month follow-up. Six-month maintenance analyses focused on outcomes that demonstrated significant posttest group differences: use of (a) reading comprehension strategies (proximal) and (b) reading comprehension questions (distal). Participant perceptions (social validity) were collected post-intervention from FRAME participants using a structured interview protocol with closed- and open-ended items. RESULTS: At the 6-month follow-up, FRAME participants demonstrated sustained but reduced improvements in strategy use relative to controls (p = .040). Between-groups differences were not maintained for reading comprehension questions (p = .091). Participants reported high acceptability and perceived relevance of FRAME, with qualitative themes reflecting perceived improvements in comprehension, self-improvement, and increased independence. CONCLUSION: Findings suggest that FRAME supports sustainable gains in reading comprehension strategy use and is perceived as meaningful and feasible for young adults with IDDs, although additional supports may be needed to promote sustained improvements in distal comprehension outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.33307218.

Humans↗

PubMed2026

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female↗

PubMed2026

The Complete Mitochondrial Genome of a Newly Recorded Chinese Species of Diglyphus sabulosus (Hymenoptera: Eulophidae) and Insights into Its Phylogenetic Position.

Diglyphus Walker, 1844 is an economically important genus which many species acting as biocontrol agents against agromyzid leafminer pests, but there is a lack of mitogenomic data on the evolutionary relationships within this genus, hindering a comprehensive understanding of its evolutionary history. We used traditional morphological methods to identify species, and present the first complete mitochondrial genome sequence and characterization of features of Diglyphus sabulosus and further infer its phylogenetic position based on the amino acid sequences of 13 protein-coding genes (PCGs). The complete mitochondrial genome of D. sabulosus is 15,690 bp in length, including 13 PCGs, 22 transfer RNA genes, 2 ribosomal RNA genes and a control region. The AT content of the whole genome sequence was 81.0%, indicating a significant AT bias. All protein-coding genes have the typical ATN as the start codon and TAA as the stop codon. Phylogenetic analysis inferred from the amino acid sequences of 13 PCGs revealed that all species within the family Eulophidae constituted a monophyletic clade, supporting the monophyly of this family. D. sabulosus and D. poppoea form a well-supported sister group, representing the species with the closest phylogenetic relationship within the analyzed taxa. In this study, the mitogenome structure was analyzed and the taxonomic status of D. sabulosus was clarified, thus providing a theoretical basis for understanding the phylogenetic relationships of Diglyphus.

Animals↗

PubMed2026

Optimizing eco-engineering pedogenesis of bauxite residues: Synergistic effects of humus and FeSO4/sulfur on microbial community and function.

Eco-engineered pedogenesis represents a promising approach for soil amelioration of bauxite residues (BRs) through exogenous organic matter. However, the role of humus in mediating this process remains poorly understood, significantly impeding the eco-engineering rehabilitation of BRs. In this study, we conducted pot experiments and subsequent microbial analysis to evaluate the individual improvement of humic acid (HA), fulvic acid (FA), and corn straw (SWZ) on the BRs' pedogenesis. High-throughput sequencing analysis revealed that both FA and SWZ were more effective than HA in steering microbial community assembly, as community diversity, dominant taxa enrichment, and species' interaction were all significantly higher (p < 0.05) in the FA/SWZ treatments than in HA treatments. Notably, the combination of FA with FeSO4 specifically enriched halophilic taxa, while FA coupled with sulfur (S) significantly improved the connectivity and complexity of the microbial network, as the average connection degree increasing from 1.008 to 1.113. Hydrolytic enzyme activity assays further indicated that FA, especially when combined with S, was the most effective treatment in restoring microbial function during BR pedogenesis. These findings highlight FA as a critical driver of microbial restructuring and functional recovery in BRs. Moreover, its efficacy can be enhanced by co-amendment with FeSO4 or S. This study provides important theoretical and practical insights for optimizing organic-inorganic amendment strategies to accelerate the eco-engineering pedogenesis of bauxite residues.

Humic Substances↗

PubMed2025

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1‑chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals↗

PubMed2026

Hypothalamic-Pituitary Axis Involvement in Primary Central Nervous System Lymphoma.

CONTEXT: Primary central nervous system lymphoma (PCNSL) is a rare malignancy that may involve the hypothalamic-pituitary axis (HPA), leading to underrecognized but clinically significant endocrine dysfunction. OBJECTIVE: This work aims to characterize the spectrum and patterns of HPA-related endocrine disturbances in patients with PCNSL. DATA SOURCES: A systematic search was conducted in PubMed, EMBASE, Scopus, and Web of Science, supplemented by gray literature. The search concluded in February 2025. STUDY SELECTION: We included studies reporting adult PCNSL cases with documented dysfunction of at least one hormonal axis. Exclusion criteria were preexisting hypopituitarism or lack of endocrine data. DATA EXTRACTION: Data on demographics, tumor localization, hormonal axes affected, radiological findings, treatment, and outcomes were extracted. Risk of bias was assessed using JBI tools. RESULTS: Ninety-nine cases met the inclusion criteria. Diffuse large B-cell lymphoma accounted for 84% of cases. Endocrine dysfunction included isolated adenohypophyseal involvement (46%), neurohypophyseal (8%), and combined (45%). The most affected pituitary axes were the gonadal and thyroid axes, with 89.7% and 89.2% involvement, respectively. Hypothalamic tumors were strongly associated with combined dysfunction (odds ratio = 9.47; 95% CI, 3.76-23.86; P < .001). Persistent endocrinopathy was more frequent in progressive disease. No direct association was found between endocrine dysfunction and mortality. CONCLUSION: HPA dysfunction in PCNSL is frequent and often underdiagnosed. Hypothalamic involvement is associated broader hormonal impairment. Routine hormonal screening and multidisciplinary management should be standard in PCNSL care to minimize complications and improve outcomes.

Humans↗

PubMed2026

A systematic review of the impact of Mental Health First Aid on medical, nursing and allied healthcare professional students.

BACKGROUND: Healthcare professional (HCP) students are at high risk of mental health problems, but stigma and fear of career repercussions often deter them from seeking help. Mental Health First Aid (MHFA) is a globally disseminated course teaching the public to identify and respond to people experiencing mental health problems. MHFA training may address some of the challenges faced by HCP students, by improving mental health knowledge and by enhancing well-being and peer support. AIMS: To systematically review the available literature regarding the impact of MHFA training on HCP students' mental health literacy, confidence and intentions to provide help, stigma, peer support and self-care. METHOD: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (International Prospective Register of Systematic Reviews ID: CRD42024589509), five databases were searched. Primary studies evaluating the above outcome measures in HCP students were included. Two authors independently screened references and extracted data. Quality was assessed using the Modified Medical Education Research Study Quality Instrument and Cochrane Risk of Bias tools. A narrative synthesis was performed. RESULTS: Of 2367 records screened, 26 met inclusion criteria. Confidence in supporting others and mental health literacy showed the most consistent improvements following MHFA training, whereas evidence for changes in stigma was mixed. Peer support, self-care and student well-being were infrequently examined, although qualitative data suggested that MHFA had improved openness to help-seeking. CONCLUSIONS: MHFA shows promise in enhancing mental health literacy, confidence and intentions, and in reducing stigma, particularly when supplemented with experiential learning. HCP students may benefit from tailoring of such courses to their specific needs, fostering a culture of peer support, enhancing well-being and introducing basic concepts in mental health.

MHFA↗

PubMed2025

Social Responsiveness as a Mediator in Adapted Cognitive Behavioral Therapy for Autistic Youth with Maladaptive and Interfering Anxiety.

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N = 167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) with social skill supports. The primary outcome measure was the Pediatric Anxiety Rating Scale. Social responsiveness was assessed with the Social Responsiveness Scale, Second Edition. Participants' general mental health was assessed as a secondary outcome using the Brief Problem Checklist. Mediation was tested using the SPSS PROCESS macro. Analyses suggested that the effect of adapted CBT on anxiety was mediated by its effects on social responsiveness, with a statistically significant indirect effect. Youth randomly assigned to adapted CBT exhibited better overall mental health at posttreatment compared to those randomized to the other conditions, and this effect was also mediated by improved social responsiveness. CBT adapted to address some of the social needs of autistic youth may enhance mental health outcomes by supporting social responsiveness, perhaps increasing the ease and effectiveness with which some youth can navigate potentially stressful situations such as entering and participating in group activities.

Humans↗

PubMed2026

Metformin Adherence and Risk of Polyneuropathy in Type 2 Diabetes Mellitus: An International Matched Cohort Study with Independent Validation.

BACKGROUND: Metformin is a popular first-line glucose-lowering medication for type 2 diabetes mellitus (T2DM). Although metformin reduces the risks of various complications of diabetes, its potential to cause polyneuropathy by depleting vitamin B12 levels is concerning. This study investigated whether the adherence or discontinuation of metformin after adding-on a second-line antiglycemic agent increases the risk of polyneuropathy in patients with T2DM. METHODS: Data from TriNetX were obtained, and patients with T2DM who were receiving second-line antiglycemic agents were divided into metformin-adherent and metformin-nonadherent groups based on prescription claims data. Neuropathy incidence was evaluated using diagnostic claims and nerve conduction examinations. For independent confirmation and external validation of the primary findings, we used data from the National Health Insurance Research Database (NHIRD) of Taiwan. RESULTS: After matching, 58,027 patients were included in each group. Compared with metformin adherent patients, metformin nonadherent patients had a higher risk of polyneuropathy (adjusted hazard ratios [aHR] 1.26; 95% confidence interval [CI] 1.23-1.29; P < 0.001). Risks of diabetic foot ulcer, amputation, neuropathy-related medication use, and bone fracture were also higher among nonadherent patients. Sensitivity analyses confirmed the robustness of findings. In the validation NHIRD cohort (31,384 matched pairs), metformin nonadherence remained associated with increased polyneuropathy risk (aHR 1.25; 95% CI 1.10-1.42; P < 0.001). CONCLUSIONS: Metformin adherence in patients with T2DM who require second-line treatment may reduce the risk of polyneuropathy; vitamin B supplementation may enhance this benefit.

Humans↗

PubMed2026

Protein profiling and GC-MS product analysis provide insights into lignite solubilization and bioconversion by Lysinibacillus sphaericus strain SH19.

Lignite biosolubilization offers a mild route for valorizing low-rank coal, although the microbial processes that accompany solubilization remain incompletely defined. Here, an endogenous isolate designated Lysinibacillus sphaericus strain SH19 was evaluated using nitric-acid-pretreated Shengli lignite. Under the selected working conditions (4 M nitric-acid pretreatment, initial pH 8, 40°C, and 16 days), the apparent solubilization rate reached 66.81%. Changes in A450, residual solid mass, culture pH, and extracellular protein concentration showed that chemical pretreatment and bacterial culture were both associated with the release of soluble lignite-derived material. SDS-PAGE and two-dimensional electrophoresis revealed treatment-associated differences in extracellular and intracellular protein patterns. LC-MS/MS analysis of excised protein spots yielded 85 candidate protein assignments; the revised supplementary table reports PEAKS scores, sequence coverage, peak area, and unique-peptide counts and highlights the limited support for several entries. GC-MS analysis produced 33 tentative library assignments in the solubilized fraction, but siloxane- and silyl-related signals were treated as possible analytical background, and no pathway was inferred from these assignments alone. Together, the data identify strain SH19 as a promising lignite-biosolubilizing isolate and provide candidate proteins and product signals for future validation. The proposed process model remains exploratory because direct enzyme assays, inhibitor experiments, carbon-balance measurements, transcriptomic or genetic validation, complete GC-MS blank subtraction, and authentic-standard confirmation were not available.

Bacillaceae↗

PubMed2026

Autophagy activation in granulosa cells as a mechanism of astaxanthin action: evidence from a pilot randomised trial in PMOS-associated infertility.

Astaxanthin (AST) has been reported to influence oxidative stress, endoplasmic reticulum stress, and apoptosis in women with polyendocrine metabolic ovarian syndrome (PMOS), formerly referred to as polycystic ovary syndrome (PCOS), but its effects on granulosa-cell (GC) autophagy remain unclear. Given the central role of autophagy in follicular development, this triple-blind, placebo-controlled pilot randomised trial evaluated whether AST modulates autophagy-related signalling in GCs and how these molecular effects relate to ovarian response. Fifty women with PMOS-related anovulatory infertility were enrolled between November 2023 and September 2024 and received AST (12 mg/day) or placebo for six weeks prior to oocyte retrieval; forty-four completed the study (21 AST, 23 placebo). Primary exploratory endpoints were molecular markers of adenosine monophosphate-activated protein kinase (AMPK)-autophagy signalling, and primary clinical outcomes included ovarian response indicators and cleavage stage embryo quality. AST supplementation increased autophagy-related gene 7 (ATG7) expression, enhanced autophagy flux, reduced apoptosis, and showed a trend toward increased AMPK activation. Before adjustment, AST improved oocyte maturity rate (OMR) and increased mature (metaphase II; MII) oocyte yield. After adjusting for age, body mass index, and anti-mullerian hormone level, total oocyte and MII oocyte yields remained significantly higher with AST, while OMR became non-significant. Among embryology outcomes, both the top-ranking embryo rate and the number of embryos suitable for cryopreservation were significantly higher with AST after adjustment. Pregnancy outcomes were numerically higher but not statistically significant. This pilot trial suggests that AST activates autophagy- and apoptosis-related pathways in GCs and may enhance oocyte competence and embryo quality in PMOS. Larger studies are needed to confirm these mechanistic and clinical effects.

Female↗