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Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future.

The role of trimethylamine oxide (TMAO) in patients with cognitive impairment remains controversial. This study aimed to assess the association between TMAO and its precursors and the prevalence of cognitive impairment. PubMed, Embase, and Web of Science databases were searched for studies that met the inclusion criteria from their inception to 14 September 2024, and references were manually searched to identify any additions. Odds ratio (OR) was assessed by random-effects modeling, subgroup analyses to identify potential sources of heterogeneity, and the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) Inventory for qualitative evaluation. Nine studies involving 82,246 participants were included in the analysis. Meta-analyses suggested that elevated TMAO levels were strongly associated with an increased risk of cognitive impairment (OR: 1.39, 95% confidence interval [95%CI]: 1.09-1.77,  < 0.05, I :60%), and consistent results were obtained across all subgroups examined and sensitivity analyses. However, in the TMAO dose-response meta-analysis and TMAO precursor meta-analyses, the results were not significantly different (dietary choline: OR: 0.93, 95%CI: 0.78-1.10, = 0.385, I :68%, plasma choline: OR: 0.65, 95%CI: 0.41-1.02,  = 0.063, I :76%, plasma betaine: OR: 0.74, 95%CI: 0.52-1.05,  = 0.094, I :61%). We found that high TMAO concentrations were positively associated with the risk of cognitive impairment. TMAO is expected to be a potential risk predictor and therapeutic target for cognitive impairment. However, more high-quality studies are needed to further investigate the dose relationship between circulating TMAO concentrations and cognitive impairment. PROSPERO, identifier: CRD42023464543.

Patients with type 2 diabetes mellitus (T2DM) often exhibit dysregulated lipid metabolism, which contributes to the development and progression of complications, such as cardiomyopathy and nephropathy. Lipid droplet (LD) dynamics involve several processes, such as synthesis, lipolysis, and lipophagy. They also interact with organelles, such as the endoplasmic reticulum, mitochondria, and Golgi apparatus. These dynamic behaviors are essential for the maintenance of cellular energy homeostasis. Under physiological conditions, LDs in pancreatic β-cells are involved in lipid metabolism that regulates insulin secretion, while also isolating harmful lipids to protect β-cells from damage due to nutrient excess. In the adipose tissue, LDs respond to nutrient fluctuations by modulating lipolysis and releasing free fatty acids (FFAs) and glycerol. Glycerol can enter the liver for gluconeogenesis and changes in FFA levels affect systemic insulin sensitivity, thereby influencing glucose uptake by skeletal muscles and contributing to whole-body glucose homeostasis. Under pathological conditions, abnormal LD accumulation can lead to ectopic lipid deposition and lipotoxicity, exacerbating T2DM and its complications in target organs, such as the heart, kidneys, retina, and brain. Lifestyle interventions, such as diet and exercise, influence LD homeostasis in tissues affected by T2DM. Pharmacological agents, including certain antidiabetic and lipid-lowering drugs as well as bioactive natural products, have demonstrated tissue-specific regulatory effects on LD dynamics. Emerging therapeutic strategies targeting LDs, such as photodynamic therapy, gene editing, and gut microbiota modulation, are also being investigated. In summary, a deeper understanding of the physiological and pathological roles of LDs in different organs may offer targeted and integrated treatment options for T2DM and its associated complications.

Background Diabetes-associated cognitive dysfunction (DACD), a prevalent complication of diabetes with learning, memory, and executive function impairments, lacks targeted therapeutic options. While trace elements, oxidative stress, and inflammation are linked to DACD, the role of serum copper and its interaction with inflammatory/oxidative biomarkers in cognitive regulation remains unclear in diabetic populations. Methods This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014, including 1,149 participants (861 non-diabetic, 288 diabetic). Cognitive function was assessed via the Animal Fluency Test (AFT) and Digit Symbol Substitution Test (DSST). Serum copper levels were measured, alongside inflammatory indices: neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, neutrophil-to-monocyte-lymphocyte ratio, systemic immune-inflammation index and systemic inflammation response index; and oxidative stress markers: γ-glutamyl transferase, uric acid, and high-density lipoprotein cholesterol (HDL-C). Associations were analyzed using multivariable linear regression, causal mediation analysis, restricted cubic spline models and sex/age subgroup stratification. Results Diabetic participants had lower DSST scores than non-diabetic individuals ( P  < 0.001). In diabetic participants, serum copper was negatively associated with AFT scores (β = − 0.132, P  = 0.034) and positively correlated with HDL-C (β = 0.559, P  = 2.11e-06). HDL-C was the sole factor that statistically mediated the association between serum copper and DSST scores (average causal mediation effect = 0.095, 95% CI: 0.046–0.153, P  < 0.001). A non-linear relationship emerged: HDL-C remained stable at serum copper < 20 µg/dL but increased significantly when copper exceeded 25 µg/dL ( P  < 0.001). Stratified analyses revealed threshold heterogeneity (all P  < 0.05): males had a lower serum copper threshold (24.5 µg/dL, 95% CI: 21.8–27.2) than females (26.1 µg/dL, 95% CI: 23.4–28.8), and adults ≥ 65 years had a higher threshold (27.3 µg/dL, 95% CI: 24.5–30.1) than those < 65 years (23.8 µg/dL, 95% CI: 21.1–26.5). Conclusions This study identifies a diabetes-specific statistical association between serum copper, HDL, and cognitive function in DACD. The 25 µg/dL copper threshold (exploratory inflection point) marks where HDL-C-mediated effects become prominent, while sex- and age-specific threshold differences highlight population heterogeneity. This threshold offers a reference for trace element-lipid interaction research but requires validation in independent cohorts before potential use in DACD risk stratification.

Rising ambient temperatures and the increasing frequency of training and competition in hot climates have made heat stress a major challenge in football. Under such conditions, players experience greater cardiovascular and thermoregulatory strain, faster glycogen use, higher perceived exertion, and progressive impairment in repeated high-intensity actions and decision-making. These responses have intensified interest in nutritional strategies that might complement heat acclimation, hydration/electrolyte planning, cooling practices, and recovery management. This narrative review critically synthesizes current evidence on nutritional interventions that may be relevant to football performed in the heat, with emphasis on hydration and electrolyte replacement, carbohydrate–protein strategies, taurine, branched-chain amino acids (BCAAs), creatine, menthol, antioxidant- and nitrate-related approaches, and selected multi-ingredient products. Across the available literature, hydration/electrolyte planning and carbohydrate–protein feeding remain the practical foundation, menthol appears most consistently useful for perceptual cooling, creatine seems safe and potentially helpful for repeated-sprint support, and taurine is promising but still supported by relatively few trials. By contrast, evidence for BCAAs, antioxidants, nitrates, and caffeine as stand-alone heat strategies, as well as for many compound supplements, remains inconsistent, context-specific, or too indirect for strong football-specific endorsement. Overall, the evidence base remains heterogeneous in study quality, protocol design, exercise mode, and sport specificity. A substantial proportion of the available data is derived from cycling, endurance, or laboratory heat-exercise models rather than football-specific trials. Accordingly, any practical recommendation should be interpreted cautiously and embedded within broader heat-management strategies. Future work should prioritize ecologically valid randomized controlled trials in football or football-like intermittent protocols, with transparent reporting of dose, timing, perceptual outcomes, and match-relevant performance measures.

[This corrects the article DOI: 10.3389/fnagi.2024.1465457.].

Background: Diabetic kidney disease (DKD) is an important public health problem worldwide that increases the mortality of patients and incurs high medical costs. Traditional Chinese Medicine injections (TCMIs) are widely used in clinical practice. However, their efficacy is unknown owing to a lack of definitive evidence. This study conducted a network meta-analysis (NMA) to evaluate the efficacy and safety of traditional Chinese medicine injections in the treatment of DKD to provide a reference for clinical treatment. Methods: Total 7 databases had been searched, which included PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese scientific journal database (VIP), WanFang, and SinoMed. Only randomised controlled trials (RCT) had been included for analysis. The retrieval time limit was from the establishment of the database until 20 July 2022. Cochrane Risk of Bias 2.0 tool was used to evaluate the quality of the studies. Network meta-analyses, and Trial Sequential Analyses (TSA) were used to analysis the effectiveness of the included RCTs for DKD. The Stata 15.1 and R 4.0.4 were used to perform the network meta-analysis. Sensitivity analysis was used to assess the robustness of the findings. The effect of the intervention evidence are summarized on the basis of the minimum background framework. Results: NMA showed that the total effective rate of SMI, DCI, DHI, HQI, and SKI combined with alprostadil injection (PGE1) was better than PGE1 single used. Based on the surface under the cumulative ranking curve values, PGE1+DHI was the most effective for urinary albumin excretion rate and 24 h urinary albumin, PGE1+HQI was the most effective for the total response rate and β2-MG, and PGE1+SKI was the most effective for serum creatinine and blood urea nitrogen. Cluster analysis found that PGE1+HQI and PGE1+SKI could be the best treatments in terms of primary outcome measures. PGE1+SKI was found to be most effective on glomerular filtration function. PGE1+DHI was most effective for urinary protein-related indices. Conclusion: The efficacy of TCMI combined with PGE1 was higher than PGE1 single used. PGE1+HQI and PGE1+SKI were the most effective treatments. The safety of TCMI treatment should be investigated further. This study needs to be validated using large-sample, double-blind, multicentre RCTs. Systematic Review Registration : [ https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=348333 ], identifier [CRD42022348333].

The southwestern Tarim Basin, shaped by the far-field effects of the India-Eurasia collision, serves as a critical archive for reconstructing source-to-sink dynamics and tectonic evolution in a Cenozoic intracontinental foreland setting. This study presents detrital zircon U-Pb geochronology and trace element data from sands of the Yulongkash and Karakash Rivers, major tributaries of the Hotan River draining the West Kunlun Orogenic Belt. Our results reveal distinct provenance signatures between the two tributaries: Yulongkash river sands (HT1) exhibit dominant Triassic (~208 Ma) and Early Paleozoic (~418 Ma) zircon populations, sourced primarily from the South Kunlun and Tianshuihai terranes, whereas Karakash river sands (MY1) are characterized by Early Paleozoic (~460 Ma) and Precambrian zircons, reflecting predominant contributions from the North Kunlun Terrane. Integration with published datasets highlights systematic spatial variations in detrital zircon age spectra, controlled by bedrock heterogeneity, fluvial geomorphology, and sediment mixing efficiency. Furthermore, crustal thickness reconstructions based on zircon trace elements constrain the terminal closure of the Proto-Tethys Ocean to ~420–440 Ma (peak crustal thickness: ~80 km) and the Paleo-Tethys Ocean to the Late Triassic (~210 Ma). These findings not only refine the provenance framework of the Hotan River drainage system but also provide critical insights into the timing of Tethyan ocean closures and the tectonic evolution of the West Kunlun Orogenic Belt, emphasizing the utility of detrital zircon records in deciphering orogenic histories within complex intracontinental settings.

Cytosolic DNA sensing, the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is an important novel role in the immune system. Multiple STING agonists were developed for cancer therapy study with great results achieved in pre-clinical work. Recent progress in the mechanical understanding of STING pathway in IFN production and T cell priming, indicates its promising role for cancer immunotherapy. STING agonists co-administrated with other cancer immunotherapies, including cancer vaccines, immune checkpoint inhibitors such as anti-programmed death 1 and cytotoxic T lymphocyte-associated antigen 4 antibodies, and adoptive T cell transfer therapies, would hold a promise of treating medium and advanced cancers. Despite the applications of STING agonists in cancer immunotherapy, lots of obstacles remain for further study. In this review, we mainly examine the biological characters, current applications, challenges, and future directions of cGAS-STING in cancer immunotherapy.

Background As obesity becomes more prevalent, it becomes more common among patients considering orthopaedic surgery, including spinal surgery. However, there is some controversy regarding whether obesity is associated with complications, failed reconstructions, or reoperations after spinal surgery. Questions/purposes We wished to determine, in patients undergoing spine surgery, whether obesity is associated with (1) surgical site infection, (2) mortality and the need for revision surgery after spinal surgery, and (3) increased surgical time and blood loss. Methods A systematic literature search was performed to collect comparative or controlled studies that evaluated the influence of obesity on the surgical and postoperative outcomes of spinal surgery. Two reviewers independently selected trials, extracted data, and assessed the methodologic quality and quality of evidence. Pooled odds ratios (OR) and mean differences (MD) with 95% CIs were calculated using the fixed-effects model or random-effects model. Data were analyzed using RevMan 5.1. MOOSE criteria were used to ensure this project’s validity. Thirty-two studies involving 97,326 patients eventually were included. Results Surgical site infection (OR, 2.33; 95% CI, 1.94–2.79), venous thromboembolism (OR, 3.15; 95% CI, 1.92–5.17), mortality (OR, 2.6; 95% CI, 1.50–4.49), revision rate (OR, 1.43; 95% CI, 1.05–1.93) operating time (OR, 14.55; 95% CI, 10.03–19.07), and blood loss (MD, 28.89; 95% CI, 14.20–43.58), were all significantly increased in the obese group. Conclusion Obesity seemed to be associated with higher risk of surgical site infection and venous thromboembolism, more blood loss, and longer surgical time. Future prospective studies are needed to confirm the relationship between obesity and the outcome of spinal surgery.