Graphene quantum dots (GQDs) have emerged as promising nanomaterials in cancer therapy because of their unique physicochemical properties. This review comprehensively analyzes the roles of GQDs in cancer diagnostics and treatment, highlighting their biocompatibility, tunable photoluminescence, and surface functionalization capabilities. GQDs exhibit minimal toxicity, efficient cellular uptake, and favorable biodistribution, making them suitable for targeted drug delivery, photothermal therapy (PTT), and photodynamic therapy (PDT). Their intrinsic fluorescence also enables real-time bioimaging, supporting theranostic applications. This study explores their mechanisms of action, including reactive oxygen species (ROS) generation, heat-induced ablation, and pH-responsive drug release. GQDs have demonstrated efficacy across various cancers, such as breast, lung, brain, liver, and pancreatic cancers, through enhanced drug/gene delivery, biosensing, and image-guided therapy. Despite encouraging preclinical results, challenges related to toxicity profiling, standardization, regulatory frameworks, and scalability remain significant barriers to clinical translation. This review emphasizes the therapeutic versatility of GQDs and underscores the need for further research to overcome translational hurdles and realize their full potential in personalized cancer care.

Fibrotic diseases place a substantial burden on health and the economy, with limited treatment options. Therefore, effective therapeutic strategies are urgently needed. Emodin, a natural compound with diverse biological activities, has been demonstrated in multiple studies over recent years to have potential therapeutic effects on fibrotic diseases. This review aims to provide a comprehensive overview of the existing research on emodin’s pharmacological effects and mechanisms in inhibiting fibrotic disease, with a focus on its therapeutic advantages and systemic mechanisms. Recent studies have shown that emodin plays a role in combating fibrotic diseases by suppressing the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α; it alleviates inflammation by inhibiting the NF-κB signaling pathway and preventing the degradation of IκB. Emodin also suppresses the activation of the MAPK pathway, enhances the expression of antioxidant enzymes, and influences the metabolism of the extracellular matrix (ECM). Thus, emodin is highlighted for its potential as an antifibrotic agent, and future research directions are proposed to deepen our understanding and develop novel treatment strategies for fibrotic diseases.

Osteoarthritis (OA) is a prevalent degenerative and inflammatory disease posing a significant financial and medical burden on patients and society. Lactic acid, the terminal metabolite of glycolysis, is recognized as a pivotal signaling molecule governing diverse physiological and pathological processes, particularly in cancer and inflammatory diseases. Emerging evidence suggests that metabolic disorders are closely associated with OA, which may provide a metabolic lens for further exploring its mechanisms. Glycolytic reprogramming is now recognized as a hallmark of OA, leading to the pronounced accumulation of lactic acid within the joint microenvironment. This review synthesizes current evidence to elucidate the role of lactic acid in OA pathogenesis. We summarize the mechanism of glycolytic reprogramming in chondrocytes and macrophages under pathological conditions. Furthermore, we demonstrate that lactic acid exacerbates cartilage degeneration while simultaneously promoting inflammation resolution. These dual roles are mediated by extracellular acidification, HCAR1, and lactylation. Given that duality, we suggest that redirecting lactate flux presents considerable potential as a therapeutic approach for the prevention and management of OA.

Familial hypercholesterolemia (FH) is a heritable condition that disrupts the body’s ability to clear low-density lipoprotein cholesterol (LDL-C), commonly known as “bad cholesterol” from the bloodstream. This leads to persistently elevated LDL levels from birth, significantly increasing the risk of premature atherosclerosis and cardiovascular events, such as heart attack and stroke. This occurs due to variations in genes such as low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). The treatments that are available for FH include pharmacological interventions, microbiome-based treatments, molecular approaches, nanotechnology methods, surgical procedures, nutraceuticals, herbal therapy, yoga and physical fitness methods, along with lifestyle management. This review discusses the adverse effects associated with various conventional treatment methods for hypercholesterolemia and the need for a safe and effective approach for the treatment of this genetic condition. An integrated approach combining pharmacological, molecular, and lifestyle interventions has emerged as a pragmatic solution. Yoga and fitness-based therapies positively impact lipid profiles, offering non-pharmacological and holistic adjunctive options. This comprehensive approach addresses the multifaceted aspects of FH management, considering genetic factors, socioeconomic considerations, and individualized patient needs.

This study aimed to investigate the protective effects of berberine (BBR) on pancreatic β-cells and explore its underlying molecular mechanisms via a proteomics-based approach.

Using db/db mice as a diabetes model, BBR was administered at doses of 100 mg/kg and 200 mg/kg for 8 weeks. The protective effects were assessed through fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), pancreatic histopathological analysis, and TUNEL staining. Proteomic analysis employing the data-independent acquisition (DIA) method identified differentially expressed proteins (DEPs), whereas Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to identify potential pathways. Molecular docking, surface plasmon resonance (SPR), and immunohistochemistry (IHC) were performed to validate key target proteins.

BBR significantly reduced blood glucose levels, improved insulin resistance, enhanced insulin secretion, and reversed pathological changes in pancreatic tissue, thereby alleviating β-cell damage. Proteomic analysis identified 171 DEPs, implicating the AGE/RAGE signaling pathway as a key mechanism through which BBR exerts its protective effects. The results of molecular docking, SPR and IHC confirmed that BBR markedly inhibited the activation of the AGE/RAGE pathway.

These findings suggest that BBR alleviates pancreatic β-cell damage, potentially through regulation of the AGE/RAGE pathway, providing insights into its therapeutic potential for diabetes management.

Glioma is a highly lethal tumor of the central nervous system (CNS) with limited therapeutic options. Recent evidence has highlighted the role of dysregulated alternative splicing in glioma progression. Although OY-TES-1 has been proposed as a potential therapeutic target, its splice isoforms have not been fully characterized. This study aimed to identify the clinically relevant splice variant of OY-TES-1 associated with glioma progression and to evaluate its potential as a target for innovative therapeutic strategies against this challenging disease.

The potential splicing patterns of OY-TES-1, along with their relative frequency and correlation with patient survival, were analyzed via the TCGA SpliceSeq and OncoSplicing databases. RNA-Seq by expectation maximization (RSEM) values and clinicopathological data for all OY-TES-1 gene transcripts were downloaded from the UCSC Xena database, and Cox regression analysis was performed for both univariate and multivariate prognostic assessments. The expression of OY-TES-1 mRNA in glioma and normal brain tissues was detected via RT-PCR. The relationships between OY-TES-1 mRNA expression and the clinicopathological characteristics of glioma patients were analyzed via the χ² test. OY-TES-1-V5a was overexpressed in glioma cells through transient transfection with plasmids as well as stable transfection with lentivirus for further functional analysis. Glioma cell proliferation was assessed via the Cell Counting Kit-8 (CCK-8) assay. Migration and invasion abilities were evaluated via wound healing, Transwell, and Transwell Matrigel assays. Apoptosis was analyzed by flow cytometry.

Bioinformatic analysis revealed four alternative splice variants of OY-TES-1 in glioma, among which OY-TES-1-V5a presented a relatively high percent spliced-in (PSI) value that was associated with significantly shorter overall survival. OY-TES-1-V5a was further identified as an independent prognostic risk factor for glioma patients, as its mRNA expression was significantly associated with Karnofsky performance status (KPS), tumor grade, and isocitrate dehydrogenase 1 (IDH1) mutation status. RT-PCR validation confirmed that OY-TES-1-V5a was overexpressed in glioma tissues compared with normal brain tissues. Functionally, forced expression of OY-TES-1-V5a enhanced glioma cell proliferation, migration, and invasion while suppressing apoptosis.

The OY-TES-1 splice variant V5a is highly expressed in glioma, is associated with poor prognosis, and actively drives malignant behavior, indicating its potential utility as a prognostic biomarker and a candidate target for therapeutic intervention.

Bronchiolar adenoma (BA) is a peripheral pulmonary neoplasm characterized by a bilayered cell structure composed of basal cells and luminal cells. Owing to its low incidence and limited research data, clinicians and pathologists still have an insufficient understanding of this disease. This study aims to characterize the morphological, immunohistochemical, and genetic features of BA and its variants, and to determine whether BA can progress to a malignancy.

Among these 33 cases, 21 were histologically characterized by double-layered tumors with continuous basal cell layers. Six patients exhibited a partial classic bilayer, transitioning from a bilayer to a monolayer in certain lesion areas (mixed-type BAs). Six other BA-like tumors with monolayered components might represent the early stage of malignant transformation of BA. Next-generation sequencing analysis was conducted on 33 cases to elucidate the genetic spectrum.

All the cellular components exhibited a relatively mild morphology. Immunohistochemical analysis revealed that basal cells coexpressed p40 and cytokeratin 5/6. Thyroid transcription factor 1 was expressed in the double-cell layer, which consists of ciliated columnar epithelial cells, basal cells, nonciliated columnar epithelial cells, and cuboidal epithelial cells. The pan-cancer gene panel was used to observe driver alterations in 9 of 21 classic bilayered BAs (43%), 2 of 6 mixed-type BAs (33%), and 3 of 6 monolayered BA-like lesions (50%). Genetically, monolayered BA-like lesions shared some alterations with classic BAs in mutational signatures, whereas NKX2-1 mutations were enriched only in monolayered BA-like lesions.

These findings underscore the histopathological and genetic characteristics of BA and its variants, suggesting that monolayered BA-like lesions have the potential to develop into lung adenocarcinoma. In the future, more cases should be recruited to further explore the malignant transformation of this specific entity via the multidimensional spectrum.

This study aimed to investigate the associations of the triglyceride-glucose (TyG) index with kidney function decline, cardiovascular disease (CVD) events, and all-cause mortality across different glucose tolerance statuses.

We analyzed 8,434 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. The primary outcomes were kidney function decline, CVD events, and all-cause mortality. Associations between the TyG index and outcomes were evaluated using binary logistic regression models.

During a 5-year follow-up, 150 participants (1.80%) developed kidney function decline, 357 (4.30%) experienced CVD events, and 335 (4.00%) died from all causes. An elevated TyG index was associated with increased risks of kidney function decline, nonfatal CVD events, and all-cause mortality in the overall population and among participants with diabetes (quartile 4 [Q4] vs. quartile 1 [Q1]: hazard ratio [HR] [95% confidence interval, P-value] = 4.97 [1.41–31.71, P = 0.034], 4.63 [1.25–30.19, P = 0.047], and 4.54 [1.70–15.88, P = 0.007], respectively). These associations were not statistically significant in participants with normal glucose tolerance or prediabetes. Notably, an elevated TyG index was significantly associated with increased risk of fatal CVD events in the overall population and across all glucose tolerance subgroups, with the strongest association observed in participants with prediabetes rather than diabetes.

The TyG index is significantly associated with the risks of kidney function decline, CVD events, and all-cause mortality, and these associations differ by glucose tolerance status.

Electroacupuncture (EA) has emerged as a clinically adopted complementary modality in the management of respiratory and digestive disorders. This investigation sought to elucidate the therapeutic potential of EA against sepsis-induced pulmonary and gastrointestinal injuries, with particular emphasis on delineating its multimodal mechanistical pathways.

Sepsis was induced in C57BL/6 mice by administeringting lipopolysaccharide (LPS) one hour after EA intervention at the Zusanli (ST36) and Tianshu (ST25) acupoints for eight days. Inflammatory responses and barrier function were evaluated in the lung and colon tissues. Hematoxylin and Eosin (H&E) staining was performed on lung tissues, while colon tissues were subjected to H&E staining, Wheat Germ Agglutinin-Fluorescein Isothiocyanate (WGA-FITC) staining, and Alcian Blue staining. Additionally, Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blotting were used to explore potential molecular mechanisms. Furthermore, 16S rRNA gene sequencing was employed to analyze changes in the gut microbiota.

EA ameliorated both pulmonary injury and intestinal damage in septic mice. This protective effect was mediated through significant attenuation of pulmonary and intestinal inflammation, coupled with partial restoration of gut microbiota homeostasis. Specifically, EA inhibited the activation of Nod-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and mitogen-activated protein kinase (MAPK) pathways, and upregulated the transcription of lung barrier-related factors (MMP2, MMP9, Occludin) in the lung. In addition, EA improved inflammation and reduced damage to the intestinal mucosal barrier in the colon. This was accomplished by decreasing the expression of pro-inflammatory cytokines (IL-1β, TNF-α) and increasing the levels of mucin and glycoproteins. Furthermore, EA intervention altered the structure of the gut microbiota, resulting in a significant increase in the abundance of beneficial bacteria, such as Ruminococcaceae and Roseburia.

EA is a potential adjunct therapy for sepsis-related pulmonary and intestinal injury. The mechanism involves the inhibition of the NLRP3 inflammasome and remodeling of the gut microbiota.

Fluid management in patients with septic shock and coexisting heart failure is a critical challenge, as it requires balancing resuscitation and the risk of fluid overload. This study investigated the potential of the fluid accumulation index (FAI), which is measured serially during the initial 72 h of intensive care unit (ICU) care, to provide dynamic prognostic information to guide fluid management in this high-risk population.

Restricted cubic spline (RCS) analysis was used to explore the relationships between FAI levels at different time points within 72 h of ICU admission and ICU mortality. Associations were quantified via multivariate Cox proportional hazards models. Subgroup analyses and Kaplan‒Meier survival curves were used to evaluate the consistency of associations and differences in survival between groups.

A total of 643 patients with septic shock and concurrent heart failure were included, among whom 127 died. The RCS revealed a significant nonlinear relationship between FAI levels at various time points and ICU mortality. The optimal FAI cutoff values decreased over time: the cumulative values were 0.87 at 24 h, 0.59 at 48 h, and 0.56 at 72 h. The cutoff values for specific intervals were 0.27 for the 24–48 h period (2–24 h-FAI) and 0.12 for the 48–72 h period (3–24 h-FAI). In the fully adjusted model, FAI values exceeding these time-specific thresholds were significantly associated with increased ICU mortality (24 h-FAI > 0.87, HR = 1.96, P = 0.0251; 2–24 h-FAI > 0.27, HR = 2.07, P = 0.0051; 48 h-FAI > 0.59, HR = 2.50, P = 0.0005; 3–24 h-FAI > 0.12, HR = 2.05, P = 0.0091; 72 h-FAI > 0.56, HR = 2.97, P < 0.0001). These associations remained consistent across most predefined subgroups.

FAI serves as a dynamic and independent prognostic marker for critically ill patients with septic shock and heart failure during the first 72 h of ICU admission. A key finding was the time-dependent decline in the optimal FAI cutoff values (0.87 at 24 h vs. 0.12 for the 3–24 h period). This temporal decline supports a shift in fluid management strategy from an initial liberal approach toward a conservative strategy after the first 24 h, which may mitigate mortality risk.

To investigate the inhibitory effects of mitofusin 2 (MFN2) on hepatic stellate cell (HSC) activation and liver fibrosis progression in nonalcoholic fatty liver disease (NAFLD) through the inhibition of β-catenin nuclear translocation.

In vitro, primary mouse HSCs were treated with palmitic acid (PA), and MFN2 expression was modulated using lentiviral overexpression or knockdown. Fibrotic markers and β-catenin localization were analyzed via Western blot, cellular fractionation, and immunofluorescence. In vivo, liver fibrosis was induced in C57BL/6 J mice using a high-fat diet (HFD) combined with CCl₄ injections. MFN2 was systemically overexpressed or silenced via AAV2 vectors delivered through tail vein injection. Liver tissues were examined histologically and biochemically for fibrosis progression.

PA treatment markedly downregulated MFN2 and upregulated fibrotic markers in HSCs. Overexpression of MFN2 strongly suppressed HSC activation, reduced α-SMA and N-cadherin levels, and significantly inhibited β-catenin nuclear accumulation. Conversely, MFN2 knockdown exacerbated fibrotic responses and promoted β-catenin translocation. In mice, MFN2 overexpression substantially attenuated collagen deposition and improved liver histology, while MFN2 silencing significantly aggravated fibrosis and enhanced β-catenin signaling.

MFN2 inhibits HSC activation and liver fibrosis by suppressing β-catenin nuclear translocation, making it a promising therapeutic target for NAFLD-related fibrosis and associated complications, such as hepatocellular carcinoma.

Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD) undergoing maintenance dialysis. To further clarify this critical relationship, we conducted a prospective study to evaluate the prognostic significance of calcification in different segments of the thoracic aorta for all-cause mortality in this patient population.

This prospective study enrolled stable adult patients who were undergoing maintenance hemodialysis (MHD) at our center between July 2019 and December 2020 and who had available chest X-rays or computed tomography (CT) scans. Thoracic aortic calcification (TAC) was assessed via chest CT or X-ray imaging. Cox proportional hazards models and Kaplan‒Meier curves were used to describe the risk factors for mortality.

At a mean follow-up of 3.95 years, 18 of 62 patients had died. Cox proportional hazards regression models demonstrated that elevated systolic blood pressure (HR 1.029), aortic arch calcification (AAC) (HR 1.104), and descending thoracic aortic calcification (DTAC) (HR 1.066) were independent risk factors for all-cause mortality in patients with MHD (all P < 0.05). Additionally, the presence of severe DTAC or severe AAC emerged as an independent risk factor for death in this patient population (log-rank test, P < 0.05).

AAC and DTAC are important predictors of all-cause mortality among patients undergoing maintenance hemodialysis.

Huaier, a traditional Chinese medicine (TCM) approved by the National Medical Products Administration (NMPA) of China for cancer therapy, demonstrates broad antitumor activity. However, its potential to overcome resistance to gefitinib, a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in non-small cell lung cancer (NSCLC) and the underlying mechanisms remain unclear. This study aimed to determine whether Huaier aqueous extract enhances the efficacy of gefitinib against resistant NSCLC and to elucidate the molecular basis of this effect.

Cell proliferation was evaluated using the Cell Counting Kit-8 and colony formation assays. Apoptosis, reactive oxygen species (ROS), and lipid ROS were measured using flow cytometry, and mitochondrial morphology was examined using transmission electron microscopy. RNA sequencing and integrated bioinformatics analyses of GEO datasets were performed to identify ferroptosis-related genes, which were validated by qPCR and Western blotting. The in vivo efficacy was assessed using a PC-9GR xenograft model.

Huaier aqueous extract significantly enhanced the sensitivity of gefitinib-resistant NSCLC cells to gefitinib in vitro, and suppressed tumor growth in vivo. Mechanistically, the combined treatment activated the ferroptosis pathway, accompanied by the upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4). Pharmacological inhibition of ferroptosis or ACSL4 partially attenuated the antitumor effect, confirming their key roles in mediating the synergistic activity of Huaier aqueous extract and gefitinib.

Huaier aqueous extract reversed gefitinib resistance in NSCLC cells by promoting ACSL4-dependent ferroptosis, thereby providing a promising therapeutic strategy for improving EGFR-TKI efficacy.

The benefits of caffeine to human health have been widely reported, but the association between caffeine intake and mortality among patients with chronic kidney disease (CKD) has been rarely reported in large epidemiologic studies. This study aimed to investigate the association between caffeine intake and mortality among CKD patients.

Our study was conducted among non-dialysis CKD patients in the 2003–2016 National Health and Nutrition Examination Survey (NHANES). Weighted COX regression analysis was used to explore the linear relationship between caffeine intake and mortality among CKD patients (including all-cause mortality, as well as mortality due to cardiovascular disease, cancer, cerebrovascular disease, nephropathy, and influenza or pneumonia). Restricted cubic spline analysis was performed to explore the nonlinear relationship. Finally, threshold effects were analyzed through fitting a two-piecewise linear regression model.

In a fully adjusted model, no significant linear association was found between caffeine intake and mortality. However, there was a U-shaped association between caffeine intake and all-cause mortality (inflection point: 277 mg). Moreover, there was a J-shaped association between caffeine intake and cardiovascular mortality (inflection point: 252 mg) and cancer mortality (inflection point: 79 mg).

All-cause mortality was reduced in CKD patients when caffeine intake was less than 277 mg (about 1.85 cups of Americano). However, excessive caffeine intake was associated with increased all-cause mortality, cardiovascular mortality and cancer mortality in this population.

This study aimed to investigate the association between laboratory biomarkers and short-term poor prognosis in patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and to develop a risk stratification model.

A retrospective analysis was conducted on clinical data from 117 EBV-HLH patients admitted to our hospital between June 2016 and December 2024. Patients were classified into poor prognosis (n = 48) and good prognosis (n = 69) groups based on 28-day outcomes. Potential predictors were screened by univariable logistic regression and receiver operating characteristic (ROC) curve analysis, and a composite laboratory-based risk scoring system was subsequently constructed.

The poor prognosis group exhibited significantly higher levels of urea (UREA), direct bilirubin (DB), high-sensitivity cardiac troponin I (hscTnI), serum ferritin (Ferr), and prothrombin time (PT) than the good prognosis group did (all P < 0.05). ROC analysis determined the optimal cutoff values and corresponding odds ratios (ORs) for poor prognosis as follows: UREA (≥ 5.4 mmol/L, OR = 5.911), DB (≥ 10.0 μmol/L, OR = 2.524), hscTnI (≥ 7.4 pg/mL, OR = 2.747), Ferr (≥ 12,422 μg/L, OR = 2.366), and PT (≥ 14.1 s, OR = 3.221). A 0–5-point risk score model was constructed based on these thresholds. The incidence of poor prognosis increased progressively with the score: 23.08% (score 0–1), 27.59% (score 2), 45.00% (score 3), 66.67% (score 4), and 92.30% (score 5). Each 1-point increase in the score was associated with an OR of 1.915 for poor prognosis.

The composite risk scoring system incorporating UREA, DB, hscTnI, Ferr, and PT showed satisfactory predictive performance for short-term outcomes in EBV-HLH patients. A score of ≥3 identifies high-risk individuals who may benefit from intensified immunomodulatory therapy, thereby facilitating individualized and stratified clinical management.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with metabolic dysregulation. This study aimed to investigate the role of homogentisic acid (HGA), a tyrosine metabolite, in AD pathogenesis and explore its potential as a noninvasive diagnostic biomarker.

Human saliva samples from AD patients and controls were analyzed. In vivo experiments were conducted using APP/PS1 (Aβ-driven) and P301S (tauopathy-focused) mouse models, which received exogenous HGA via gavage. Key techniques included behavioral tests (Morris water maze, novel object recognition, fear conditioning), Western blot, immunofluorescence, real-time PCR, and mass spectrometry to assess cognitive function, blood–brain barrier (BBB) integrity, Aβ aggregation, synaptic protein expression, and HGA metabolism. In vitro experiments were performed on HT22, SY5Y cells, and primary brain microvascular endothelial cells (BMECs) to verify HGA’s direct effects.

Salivary HGA levels were higher in AD patients than in controls, correlating with BBB impairment. Exogenous HGA significantly exacerbated cognitive deficits, BBB leakage, Aβ deposition, and loss of synaptic proteins (PSD93, synaptophysin) in mice, with effects more pronounced in the APP/PS1 than in the P301S model. In vitro, HGA exerted dose-dependent neurotoxicity, promoted Aβ aggregation, and downregulated tight junction proteins (claudin-5, occludin, ZO-1) in BMECs. Mechanistically, AD patients showed reduced expression of HGA-metabolizing enzymes (homogentisate 1,2-dioxygenase, maleylacetoacetate isomerase) and downstream metabolites, indicating impaired HGA catabolism. These findings confirm HGA promotes AD progression via two mutually reinforcing pathways: (1) accelerating Aβ aggregation and synaptic dysfunction; (2) disrupting BBB integrity through downregulating tight junction proteins.

This study identifies salivary HGA as a potential noninvasive biomarker and highlights targeting HGA metabolism or BBB protection as promising strategies for early AD intervention.

Non-communicable diseases (NCDs), characterized by long duration, gradual progression, and high morbidity, have emerged as a fundamental threat to global public health. Furthermore, dramatic climate change may exacerbate existing trends that worsen the burden of NCDs. Therefore, this study aimed to systematically investigate the patterns and trends of NCDs attributed to nonoptimal temperatures from 1990 to 2021.

We utilized data from the Global Burden of Disease Study (GBD) 2021 to assess the temporal trends in age-standardized rates (ASR) of deaths and disability-adjusted life-years (DALYs) related to nonoptimal temperature-associated NCDs across 204 countries and territories from 1990 to 2021. Decomposition analysis was applied to quantify the contribution of key factors to this burden. The autoregressive integrated moving average (ARIMA) model was employed to predict trends over the next decade.

Globally in 2021, NCDs attributable to high temperature (Hi-Tem) accounted for an estimated 302,464.7 deaths (95% uncertainty interval [UI]: 171,170.6, 472,625.3) and 6,947,660.6 DALYs (95% UI: 4,013,964.7, 10,611,801.7). The ASR of Hi-Tem-related NCDs deaths and DALYs increased by 35% and 34% between 1990 and 2021. Additionally, the global burden exhibited a significant declining trend in NCDs burden caused by low temperature (Lo-Tem), with 1,477,729.8 (95% UI: 1,316,829.3, 1,631,404.8) deaths and 27,797,533.3 (95% UI: 25,270,393.5, 30,766,299.9) DALYs in 2021. China and India had the highest number of deaths and DALYs for NCDs related to Hi-Tem and Lo-Tem. In 2021, the three leading causes of the NCDs burden attributable to nonoptimal temperature were ischemic heart disease, stroke, and chronic obstructive pulmonary disease. Men and older adults were consistently vulnerable to temperature, showing the greater burden of NCDs attributable to nonoptimal temperature, and aging would exacerbate this trend. The ARIMA model projected an increasing trend in Hi-Tem-related NCDs over the coming decade, while those related to Lo-Tem would show a downward trend.

The burden of NCDs associated with Hi-Tem has conspicuously increased in recent years compared to that associated with Lo-Tem, with significant diversity across age, sex, and socio-demographic index (SDI) levels. Therefore, public health strategies should prioritize tailored interventions for heterogeneous risk profiles across vulnerable populations, integrated with climate-resilient surveillance systems and real-time adaptive response mechanisms to mitigate projected climate-mediated exacerbations of NCD burden.

To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the bacterial profile of lower respiratory tract infections (LRTIs) and the prevalence of major drug-resistant bacteria in Hubei Province, China, by comparing five-year periods before (2015–2019) and after (2020–2024) the pandemic.

A retrospective analysis was conducted on microbial culture and antimicrobial susceptibility test results from sputum and bronchoalveolar lavage fluid (BALF) samples obtained from patients with LRTIs. Pathogen distribution and the prevalence of key drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), cefotaxime/ceftriaxone-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPAE), carbapenem-resistant Acinetobacter baumannii (CRABA), ampicillin-resistant Haemophilus influenzae (ARHI), and penicillin/erythromycin-resistant Streptococcus pneumoniae (PRSP/ERSP), were compared between the two periods.

The overall number of bacterial isolates significantly increased during the post-pandemic period. Gram-negative bacteria remained dominant, although their relative composition shifted. The detection rates of common community-acquired pathogens (Haemophilus influenzae, Streptococcus pneumoniae) decreased sharply during the strict control phase (2020–2022) but rebounded from 2023 to 2024. The overall prevalence of most key drug-resistant bacteria followed a decreasing trend. Notably, the detection rates of MRSA and cefotaxime/ceftriaxone-resistant Enterobacterales decreased most markedly (> 15%). The prevalence of CRE and CRABA followed a “decrease-then-increase” trend, while carbapenem-resistant Klebsiella pneumoniae detection rates remained higher than the 2015 baseline, and carbapenem-resistant Escherichia coli  prevalence was on par with the 2015 level in 2024. Although the detection rate of CRABA tended to decrease, it remained above 60%. In contrast, the detection rate of the ERSP was consistently high (> 90%), whereas that of the ARHI exhibited a continuous upward trend (increasing by more than 30%).

The COVID-19 pandemic significantly altered the bacterial ecology and resistance patterns of LRTIs. While stringent public health measures initially suppressed the transmission of some resistant pathogens, they may have facilitated the subsequent emergence and spread of more formidable drug-resistant bacteria. Continuous surveillance and reinforced infection control measures are crucial in the post-pandemic era.

Emerging evidence implicates neuroinflammation in the pathogenesis of major depressive disorder (MDD), yet the role of memory B cells remains unclear. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) study and Bayesian colocalization analyses to investigate the causal relationships between memory B-cell traits and MDD risk.

MDD summary data were gathered from a meta-analysis of genome-wide association studies (GWASs), whereas memory B-cell genetic variations were sourced from GWASs on immune phenotypes. MR analysis utilized the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Moreover, various sensitivity analyses, including Cochran’s Q test, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), MR-Egger intercept test and Leave-one-out (LOO) analysis, were performed to confirm MR result stability. Bayesian colocalization analyses were also conducted to identify genetic loci shared between memory B cells and MDD.

Our results indicated that genetically predicted increased CD27 protein expression on memory B cells causally elevated MDD risk (ORs: 1.025–1.063, P_FDR < 0.05). Conversely, MDD did not causally affect memory B-cell traits. Additionally, the colocalization analysis revealed no shared genetic variants, suggesting distinct biological pathways.

These findings highlight CD27 as a potential novel biomarker and therapeutic target in MDD, warranting further clinical validation in the future.