The endocrine-microbiome axis extends the estrobolome concept, recognizing gut microbes as active endocrine partners. Bacteria modulate estrogen recycling via diverse enzymes and produce SERM-like metabolites, while host hormones shape microbial communities. This bidirectional crosstalk influences hormone-driven carcinogenesis through inflammation, genomic instability, and epigenetic changes. Therapeutic opportunities include precision probiotics and selective enzymatic inhibition. Advancing the field requires causal models, multi-omics integration, and sex as a biological variable.

Protons critically regulate cancer cell behavior, metabolism, and signaling pathways, making intracellular pH modulation a promising therapeutic strategy. Yet, precise spatiotemporal control of proton levels remains a formidable challenge. In this study, we introduce a near-infrared (NIR)-controlled nanoscale proton delivery system using upconversion nanoparticles (UCNPs) coated with photoacid (PA) and ferrocene (Fc). Upon 980 nm NIR stimulation, UCNPs emit UV-visible emission (300-500 nm), activating surface-bound PA to induce transient H+ release and acidify the tumor microenvironment in vivo. This acute acidic stress reduces tumor cell glucose uptake by 50% and suppresses mechanistic target of rapamycin (mTOR) signaling, triggering excessive autophagy that functionally drives mitochondrial dysfunction and intrinsic apoptosis-a process we define as proton-mediated autophagy-induced apoptosis (PAA). Fc, a biodegradable peroxidase mimic and a non-fluorescent quencher, is incorporated to enable real-time visual quantification of proton accumulation via H+-triggered biodegradation, restoring the NIR upconversion luminescence (at 800 nm) of UCNPs. Following intravenous administration, the nanoagent achieves a six-fold reduction in tumor weight and elevates proton levels in glioma, effectively triggering PAA under non-invasive NIR irradiation. This work establishes a spatiotemporally controlled platform for intratumoral proton dynamics, enabling precision cancer theranostics.

Kidney injury is a clinical condition characterized by a rapid decline in renal function, associated with high morbidity and mortality. This study aimed to investigate the protective effects and mechanism of oridonin against cadmium-induced kidney injury in mice. A mouse model of cadmium-induced kidney injury was established by cadmium administration. Inflammatory cytokines were tested by ELISA. Protein expression was measured by western blot analysis. Oridonin treatment reduced cadmium-induced serum creatinine and blood urea nitrogen (BUN), kidney myeloperoxidase (MPO) activity, and TNF-α and IL-1β production. Oridonin also alleviated pathological changes in the kidney caused by cadmium. Furthermore, cadmium-induced hypoxia-inducible factor-1α (HIF-1α), NLRP3 inflammasome and NF-κB activation were inhibited by oridonin. Oridonin also suppressed cadmium-induced ferroptosis. In addition, oridonin upregulated SIRT1 expression and the protective effects of oridonin on cadmium-induced inflammation and ferroptosis were abolished by SIRT1 inhibitor. In conclusion, oridonin attenuates cadmium-induced kidney injury by activating SIRT1, which in turn suppresses inflammation and ferroptosis.

During X chromosome inactivation (XCI), Xist RNA establishes silencing by coating the chromosome in cis and binding diverse proteins to promote formation of a heterochromatic domain. However, Xist repeat B role beyond initiation of XCI remains unclear. Here, we find that loss of Xist repeat B in female mice allows survival and leads to a small body size persisting throughout life. Epigenetic and transcriptomic analyses reveal low levels of H3K27me3 and H2AK119ub occupancy on the X chromosome, except in certain CpG island regions, and partial reactivation of X-linked genes on the inactive X across multiple tissues. Notably, overdosage of Usp9x promotes centrosome amplification and chromosome instability. We further demonstrate that Usp9x overdosage alters asymmetric cell division, thereby affecting the process of cell differentiation. Thus, Xist repeat B is necessary for gene-specific silencing during XCI maintenance and impacts cell proliferation and differentiation during development. This provides insights into repeat B importance in maintaining XCI.

D-1553 (garsorasib) is a novel and selective oral KRASG12C inhibitor. This study aims to evaluate the effect of food on the single-dose pharmacokinetics (PK) of D-1553 tablet in healthy Chinese subjects. Also the safety and tolerability of single-dose D-1553 in subjects are also evaluated. A randomized, open-label, single-dose, two-intervention (fed vs fasting), two-period, two-sequence crossover study was performed on 14 healthy Chinese subjects. Plasma concentrations of D-1553 were determined by the liquid chromatography-tandem mass spectrometry method. Safety evaluations were carried out during the study period. The main PK parameters of the two formulations of D-1553 were calculated by non-compartmental analysis using Phoenix WinNonlin (Version 8.3) software. The geometric mean ratios (90

Neuroinflammation is involved in the development of depression and may induce depression-like behaviors by affecting metabolism through interactions with circadian rhythms. As the hub of metabolism, mitochondria are regulated by various types of metabolism and release signals that regulate cellular functions. In this study, we performed transcriptomic analysis of the hippocampus of IL-33-overexpressing mice to provide new ideas to explore the pathogenesis of inflammation-mediated depression at the transcriptional level. Male C57BL/6J mice and IL-33-overexpressing mice were subjected to behavioral tests. The hippocampus was extracted during the light or dark period, and differential gene expression analysis was conducted using RNA sequencing. Differential gene enrichment analysis was performed, as well as multilayered analysis of mitochondrial transcriptional rhythms by integrating the regulatory networks and Mito 3.0 database. The results were further verified using RT-qPCR. IL-33-overexpressing mice exhibited depressive behaviors associated with rhythmic disorders and shortened circadian cycles. Differential KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis showed that the top 20 pathways with the lowest p-values included mood-related, immune-related, and circadian rhythm-related pathways. Differential gene GO (Gene Ontology) enrichment analysis showed that 20 of the top 30 pathways with the lowest p-values were related to metabolism. Transcriptome data from IL-33-overexpressing mice showed that the mitochondrial-encoded subunit of the oxidative respiratory complex showed predominantly increased expression during the light period. Metabolic disorders and disrupted mitochondrial transcriptional rhythm were also observed. Weighted gene correlation network analysis showed that the circadian cycle is associated with depression-like behavior disorders. Network analysis showed that circadian-related genes were enriched in mitochondrial pathways related to metabolism and oxidative phosphorylation. Multilayer analysis of mitochondrial transcriptional rhythms using the mitochondrial database Mito 3.0 revealed that mitochondrial dynamics and surveillance pathways were the most enriched. The depressive behavior in mice caused by long-term IL-33 stimulation may be related to changes in the transcriptional rhythms of metabolism-related genes and the interaction between mitochondria and clock genes. This suggests that mitochondrial transcriptional rhythms are central to the pathogenesis of microinflammation-induced depression, further supporting the potential of mitochondria as a target for the prevention and treatment of depression.

As a typical organophosphate ester compound, tris(1,3-dichloro-2-propyl) phosphate (TDCPP) exhibits both estrogenic activity and genotoxicity. However, the involvement of estrogen signaling pathways in TDCPP-induced genotoxicity remains unclear. This study evaluated the effects of TDCPP (0.001-200 μM) on DNA damage and repair-related endpoints in GT1-7 mouse hypothalamic cells, and examined the roles of estrogen nuclear receptors (ERα/β) and G protein-coupled estrogen membrane receptor 1 (GPER1), as well as their downstream ERK1/2 and AKT signaling pathways, in TDCPP-induced DNA damage. Our results showed that TDCPP exposure elevated intracellular levels of reactive oxygen species (ROS) and malondialdehyde (MDA), induced DNA damage and G2/M cell cycle arrest, and increased mitochondrial damage and micronucleus formation. In addition, TDCPP significantly increased the protein expression of ATM and γ-H2AX, key markers of DNA double-strand breaks (DSBs), and upregulated the mRNA expression of most DSB repair-related genes, while downregulated mRNA expression of most DNA single-strand break (SSB) repair-related genes. TDCPP also upregulated both protein and gene expression of GPER1 and enhanced ERK1/2 phosphorylation. Pretreatment with the GPER1 inhibitor G15 or the ERK1/2 inhibitor U0126 significantly suppressed TDCPP-induced upregulation of ATM and γ-H2AX protein expression, reversed changes in mRNA levels of DSB/SSB repair-related genes, and reduced TDCPP-induced DNA damage in GT1-7 cells. These findings indicate that TDCPP activates the GPER1-ERK1/2 signaling pathway, which plays a critical role in mediating its DNA-damaging effects. CAPSULE: TDCPP induced DNA damage in GT1-7 cells by activating GPER1-ERK1/2 signaling pathway.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, tissue damage, and fibrosis, significantly affecting the quality of life. While there are currently some effective treatments available, they often come with side effects. There is an urgent need to find new treatments that can further improve therapeutic outcomes and reduce side effects. Our study investigates the role of Mesenchymal Stem Cell exosomes (MSC-exo) combined with Ginsenoside Rh2 (Rh2) in the treatment of RA. We specifically focus on how this combined strategy influences macrophage polarization and pyroptosis. This research utilized a collagen-induced rat arthritis model. The study findings reveal that the combination of MSC-exo combined with Rh2 can inhibit the polarization of M1 macrophages, increase the proportion of M2-like macrophages, and suppress M1-like macrophage pyroptosis via the NLRP3/Caspase11/GSDMD-N pathway. In the rat arthritis model, the combination of MSC-exo and Rh2 showed synergistic therapeutic effects. This research contributes to a deeper understanding of RA’s pathogenesis and presents new potential targeted therapeutic interventions. The combined application of MSC-exo and Rh2 offers promising insights for future innovative strategies in RA treatment, paving the way for more effective management of this autoimmune disease.

Necroptosis, a form of programmed cell death, initiates a series of biological responses and further culminates in necroinflammatory processes, consequently limiting the efficacy of cytokine antagonists in treating inflammatory diseases. To address this issue, DNAzyme R3-Dz specifically targeting receptor-interacting protein kinase 3 (RIP3) mRNA, a necrosome component, has been successfully developed and studied to elucidate the mechanism in cleaving its target mRNA. Then a polyamidoamine (PAMAM) derivative was constructed through the modification of nucleobase analog (termed AP) to achieve the R3-Dz delivery to macrophages. The AP/R3-Dz nanoparticles effectively downregulated the RIP3 expression, leading to subsequent decrease in the levels of reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), ultimately inhibiting the necroinflammatory processes mediated by the NOD-like receptor family pyrin domain-containing 3 (NLRP3). Finally, AP/R3-Dz nanoparticles and their combination with the NLRP3 inhibitor MCC950 suppressed the necrotic phenotype and ameliorated the disease progression in diverse models, including gouty arthritis, autoimmune hepatitis and rheumatoid arthritis. In summary, the AP/R3-Dz nanoparticles in combination with MCC950 have been demonstrated to achieve the intervention in necroptosis and inflammation by dual disruption of the intricate feedback loop of necroinflammation and thus have promising potential in the treatment of inflammatory diseases.

Objective To observe the effect of electroacupuncture(EA)at"Tianshu"(ST25)and"Zusanli"(ST36)on NOD-like receptor protein 3(NLRP3)/cysteine aspartate specific protease 1(Caspase-1)/gasdermin D(GSDMD)pyroptosis signaling pathway in ulcerative colitis(UC)mice,so as to explore its mechanism in improving UC by protecting intestinal barrier.Methods Fifty male C57BL/6 mice were randomly divided into normal,model,EA,sham acupuncture and medication groups,with 10 mice in each group.The UC mouse model was established by 3%DSS solution free drinking for 7 consecutive days.The mice in the EA group received EA(2 Hz/10 Hz,0.2 mA)at bilateral ST25 and ST36 for 20 min,while the mice in the sham acupuncture group received only sham acupuncture(light and shallow acupunture at ST25 and ST36).Mice in the medication group were orally administered mesalazine(33.4 g/kg)solution.All the interventions were performed once daily for a total of 7 days.The changes of body weight,stool shape and hematochezia of mice,the disease activity index(DAI)score,and the length of colon were recorded.The intestinal mucosal permeability was observed by in vivo small animal imaging system.HE staining was used to observe the pathological changes of colon tissue.TUNEL staining was used to observe the apoptosis of colon cells.The contents of interleukin(IL)-18 and IL-1β in serum were detected by ELISA.The average fluorescence intensity of tumor necrosis factor-α(TNF-α)and IL-6 in colon tissue was detected by immunofluorescence.The positive expression of IL-18 and IL-1β in colon tissue was detected by immunohistochemistry.The relative expression levels of zonula occludens-1(ZO-1),Occludin,NLRP3,Caspase-1 and GSDMD in colon tissue were detected by Western blot.The mRNA expressions of NLRP3,Caspase-1 and GSDMD in colon tissue were detected by qPCR.Results After modeling,the DAI,inflammatory infiltration,number of apoptotic cells,fluorescence intensity of TNF-α,IL-6 and FITC,positive expression rate of IL-18 and IL-1β,mRNA and protein expression levels of NLRP3,Caspase-1 and GSDMD,serum IL-18 and IL-1β contents were significantly increased(P<0.01)in the model group relevant to the normal group.At the same time,the colon length,ZO-1 and Occludin protein expression were significantly reduced(P<0.01).The increased DAI,inflammatory infiltration,number of apoptotic cells,fluorescence intensity of TNF-α,IL-6 and FITC,positive rate of IL-18 and IL-1β,mRNA and protein expression levels of NLRP3,Caspase-1 and GSDMD,serum IL-18 and IL-1β contents,and the decreased colon length,ZO-1 and Occludin protein expression were all reversed after the EA and medication interventions compared with the model group and in the EA group than in the sham acupuncture group(P<0.01,P<0.05).Conclusion EA can protect the intestinal mucosal permeability in UC mice,which may be related to its functions in regulating the NLRP3/Caspase-1/GSDMD axis and inhibiting pyroptosis,thereby alleviating the inflammatory injury of intestinal mucosa.

9-Chlorophenanthrene (9-ClPhe) is the most widely distributed chlorinated polycyclic aromatic hydrocarbons (ClPAHs) in environmental matrices such as the atmosphere, aquatic environments. However, the long-term low-dose toxicity of 9-ClPhe remains unclear. This study aimed to elucidate the effects and underlying mechanisms of 9-ClPhe on hepatic lipid accumulation and circadian rhythm disruption in C57BL/6 mice following a 90-day continuous exposure. Utilizing histopathological analyses and biochemical assays, we demonstrated that exposure to low-dose 9-ClPhe resulted in significant lipid accumulation in the liver. Peroxisome proliferator-activated receptor α (PPARα) activator (WY14643) was found to attenuate this hepatic lipid accumulation, indicating a critical role for PPARα in mitigating 9-ClPhe-induced effects. Moreover, our findings showed that 9-ClPhe reduced brain and muscle arnt-like protein 1 (BMAL1) protein expression, pivotal for PPARα activation, while melatonin administration restored BMAL1 levels, thereby alleviating lipid accumulation. Notably, co-immunoprecipitation assays revealed a binding interaction between aryl hydrocarbon receptor (AHR) and BMAL1, suggesting that 9-ClPhe activated AHR, leading to its interaction with BMAL1 and circadian disruption. Meanwhile, treatment with the AHR inhibitor (CH223191) mitigated 9-ClPhe-induced lipid accumulation and circadian disturbances. Collectively, our findings demonstrated that chronic low-dose 9-ClPhe exposure promoted hepatic lipid accumulation by activating the AHR-BMAL1 interaction, leading to circadian perturbation. These results highlighted the potential of low-dose 9-ClPhe to drive lipid accunmulation through circadian disruption.

BACKGROUND:Oxidative stress (OS) is linked to the development of multiple sclerosis (MS), but the causal relationship in terms of genetic pathophysiology remains ambiguous. We employed Mendelian randomization (MR) and colocalization analysis to explore the relationship between OS genes and MS, utilizing an integrative multi-omics approach. METHODS:We obtained data from a genome-wide association study (GWAS) of MS from the International Multiple Sclerosis Genetics Consortium (Discovery phase) and the FinnGen study (Replication phase). Mendelian randomization analyses were conducted using summary data to evaluate the association between molecular features of OS-related genes and MS. Additional colocalization analyses were undertaken to ascertain whether the identified signal pairs shared causal genetic variants. RESULTS:Integration of multi-omics data, including mQTL-eQTL and eQTL-pQTL, revealed that the STAT3 gene is associated with MS, supported by Level 1 evidence. The CR1 gene shows an association with MS risk, evidenced by Level 3 support. Methylation at cg24718015 and cg17833746 in the STAT3 gene correlates with reduced expression of STAT3. At the protein level, high circulating levels of STAT3 are inversely associated with MS risk (OR: 0.43, 95% CI, 0.33-0.54). Elevated levels of TNFRSF1A are also linked with a decreased risk of MS (OR: 0.21; 95% CI, 0.12-0.37), while higher levels of CR1 are positively associated with an increased risk of MS (OR: 1.17; 95% CI, 1.08-1.27). CONCLUSION:This study identifies specific OS genes that are associated with MS and enhances our understanding of its pathogenesis.

BACKGROUND:Post hepatectomy liver failure (PHLF) is associated with high mortality. However, its pathophysiology remains unclear. This study explores the interactions among inflammation, fatty acids, and lipid peroxidation in the development of PHLF. METHODS:Using mouse models of 70% (regeneration) and 86% (failure) partial hepatectomy, we examined neutrophil activity, TNF-α signaling, CD36-mediated palmitic acid transport, and ACSL4-dependent lipid peroxidation. Neutrophils were depleted via anti-Ly6G antibodies, and TNF-α, CD36 and ACSL4 were inhibited by etanercept, sulfosuccinimidyl oleate sodium and PRGL493, respectively. The analyses included transcriptomics, immunofluorescence, immunohistochemistry, flow cytometry, and oxidative stress assessments. RESULTS:The 86% hepatectomy model showed marked neutrophil infiltration and TNF-α release at 6 h and 1 day post-surgery. Neutrophil depletion reduced TNF-α, attenuated liver injury, and improved survival in the 86% model. TNF inhibition (Etanercept) decreased hepatic lipid accumulation and oxidative stress, enhancing survival. TNF-α elevated palmitic acid in hepatocytes, whereas etanercept reduced it. TNF-α promotes palmitic acid accumulation through CD36-mediated fatty acid uptake rather than de novo Lipogenesis. Palmitic acid enhanced lipid peroxidation and mortality, while ACSL4 expression increased in response to both TNF-α and palmitic acid. ACSL4 inhibition lessened oxidative injury and improved outcomes. CONCLUSION:Neutrophil-derived TNF-α drives hepatic palmitic acid accumulation and ACSL4-dependent lipid peroxidation, promoting liver injury after extensive hepatectomy. Targeting TNF-α or ACSL4 mitigates oxidative stress and improves survival, suggesting a therapeutic approach for preventing PHLF.

The DNA repair enzyme 8-oxoguanine DNA glycosylase-1 (OGG1) plays a crucial role in the initiation of DNA base excision repair pathway by recognizing and excising the oxidative base lesions including 7,8-dihydro-8-oxoguanine (8-oxoG). Beyond its canonical function in DNA repair, OGG1 has been implicated in regulating inflammation-related genes, growth factor expression, and various cell death pathways, including apoptosis, parthanatos, and autophagy. These mechanisms are often involved in obstetric and gynecological disorders, which are frequently characterized by inflammation, endothelial dysfunction, and dysregulated cell death. As such, OGG1 emerges as a potential therapeutic target for these conditions. However, comprehensive reviews detailing OGG1’s mechanistic roles in reproductive diseases remain scarce. This review aims to synthesize current knowledge primarily on non-canonical functions of OGG1, with a focus on its potential involvement in disorders such as endometriosis, polycystic ovary syndrome, uterine fibroids, and malignancies, and to highlight its promise as a therapeutic target.

Numerous studies have demonstrated a significant association between serum copper (Cu) levels and abnormal glucose metabolism. However, there is a notable lack of research specifically examining the relationship between serum Cu concentration and type 2 diabetes mellitus (T2DM) in the elderly population. Consequently, this study aims to investigate the potential association between serum Cu concentration and T2DM in elderly adults. A total of 565 participants were recruited from the outpatient and inpatient geriatric departments of the First Hospital of Jilin University between July 2021 and July 2023. Logistic regression models were employed to explore the association between serum Cu concentration and the risk of diabetes mellitus, with odds ratios (ORs) and 95

Plectropomus leopardus is a marine fish species with high economic value, and its market price is related to its body coloration. During artificial aquaculture, as the farming scale expands, environmental fluctuations often induce stress responses in P. leopardus, leading to gradual darkening or blackening of body coloration. This discoloration reduces the species’ commercial value and has become a major factor limiting the sustainable and rapid development of the P. leopardus aquaculture industry. This study used molecular cloning, RNA interference (RNAi), yeast two-hybrid assays, and co-immunoprecipitation experiments to validate the effects of jnk1 and p38 genes on body coloration. The dsRNA was successfully synthesized, and the optimal injection dosage and interference duration were determined, providing technical support for subsequent functional studies of the jnk1 and p38 genes. Yeast two-hybrid assays revealed that the jnk1 and mitf proteins could be co-expressed in the yeast system, whereas no expression was detected between p38 and mitf in yeast. Furthermore, co-immunoprecipitation (Co-IP) analysis confirmed the interaction between jnk1 and mitf proteins, as Western blot detection following immunoprecipitation revealed clear signals for both jnk1 and mitf in the IP group. Following RNAi of jnk1 and p38, the expression levels of melanogenesis-related genes, including microphthalmia-associated transcription factor (mitf), dopachrome tautomerase (dct), melanocortin 1 receptor (mc1r), and tyrosinase (tyr), were significantly downregulated. Among these, dct showed the most pronounced decrease, with an 80% reduction following jnk1-dsRNA injection and a 50% reduction after p38-dsRNA injection. Both yeast two-hybrid and co-immunoprecipitation results showed that jnk1 interacted with mitf, suggesting a direct involvement of jnk1 in the regulation of body coloration in P. leopardus. A direct interaction was identified between jnk1 and mitf, and the binding of jnk1 to mitf was found to modulate mitf activity, thereby regulating the transcription of downstream melanogenesis-related genes and influencing the melanin biosynthesis process in P. leopardus. This study not only enriches the theoretical understanding of body color variation in P. leopardus but also provides a valuable reference for further investigating the functional roles and potential applications of jnk1 and p38 in the regulation of melanogenesis.

In the reform of medical laboratory courses, innovative teaching methods and the development of a teaching assessment system are crucial. However, in past practices, assessments have encountered some issues: a greater emphasis on recording outcomes, neglecting supervision of the process; a focus on summarizing writing, overlooking the importance of analysis and improvement. In the teaching process of Jilin University’s Oncological Rehabilitation Experimental Teaching Demonstration Center, the Peer-Assisted Learning (PAL) model is employed to enhance students’ learning approaches. The innovative incorporation of Direct Observation of Procedural Skills (DOPS) and Mini-Clinical Evaluation Exercise (Mini-CEX) facilitates effective assessment and feedback. The combination of these reform measures not only addresses issues in experimental teaching but also enhances the internalization of students’ knowledge and skills. In this study, we applied the evaluation systems of Direct Observation of Procedural Skills and Mini-Clinical Evaluation Exercise (Mini-CEX) to the comprehensive laboratory course in oncological rehabilitation. We utilized questionnaires to assess the impact of these reforms on students, aiming to evaluate the effectiveness of the course modifications. Statistical analysis of the data revealed a high level of student approval and a strong willingness to learn under the new evaluation system. Compared to traditional teaching methods, the introduction of DOPS and Mini-CEX significantly enhanced students’ overall competencies and improved the quality of the oncological rehabilitation course. Our approach represents an innovative reform, suggesting that incorporating DOPS and Mini-CEX into teaching could provide a widely applicable and promising new educational method. This paper explores and systematically elaborates on the reform and practice of the teaching model and formative assessment in the comprehensive laboratory course of oncological rehabilitation.

BackgroundSarcopenia frequently occurs as a comorbidity in individuals with COPD. However, research on the impact of Appendicular Skeletal Muscle Mass (ASM) on survival in COPD patients is scarce. Moreover, there is a lack of research on the association between dietary pro-inflammatory capacity and sarcopenia in COPD.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering the years 1999 to 2006 and 2011 to 2018. We aimed to investigate the relationship between the Dietary Inflammatory Index (DII) and sarcopenia prevalence among adults diagnosed with COPD in the United States. Furthermore, we sought to explore the relationship between sarcopenia, ASMI, and all-cause mortality. The study included a total of 1,429 eligible adult participants, divided into four groups based on quartiles of DII, with adjustments for sample weights. Methodologically, we used multivariable logistic regression analyses and to examine the association between DII and sarcopenia. Additionally, we used restricted cubic spline (RCS) tests to evaluate potential non-linear relationships. To assess the effect of sarcopenia on overall all-cause mortality, we used Kaplan–Meier models and Cox proportional hazards models. Moreover, we used RCS analyses to investigate potential non-linear relationships between ASMI and all-cause mortality. Subgroup analyses were conducted to confirm the reliability of our study findings.ResultsIn our COPD participant cohort, individuals with higher DII scores were more likely to be female, unmarried, have lower educational attainment, and show lower ASMI. Using multivariable logistic regression models, we found a positive association between the highest quartile of DII levels and sarcopenia incidence [Odds Ratio (OR) 2.37; 95% Confidence Interval (CI) 1.26–4.48; p = 0.01]. However, analysis of RCS curves did not show a non-linear relationship between DII and sarcopenia. Throughout the entire follow-up period, a total of 367 deaths occurred among all COPD patients. Kaplan–Meier survival curves showed a significantly higher all-cause mortality rate among individuals with concurrent sarcopenia (p < 0.0001). Cox proportional hazards model analysis showed a 44% higher risk of all-cause mortality among COPD patients with sarcopenia compared to those without sarcopenia [Hazard Ratio (HR): 1.44; 95% CI 1.05–1.99; p < 0.05]. Additionally, our final RCS analyses revealed a significant non-linear association between ASMI levels and all-cause mortality among COPD patients, with a turning point identified at 8.32 kg/m2. Participants with ASMI levels above this inflection point had a 42% lower risk of all-cause mortality compared to those with ASMI levels below it (HR 0.58; 95% CI 0.48–0.7).ConclusionWe observed a significant association between concurrent sarcopenia and an increased risk of all-cause mortality in COPD patients within the United States. Moreover, ASMI demonstrated a non-linear association with all-cause mortality, with a critical threshold identified at 8.32 kg/m2. Our findings also revealed an association between DII and the presence of sarcopenia. Consequently, further investigations are warranted to explore the feasibility of dietary DII adjustments as a means to mitigate muscle wasting and enhance the prognosis of COPD.