The obesity paradox in bone health: high prevalence of osteoporosis and its non-linear association with BMI among urban elderly in China

Scientific Reports · 2026-04-24

Osteoporosis is a major public health concern in aging populations. Although data from rural Chinese populations are available, large-scale epidemiological studies on osteoporosis prevalence and its risk factors, particularly the complex relationship with body mass index (BMI), remain limited among urban community-dwelling elderly in China. A community-based cross-sectional study was conducted from April to August 2025 among elderly residents (aged ≥ 60 years) in Jiangling Sub-district, Suzhou. Participants were derived from a government-sponsored, non-mandatory health examination program through a two-stage voluntary process. Bone mineral density (BMD) was measured at the non-dominant distal radius using portable dual-energy X-ray absorptiometry (pDXA). Osteoporosis was defined as a T-score ≤ -2.5. Multivariate logistic regression was used to identify factors associated with osteoporosis. Among 6,496 participants (mean age 74.2 years, 55.2% female), the overall prevalence of osteoporosis was 46.7%. Prevalence was significantly higher in women (65.8%) than in men (23.2%) and increased markedly with age (from 32.6% in 60–69 years to 58.7% in ≥ 80 years). A non-linear relationship with BMI was observed: the highest prevalence was in the obese group (63.3%), followed by normal weight (50.1%), underweight (45.7%), and overweight (37.5%) groups. After adjusting for age and gender, female sex (OR = 6.28, 95% CI: 5.50–7.18) and obesity (OR = 2.18, 95% CI: 1.84–2.59) were independent risk factors, while overweight was protective (OR = 0.69, 95% CI: 0.60–0.80). This novel U-shaped relationship challenges conventional wisdom regarding the protective effect of higher body weight on bone health and suggests the existence of an optimal weight range for bone health in elderly populations. This study reveals a high prevalence of osteoporosis in an urban Chinese elderly population. The finding that obesity is an independent risk factor while overweight is protective challenges conventional wisdom and suggests that maintaining an optimal weight range (overweight by Chinese standards) may be crucial for bone health. Public health strategies should integrate targeted osteoporosis screening and promote evidence-based optimal weight management for bone health in urban elderly communities.

Improved Hypoxic Microenvironment By Nanoformulation For Effective T Cell Therapy In Mice Model

International Journal of Nanomedicine · 2025-08-01 · 2 citations

Introduction: Adoptive cell therapy (ACT) has emerged as a powerful strategy for eliciting tumor regression. However, its efficacy in solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment (TME). We developed a tumor microenvironment-responsive mesoporous silica nanosphere (MSN) formulation co-loaded with the immunostimulant imiquimod (R837), zinc peroxide (ZnO 2 ), and manganese peroxide (MnO 2 ) to alleviate hypoxia and enhance dendritic cell (DC)-mediated antitumor immunity. Methods: The immunostimulatory efficacy of our nanoparticles was evaluated in vitro using DC activation assays and in vivo in an H22 murine hepatocellular carcinoma model. Flow cytometry was employed to assess immune cell populations in tumors and lymph nodes, while immunofluorescence microscopy was used to analyze tumor hypoxia and T cell infiltration. Results: The oxygen-generating MSN formulation effectively alleviated intratumoral hypoxia, promoted DC maturation (CD80 + CD86 + ), and facilitated effector CD8 + T cell infiltration into tumors. In vivo, co-administration of the nanoformulation with ACT led to enhanced tumor suppression and systemic antitumor immune responses without evident toxicity to major organs. Conclusion: This oxygen-producing immunomodulatory nanoplatform remodels the immunosuppressive TME and significantly enhances the efficacy of ACT in solid tumors, offering a promising strategy for overcoming current barriers in T cell-based immunotherapy. Plain Language Summary: Adoptive T cell therapy is a promising treatment that uses a person’s own immune cells to fight cancer. However, it does not work well in solid tumors because the tumor environment is often low in oxygen and blocks immune responses. To solve this problem, our research team developed tiny particles, called MSN-R837-MnO 2 /ZnO 2 nanoparticles, that are specially designed to help immune cells work better in tumors. These nanoparticles respond to the acidic conditions found in solid tumors. Once they arrive at the tumor site, they do several important things:They release oxygen to improve the low-oxygen conditions (called hypoxia) inside the tumor.They activate immune cells called dendritic cells (DCs), which help trigger stronger immune attacks. They support the activity of adoptive T cells, which are the key cancer-fighting cells used in this therapy.In tests on mice with liver tumors, we found that these nanoparticles reduced tumor growth, improved oxygen levels in the tumor, and helped immune cells enter and stay active inside the tumor. Mice treated with our approach lived longer and had fewer side effects. This study shows that carefully designed nanoparticles can create a more supportive environment for immune cells in solid tumors. Our work could help make adoptive T cell therapy more effective and safer for people with difficult-to-treat cancers in the future. Keywords: adoptive T cell therapy, hypoxia, nanoparticles, tumor microenvironment

Association and interaction of blood homocysteine and p‐tau217 levels with temporal cortical thinning and cognitive impairment in Alzheimer's disease

Alzheimer s & Dementia · 2025-07-01 · 4 citations

INTRODUCTION: The relationships between blood homocysteine (Hcy), amyloid beta (Aβ), tau pathology, and their combined effects on cortical thinning and cognitive impairment in Alzheimer's disease (AD) remain poorly understood. METHODS: Participants were stratified into Aβ+ and Aβ- groups by positron emission tomography. Blood levels of Hcy, AD biomarkers (phosphorylated tau-217 [p-tau217], p-tau181, and Aβ), cortical thickness (via magnetic resonance imaging), and cognitive performance were assessed. RESULTS: Aβ+ individuals exhibited increased blood Hcy and p-tau217 levels, which negatively correlated with temporal cortical thickness and cognitive function. A significant interaction between Hcy and p-tau217 was observed in Aβ+ participants, with high Hcy exacerbating the detrimental effects of p-tau217 on temporal cortical thinning and cognitive deficits. In Aβ- individuals, Hcy levels were independently associated with tau pathology. DISCUSSION: Increased Hcy and p-tau217 levels synergistically contribute to cortical thinning and cognitive impairment, highlighting that Hcy may be a modifiable risk factor for AD progression. Highlights Increased blood levels of homocysteine (Hcy) and phosphorylated tau-217 (p-tau217) are independently and interactively associated with temporal cortical thinning and cognitive deficits. Hcy may predominantly affect tau pathology compared to amyloid aggregation, with its impact on neurodegeneration depending on coexisting pathologies. Hcy may serve as a supplementary indicator rather than as an independent predictor in Alzheimer's disease. Hcy may serve as a modifiable risk factor, whereas p-tau217 as a superior diagnostic biomarker and potential therapeutic target.

The Intrinsic Innate Immunity of Hepatocytes Suppresses HBV Replication and Is Antagonized by HBx

Viruses · 2025-12-10

(1) Background: Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of viruses that interact with hepatocytes. HBV infection is a major global health problem. Most adults clear the infection quickly after being infected with HBV, while a few people develop chronic HBV infection. It is well-known that the early innate immune response of host cells plays an important role in the fight against virus infection. However, the interactions between HBV and the intrinsic innate immune system of hepatocytes are still not fully understood. The aim of this study was to confirm the interaction between HBV and hepatocytes, and to identify the interferon-stimulated genes (ISGs) regulated by HBx and their expression in association with HBV-associated HCC (HBV-HCC), so that we can refine our understanding of the interaction between HBV and ISGs and its potential influence on HBV-HCC. (2) Methods: We analyzed data concerning the stimulation of IFN-dependent genes in primary human hepatocytes (PHHs) transfected with pathogen DNA mimetics or infected with HBV in the GSE69590 database. Bioinformatic methods, such as GSEA, GO, and KEGG, were used to analyze the differentially expressed innate immunity genes and their related pathways to identify candidate intrinsic innate immune factors. qPCR on HepG2 and Huh7 cells, which highly express HBx, was used to detect relevant intrinsic innate immune factors. qPCR, RNAi, and Elisa methods were used to identify intrinsic innate immune factors in HBV-integrated HepG2.2.15 cells, and bioinformatics analysis was conducted on the HBV-infected tissues and cells in the GEO database. (3) Results: Inhibition of the JAK-STAT pathway enhanced HBV replication in HepG2 cells transfected with HBV plasmid and HepG2-NTCP cells infected with HBV. GSEA analysis of the GSE69590 data revealed significant changes in intrinsic innate immune pathways during HBV infection with PHH for 40 h. A total of 84 differentially expressed, candidate innate immunity genes were identified in GSE69590. Validation showed that TRIM22 and TRIM56 were down-regulated when HBx was expressed. Consistently, TRIM22 and TRIM56 were up-regulated following inhibition of HBx by transfection of HBx siRNA into HepG2.2.15 cells, and HBV pgRNA was up-regulated following down-regulated expression of TRIM22 and TRIM56 in HEK293 cells. Receiver operating characteristics (ROC) and overall survival (OS) analysis of 204 HBV-HCC patients showed that expression of TRIM22 was closely associated with HBV-HCC, and high expression of TRIM22 was associated with longer survival. (4) Conclusions: Innate immunity genes TRIM22 and TRIM56 are regulated by HBx, and higher expression of TRIM22 is closely related to longer survival of HBV-HCC patients.

GRPEL2 Modulates Apoptosis in Esophageal Squamous Cell Carcinoma via the JNK Signaling Pathway

Molecular Carcinogenesis · 2025-06-11

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide with a low survival rate due to a lack of therapeutic targets. Here we found that the mitochondria-related gene GrpE-like 2 (GRPEL2) transcript levels are significantly upregulated in ESCC patient samples, and its high expression predicts poor prognosis. Knockdown of GRPEL2 aggravated suppressed cell proliferation and colony formation. Conversely, overexpression of GRPEL2 promotes ESCC cell proliferation both In Vitro and In Vivo. We delved deeper into the effects of GRPEL2 on mitochondrial function and found that the depletion of GRPEL2 induced mitochondrial dysfunction and cellular apoptosis. Mechanistically, our RNA-Seq analysis revealed that suppression of GRPEL2 expression triggers activation of the MAPK/JNK signaling pathway. Additionally, the apoptosis induced by GRPEL2 loss can be largely reversed by treatment with SP600125, a JNK inhibitor. To further enhance the feasibility of targeting GRPEL2 for inhibiting ESCC proliferation in practical applications, we conducted computer-based drug screening to identify potential GRPEL2 inhibitors. We identified Vandetanib, a known antitumor agent, as a promising molecule that not only exhibits robust binding activity but also effectively reduces GRPEL2 protein levels. In conclusion, the data presented herein implicate GRPEL2 as a pivotal regulator in ESCC, modulating the MAPK/JNK signaling cascade to potentiate apoptosis, thereby offering a specific therapeutic vulnerability for targeting ESCC.

Irradiation of prostate cancer alters circulating small extracellular vesicle functions

Scientific Reports · 2025-07-02

It is known that β1 integrins and a downstream signaling molecule c-Src are upregulated in prostate cancer (PrCa) tissues, are co-expressed in circulating small extracellular vesicles (sEVs) and contribute to cancer progression. Here, we demonstrate that sEVs from PrCa patients show robust expression of both β1 integrins and c-Src. The impact of irradiation, a widely used therapy for the treatment of PrCa, on circulating sEVs is however not fully understood. We show that sEVs isolated from the plasma of transgenic adenocarcinoma of mouse prostate (TRAMP) mice, stimulate migration and anchorage-independent growth of recipient cancer cells, but sEVs are not active when isolated from mice that had undergone pelvic irradiation of PrCa. In addition, circulating sEVs from irradiated mice do not show co-sedimentation of β1 integrins and either c-Src or sEV markers, previously observed in sEVs from non-irradiated mice, but show reduced expression of c-Src. To rule out that the observed effect of irradiation on sEVs is not due to reduced tumor size, we demonstrate that irradiation of PrCa cells in vitro diminishes sEV capability to stimulate recipient cell anchorage-independent growth. Irradiation-induced changes in the composition of circulating sEVs illustrate a tumor-suppressive effect of radiation, which may have potential therapeutic implications.

Table S5 from An African-Specific Variant of <i>TP5</i>3 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression

2025-12-11

<p>Secondary Validations of top drug hits from HCT116 WT vs Y107H clones.</p>

Zoonotic diseases in China: epidemiological trends, incidence forecasting, and comparative analysis between real-world surveillance data and Global Burden of Disease 2021 estimates

Infectious Diseases of Poverty · 2025-07-04 · 16 citations

BACKGROUND: Zoonotic diseases remain a significant public health challenge in China. This study examines the temporal trends, disease burden, and demographic patterns of major zoonoses from 2010 to 2023. METHODS: This study analyzed data from China's National Notifiable Infectious Disease Reporting System (NNIDRS, 2010-2023) on nine major zoonoses, including echinococcosis, brucellosis, leptospirosis, anthrax, leishmaniasis, encephalitis (Japanese encephalitis), hemorrhagic fever, rabies, and schistosomiasis. Joinpoint regression was applied to assess annual trends in incidence rates, while autoregressive integrated moving average (ARIMA) and exponential smoothing models were used to forecast incidence trends from 2024 to 2035. To assess the performance of the Global Burden of Disease (GBD) 2021 model in China, disease-specific multipliers-defined as the ratio of GBD estimates to national surveillance data-along with their corresponding 95% confidence intervals (CIs) were calculated to quantify discrepancies and evaluate the consistency between modeled estimates and empirical observations. RESULTS: From 2010 to 2023, the incidence rates of leptospirosis [average annual percent change (AAPC) = - 5.527%, 95% CI: - 11.054, - 0.485], encephalitis (AAPC = - 16.934%, 95% CI: - 23.690, - 11.245), hemorrhagic fever (AAPC = - 5.384%, 95% CI: - 7.754, - 2.924), rabies (AAPC = - 20.428%, 95% CI: - 21.076, - 19.841), and schistosomiasis (AAPC = - 28.378%, 95% CI: - 40.688, - 15.656) showed a declining trend in China. In contrast, brucellosis exhibited a modest but statistically significant increase (AAPC = 0.151%, 95% CI: 0.031, 0.272). For most diseases, incidence rates were consistently higher in males than females. Children aged 0-5 years accounted for a substantial proportion of encephalitis and leishmaniasis cases, while adults aged 14-65 years represented the primary affected group across the majority of diseases. Occupationally, farmers and herders were the most affected populations. Compared to national surveillance data, the GBD 2021 model substantially overestimated the burden of zoonotic diseases in China, particularly for echinococcosis (by 3.611-7.409 times) and leishmaniasis (by 3.054-10.500 times). CONCLUSION: The study revealed significant decline in several major zoonoses in China, while brucellosis showed a continued upward trend. These findings highlight the urgent need for a One Health-based prevention and control system to interrupt cross-species transmission and reduce long-term public health risks.

Sex differences in brain activity and connectivity in late-life depression

Psychoradiology · 2025-11-30 · 1 citations

Background: There are notable sex differences in the symptoms and treatment response of late-life depression (LLD); however, the underlying static and dynamic abnormalities in brain function that may drive these disparities remain unclear. This study was to investigate sex-specific aberrant brain activity in LLD. Methods: We recruited 75 LLD patients and 164 healthy controls (HCs). Static and dynamic metrics of amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) were compared across four groups (LLD-female, LLD-male, HC-female, and HC-male). Correlation and moderation analyses were then used to examine whether sex moderated the associations between brain activity, cognitive impairment, and depressive symptoms. Results: First, significant interaction effects between diagnosis (LLD vs. HCs) and sex were found for ALFF in the left paracentral lobule, ReHo in the right superior temporal gyrus, and static FC (sFC) between the right superior temporal gyrus and left middle frontal gyrus. Second, in LLD-female, ReHo (right superior temporal gyrus) and sFC (right superior temporal gyrus-left middle frontal gyrus) correlated with weight, and ALFF (left paracentral lobule) correlated with visuospatial skills. Third, sex significantly moderated the relationships between ReHo (right superior temporal gyrus) and cognition, ALFF (left paracentral lobule) and depressive symptoms, and sFC (right superior temporal gyrus-left middle frontal gyrus) and depressive symptoms in the LLD group. Conclusion: Our study highlights sex differences in static brain activity related to cognitive impairment and depressive symptoms in LLD, indicating sex-specific neurobiological underpinnings for this disorder.

mTORC1/2 inhibition induces tumor regression in CDK4/6 inhibitor-insensitive acral melanoma

Cancer Gene Therapy · 2025-11-24