The lncRNA TRG-AS1 promotes the growth of colorectal cancer cells through the regulation of P2RY10/GNA13.

BACKGROUND: The lncRNA TRG-AS1 and its co-expressed gene P2RY10 are important for colorectal cancer (CRC) occurrence and development. The purpose of our research was to explore the roles of TRG-AS1 and P2RY10 in CRC progression. METHODS: The abundance of TRG-AS1 and P2RY10 in CRC cell lines (HT-29 and LoVo) and normal colon cells FHC was determined and difference between CRC cells and normal cells was compared. LoVo cells were transfected with si-TRG-AS1 and si-P2RY10 constructs. Subsequently, the viability, colony formation, and migration of the transfected cells were analyzed using cell counting kit-8, clonogenicity, and scratch-wound/Transwell® assays, respectively. Cells overexpressing GNA13 were used to further explore the relationship between TRG-AS1 and P2RY10 along with their downstream functions. Finally, nude mice were injected with different transfected cell types to observe tumor formation in vivo. RESULTS: TRG-AS1 and P2RY10 were significantly upregulated in HT-29 and LoVo compared to FHC cells. TRG-AS1 knockdown and P2RY10 silencing suppressed the viability, colony formation, and migration of LoVo cells. TRG-AS1 knockdown downregulated the expression of P2RY10, GNA12, and GNA13, while P2RY10 silencing downregulated the expression of TRG-AS1, GNA12, and GNA13. Additionally, GNA13 overexpression reversed the cell growth and gene expression changes in LoVo cells induced by TRG-AS1 knockdown or P2RY10 silencing. In vivo experiments revealed that CRC tumor growth was suppressed by TRG-AS1 knockdown and P2RY10 silencing. CONCLUSIONS: TRG-AS1 knockdown repressed the growth of HT-29 and LoVo by regulating P2RY10 and GNA13 expression.

The geriatric nutrition risk index is longitudinally associated with incident Sarcopenia: evidence from a 5-year prospective cohort.

BACKGROUND: Previous studies investigating the association between the geriatric nutrition risk index (GNRI) and sarcopenia either lacked longitudinal evidence or narrowly focused on specific populations. AIMS: We aimed to reveal longitudinal associations of GNRI with sarcopenia risk in community-dwelling Chinese. We also investigated interaction effects of potential factors on such associations. METHODS: We included participants aged ≥ 50 years with sufficient data from the WCHAT study who did not have sarcopenia at baseline and completed sarcopenia assessment during follow-up. GNRI was calculated according to the formula based on serum albumin, height and weight. Sarcopenia was diagnosed according to the 2019 AWGS consensus. Longitudinal associations between GNRI and sarcopenia were estimated by logistic regression with GNRI as either a continuous or categorical variable by tertiles, using generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1907 participants without baseline sarcopenia were finally included, of whom 327 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, sarcopenia risk decreased with each one standard deviation increase in GNRI (ORadjusted=0.36, 95% CI 0.31-0.43), and it also decreased successively from the lowest (< 111.2) through middle (111.2-117.7) to the highest (≥ 117.8) tertile of the GNRI level (P for trend < 0.001). Similar results were yielded by GEE. Such associations generally remained robust across subgroups with distinct characteristics, while significant differences were observed between different age groups (≥ 65 vs. <65 years) (interaction P-value < 0.05). CONCLUSION: GNRI is longitudinally associated with sarcopenia risk with possibly age-specific differences in association magnitude, which holds implications for policymakers to conduct population-based risk assessment.

Immunotherapy combined with chemotherapy in the treatment for rare primary mucoepidermoid carcinoma of the liver: a case report.

Primary mucoepidermoid carcinoma of the liver (PMCL) is rare in the hepatic system, with no standard treatment and poor prognosis with a median overall survival of only 120 days. PMCL with immunotherapy has not been reported yet. Here, we present a case of PMCL treated by immunotherapy and chemotherapy. A 64-year-old male with PMCL underwent partial right hepatectomy and liver lesion resection on 19 June 2020. Two months later, the chest computed tomography indicated the presence of multiple nodules in both lungs with higher tumor markers. Considering the presence of a tumor metastasis, the patient received four courses of immunotherapy plus mGEMOX chemotherapy from 8 September 2020. The patient tolerated the combined therapy well, with red moles on the face and chest which were considered as grade 1 reactive cutaneous capillary endothelial proliferation. He also had grade 2 thrombocytopenia and leucopenia after the first course of chemotherapy, but no neutropenia, fatigue, vomiting or diarrhea. However, his disease progressed. The patient refused further treatment and died on 20 April 2021. The overall survival time after diagnosis was 301 days. We describe here the first case report on immunotherapy treatment for PMCL. That suggested immunotherapy combined with chemotherapy may be an option after a hepatic lobectomy for PMCL.

Multidomain interventions for non-pharmacological enhancement (MINE) program in Chinese older adults with mild cognitive impairment: a multicenter randomized controlled trial protocol.

BACKGROUND: Dementia is characterized by progressive neurodegeneration and therefore early intervention could have the best chance of preserving brain health. There are significant differences in health awareness, living customs, and daily behaviors among Chinese older adults compared to Europeans and Americans. Because the synergistic benefits of multidomain non-pharmacological interventions are consistent with the multifactorial pathogenicity of MCI, such interventions are more appealing, easier to adhere to, and more relevant to daily life than single-mode interventions. One of the aims of this study is to verify the effect of multidomain intervention strategies for MCI patients based on Chinese population characteristics, and the other is to establish a biobank and image database to investigate the pathogenesis and pathways of cognitive impairment. METHODS: Our study was designed as a national multicenter, community-based randomized controlled trial (RCT). Twelve medical institutions in ten Chinese cities will participate in our study from 2020 to 2024, and 1080 community residents aged 50 and above will be enrolled as participants. Each sub-center will be responsible for 90 participants (30 people per community) across three communities (non-contact control group, health education group, and multidomain intervention group). The community will be the basic unit of the present study, and all participants in each community will receive the same intervention/control measure. Three working groups are set up in each sub-center to manage the three communities independently to minimize interference at the implementation level between the groups. The multidomain intervention group will receive integrated interventions including exercise, nutrition, sleep, health education and mindfulness meditation. All data generated by the research will be analyzed and processed by statistical software (such as SPSS 21.0, Python 3.0, etc.), and part of the research data will be displayed in the form of graphs and tables. DISCUSSION: In order to achieve a high-quality community intervention study, it is crucial to have a well-designed experimental protocol that follows rigorous scientific methodology. In addition, effective management of quality control measures and monitoring compliance throughout the study process are essential components. This study provides a detailed discussion of stakeholder compliance, research quality control, potential harm and mitigation, auditing, and future plans in order to better address research issues. TRIAL REGISTRATION: ChiCTR2000035012 (July 27, 2020).

Association between Dietary Inflammatory Index and serum Klotho concentration among adults in the United States.

BACKGROUND: Klotho is a hormone that emerges as an antiaging biomarker. However, the influence of the dietary pattern's inflammatory potential on serum Klotho levels in human populations, especially in a general adult population, remains unknown. This study aimed to evaluate the relationship between the dietary inflammatory index (DII) and serum Klotho concentrations in individuals living in the United States.  METHODS : From the 2007-2016 National Health and Nutrition Examination Survey database, data of participants who completed the full 24-h dietary history and underwent serum Klotho testing were analyzed. The association between DII and serum Klotho concentrations was estimated using multivariable linear regression models. We also conducted segmented regression model to examine the threshold effect of DII on serum Klotho concentrations. RESULTS: A total of 10,928 participants were included, with a median serum Klotho concentration of 805.20 pg/mL (IQR: 657.58 - 1001.12) and a median DII of 1.43 (IQR: - 0.16 - 2.82). Multivariable regression showed that participants with high DII scores were associated with low serum Klotho concentrations; when classifying DII into quartiles, after full adjustment, participants in DII quartiles 3 and 4 showed a decrease in Klotho levels (25.27 and 12.44 pg/ml, respectively) compared with those in the lowest quartile (quartile 1) (95% CI: - 41.80, - 8.73 and - 29.83, 4.95, respectively; P for trend = 0.036). The segmented regression showed that the turning point value of DII was - 1.82 (95% CI: - 2.32, - 0.80). A 1-unit increase in DII was significantly associated with lower Klotho levels by - 33.05 (95% CI: - 52.84, - 13.27; P = 0.001) when DII ranges from - 5.18 to - 1.82; however, the relationship was not significant when DII ranges from - 1.82 to 5.42 (P > 0.05). Furthermore, stratified analyses indicated that the observed associations between DII and serum Klotho concentration were stronger among those aged ≥ 56 years, those with normal weight, and those without chronic kidney disease (P for interaction = 0.003, 0.015, and 0.041, respectively). CONCLUSIONS: In summary, we indicated that there was a dose-response relationship between DII and serum Klotho concentrations, suggesting that adhering to an anti-inflammatory diet has beneficial effects on aging and health by increasing the serum Klotho concentration.

Potential association between frailty and pTau in community-dwelling older adults.

BACKGROUND: Frailty is a geriatric syndrome characterized by a decline in physiological reserves, and multiple factors contribute to the occurrence and development of frailty. Growing evidence supports a strong link and overlap between frailty and cognitive impairment, but the mechanisms involved have not yet been fully elucidated. AIM: To identify associations between 12 plasma cognition-related biomarkers and frailty in community-dwelling older adults. METHODS: A total of 375 participants (age 70.9 ± 5.8, 165 men and 210 women) were included in this study. Frailty was assessed using the modified Fried frailty phenotype. Participants were divided into not-frail group (n = 313) and frail group (n = 62). Twelve plasma cognitive biomarkers were detected by enzyme-linked immunosorbent assay (ELISA). Multinomial logistic regression was used to explore the association between different biomarkers and frailty status. RESULTS: Among the 12 biomarkers, only pTau was higher in frail individuals than in their not-frail peers (471.3 ± 58.1 pg/mL vs. 451.9 ± 61.1 pg/mL, p = 0.022). No other biomarkers had any significant association with frailty, including total-Tau (tTau), neurofilament light (NFL), amyloid-ß 40 (Aß40), amyloid-ß 40 (Aß42), S100 calcium binding protein B (S100B), visinin-like protein 1 (VLP-1), Alzheimer-associated neuronal thread protein (AD7cNTP), ß-amyloid precursor protein (ßAPP), chitinase-3-like-1 (CHI3L1), soluble complement receptor 1 (sCR1) and heart-type fatty acid binding protein (hFABP). Furthermore, pTau was compared between negative and positive subject groups for each individual criterion of frailty. Significantly higher levels of pTau were observed in those who were positive for the criteria of low grip strength (451.2 ± 61.4 pg/mL vs. 469.1 ± 57.6 pg/mL, p = 0.019), exhaustion (451.2 ± 61.6 pg/mL vs. 466.4 ± 58.4 pg/mL, p = 0.035) and low physical activity (451.1 ± 60.7 pg/mL vs. 465.7 ± 60.7 pg/mL, p = 0.034) when compared to those who were negative for each corresponding criterion. Finally, in the multivariable-adjusted analysis, the association between pTau and frailty was statistically significantly associated (OR: 1.40, 95% CI: 1.04-1.89), even after adjusting. CONCLUSIONS: The present study found a potential association between pTau and frailty. Future works should monitor the longitudinal trajectory of changes of pTau concentrations in frailty older adults. A better understanding of the molecular mechanisms behind will contribute to biomarker research in frailty.

Crack Unet: Crack Recognition Algorithm Based on Three-Dimensional Ground Penetrating Radar Images.

Three-dimensional (3D) ground-penetrating radar is an effective method for detecting internal crack damage in pavement structures. Inefficient manual interpretation of radar images and high personnel requirements have substantially restrained the generalization of 3D ground-penetrating radar. An improved Crack Unet model based on the Unet semantic segmentation model is proposed herein for 3D ground-penetrating radar crack image processing. The experiment showed that the MPA, MioU, and accuracy of the model were improved, and it displayed better capacity in the radar image crack segmentation task than current mainstream algorithms do, such as deepLabv3, PSPNet, and Unet. In the test dataset without cracks, Crack Unet is on the same level as deepLabv3 and PSPNet, which can meet engineering requirements and display a significant improvement compared with Unet. According to the ablation experiment, the MPA and MioU of Unet configured with PMDA, MC-FS, and RS modules were larger than those of Unet configured with one or two modules. The PMDA module adopted by the Crack Unet model showed a higher MPA and MioU than the SE module and the CBAM module did, respectively. The results show that the Crack Unet model has a better segmentation ability than the current mainstream algorithms do in the task of the crack segmentation of radar images, and the performance of crack segmentation is significantly improved compared with the Unet model. The Crack Unet model has excellent engineering application value in the task of the crack segmentation of radar images.

Low lean mass and cognitive performance: data from the National Health and Nutrition Examination Surveys.

BACKGROUND: Low lean mass and cognitive impairment are both age-related diseases. In addition, these conditions share many risk factors. However, the association between them has been controversial in recent years. OBJECTIVE: To investigate the association between low lean mass and cognitive performance in U.S. adults using NHANES data from 1999 to 2002. METHODS: A total of 2550 participants were identified in the National Health and Nutrition Examination Survey Database (1999-2002). The independent variable was low lean mass, and the dependent variable was cognitive performance. Men and women were classified as having low lean mass if appendicular lean mass (ALM) adjusted for BMI (ALMBMI) was < 0.789 and < 0.512, respectively. Cognitive performance was assessed using the Digit Symbol Substitution Test (DSST). Higher scores on the DSST indicated better cognitive performance. The covariates included sex, age, race, poverty income ratio, comorbidity index, educational level, physical activity and smoking status. RESULTS: For the primary outcome, our multivariate linear regression analysis indicated that participants without low lean mass were associated with better cognitive performance (ß = 1.50; 95% CI [0.12-2.89]). Subgroup analysis results indicated that the association was similar in sex, age, race, poverty income ratio, comorbidity index, educational level, physical activity and smoking status. CONCLUSIONS: Participants without low lean mass were associated with better cognitive performance. We might be able to improve cognitive performance by treating low lean mass, thus providing an opportunity for intervention at a younger age.

Tumor-associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen.

The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor-associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2ß1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2ß1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.

Serum Albumin Is Negatively Associated with Hemorrhagic Transformation in Acute Ischemic Stroke Patients.

BACKGROUND AND OBJECTIVE: Hemorrhagic transformation (HT) is a major complication of acute ischemic stroke (AIS). Serum albumin is known for its neuroprotective effects and is a marker of improved AIS patient outcomes. However, it is not known whether there is a relationship between serum albumin and HT. METHODS: AIS patients admitted to the Department of Neurology of West China Hospital from 2012 to 2016 were prospectively and consecutively enrolled. Baseline characteristics were collected. HT during hospitalization was diagnosed by brain imaging. Multivariate logistic regression analysis was performed to determine the relationship between serum albumin and HT. Confounding factors were identified by univariate analysis. Stratified logistic regression analysis was performed to identify effect modifiers. RESULTS: A total of 1996 AIS patients were recruited, of whom 135 (6.8%) developed HT. Serum albumin negatively correlated with HT. Patients in the upper serum albumin tertile (42.6-54.1 g/L) had a 46% lower risk of HT than patients in the lower tertile (19.3-39.1 g/L) after adjustment for potential confounders (OR 0.54, 95% CI 0.29-0.99, p = 0.04). Risk of HT decreased stepwise with higher serum albumin tertile (p for trend = 0.04). There was a significant interaction between serum albumin and age (p = 0.02), with no significant correlation between serum albumin and HT in patients over 60 years of age. CONCLUSIONS: Higher serum albumin is associated with lower HT risk in a dose-dependent manner in AIS patients younger than 60 years.

Association between Red Blood Cell Distribution Width and Hemorrhagic Transformation in Acute Ischemic Stroke Patients.

BACKGROUND: Hemorrhagic transformation (HT) is a frequent complication of acute ischemic stroke (AIS). Red blood cell distribution width (RDW) is a cost-effective parameter associated with incidence and prognosis of cerebrovascular diseases. The purpose of this study was to assess whether RDW is associated with HT in AIS patients. METHODS: AIS patients within 24 h from stroke onset between January 1, 2014, and December 31, 2018, were consecutively enrolled. Blood samples were collected. The primary outcome was HT, which was diagnosed by follow-up brain image and classified into hemorrhagic infarct (HI) and parenchymal hematoma (PH). Multivariate logistic regression analysis was performed to determine the relationship between RDW and HT as well as its subtypes. Potential effect modifier was identified by stratified logistic regression analysis. RESULTS: Among the included 1383 patients, 220 (15.9%) developed HT (HI in 103 and PH in 117). Elevated RDW levels were associated with an increased risk of HT when 2 extreme tertiles were compared (OR 1.60, 95% CI 1.04-2.44, p = 0.031). The risk of HT increased stepwise across RDW tertiles (p for trend = 0.042). RDW significantly correlated with HI rather than PH. The association between RDW and HT could be modified by reperfusion therapy (p for interaction = 0.010), with no significant association between RDW and HT among patients underwent reperfusion therapy. CONCLUSIONS: Elevated RDW level was related to increased risk of HT among AIS patients without reperfusion therapy.

Effects of the blood urea nitrogen to creatinine ratio on haemorrhagic transformation in AIS patients with diabetes mellitus.

BACKGROUND: The effect of the blood urea nitrogen (BUN) to creatinine (Cr) ratio (henceforth BUN/Cr) on haemorrhagic transformation (HT) of acute ischaemic stroke (AIS) patients is unclear. METHODS: AIS patients in the West China Hospital, Sichuan University, Chengdu, China, admitted within seven days from stroke onset (2012-2016) were included in the study. Baseline data, including BUN and Cr levels, were collected. The outcome was defined as HT during hospitalization. RESULTS: In this study, 1738 participants with an average age of 62.7 ± 14.0 years were included. After adjusting potential confounders (age, blood platelet, albumin, stroke severity, triglycerides and low-density lipoprotein [LDL]), multivariate logistic regression analyses indicated that BUN/Cr is independently associated with HT. The nonlinear relation between BUN/Cr and HT was explored in a dose-dependent manner, with an apparent inflection point of 30.71. On the left and right sides of the inflection point, the odds ratio (OR) and 95% confidence interval (CI) were 1.05 (1.02-1.08) and 0.96 (0.88-1.05), respectively. Interaction between BUN/Cr and diabetes mellitus (DM) and HT (P for interaction = 0.0395) was noted. BUN/Cr showed positive correlation with HT in DM patients (OR = 1.07; 95% CI: [1.02, 1.12]) but no significant relationship with HT in patients without DM. CONCLUSION: BUN/Cr is significantly associated with HT in AIS patients in a linear fashion, with an apparent cut point demarcating the HT difference. When the patients have DM, BUN/Cr is positively correlated with HT. These results support a revision in how we anticipate the prognosis for AIS patients.

Reversal of docetaxel resistance in prostate cancer by Notch signaling inhibition.

Acquired docetaxel (Doc) resistance in hormone-refractory prostate cancer (HRPC) remains an ongoing clinical challenge, resulting in failed chemotherapy and tumor recurrence. However, the mechanism of Doc-resistance development in prostate cancer cells is still unclear. Here, we observed a subpopulation of prostate cancer cells, in both Doc-resistant cell lines and the tumors of patients with HRPC, which show stem cell markers and greater tumorigenic potential. Those stem-like prostate cancer cells show high expression of ABCB1, which encodes multidrug resistance-related protein P-glycoprotein, leading to the Doc-resistance in prostate cancer. Moreover, we found that Notch signaling pathway activation in Doc-resistant cell lines and tumor tissues of patients with HRPC correlated with tumorigenicity and the development of Doc resistance. Here, we revealed that a combination of Doc and a Notch signaling inhibitor overcomes Doc resistance and increases the survival of mice with Doc-resistant xenografts. Therefore, targeting the Notch signaling pathway may be a promising strategy to overcome the Doc-resistant cancer in the clinic.

Outcomes of bisphosphonate and its supplements for bone loss in kidney transplant recipients: a systematic review and network meta-analysis.

BACKGROUND: Mineral bone disease constitutes a common complication of post-kidney transplantation, leading to great disability. As there is no consensus on the optimal treatment for post-kidney transplant recipients (KTRs), we aimed to evaluate the efficacy and safety of bisphosphonate and its combined therapies. METHODS: We incorporated relevant trials to perform a network meta-analysis from direct and indirect comparisons. We searched PubMed, Embase and the CENTRAL and the reference lists of relevant articles up to August 1, 2017, for randomized controlled trials. The primary outcome was bone mineral density (BMD) change at the femoral neck and the lumbar spine. RESULTS: From a total of 864 citations, 18 randomized controlled trials with a total of 1200 participants were included. Five different regimens were considered. Bisphosphonate plus calcium revealed a significant gain in percent BMD change than calcium alone at the femoral neck (mean difference (MD), 5.83; 95% credible interval (CrI), 1.61 to 9.27). No significant difference was detected when restricting to absolute terms. At the lumbar spine, bisphosphonate and calcium with or without vitamin D analogs outperformed calcium solely (MD, 0.07; 95% CrI, 0.00 to 0.13; MD, 0.06; 95% CrI, 0.02 to 0.09). Compared to calcium with vitamin D analogs, adding bisphosphonate was associated with marked improvement (MD, 0.03; 95% CrI, 0.00 to 0.05). Considering percent terms, combination of bisphosphonate with calcium and vitamin D analogs showed greater beneficial effects than calcium alone or with either vitamin D analogs or calcitonin (MD, 10.51; 95% CrI, 5.92 to 15.34; MD, 5.48; 95% CrI, 2.57 to 8.42; MD, 6.39; 95% CrI, 0.55 to 12.89). Both bisphosphonate and vitamin D analogs combined with calcium displayed a notable improvement compared to calcium alone (MD, 7.24; 95% CrI, 3.73 to 10.69; MD, 5.02; 95% CrI, 1.20 to 8.84). CONCLUSIONS: Our study suggested that additional use of bisphosphonate was well-tolerated and more favorable in KTRs to improve BMD.

The Accuracy of Serum Matrix Metalloproteinase-9 for Predicting Hemorrhagic Transformation After Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Hemorrhagic transformation is a serious complication of acute ischemic stroke, which may cause detrimental outcomes and the delayed use of anticoagulation therapy. Early predicting and identifying the patients at high risk of hemorrhagic transformation before clinical deterioration occurrence become a research priority. OBJECTIVE: To study the value of plasma matrix metalloproteinase-9 predicting hemorrhagic transformation after ischemic stroke. METHODS: We searched PubMed, Ovid, Cochrane Library, and other 2 Chinese databases to identify literatures published up to September 2017 and performed meta-analysis by STATA (version 12.0, StataCorp LP, College Station, TX). RESULTS: Twelve studies incorporating 1492 participants were included and 7 studies were included in the quantitative statistical analysis. The pooled sensitivity was 85% (95% confidence interval [CI]: 75%, 91%) and the pooled specificity was 79% (95% CI: 67%, 87%). The area under the receiver operating characteristic curve was .89 (95% CI .86, .91). Significant heterogeneity for all estimates value existed (all the P value < .05 and I2 > 50%). There is no threshold effect with P value greater than .05 of the correlation coefficient. Meta-regression and subgroup analysis showed cut-off value and hemorrhagic subtype contributed to heterogeneity. Deeks' funnel plot indicated no significant publication bias for 7 quantitative analysis studies. CONCLUSIONS: Matrix metalloproteinase-9 has high predictive value for hemorrhagic transformation after acute ischemic stroke. It may be useful to test matrix metalloproteinase-9 to exclude patients at low risk of hemorrhage for precise treatment in the future clinical work.

Longitudinal associations between social support and sarcopenia: findings from a 5-year cohort study in Chinese aged ≥50 years.

OBJECTIVES: We aimed to investigate longitudinal associations of overall social support and its sub-domains with risk of sarcopenia and its related traits in community-dwelling Chinese aged ≥ 50 years. We also explored interaction effects of potential factors on such associations. DESIGN: A prospective cohort study. SETTING: Community-based setting in western China. PARTICIPANTS: We included participants aged ≥50 years with complete information necessary for analysis from the WCHAT study who did not have sarcopenia at baseline (2018) and had sufficient data for sarcopenia assessment during 2021-2023. MEASUREMENTS: Exposures included overall social support, subjective support, objective support and support utilization, which were assessed with the Social Support Rating Scale. Outcomes included sarcopenia, low muscle mass (LMM), low muscle strength and low physical performance, which were diagnosed with the 2019 AWGS consensus. Longitudinal associations between the exposures and outcomes were estimated by logistic regression, with generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1905 participants were finally included in the analytic sample, of whom 326 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, higher degree of overall social support (OR = 0.87, 95%CI 0.76-0.99), subjective support (OR = 0.88, 95%CI 0.77-0.99) and support utilization (OR = 0.87, 95%CI 0.77-0.99) correlated with lower sarcopenia risk, among which higher support utilization degree was indicative of lower risk for LMM (OR = 0.88, 95%CI 0.79-0.98). GEE further revealed that overall support degree was negatively associated with risk for sarcopenia (OR = 0.86, 95%CI 0.76-0.98) and LMM (OR = 0.87, 95%CI 0.77-0.99). Objective support was neither significantly associated with sarcopenia nor its traits. No significant interaction effect was observed between overall support and the concerned confounders on sarcopenia (interaction P-value > 0.05). CONCLUSION: Overall social support degree was negatively associated with sarcopenia risk, possibly primarily through affecting muscle mass rather than muscle strength or physical performance, and such an association remained robust across subgroups with distinct characteristics. This holds implications for policymakers to conduct population-based risk assessment, and supportive strategies against sarcopenia should focus on enhancing subjective support and support utilization rather than objective support alone.

The mixed effect of Endocrine-Disrupting chemicals on biological age Acceleration: Unveiling the mechanism and potential intervention target.

INTRODUCTION: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein-protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. RESULTS: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. CONCLUSION: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer.

BACKGROUND: Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. METHODS: The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin ß8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. RESULTS: Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. CONCLUSIONS: The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

"Urological age" as a proxy of healthy longevity: analysis of prospective population-based cohorts in U.S. and China.

BACKGROUND: Assessing urinary symptoms poses a complex challenge for primary care practitioners. In evaluating urological function, our approach involves constructing an urological age through the analysis of laboratory parameters and indicators of the urinary system. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES), urological laboratory tests and age-related symptoms were included in the development of urological age (UA) and urological age acceleration (UAA) through the Klemera Doubal method. In relation to mortality associated with UAA, the metric was categorized into grades (0, 1, 2) as a discrete variable. We investigated the correlation between UAA and its grades with mortality, conducted survival analysis based on UAA grades, and explored the correlation between multisystem ageing-related disorders and UAA grades based on the NHANES and the West China Natural Population Cohort Study. RESULTS: UA was related to age with the r to 0.85 in men and 0.84 in women. Each year the increase in UAA was related to higher 1% and 4% mortality for men and women. Those with UAA grades 1 and 2 were associated with more risk of mortality than individuals with UAA grade 0 (men 8% and 40%, women 24% and 157%). The advanced UAA grades kept pace with multisystem ageing. Healthy diets and lifestyle habits are associated with lower UAA. CONCLUSION: Urological age is related to multisystem ageing and increases mortality risk, and urological age can be used to screen high-risk individuals and inform precision clinical development for ageing intervention.

Carcinogenic health outcomes associated with endocrine disrupting chemicals exposure in humans: A wide-scope analysis.

Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.