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Abstract Rest–activity behavior clusters within individuals to form patterns are of significant importance to their intrinsic capacity (IC), yet they have rarely been studied. A total of 1253 community-dwelling older adults were recruited between July and December 2021 based on the baseline survey database of the Fujian Prospective Cohort Study on Aging. Latent profile analysis was used to identify profiles of participants based on rest–activity behaviors, whereas logistic regression analysis was carried out to investigate the relationship between profiles and IC. We identified three latent profiles including: (1) Profile 1—labeled “Gorillas”: High physical activity (PA), moderate sedentary behaviors (SB), screen time (ST) and sleep (n = 154, 12%), (2) Profile 2—labeled as “Zebras”: Moderate PA, low SB, ST and high sleep (n = 779, 62%), and (3) Profile 3—labeled as“Koalas”: High SB, ST, low PA and sleep (n = 320, 26%). Logistic regression revealed a negative correlation between low IC and the “Gorillas” profile (β = − 0.945, P

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects. Methods The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice. Results Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive. Conclusions Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People’s Hospital in 2021 (ChiCTR1900024415).

Adverse cardiac mechanical remodeling is critical for the progression of heart failure following myocardial infarction (MI). We previously demonstrated the involvement of RIP3-mediated necroptosis in the loss of functional cardiomyocytes and cardiac dysfunction post-MI. Herein, we investigated the role of RIP3 in NOD-like receptor protein 3 (NLRP3)-mediated inflammation and evaluated the effects of RIP3 knockdown on myocardial mechanics and functional changes after MI. Our findings revealed that mice with MI for 4 weeks exhibited impaired left ventricular (LV) myocardial mechanics, as evidenced by a significant decrease in strain and strain rate in each segment of the LV wall during both systole and diastole. However, RIP3 knockdown ameliorated cardiac dysfunction by improving LV myocardial mechanics not only in the anterior wall but also in other remote nonischemic segments of the LV wall. Mechanistically, knockdown of RIP3 effectively inhibited the activation of the nuclear factor kappa-B (NF-κB)/NLRP3 pathway, reduced the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the heart tissues, and mitigated adverse cardiac remodeling following MI. These results suggest that downregulation of RIP3 holds promise for preventing myocardial inflammation and cardiac mechanical remodeling following MI by regulating the NF-κB/NLRP3 pathway.

Background: The pathogens causing unexplained pneumonia in both HIV-infected or HIV-unfected patients are likely to be complex. This retrospective study aimed to characterize the etiology of pneumonia in HIV-infected and HIV-uninfected patients using bronchoalveolar lavage fluid (BALF) analysis with metagenomic next-generation sequencing (mNGS) and X-pert MTB/RIF. Methods: Between January 2022 and May2024, 141 HIV-infected and 104 HIV-uninfected patients admitted to Nanjing Second Hospital with pneumonia were included. BALF samples were collected and analyzed using mNGS to detect bacteria, fungi, viruses, tuberculosis (TB) and non-tuberculous mycobacteria (NTM), and X-pert for TB detection. Clinical data including CD4 T-cell counts, comorbidities, and ART status were collected and analyzed. Results: HIV-uninfected patients were found to be older and exhibited a higher prevalence of comorbidities compared to HIV-infected patients. Despite higher median CD4 T-cell counts in HIV-uninfected individuals (412 cells/μL vs. 31 cells/μL in HIV-infected), TB detection rates using X-pert and mNGS were lower than anticipated, particularly in HIV-infected patients. Mixed-pathogen infections were significantly more prevalent in HIV-infected patients, especially those with lower CD4 T-cell counts. ART use showed variable impacts on pathogen diversity, with longer treatment durations associated with reduced infection complexity but persistent immunodeficiency in some cases.In patients with pneumonia, whether HIV-infected or HIV-uninfected, pathogens often exhibit complexity, underscoring the critical role of timely mNGS and X-pert analysis of BALF for early pathogen detection.

Live fish transportation plays a crucial role in realizing the value of aquaculture in sturgeons. However, hypoxia and hypercapnia are the major issues during the high-density transportation of live fish. Therefore, monitoring the changing environmental factors (such as water temperature, salinity, and pH) or anesthesia methods (MS-222, dissolved CO2, or low-voltage direct electrical current), which can potentially alter the oxygen consumption of fish, are crucial for a better understanding of the necessary conditions for live fish transportation. A semi-open respirometry system was used to quantify the oxygen consumption and respiration frequency of hybrid sturgeon (Acipenser baeri♀×Acipenser schrencki♂). The results indicate that the oxygen consumption rate and respiration frequency of hybrid sturgeon increased linearly with water temperature from 1.4 °C to 25°C. The oxygen consumption rate of hybrid sturgeon increased with the increase of salinity in the range from 3 to 10 ‰ in 9 hours (P < 0.05). Respiration frequency decreased but did not affect the oxygen consumption rate when pH was from 8.1 to 9.8. Exposure to low-voltage direct electrical current ranging from 0.4 to 1.0 V/cm significantly increased the respiration frequency (P < 0.05). The oxygen consumption rate maintained below 1 mg/(g·h) when CO2 concentration ranges from 8.5 to 67.85 mg/L. Compared with the change of oxygen consumption rate and respiration frequency with MS-222 at the range from 5 to 30 mg/L, immersion of fish into more than 8.5–67.85 mg/L dissolved CO2 in water could as an alternative anesthetic method for hybrid sturgeon. These findings in the study may contribute to the culture, live fish transportation, and basic research in hybrid sturgeon.

Abstract Liver fibrosis can cause hepatitis B virus (HBV)‐associated hepatocellular carcinoma. Menstrual blood‐derived mesenchymal stem cells (MenSCs) can ameliorate liver fibrosis through paracrine. Single‐cell RNA sequencing (scRNA‐seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation to target liver fibrosis. This study established HBV transgenic (HBV‐Tg) mouse model of carbon tetrachloride (CCl4)‐induced liver fibrosis and demonstrated that MenSCs migrated to the injured liver to improve serological indices and reduce fibrotic accumulation. RNA‐bulk analysis revealed that MenSCs mediated extracellular matrix accumulation and cell adhesion. Liver parenchymal cells and nonparenchymal cells were identified by scRNA‐seq in the control, CCl4, and MenSC groups, revealing the heterogeneity of fibroblasts/HSCs. A CellChat analysis revealed that diminished intercellular adhesion molecule (ICAM) signaling is vital for MenSC therapy. Specifically, Icam1 in aHSCs acted on Itgal/Itgb2 and Itgam/Itgb2 in neutrophils, causing decreased adhesion. The expression of Itgal, Itgam, and Itgb2 was higher in CCl4 group than in the control group and decreased after MenSC therapy in neutrophil clusters. The Lcn2, Pglyrp1, Wfdc21, and Mmp8 had high expression and may be potential targets in neutrophils. This study highlights interacting cells, corresponding molecules, and underlying targets for MenSCs in treating HBV‐associated liver fibrosis.

BackgroundPre-frailty represents an ideal window of opportunity to potentially prevent frailty and disability. Early and effective interventions to delay or reverse pre-frailty are public health imperative. The present trial aims to evaluate the effectiveness and underlying mechanisms of mobile health (mHealth) platform-supported lifestyle-integrated multicomponent exercise (PF-Life) to reverse pre-frailty in community-dwelling older adults.MethodsThis is an open-label, prospective, two-arm parallel randomized controlled trial with allocation concealment and outcome assessment blinding. We aim to recruit 140 pre-frail community-dwelling older adults who will be randomized into two groups. The control group will receive a health education program, while the intervention group will receive PF-Life training as planned for 1 year. The proportion of pre-frailty, functional performance (muscular strength, aerobic capacity, flexibility, and balance), body composition, and physical activity will be measured at pre-intervention, post-intervention, and 12-month follow-up. Inflammatory biomarkers will also be collected to explore the underlying mechanisms.DiscussionThis is the first study to evaluate the effects of a novel digital lifestyle-integrated multicomponent exercise for pre-frail older people. The results of this trial will provide much-needed information on the short-and long-term effects of PF-Life based on functional performance and body composition. Meanwhile, inflammatory biomarkers and physical activity levels will be used to elucidate the underlying mechanisms of PF-Life. The findings from this trial will provide evidence for the effectiveness of lifestyle multicomponent exercise intervention supported by the mHealth platform that may reverse or even halt the onset of frailty.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=176477, identifier ChiCTR2200063431.

There are few tumor cell subpopulations with stem cell characteristics in tumor tissue, defined as cancer stem cells (CSCs) or cancer stem-like cells (CSLCs), which can reconstruct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited generation. The microenvironment that CSCs depend on consists of various cellular components and corresponding medium components. Among these factors existing at a variety of levels and forms, cytokine networks and numerous signal pathways play an important role in signaling transduction. These factors promote or maintain cancer cell stemness, and participate in cancer recurrence, metastasis, and resistance. This review aims to summarize the recent molecular data concerning the multilayered relationship between CSCs and CSC-favorable microenvironments. We also discuss the therapeutic implications of targeting this synergistic interplay, hoping to give an insight into targeting cancer cell stemness for tumor therapy and prognosis.

Objective To investigate the relationship between triglyceride glucose (TyG) index and the total load of cerebral small vessel disease (CSVD) and its different imaging markers. Methods A total of 202 patients with CSVD admitted to The Third Hospital of Hebei Medical University from January 2020 to May 2022 were selected. The clinical data of all patients were collected and TyG index was calculated. The lacunes, cerebral microbleeds (CMBs), white matter hyperintensity (WMH) and enlarged perivascular space (EPVS) were evaluated by MRI, and total load of CSVD score was calculated. Results 1) TyG index and total load of CSVD score: Logistic regression analysis showed the male (OR = 2.245, 95%CI: 1.017-4.957; P = 0.045), increase of age (OR = 1.084, 95%CI: 1.046-1.124; P = 0.000), hypertension (OR = 2.457, 95%CI: 1.189-5.078; P = 0.015) and increase of TyG index (OR = 2.657, 95%CI: 1.353-5.216; P = 0.005) were risk factors for moderate and severe total load of CSVD. 2) TyG index and imaging markers of CSVD: Logistic regression analysis showed the increase of TyG index was the risk factor of moderate and severe WMH (OR = 2.313, 95%CI: 1.095-4.885; P = 0.028), CMBs (OR = 1.690, 95%CI: 1.011-2.824; P = 0.045), lacunes (OR = 2.087, 95%CI: 1.235-3.525; P = 0.006), moderate and severe EPVS in basal ganglia (OR = 2.005, 95%CI: 1.190-3.378; P = 0.009). Conclusions TyG index is associated with the total load and various imaging markers of CSVD, which can be used as a valuable biomarker to evaluate CSVD and its severity.

Abstract Background Frailty is an age-related geriatric syndrome that leads to a series of clinically negative events. A better understanding of the factors associated with frailty assists in preventing its progression. The triglyceride-glucose (TyG) index, a simple alternative index of insulin resistance, has not yet been proven to be associated with frailty. The present study aimed to investigate the association between the TyG index and its trajectory with frailty from a cross-sectional, retrospective and prospective level based on an ongoing cohort. Methods This longitudinal study included 1,866 older residents from the “Fujian prospective aging cohort” (ChiCTR 2,000,032,949). The TyG index was calculated as ln [fasting triglyceride (mg/dL) ╳ fasting plasma glucose (mg/dL)/2] and group-based trajectory model (GBTM) was applied to identify the trajectory of TyG index. The association between different trajectory groups of TyG index with frailty risk were estimated using multinomial logistic regression analysis. Results In the cross-sectional analysis, the highest quartile of the TyG index was associated with an increased risk of frailty (TyG index Q4 vs. Q1, OR = 1.50, 95% CI 1.00–2.25, P = 0.048). Restricted cubic splines demonstrated an increasing trend for TyG index and frailty risk. During a follow-up of ten years, three distinct trajectories of the TyG index were identified: low-stable (n = 697, 38.3%), moderate-stable (n = 910, 50.0%) and high-stable (n = 214, 11.7%). Compared with those in the stable-low group of TyG index trajectory, the ORs (95% CI) of prefrailty and frailty risk were 1.79 (95% CI 1.11–2.88) and 2.17 (95% CI 1.01–3.88) for the high-stable group, respectively (P = 0.017 and P = 0.038). In the subgroup analysis, the association of the high-stable trajectory of TyG and frailty status were only observed in subjects with BMI ≥ 24 kg/m2. Prospectively, the highest quartile of the TyG index was associated with a 2.09-fold significantly increased risk of one-year ADL/IADL decline (P = 0.045). Conclusions The present study suggests a potential role for a high and sustainable level of TyG index in the risk of frailty. The trajectories of the TyG index can help to identify older individuals at a higher risk of frailty who deserve primitive preventive and therapeutic approaches.

Abstract Background Coronavirus disease 2019 (COVID-19) vaccine has played a major role in ending the pandemic. However, little is known about the influence of COVID-19 vaccine on the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). Objectives The goal of this study is to explore whether COVID-19 vaccine impacts the efficacy of immune checkpoint inhibitors (ICIs) in NSCLC patients. Methods We retrospectively analyzed the survival data of ICI-treated 104 patients with stage III–IV NSCLC, who either received COVID-19 vaccination (n = 25) or no vaccination (n = 79). The potential risk factors, in particular roles of COVID-19 vaccination in the efficacy of ICIs in these patients, were evaluated. Results Our results showed significantly improved ORR (28.0% vs. 11.39%, p = 0.05) and DCR (88.0% vs. 54.43%, p = 0.005) in the COVID-19 vaccinated group compared with the non-vaccinated group. Regarding the long-term survival benefits, COVID-19 vaccine showed profound influence both on the PFS (HR = 0.16, p = 0.021) and OS (HR = 0.168, p = 0.019) in patients with NSCLC under ICIs treatment. The PFS (p

Geothermal energy, being a clean energy source, has immense potential, and accurate wellbore modeling is crucial for optimizing the drilling process and ensuring safety. This paper presents a novel geothermal wellbore model based on the drift-flux approach, tested under three different temperature and pressure well conditions. The proposed model integrates the conservation equations of mass, momentum, and energy, incorporating the gas–liquid two-phase flow drift-flux model and heat transfer model. The key features include handling the heat transfer between the formation and the wellbore, addressing the slip relationship between the gas and liquid phases, and accounting for wellbore friction. The nonlinear equations are discretized using the finite difference method, and the highly nonlinear system is solved using the Newton–Raphson method. The numerical simulation, validation, and comparison with existing models demonstrate the enhanced accuracy of this model. In our tests, the model achieved a high accuracy in calculating the bottom-hole pressure and temperature, with mean relative errors (MREs) significantly lower than those of other models. For example, the MREs for the bottom-hole pressure and temperature of the Rongxi area well in Xiongan, calculated by this model, are 1.491% and 1.323%, respectively. These results offer valuable insights for optimizing drilling parameters and ensuring drilling safety. Comparisons indicate that this approach significantly outperforms others in capturing the complex dynamics of geothermal wellbores, making it a superior tool for geothermal energy development.

Hydrogen-rich water (HRW) is widely recognized for its growth promoting, antioxidant, and anti-inflammatory properties. However, little is known about the role of HRW in aquaculture. This study aims to investigate how different concentrations of HRW affect the growth performance, digestive ability, antioxidant capacity, mTOR signaling pathway, and gut microbiota of juvenile largemouth bass. We randomly assigned 360 fish (13.73 ± 0.1 g) to three treatments. The control group was maintained in regular water, while the treatment groups were treated with different concentrations of H2 dissolved in water, which were H1 (179.65 ± 31.95 ppb) and H2 (280.65 ± 64.43 ppb), respectively. Through an analysis of the three treatments, it was found that H1 significantly increased the final body weight, weight gain rate, specific growth rate, and survival rate, and reduced the feed conversion ratio (p < 0.05). In addition, the trypsin activity was significantly increased in the intestine (p < 0.05), and the expression of genes related to the glucose metabolism (pk and pepck) and mTOR (tor, akt, s6k1, 4ebp1, and ampka) signaling pathways were significantly increased in the liver in H1 (p < 0.05). The relative abundance of Blautia in the gut microbiota (p < 0.05) was significantly increased in H1. Therefore, these results indicated that H1 can significantly improve growth performance, promote intestinal digestion, activate the glucose metabolism pathway and mTOR signaling pathway, and increase the abundance of beneficial bacteria in the gut of largemouth bass. These findings provided valuable support for the application of HRW to support the healthy aquaculture of largemouth bass.