Association between ideal cardiovascular health and abnormal glucose metabolism in the elderly: evidence based on real-world data.

BACKGROUND: Limited information is available on the effect of ideal cardiovascular health (CVH) and abnormal glucose metabolism in elderly people. We aimed to analyze the prevalence of CVH behaviors, abnormal glucose metabolism, and their correlation in 65 and older people. METHODS: In this study, randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used. Recruiting was carried out between January 2020 and December 2020, and 1984 participants aged 65 years or older completed the study. RESULTS: The prevalence of abnormal glucose metabolism in this group was 26.7% (n = 529), among which the prevalence of impaired fasting glucose (IFG) was 9.5% (male vs. female: 8.7% vs 10.1%, P = 0.338), and the prevalence of type 2 diabetes mellitus (T2DM) was 19.0% (male vs. female: 17.8 vs. 19.8%, P = 0.256). The ideal CVH rate (number of ideal CVH metrics ≥ 5) was only 21.0%. The risk of IFG and T2DM decreased by 23% and 20% with each increase in one ideal CVH metrics, with OR (95%CI) of 0.77(0.65-0.92) and 0.80(0.71-0.90), respectively (P -trend < 0.001). TyG fully mediated the ideal CVH and the incidence of T2DM, and its mediating effect OR (95%CI) was 0.88(0.84-0.91). CONCLUSIONS: Each increase in an ideal CVH measure may effectively reduce the risk of abnormal glucose metabolism by more than 20%.

Dose-response association between Chinese visceral adiposity index and cardiovascular disease: a national prospective cohort study.

Background: Chinese visceral adiposity index (CVAI) is a reliable visceral obesity index, but the association between CVAI and risk of cardiovascular disease (CVD) remains unclear. We explored the associations of CVAI with incident CVD, heart disease, and stroke and compared the predictive power of CVAI with other obesity indices based on a national cohort study. Methods: The present study included 7,439 participants aged ≥45 years from China Health and Retirement Longitudinal Study (CHARLS). Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines analyses were adopted to model the dose-response associations. Receiver operator characteristic (ROC) analyses were used to compare the predictive ability of different obesity indices (CVAI, visceral adiposity index [VAI], a body shape index [ABSI], conicity index [CI], waist circumference [WC], and body mass index [BMI]). Results: During 7 years' follow-up, 1,326 incident CVD, 1,032 incident heart disease, and 399 stroke cases were identified. The HRs (95% CI) of CVD, heart disease, and stroke were 1.50 (1.25-1.79), 1.29 (1.05-1.57), and 2.45 (1.74-3.45) for quartile 4 versus quartile 1 in CVAI. Linear associations of CVAI with CVD, heart disease, and stroke were observed (P nonlinear >0.05) and per-standard deviation (SD) increase was associated with 17% (HR 1.17, 1.10-1.24), 12% (1.12, 1.04-1.20), and 31% (1.31, 1.18-1.46) increased risk, respectively. Per-SD increase in CVAI conferred higher risk in participants aged<60 years than those aged ≥60 years (P interaction<0.05). ROC analyses showed that CVAI had higher predictive value than other obesity indices (P<0.05). Conclusions: CVAI was linearly associated with risk of CVD, heart disease, and stroke and had best performance for predicting incident CVD. Our findings indicate CVAI as a reliable and applicable obesity index to identify higher risk of CVD.

TCAF1 promotes TRPV2-mediated Ca2+ release in response to cytosolic DNA to protect stressed replication forks.

The protection of the replication fork structure under stress conditions is essential for genome maintenance and cancer prevention. A key signaling pathway for fork protection involves TRPV2-mediated Ca2+ release from the ER, which is triggered after the generation of cytosolic DNA and the activation of cGAS/STING. This results in CaMKK2/AMPK activation and subsequent Exo1 phosphorylation, which prevent aberrant fork processing, thereby ensuring genome stability. However, it remains poorly understood how the TRPV2 channel is activated by the presence of cytosolic DNA. Here, through a genome-wide CRISPR-based screen, we identify TRPM8 channel-associated factor 1 (TCAF1) as a key factor promoting TRPV2-mediated Ca2+ release under replication stress or other conditions that activate cGAS/STING. Mechanistically, TCAF1 assists Ca2+ release by facilitating the dissociation of STING from TRPV2, thereby relieving TRPV2 repression. Consistent with this function, TCAF1 is required for fork protection, chromosomal stability, and cell survival after replication stress.

Harnessing the power of polyethyleneimine in modifying chitosan surfaces for efficient anion dyes and hexavalent chromium removal.

In this investigation, synthesis of a surface-functionalized chitosan known as amino-rich chitosan (ARCH) was achieved by successful modification of chitosan by polyethyleneimine (PEI). The synthesized ARCH was characterized by a specific surface area of 8.35 m2 g-1 and a microporous structure, with pore sizes predominantly under 25 nm. The Zeta potential of ARCH maintained a strong positive charge across a wide pH range of 3-11. These characteristics contribute to its high adsorption efficiency in aqueous solutions, demonstrated by its application in removing various anionic dyes, including erioglaucine disodium salt (EDS), methyl orange (MO), amaranth (ART), tartrazine (TTZ), and hexavalent chromium ions (Cr(VI)). The adsorption capacities (Qe) for these contaminants were measured at 1301.15 mg g-1 for EDS, 1025.45 mg g-1 for MO, 940.72 mg g-1 for ART, 732.96 mg g-1 for TTZ, and 350.15 mg g-1 for Cr(VI). A significant observation was the rapid attainment of adsorption equilibrium, occurring within 10 min for ARCH. The adsorption behavior was well-described by the Pseudo-second-order and Langmuir models. Thermodynamic studies indicated that the adsorption process is spontaneous and endothermic in nature. Additionally, an increase in temperature was found to enhance the adsorption capacity of ARCH. The material demonstrated robust stability and selective adsorption capabilities in varied conditions, including different organic compounds, pH environments, sodium salt presence, and in the face of interfering ions. After five cycles of adsorption, ARCH maintained about 60% of its initial adsorption capacity. Due to its efficient adsorption performance, simple synthesis process, low biological toxicity, and cost-effectiveness, ARCH is a promising candidate for future water treatment technologies.

Efficient adsorption of selenium (Se(IV) and Se(VI)) from water using Acacia senegal polysaccharide with multiple amine groups: Synthesis and application.

In this study, an amine-rich gel (ARAS) was prepared by chemically altering Acacia senegal (AS). ARAS acts as an adsorbent for selenium. Owing to the introduction of amino functional groups and a remarkable specific surface area (91.89 g/m2), ARAS shows maximum adsorption capacities at 75 and 130 mg g-1 for Se(IV) and Se(VI), respectively. The removal efficiency of ARAS is higher (ωSeIV = 98.2 % and ωSeVI = 98.6 %) at lower concentrations (CSeIV = 100 ppm and CSeVI = 95 ppm) and the adsorption equilibrium is achieved within 60 min. The adsorption process of Se (IV) and Se (VI) via ARAS is elucidated using the Quasi-Second-Order kinetic and Langmuir models. The enhanced adsorption capacity of the adsorbent could be attributed to the synergistic effects of electrostatic attraction, hydrogen bonding, and specific physicochemical properties. Thermodynamic studies reveal that the surface adsorption process is spontaneous and exothermic. Notably, ARAS maintains remarkable adsorption stability under a variety of solution conditions, including variable pH (4-11), NaCl concentrations (0-1 M), and the presence of organic solvents. It retains approximately 60 % of its initial adsorption capacity for Se(IV) and Se(VI) after three adsorption cycles. Therefore, ARAS with its cost-effectiveness and exceptional performance shows considerable potential for applications in water treatment.

Pan-cancer analyses reveal GTSE1 as a biomarker for the immunosuppressive tumor microenvironment.

G2 and S phase-expressed-1 (GTSE1) has been reported to be associated with poor prognosis in many cancer types. However, the knowledge of GTSE1 across 33 cancer types remains scarce, and the mechanisms by which GTSE1 promotes cancer development remain incompletely understood. R language and TIMER2.0 were used to analyze the clinical relevance of GTSE1 across > 10,000 subjects representing 33 cancer types based on the cancer genome atlas databases. The expression of GTSE1 was upregulated in almost all cancer types and hyperactivity of GTSE1 is likely to induce DNA repair response and positively correlates with the tumor mutational burden and microsatellite instability which are both promising predictive biomarkers for immunotherapy. GTSE1 was upregulated in TP53 mutation patients. Additionally, GTSE1 also positively correlates with tumor purity and tumor infiltration of immune-suppressive myeloid-derived suppressor cells. Consistently, high expression of GTSE1 is associated with poor patient survival in many cancer types. Conclusion: Our study provides new insights into the diagnostic and prognostic role of GTSE1 in cancers and suggests therapeutic approaches for GTSE1-overexpressing cancers by targeting DNA repair response, and the tumor immune microenvironment.

Dose-response association of Chinese visceral adiposity index with comorbidity of hypertension and diabetes mellitus among elderly people.

Background: Chinese visceral adiposity index (CVAI) is a reliable indicator of visceral obesity, but little is known about the association of CVAI with comorbidity of hypertension (HTN) and diabetes mellitus (DM). This study aimed to explore the associations of CVAI with HTN-DM comorbidity, HTN or DM, HTN, and DM in elderly people and evaluate the mediating role of insulin resistance in the associations. Methods: A total of 3,316 Chinese participants aged ≥60 years were included in this cross-sectional study. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were applied to explore the dose-response associations. Mediation analyses were used to assess the mediating effect of triglyceride-glucose (TyG) index in the associations. Results: The prevalence rate of HTN-DM comorbidity, HTN or DM, HTN, and DM was 13.78%, 72.26%, 67.16%, and 18.88%, respectively. Linear associations between CVAI and HTN-DM comorbidity, HTN or DM, HTN, and DM were found, and ORs (95%CIs) were 1.45 (1.30-1.61), 1.39 (1.28-1.52), 1.36 (1.25-1.48), and 1.28 (1.16-1.41) for per SD increase in CVAI. Compared with quartile 1 of CVAI, the risk of HTN-DM comorbidity, HTN or DM, HTN, and DM increased 190%, 125%, 112%, and 96% for quartile 4. In addition, we found TyG index playing a key role in the associations of CVAI with HTN-DM comorbidity, HTN or DM, and DM. Conclusion: CVAI is linearly and positively correlated with HTN-DM comorbidity, HTN or DM, HTN, and DM. The potential mechanism is insulin resistance largely mediating the associations.

Cytosolic DNA sensing by cGAS/STING promotes TRPV2-mediated Ca2+ release to protect stressed replication forks.

The protection of DNA replication forks under stress is essential for genome maintenance and cancer suppression. One mechanism of fork protection involves an elevation in intracellular Ca2+ ([Ca2+]i), which in turn activates CaMKK2 and AMPK to prevent uncontrolled fork processing by Exo1. How replication stress triggers [Ca2+]i elevation is unclear. Here, we report a role of cytosolic self-DNA (cytosDNA) and the ion channel TRPV2 in [Ca2+]i induction and fork protection. Replication stress leads to the generation of ssDNA and dsDNA species that, upon translocation into cytoplasm, trigger the activation of the sensor protein cGAS and the production of cGAMP. The subsequent binding of cGAMP to STING causes its dissociation from TRPV2, leading to TRPV2 derepression and Ca2+ release from the ER, which in turn activates the downstream signaling cascade to prevent fork degradation. This Ca2+-dependent genome protection pathway is also activated in response to replication stress caused by oncogene activation.

Analysis of the Dust-Concentration Distribution Law in an Open-Pit Mine and Its Influencing Factors.

In this study, a solar-powered multipoint network monitoring method was used to record dust-particle concentrations and meteorological indicators in the Anjialing open-pit coal mine in the Pingshuo mining area. The factors influencing the concentrations of particulate matter of different maximum diameters (PM2.5, PM10, and total suspended particulates; TSPs) and the regularity of the spatial distribution were examined. The results show that the highest dust concentration and thus the most serious dust pollution occur in winter, and the lowest dust concentration is found in summer. There are peaks in dust concentration in December and January to February, and the pollution is more serious at these times. On a given day, the pollution is higher between 11:00 and 13:00, but it does not exceed the 24 h air concentration limits specified in the Chinese Ambient Air Quality Standard (GB3095-2012). It was found that the PM2.5 and PM10 concentrations are positively correlated with humidity and air pressure, and they are negatively correlated with wind speed, temperature, and noise. The TSP concentration is positively correlated with temperature and negatively correlated with humidity. The results of this study provide theoretical guidance and a reference for the distribution law of dust concentration in open-pit coal mines.

Time-Aware Missing Healthcare Data Prediction Based on ARIMA Model.

Healthcare uses state-of-the-art technologies (such as wearable devices, blood glucose meters, electrocardiographs), which results in the generation of large amounts of data. Healthcare data is essential in patient management and plays a critical role in transforming healthcare services, medical scheme design, and scientific research. Missing data is a challenging problem in healthcare due to system failure and untimely filing, resulting in inaccurate diagnosis treatment anomalies. Therefore, there is a need to accurately predict and impute missing data as only complete data could provide a scientific and comprehensive basis for patients, doctors, and researchers. However, traditional approaches in this paradigm often neglect the effect of the time factor on forecasting results. This paper proposes a time-aware missing healthcare data prediction approach based on the autoregressive integrated moving average (ARIMA) model. We combine a truncated singular value decomposition (SVD) with the ARIMA model to improve the prediction efficiency of the ARIMA model and remove data redundancy and noise. Through the improved ARIMA model, our proposed approach (named MHDP SVD_ARIMA) can capture underlying pattern of healthcare data changes with time and accurately predict missing data. The experiments conducted on the WISDM dataset show that MHDP SVD_ARIMA approach is effective and efficient in predicting missing healthcare data.

Context-dependent pro- and anti-resection roles of ZKSCAN3 in the regulation of fork processing during replication stress.

Uncontrolled resection of replication forks under stress can cause genomic instability and influence cancer formation. Extensive fork resection has also been implicated in the chemosensitivity of "BReast CAncer gene" BRCA-deficient cancers. However, how fork resection is controlled in different genetic contexts and how it affects chromosomal stability and cell survival remains incompletely understood. Here, we report a novel function of the transcription repressor ZKSCAN3 in fork protection and chromosomal stability maintenance under replication stress. We show disruption of ZKSCAN3 function causes excessive resection of replication forks by the exonuclease Exo1 and homologous DNA recombination/repair protein Mre11 following fork reversal. Interestingly, in BRCA1-deficient cells, we found ZKSCAN3 actually promotes fork resection upon replication stress. We demonstrate these anti- and pro-resection roles of ZKSCAN3, consisting of a SCAN box, Kruppel-associated box, and zinc finger domain, are mediated by its SCAN box domain and do not require the Kruppel-associated box or zinc finger domains, suggesting that the transcriptional function of ZKSCAN3 is not involved. Furthermore, despite the severe impact on fork structure and chromosomal stability, depletion of ZKSCAN3 did not affect the short-term survival of BRCA1-proficient or BRCA1-deficient cells after treatment with cancer drugs hydroxyurea, PARPi, or cisplatin. Our findings reveal a unique relationship between ZKSCAN3 and BRCA1 in fork protection and add to our understanding of the relationships between replication fork protection, chromosomal instability, and chemosensitivity.

Association between red blood cell distribution width-to-albumin ratio and diabetic retinopathy.

BACKGROUND: Diabetes mellitus (DM) has shown a trend of reaching pandemic levels in the world. Chronic inflammation is a key factor in the development of diabetic retinopathy (DR). Red blood cell distribution width-to-albumin ratio (RA) is used to assess immune status and the immune response. Our study was conducted to assess the association between DR and RA levels to determine the value of RA in predicting DR. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2006, The RA was calculated as the Red Blood Cell Distribution Width/Albumin Ratio. Multivariable logistic regression and propensity score-matched analysis were used to examine the association between RA and DR levels. RESULTS: The clinical and demographic features of the 1,751 patients with DM. The eligible participants included 874 females and 870 males with mean age 62.2 ± 14.0 years, and mean RA 3.2 ± 0.5. RA ≥ 2.9659 was a risk factor for DR (OR = 1.66 95% CI: 1.31-2.11, p < 0.0001). After adjusting for age, sex, race, education, marital status, ratio of family income to poverty, body mass index, fasting glucose, hypertension, and coronary heart disease, RA ≥ 2.9659 was an independent risk factor for DR (OR = 1.64, 95% CI: 1.23-2.19, p = 0.0008). The propensity score-matched analysis also showed that high RA was an independent risk factor for DR. CONCLUSIONS: Our study shows that RA is a risk factor for patients with DR. The findings of this study should be validated the role of RA in DR in diabetic patients.

Monitoring and prediction of dust concentration in an open-pit mine using a deep-learning algorithm.

PURPOSE: Dust pollution is currently one of the most serious environmental problems faced by open-pit mines. Compared with underground mining, open-pit mining has many dust sources, and a wide area of influence and complicated changes in meteorological conditions can result in great variations in dust concentration. Therefore, the prediction of dust concentrations in open-pit mines requires research and is of great significance for reducing environmental pollution and personal health hazards. METHODS: This study is based on monitoring of the concentration of total suspended particulate (TSP) in the Anjialing open-pit coal mine in Pingshuo. This paper proposes a hybrid model based on a long short-term memory (LSTM) network and the attention mechanism (LSTM-Attention) and applies it to the prediction of TSP concentration. The LSTM model reflects the historical process of an input time series, and the attention mechanism extracts the inherent characteristics of the input parameters to assign weights based on the importance of the influencing factors. The autoregressive integrated moving average (ARIMA) and LSTM models are also used to predict the TSP concentration. Finally, several statistical measures of error are used to evaluate the accuracy of the model and perform a sensitivity analysis. RESULTS: It was found that, in general, the TSP concentration was highest in the period 08:00-09:00 and lowest in the period 15:00-16:00. In addition to the influence of meteorological parameters and normal operations, the reason for this trend is the presence of an inversion layer above the open-pit mine. The results show that, compared with the ARIMA and LSTM models, the LSTM-Attention model is more stable and has a prediction accuracy that is 5.6% and 3.0% greater, respectively. CONCLUSION: This model can be applied to the prediction of dust concentrations in open-pit mines and provide guidance on when to carry out dust-suppression work. It has expansibility and is potentially valuable for application in a wide range of areas.

Ca2+-Stimulated AMPK-Dependent Phosphorylation of Exo1 Protects Stressed Replication Forks from Aberrant Resection.

Abnormal processing of stressed replication forks by nucleases can cause fork collapse, genomic instability, and cell death. Despite its importance, it is poorly understood how the cell properly controls nucleases to prevent detrimental fork processing. Here, we report a signaling pathway that controls the activity of exonuclease Exo1 to prevent aberrant fork resection during replication stress. Our results indicate that replication stress elevates intracellular Ca2+ concentration ([Ca2+]i), leading to activation of CaMKK2 and the downstream kinase 5' AMP-activated protein kinase (AMPK). Following activation, AMPK directly phosphorylates Exo1 at serine 746 to promote 14-3-3 binding and inhibit Exo1 recruitment to stressed replication forks, thereby avoiding unscheduled fork resection. Disruption of this signaling pathway results in excessive ssDNA, chromosomal instability, and hypersensitivity to replication stress inducers. These findings reveal a link between [Ca2+]i and the replication stress response as well as a function of the Ca2+-CaMKK2-AMPK signaling axis in safeguarding fork structure to maintain genome stability.

Leukemia-derived exosomes induced IL-8 production in bone marrow stromal cells to protect the leukemia cells against chemotherapy.

AIMS: The interplay between bone marrow stromal cells (BMSCs) and acute myeloid leukemia (AML) cells plays a critical role in AML drug resistance by secreting growth factors, cytokines, and extracellular vesicles. As kind of extracellular vesicles, exosomes consist of proteins and RNAs and regulate communication among cells. MAIN METHODS: The BMSCs, HS5 cells, and AML cells were co-cultivated with transwell membranes, and treated with different doses of AML chemotherapy drug, etoposide. KEY FINDINGS: Findings of our research proved that co-cultivation of BMSCs with AML cells defended AML against cell death triggered via etoposide, without having an impact on cell growth. An increase in the expression of the 70 kDa heat shock proteins (HSP70) as well as lysosomal associated membrane protein 3 (CD63) was observed in the exosomes from BMSC and AML, co-cultivated in conditioned media. Exosome repression in BMSC and AML co-cultivating system rebuilt the sensitivity of the KG1A cells to apoptosis triggered via etoposide, indicating that exosome modulated drug resistance in AML. Our study proved that exosomes arising from KG1A cells could propel BMSCs to generate IL-8, which could regulate the effect of etoposide treatment. Furthermore, IL-8 inhibition by its antibody increased the sensitivity of AML cells to cell death triggered via etoposide. SIGNIFICANCE: Our results suggested that exosomes secreted by AML cells is an essential communicator for the interaction of BMSCs and AML, which can protect AML cells from chemotherapy drug induced apoptosis.

[A clinical analysis of 50 cases of medicament-like dermatitis due to trichloroethylene].

OBJECTIVE: To investigate the clinical manifestations, complications and treatment of medicament-like dermatitis due to trichloroethylene (TCE), so as to provide basis for studying its etiology and mechanism. METHODS: Fifty patients with dermatitis due to TCE from 1997 to 2000 were analysed retrospectively. RESULTS: The occurrence of the dermatitis was not parallel to TCE exposure levels, without significant dose-effect relationship. This disease could be caused by both inhalation and skin exposure. The latency period of TCE dermatitis ranged from 5 to 66 days, and the average was 31.5 d (Medium). The major clinical manifestations included skin lesions, fever, superficial lymph node swelling and liver dysfunction. Infection was the major complication. Glucocorticoid was effective for treatment of this disease. CONCLUSION: The clinical manifestations due to TCE exposure were similar to dermatitis medicamentosa. The major clinical types of TCE dermatitis included exfoliative dermatitis and erythema multiforme. The dermatitis is considered to be mediated by delayed-type (IV) hypersensitivity. The key factors to treat this disease successfully included the use of glucocorticoid in time with sufficient dose and full course, professional skin care, active treatment to protect the liver and to avoid infection.