Association between visceral obesity index and diabetes: a systematic review and meta-analysis.

CONTENT: The correlation between visceral obesity index (VAI) and diabetes and accuracy of early prediction of diabetes are still controversial. OBJECTIVE: This study aims to review the relationship between high level of VAI and diabetes, and early predictive value of diabetes. DATA SOURCES: The databases of PubMed, Cochrane, Embase, and Web of Science were searched until October 17, 2023. STUDY SELECTION: After adjusting for confounding factors, the original study on the association between VAI and diabetes was analyzed. DATA EXTRACTION: We extracted odds ratio (OR) between VAI and diabetes management after controlling for mixed factors, and the sensitivity, specificity and diagnostic four grid table for early prediction of diabetes. DATA SYNTHESIS: 53 studies, comprising 595,946 participants were included. The findings of the meta-analysis elucidated that in cohort studies, a high VAI significantly increased the risk of diabetes mellitus in males (OR = 2.83 (95% CI: 2.30-3.49)) and females (OR = 3.32 (95% CI: 2.48-4.45)). The ROC, sensitivity, and specificity of VAI for early prediction of diabetes in males were 0.64 (95% CI: 0.62-0.66), 0.57 (95% CI: 0.53-0.61), and 0.65 (95% CI: 0.61-0.69), respectively, and 0.67 (95% CI: 0.65-0.69), 0.66 (95% CI: 0.60-0.71), and 0.61 (95% CI: 0.57-0.66) in females, respectively. CONCLUSIONS: VAI is an independent predictor of the risk of diabetes, yet its predictive accuracy remains limited. In future studies, determine whether VAI can be utilized in conjunction with other related indicators to early predict the risk of diabetes, to enhance the accuracy of prediction of the risk of diabetes.

Genetically Predicted Body Mass Index and Mortality in COPD.

RATIONALE: BMI is associated with COPD mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate causal mechanisms and predict risk. OBJECTIVES: To examine the associations of genetically predicted BMI with all-cause and cause-specific mortality in COPD. METHODS: We developed a polygenic score for BMI (PGSBMI) and tested for associations of the PGSBMI with all-cause, respiratory, and cardiovascular mortality in participants with COPD from the COPDGene, ECLIPSE, and Framingham Heart studies. We calculated the difference between measured BMI and PGS-predicted BMI (BMIdiff) and categorized participants into groups of discordantly low (BMIdiff < 20th percentile), concordant (BMIdiff between 20th - 80th percentile), and discordantly high (BMIdiff > 80th percentile) BMI. We applied Cox models, examined potential non-linear associations of the PGSBMI and BMIdiff with mortality, and summarized results with meta-analysis. MEASUREMENTS AND MAIN RESULTS: We observed significant non-linear associations of measured BMI and BMIdiff, but not PGSBMI, with all-cause mortality. In meta-analyses, a one standard deviation increase in the PGSBMI was associated with an increased hazard for cardiovascular mortality (HR=1.29, 95% CI=1.12-1.49), but not with respiratory or all-cause mortality. Compared to participants with concordant measured and genetically predicted BMI, those with discordantly low BMI had higher mortality risk for all-cause (HR=1.57, CI=1.41-1.74) and respiratory death (HR=2.01, CI=1.61-2.51). CONCLUSIONS: In people with COPD, higher genetically predicted BMI is associated with higher cardiovascular mortality but not respiratory mortality. Individuals with discordantly low BMI have higher all-cause and respiratory mortality compared to those with concordant BMI.

Microbial-mineral interaction experiments and density functional theory calculations revealing accelerating effects for the dolomitization of calcite surfaces by organic components.

Carbonates represent major sedimentary rocks in on the continental and oceanic crust of Earth and are often closely related to microbial activities. However, the origin of magnesium-containing carbonates, such as dolomites, has not yet been fully resolved and was debated for many years. In order to reveal the specific role of organic components and microbes on the precipitation of magnesium ions, different dolomitization experiments were carried out with various setups for the presence of eight amino acids and microbes. The Gibbs free energy for dehydration of Mg[6(H2O)]2+ and organic­magnesium complexes (OMC) at the calcite (101¯4) step edges were calculated by density functional theory (DFT). Combined results of X-ray diffraction (XRD), scanning electron microscope-energy disperse spectroscopy (SEM-EDS), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR) and high resolution transmission electron microscopy (HRTEM) indicated that magnesium ions were incorporated into the crystal lattice of calcite after calcite reacting with organic­magnesium solutions (OMS). Dolomite was formed on the surface of calcite under the presence of microbes. The Gibbs free energy barrier of asp, glu, gly, thr, tyr, lys, ser, and ala bonding to Mg[6(H2O)]2+ were 17.8, 16.2, 14.8, 16.5, 19.2, 14.5, 19.0, 17.0 kcal/mol, those are lower than that of the direct dehydration of Mg[6(H2O)]2+ of 19.45 kcal/mol. The Gibbs free barrier of OMC bonding at the acute step ([481¯] and [4¯41]) of 29.7/34.25 kcal/mol are lower than that of Mg[6(H2O)]2+ of 32.45/36.7 kcal/mol and the Gibbs free barrier of OMC bonding at the obtuse step ([481¯] and [4¯41]) of 42.07/47.6 kcal/mol are lower than that of Mg[6(H2O)]2+ of 55.4/60.34 kcal/mol. The enhancing effects of organic components and microbes on the precipitation of magnesium ions were collectively determined through experimental and theoretical calculation, thus setting up a new direction for future studies of dolomitization with a focus on microbial- mineral interactions.

Crucial roles of the optimal time-scale of water condition on grassland biomass estimation on Qinghai-Tibet Plateau.

The effect of the time-scale of water conditions on vegetation productivity has been widely studied by the academic community. However, the relationship between the time-scale of water conditions and the vegetation growth rhythm and the effect of this relationship on vegetation biomass estimation have rarely been discussed. Here, we analyzed the occurrence times of major phenological events on alpine grasslands using the widely distributed "site-dominant species" dataset and set a series of time-scales for accumulated precipitation and standardized precipitation evapotranspiration index based on phenological information. Then, we combined large-scale aboveground/belowground biomass datasets to evaluate the role of the optimal time-scale for water conditions in aboveground/belowground biomass estimation. The results showed that (1) the optimal time-scale for water conditions with the greatest effects on aboveground biomass was on the month before the end of flowering or the onset of fruit maturity. The optimal time-scale for water condition effects on belowground biomass was earlier and longer than that for the aboveground biomass. The optimal time-scales for accumulated precipitation and standardized precipitation evapotranspiration index effects on belowground biomass were at five months before the end of flowering or the beginning of fruit ripening and the three months before the first flowering, respectively. (2) The aboveground and belowground biomass were underestimated by 11 % and 9 %, respectively, when the water conditions at the optimal time-scales were ignored. (3) The interannual variability in aboveground/belowground biomass was more effectively captured by considering the optimal time-scales of water conditions, especially in water-restricted areas. Overall, this study indicated that terrestrial carbon cycle models should incorporate information on the lag-effects of the water conditions in previous periods. In the future, increasing the number of belowground biomass observations and conducting monthly belowground biomass monitoring sooner will be key to revealing the mechanisms of the belowground biomass response to climate change.

The fusion of multiple scale data indicates that the carbon sink function of the Qinghai-Tibet Plateau is substantial.

BACKGROUND: The Qinghai-Tibet Plateau is the "sensitive area" of climate change, and also the "driver" and "amplifier" of global change. The response and feedback of its carbon dynamics to climate change will significantly affect the content of greenhouse gases in the atmosphere. However, due to the unique geographical environment characteristics of the Qinghai-Tibet Plateau, there is still much controversy about its carbon source and sink estimation results. This study designed a new algorithm based on machine learning to improve the accuracy of carbon source and sink estimation by integrating multiple scale carbon input (net primary productivity, NPP) and output (soil heterotrophic respiration, Rh) information from remote sensing and ground observations. Then, we compared spatial patterns of NPP and Rh derived from the fusion of multiple scale data with other widely used products and tried to quantify the differences and uncertainties of carbon sink simulation at a regional scale. RESULTS: Our results indicate that although global warming has potentially increased the Rh of the Qinghai-Tibet Plateau, it will also increase its NPP, and its current performance is a net carbon sink area (carbon sink amount is 22.3 Tg C/year). Comparative analysis with other data products shows that CASA, GLOPEM, and MODIS products based on remote sensing underestimate the carbon input of the Qinghai-Tibet Plateau (30-70%), which is the main reason for the severe underestimation of the carbon sink level of the Qinghai-Tibet Plateau (even considered as a carbon source). CONCLUSIONS: The estimation of the carbon sink in the Qinghai-Tibet Plateau is of great significance for ensuring its ecological barrier function. It can deepen the community's understanding of the response to climate change in sensitive areas of the plateau. This study can provide an essential basis for assessing the uncertainty of carbon sources and sinks in the Qinghai-Tibet Plateau, and also provide a scientific reference for helping China achieve "carbon neutrality" by 2060.

Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tiaogan Jiejiu Tongluo Formula (TJTF), a traditional Chinese medicine formula, is modified from the well-known ancient prescription Danzhi-Xiaoyao Powder (DXP). Owing to its ability to regulate liver, strengthen spleen, detoxicating, and dredge collaterals in Chinese medicine, TJTF is usually used to treat anxiety, hypertension, alcoholic fatty liver disease in clinical application. However, the protective effect and potential molecular mechanism of TJTF on alcoholic liver injury has not fully been clarified. AIM OF THE STUDY: To explore the effect of TJTF on chronic alcoholic liver injury and figure out whether its effects were due to the regulation of lipid metabolism. MATERIAL AND METHODS: 75 male SD rats were divided into the following five groups, control group, EtOH group, TJTF high dose group, TJTF low dose group and silybin group. Then a chronic alcoholic liver injury model was established by increasing concentration of 56% ethanol in rats. The rats in each TJTF group were given the corresponding dose of TJTF, the rats in the silybin group were given silybin, the rats in the control group and the EtOH group were given distilled water by gavage, once a day for 8 consecutive weeks. The components of TJTF were analyzed by UPLC-Q-TOF-MS. Hematoxylin and Eosin (H&E) was used to assess the severity of liver injury. in the pathological examination. Periodic acid-Schiff (PAS) and oil red O staining were used to evaluate the degree of the liver glycogen accumulation and lipid deposition, respectively. The serum ALT, AST, T-CHO, TG, LDL-C, ADH, HDL-C, and ALDH levels as well as liver tissue GSH, MDA, and SOD levels were analyzed in rats. Immunohistochemistry and western blotting were used to detect lipid metabolism-related proteins expressed in rat liver. RESULTS: TJTF significantly alleviated the chronic liver injury caused by alcohol in rats, and enhanced liver function. TJTF significantly decreased AST, ALT, ADH levels and increased ALDH level of serum, and increased GSH, SOD levels and decreased MDA level of liver tissue. In addition, TJTF significantly decreased the serum T-CHO, TG and LDL-C levels and increased HDL-C level in chronic alcoholic liver injury rats by regulating the expression of lipid metabolism associated proteins including p-LKB1, p-AMPKα, p-ACC, FAS, HMGCR, SREBP-1c, PPARα and CPT-1A. The results of western blot and immunohistochemical staining confirmed that TJTF can inhibit lipid production and promote fatty acid oxidation in the liver tissue of chronic alcoholic liver injury rats by activating the LKB1-AMPKα axis and then downregulating the protein expressions of p-ACC, FAS, HMGCR and SREBP-1c, as well as promoting the protein expressions of PPARα and CPT-1A. Meanwhile, TJTF also increased the glycogen content of liver and alleviated the liver damage. CONCLUSION: According to current research, TJTF is effective in treating chronic liver damage induced by alcohol in rats. Additionally, TJTF exhibits the protective benefits by modulating LKB1-AMPKα signal axis, which in turn inhibits the synthesis of lipids and promotes the oxidation of fatty acids.

Nanoparticle-Delivered Transforming Growth Factor-ß1 siRNA Induces PD-1 against Gastric Cancer by Transforming the Phenotype of the Tumor Immune Microenvironment.

Immune checkpoint blockade (ICB) is currently considered to be an important therapeutic method, which obtained FDA approval for clinical use in gastric cancer in 2017. As a new mechanism, it was found that the effect of αPDL1 could be improved by blocking the TGF-ß1 signaling pathway, which converts the tumor immune microenvironment from the "immune-excluded phenotype" to the "immune-inflamed phenotype". Based on this phenomenon, this project was designed to prepare TGF-ß1-siRNA-loaded PEG-PCL nanoparticles conjugated to αPDL1 (siTGF-ß1-αPDL1-PEG-PCL) since we have linked similar antibodies to PEG-PCL previously. Therefore, MFC tumor-engrafted mice were established to simulate the biological characteristics of converting the phenotype of the immune microenvironment, and to study the anti-tumor effect and possible molecular mechanism. In this study, αPDL1 antibody conjugates markedly increased the cell uptake of NPs. The produced αPDL1-PEG-PCL NPs efficiently reduced the amounts of TGF-ß1 mRNA in MFC cells, converting the immune microenvironment of MFC tumors engrafted mice from the "immune-excluded phenotype" to the "immune-inflamed phenotype". PDL1-harboring gastric cancer had increased susceptibility to αPDL1. The value of this drug-controlled release system targeting the tumor microenvironment in immune checkpoint therapy of gastric cancer would provide a scientific basis for clinically applying nucleic acid drugs.

The AMPK pathway in fatty liver disease.

Lipid metabolism disorders are the primary causes for the occurrence and progression of various liver diseases, including non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) caused by a high-fat diet and ethanol. AMPK signaling pathway plays an important role in ameliorating lipid metabolism disorders. Progressive research has clarified that AMPK signal axes are involved in the prevention and reduction of liver injury. Upregulation of AMK can alleviate FLD in mice induced by alcohol or insulin resistance, type 2 diabetes, and obesity, and most natural AMPK agonists can regulate lipid metabolism, inflammation, and oxidative stress in hepatocytes, consequently regulating FLD in mice. In NAFLD and AFLD, increasing the activity of AMPK can inhibit the synthesis of fatty acids and cholesterol by down-regulating the expression of adipogenesis gene (FAS, SREBP-1c, ACC and HMGCR); Simultaneously, by increasing the expression of fatty acid oxidation and lipid decomposition genes (CPT1, PGC1, and HSL, ATGL) involved in fatty acid oxidation and lipid decomposition, the body's natural lipid balance can be maintained. At present, some AMPK activators are thought to be beneficial during therapeutic treatment. Therefore, activation of AMPK signaling pathway is a potential therapeutic target for disorders of the liver. We summarized the most recent research on the role of the AMPK pathway in FLD in this review. Simultaneously, we performed a detailed description of each signaling axis of the AMPK pathway, as well as a discussion of its mechanism of action and therapeutic significance.

Flow characteristics of open channels based on patch distribution of partially discontinuous rigid combined vegetation.

To clarify the flow characteristics of open channels under the combined distribution of vegetation in a patch, this study used the computational fluid dynamics tool FLUENT and the Reynolds stress model to design four combined and four discrete distribution modes under two different inundation states (submerged and non-submerged). The flow characteristics of longitudinally discontinuous rigid vegetation patches occupying half the width of the channel were numerically simulated. The numerical model is verified by indoor open channel flume experiments, and the obtained model data is in good agreement with the measured data. The results showed that: 1) The diameter of vegetation is an important factor affecting the wake structure. Under the submerged condition. 2)The submerged state, distribution pattern and combination form of vegetation are important factors that affect the distribution of flow velocity and change the structure of water flow. That is, the influence of vegetation distribution pattern on flow velocity and turbulence intensity under submerged condition is significantly weaker than that under non-submerged condition, and the flow velocity in non-vegetation area is significantly higher than that in vegetation area. The increase in the combined vegetation comprehensive stem thickness and the discrete degree resulted in an increase in the difference in flow velocity and turbulence intensity. 3) As the water flowed downstream, the flow velocity along the vegetated area continuously decreased, while it increased continuously along the non-vegetated area, and the difference in flow velocity between the two areas became more apparent. 4) The inundation state and combination characteristics of vegetation were important factors affecting the Reynolds stress of the channel location in the patch area.

Controlling the oxidation and wettability of liquid metal via femtosecond laser for high-resolution flexible electronics.

Liquid metal-based electronic devices are attracting increasing attention owing to their excellent flexibility and high conductivity. However, a simple way to realize liquid metal electronics on a microscale without photolithography is still challenging. Herein, the wettability and adhesion of liquid metal are controlled by combining the stirring method, femtosecond laser microfabrication, and sacrificial layer assistant. The adhesive force of liquid metal is dramatically enhanced by adjusting its oxidation. The wetting area is limited to a micro-pattern by a femtosecond laser and sacrificial layer. On this basis, a high-resolution liquid metal printing method is proposed. The printing resolution can be controlled even less than 50 µm. The resultant liquid metal pattern is applied to electronic skin, which shows uniformity, flexibility, and stability. It is anticipated that this liquid metal printing method will hold great promise in the fields of flexible electronics.

Femtosecond Laser-Induced Supermetalphobicity for Design and Fabrication of Flexible Tactile Electronic Skin Sensor.

Pursuing flexible tactile electronic skin sensors with superior comprehensive performances is highly desired in practical applications. However, current flexible tactile electronic skin sensors suffer insufficient flexibility and sensitivity, as well as high-cost and low-efficiency in fabrication, and are susceptible to contamination in sensing performances. Here, a highly sensitive all-flexible tactile sensor (AFTS) is presented with capacitive sensing that combines a double-side micropyramids dielectric layer and a liquid metal (LM) electrode. The design and fabrication of LM-based AFTS are based on supermetalphobicity induced by femtosecond laser. The supermetalphobic micropyramids lead to a high sensitivity up to 2.78 kPa-1, an ultralow limit of detection of ∼3 Pa, a fast response time of 80 ms, and an excellent durability of cyclic load over 10 000 times. The used femtosecond laser enables programmable, high-efficiency, low-cost, and large-scale fabrication of supermetalphobic double-side micropyramids, which is difficult to implement using conventional techniques. Furthermore, the outer substrates are treated by a femtosecond laser, endowing the AFTS with excellent antifouling performance and stable sensing signals in the highly humid environment. Successful monitoring of human physiological and motion signals demonstrates the potential of our developed AFTS for wearable biomonitoring applications.

An Immune-Related Prognostic Signature Predicts Overall Survival in Stomach Adenocarcinomas.

This study aimed to explore an immune response-related gene signature to predict the clinical prognosis and tumor immunity of stomach adenocarcinomas (STAD). Based on the expression and clinical data of STAD in the TCGA database, the immune cell infiltration status was evaluated using CIBERSORT and ESTIMATE methods. Samples were grouped into "hot" and "cold" tumors based on immune cell infiltration status and consensus clustering. The infiltration abundance of activated memory CD4 T cells and CD8 T cells had a significant effect on the overall survival of STAD patients. Among the three clusters, cluster 2 had a higher immune score and a significantly higher abundance of CD8 T cells and activated memory CD4 T cells were assigned as a hot tumor, while cluster 1 and 3 were assigned as a cold tumor. DEGs between hot and cold tumors were mainly enriched in immune-related biological processes and pathways. Total of 13 DEGs were related to the overall survival (OS). After the univariate and multivariable Cox regression analysis, three signature genes (PEG10, DKK1, and RGS1) was identified to establish a prognostic model. Patients with the high-risk score were associated with worse survival, and the risk score had an independent prognostic value. Based on TIMER online tool, the infiltration levels of six immune cell types showed significant differences among different copy number statuses of PEG10, DKK1, and RGS1. In this study, an immune-related prognostic model containing three genes was established to predict survival for STAD patients.

Uncertainties of soil organic carbon stock estimation caused by paleoclimate and human footprint on the Qinghai Plateau.

BACKGROUND: Quantifying the stock of soil organic carbon (SOC) and evaluating its potential impact factors is important to evaluating global climate change. Human disturbances and past climate are known to influence the rates of carbon fixation, soil physiochemical properties, soil microbial diversity and plant functional traits, which ultimately affect the current SOC storage. However, whether and how the paleoclimate and human disturbances affect the distribution of SOC storage on the high-altitude Tibetan Plateau remain largely unknown. Here, we took the Qinghai Plateau, the main component of the Tibetan Plateau, as our study region and applied three machine learning models (random forest, gradient boosting machine and support vector machine) to estimate the spatial and vertical distributions of the SOC stock and then evaluated the effects of the paleoclimate during the Last Glacial Maximum and the mid-Holocene periods as well as the human footprint on SOC stock at 0 to 200 cm depth by synthesizing 827 soil observations and 71 environmental factors. RESULTS: Our results indicate that the vegetation and modern climate are the determinant factors of SOC stocks, while paleoclimate (i.e., paleotemperature and paleoprecipitation) is more important than modern temperature, modern precipitation and the human footprint in shaping current SOC stock distributions. Specifically, the SOC stock was deeply underestimated in near natural ecosystems and overestimated in the strongly human disturbance ecosystems if the model did not consider the paleoclimate. Overall, the total SOC stock of the Qinghai Plateau was underestimated by 4.69%, 12.25% and 6.67% at depths of 0 to 100 cm, 100 to 200 cm and 0 to 200 cm, respectively. In addition, the human footprint had a weak influence on the distributions of the SOC stock. We finally estimated that the total and mean SOC stock at 200 cm depth by including the paleoclimate effects was 11.36 Pg C and 16.31 kg C m-2, respectively, and nearly 40% SOC was distributed in the top 30 cm. CONCLUSION: The paleoclimate is relatively important for the accurate modeling of current SOC stocks. Overall, our study provides a benchmark for predicting SOC stock patterns at depth and emphasizes that terrestrial carbon cycle models should incorporate information on how the paleoclimate has influenced SOC stocks.

Factors associated with serum CA125 level in women without ovarian cancer in the United States: a population-based study.

BACKGROUND: Cancer antigen 125 (CA125) is clinically used to monitor response to therapy in ovarian cancer and has been proposed for use in detecting ovarian cancer. This population-based study examines how demographic characteristics, gynecologic/reproductive history, chronic non-malignant medical conditions, history of non-ovarian cancer, lifestyle practices, and biomarkers of inflammation correlate with serum CA125 in both premenopausal and postmenopausal women without ovarian cancer across the United States. METHODS: Participants were identified from the National Health and Nutrition Examination Survey 2001-2002. Linear and logistic regression models were applied. RESULTS: Higher CA125 levels were found to correlate with younger age, Non-Hispanic White race/ethnicity, and lower body mass index. In premenopausal women (N = 1157), current smoking was associated with lower CA125 (- 24.95%, p = 0.008), and history of non-ovarian cancer was associated with higher CA125 (40.64%, p = 0.045) by multivariable linear regression; both current smoking (odds ratio (OR) = 0.42, p = 0.043) and oral contraceptive pill (OCP) use of 5-10 years (OR = 0.31, p = 0.032) were less likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. In postmenopausal women (N = 1116), coronary artery disease (CAD) history was associated with higher CA125 (28.27%, p = 0.047) by multivariable linear regression; history of CAD (OR = 5.00, p = 0.011), history of breastfeeding (OR = 2.46, p = 0.026), and increased CRP level (OR = 1.41, p = 0.042) were more likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. CONCLUSIONS: Results suggest CA125 is lower in premenopausal women who are current smokers and OCP users of moderately longer duration but higher in those with non-ovarian cancer. CA125 is higher in those postmenopausal women with CAD, history of breastfeeding and elevated CRP level. These associations can inform clinical interpretation of individual patients' CA125 levels.

Clinical Observation of Ropinirole Hydrochloride in the Treatment of Parkinson's Disease.

Parkinson's disease is a degenerative disease of the nervous system, which is more common in middle-aged and elderly people. Currently, the incidence of PD is increasing. The disease is a degenerative disease, which is irreversible and requires life-long treatment. Ropinirole hydrochloride can also be used for Parkinson's disease. Therefore, this article conducted research on this; the purpose is to further determine whether the drug can be used for Parkinson's disease. The method used in this article is a method of quantitative analysis and experimental testing. This article selects Parkinson's disease patients from the provincial hospital to conduct investigations and group experiments on these people to test the effects of different levels of ropinirole hydrochloride in the treatment of Parkinson's disease. Experimental data showed that when the dose of ropinirole was 1 mg, its peak concentration reached 24.95 and the clearance rate reached 143.42. This shows that, in the early stage of medication, it has certain benefits in disease control.

A polygenic risk score and age of diagnosis of COPD.

BACKGROUND: Genetic susceptibility may be associated with earlier onset of chronic obstructive pulmonary disease (COPD). We hypothesised that a polygenic risk score (PRS) for COPD would be associated with earlier age of diagnosis of COPD. METHODS: In 6647 non-Hispanic White (NHW) and 2464 African American (AA) participants from COPDGene, and 6812 participants from the Framingham Heart Study (FHS), we tested the relationship of the PRS and age of COPD diagnosis. Age at diagnosis was determined by: 1) self-reported age at COPD diagnosis or 2) age at visits when moderate-to-severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 2-4) was observed on spirometry. We used Cox regression to examine the overall and time-dependent effects of the PRS on incident COPD. In the COPDGene study, we also examined the PRS's predictive value for COPD at age <50 years (COPD50) using logistic regression and area under the curve (AUC) analyses, with and without the addition of other risk factors present at early life (e.g. childhood asthma). RESULTS: In Cox models, the PRS demonstrated age-dependent associations with incident COPD, with larger effects at younger ages in both cohorts. The PRS was associated with COPD50 (OR 1.55 (95% CI 1.41-1.71) for NHW, OR 1.23 (95% CI 1.05-1.43) for AA and OR 2.47 (95% CI 2.12-2.88) for FHS participants). In COPDGene, adding the PRS to known early-life risk factors improved prediction of COPD50 in NHW (AUC 0.69 versus 0.74; p<0.0001) and AA (AUC 0.61 versus 0.64; p=0.04) participants. CONCLUSIONS: A COPD PRS is associated with earlier age of diagnosis of COPD and retains predictive value when added to known early-life risk factors.

A PD1 targeted nano-delivery system based on epigenetic alterations of T cell responses in the treatment of gastric cancer.

The anticancer effects of immune checkpoint inhibitors (ICIs) have been widely examined recently. Although ICIs have been progressively improved for successful gastric cancer treatment, different trials of ICIs such as pembrolizumab and nivolumab have yielded widely variable response rates. Strategies to further improve the efficacy of ICIs are still needed. Previous studies have shown that de novo DNA methylation is acquired by PD1+CD8+ tumor-infiltrating T cells (TILs), which cause a hierarchical downregulation of cytokines such as interferon-γ (IFN-γ). The epigenetic agent 5-Aza-2'-deoxycytidine (DAC) blocks de novo DNA methylation in activated PD1+CD8+ TILs. Such a feature might help enhance the anti-tumor effect of immune checkpoint blockade (ICB) treatment. In this study, polyethylene glycol-poly(ε-caprolactone) (PEG-PCL) nanoparticles (NPs) were linked to the anti-programmed death-1 monoclonal antibody nivolumab to yield αPD1-NPs for targeting TILs with PD1 overexpression using DAC. In addition, the NPs increased DAC stability and improved IFN-γ secretion and the anti-tumor effect of ICB in vitro. Therefore, targeted delivery of DAC reverses the exhaustion of PD1+CD8+ TILs and improves T cell responses and the treatment effect of ICB. These findings suggest that nivolumab-NPs are a potential tool for the delivery of epigenetic drugs, which could enhance the anti-tumor effect of ICB in gastric cancer.

Waste to Wealth Strategy: Preparation and Properties of Lightweight Al2O3-SiO2-Rich Castables Using Aluminum Dross Waste.

Aluminum dross is a well-known industrial waste generated in the aluminium industry, and its recycling and reuse is still a worldwide issue. Herein, aluminum dross waste (ADW) was recycled to progressively replace the aggregate fraction of clay at 70, 75, 80, 85, and 90 wt% for the fabrication of Al2O3-SiO2-rich porous castable refractories. Their physical properties and mechanical behavior were assessed by the measurement of linear shrinkage rate, bulk density, apparent porosity, cold crushing strength, and thermal conductivity. The microstructure and phase evolutions were analyzed via scanning electron microscopy (SEM) and X-ray diffraction (XRD). The incorporation of 85 wt% of ADW allowed the development of a waste-containing conventional refractory castable with improved properties as compared to those of the other samples. The sustainable refractory castable exhibited decent thermal conductivity and physical and mechanical characteristics, and is suitable for application as reheating furnace lining. It is a "green" practice to partially replace the traditional raw materials with industrial waste in the manufacture of conventional refractory castables and provides environmental and economic benefits.

Secondary polycythemia in chronic obstructive pulmonary disease: prevalence and risk factors.

BACKGROUND: Secondary polycythemia is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, the prevalence of polycythemia in COPD and the contributing risk factors for polycythemia in COPD have not been extensively studied. METHODS: We analyzed the presence of secondary polycythemia in current and former smokers with moderate to very severe COPD at the five-year follow-up visit in the observational COPDGene study. We used logistic regression to evaluate the association of polycythemia with age, sex, race, altitude, current smoking status, spirometry, diffusing capacity for carbon monoxide (DLCO), quantitative chest CT measurements (including emphysema, airway wall thickness, and pulmonary artery to aorta diameter ratio), resting hypoxemia, exercise-induced hypoxemia, and long-term oxygen therapy. RESULTS: In a total of 1928 COPDGene participants with moderate to very severe COPD, secondary polycythemia was found in 97 (9.2%) male and 31 (3.5%) female participants. In a multivariable logistic model, severe resting hypoxemia (OR 3.50, 95% CI 1.41-8.66), impaired DLCO (OR 1.28 for each 10-percent decrease in DLCO % predicted, CI 1.09-1.49), male sex (OR 3.60, CI 2.20-5.90), non-Hispanic white race (OR 3.33, CI 1.71-6.50), current smoking (OR 2.55, CI 1.49-4.38), and enrollment in the Denver clinical center (OR 4.42, CI 2.38-8.21) were associated with higher risk for polycythemia. In addition, continuous (OR 0.13, CI 0.05-0.35) and nocturnal (OR 0.46, CI 0.21-0.97) supplemental oxygen were associated with lower risk for polycythemia. Results were similar after excluding participants with anemia and participants enrolled at the Denver clinical center. CONCLUSIONS: In a large cohort of individuals with moderate to very severe COPD, male sex, current smoking, enrollment at the Denver clinical center, impaired DLCO, and severe hypoxemia were associated with increased risk for secondary polycythemia. Continuous or nocturnal supplemental oxygen use were associated with decreased risk for polycythemia.