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.

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.

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.

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.

Femtosecond Laser-Induced Underwater Superoleophobic Surfaces with Reversible pH-Responsive Wettability.

Wettability-switchable surfaces have become a research hotspot because they can exhibit different superwetting states. In this paper, the copper surfaces with pH-responsive underwater-oil wettability were prepared by femtosecond laser treatment and subsequent chemical modification. The resultant surfaces showed underwater superoleophobicity in alkaline solutions but quasi-superoleophilicity in acidic solutions. The contact angles of an underwater-oil droplet on the resultant surfaces could be reversibly tuned between 157° and 12° by changing the pH of aqueous solutions. Such switchable wettability is ascribed to the modification of the alkyl and carboxylic acids groups on the laser-structured surfaces. The as-prepared surfaces have both oil-resistance and oil-collection abilities by selectively showing underwater superoleophobicity and superoleophilicity. The smart surfaces with pH-responsive oil wettability will have important applications in controlling the oil behavior in water.

Comorbidities of Rare Epilepsies: Results from the Rare Epilepsy Network.

OBJECTIVE: To describe the prevalence and characteristics of comorbidities in persons with rare epilepsies. STUDY DESIGN: Persons with rare epilepsies and caregivers of those affected were recruited through the Epilepsy Foundation and more than 30 rare epilepsy advocacy organizations affiliated with the Rare Epilepsy Network (REN). A web-based survey was conducted using a questionnaire consisting of core sections to collect data from affected persons on various aspects, including comorbidities. Comorbidity information was grouped into 15 classes, 12 of which had a stem question followed by detailed branch questions and 3 that were created from a combination of related questions. RESULTS: Of 795 persons with more than 30 different rare epilepsy diagnosis groups, one-half had ≥5 comorbidity classes and 97% were classified as complex chronic disease (C-CD). The highest number of comorbidity classes reported per person were persons with Aicardi syndrome, Phelan-McDermid syndrome (median, 7.0; IQR, 5.0-9.0), and tuberous sclerosis complex (median, 6.0; IQR, 4.0-8.0). The most common comorbidity classes were learning/developmental disability (71%), mental health issues (71%), sleep disorders (60%), brain abnormalities (52%), oral issues (49%), bone-joint issues (42%), hyper/hypotonia (42%), and eye-vision disorders (38%). The prevalence of brain abnormalities, hyper/hypotonia, eye, and cardiac disorders was significantly higher in persons first diagnosed with epilepsy at a younger age (<9 months) than in those first diagnosed at an older age (P < .05 for trend). CONCLUSIONS: Nearly all persons with rare epilepsies are medically complex, with a high prevalence of multiple comorbidities, especially those who were diagnosed with epilepsy in the first year of life. Comorbidities should be carefully considered in the diagnosis and management of persons with rare epilepsies.

Global lung function initiative 2012 reference values for spirometry in Asian Americans.

BACKGROUND: Spirometry reference values specifically designed for Asian Americans are currently unavailable. The performance of Global Lung Function Initiative 2012 (GLI-2012) equations on assessing spirometry in Asian Americans has not been evaluated. This study aimed to assess the fitness of relevant GLI-2012 equations for spirometry in Asian Americans. METHODS: Asian subjects who never smoked and had qualified spirometry data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Z-scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were separately constructed with GLI-2012 equations for North East (NE) Asians, South East (SE) Asians, and individuals of mixed ethnic origin (Mixed). In addition, Proportions of subjects with observed spirometry data below the lower limit of normal (LLN) were also evaluated on each GLI-2012 equation of interest. RESULTS: This study included 567 subjects (250 men and 317 women) aged 6-79 years. Spirometry z-scores (z-FEV1, z-FVC, and z-FEV1/FVC) based on GLI-2012 Mixed equations had mean values close to zero (- 0.278 to - 0.057) and standard deviations close to one (1.001 to 1.128); additionally, 6.0% (95% confidence interval (CI) 3.1-8.9%) and 6.4% (95% CI 3.7-9.1%) of subjects were with observed data below LLN for FEV1/FVC in men and women, respectively. In contrast, for NE Asian equations, all mean values of z-FEV1 and z-FVC were smaller than - 0.5; for SE Asian equations, mean values of z-FEV1/FVC were significantly smaller than zero in men (- 0.333) and women (- 0.440). CONCLUSIONS: GLI-2012 equations for individuals of mixed ethnic origin adequately fitted spirometry data in this sample of Asian Americans. Future studies with larger sample sizes are needed to confirm these findings.

The resistance effect of vegetation stem diameter on overland runoff under different slope gradients.

Vegetation is an important part of the natural environment and has resistance effects on overland runoff, which can effectively reduce hydraulic erosion. The effect of vegetation stem diameter and slope gradient on flow resistance is thus worthy of further study. The influence of three different slope gradients (s), three vegetation stem diameters (d) and 12 levels of unit discharge (q) on the flow resistance of a slope was simulated to systematically study the effect of vegetation stem diameter and slope gradient on overland runoff. The diameter of the vegetation stem and the slope gradient were found to have a significant resistance effect on overland runoff. Under the same slope gradient, the Darcy-Weisbach resistance factor (f) increased with an increase in the vegetation stem diameter. Under experimental conditions, the rate of change of f was analysed by linear regression, and as d increased by 1 mm, f increased by an average of 49.9%. For a given vegetation stem diameter and vegetation distribution pattern, the greater the slope gradient, the smaller the value of f, and as S increased by 1.0%, f decreased by an average of 24.5%. These results are important to optimize the slope vegetation distribution in farmland conservation.

Underwater Transparent Miniature "Mechanical Hand" Based on Femtosecond Laser-Induced Controllable Oil-Adhesive Patterned Glass for Oil Droplet Manipulation.

Development of underwater superoleophobic surfaces has captured the imagination of researchers because of their applications; especially, oil manipulation based on such surfaces has attracted much attention. Here, we show a simple and effective way to fabricate an underwater transparent miniature "mechanical hand" based on controllable oil-adhesive patterned glass using a femtosecond laser. The underwater oil-adhesive force of the patterned glasses that compose the "mechanical hand" device can be controlled from ultralow to ultrahigh by adjusting the ratio of the untreated flat glass area to the laser-ablated rough area. These surfaces also showed favorable transparency in water. Various oils such as chloroform, hexadecane, n-dodecane, decane, liquid paraffin, and petroleum ether were tested, and their repellency against the as-prepared surfaces in water medium was confirmed. Moreover, the "mechanical hand" was used to implement oil transportation, fusion, and rapid capture, which can be applied in the construction of microfluidic devices, in situ detectors, and bioreactors.

Spirometry reference values for population aged 7-80 years in China.

BACKGROUND AND OBJECTIVE: Lung function tests are widely used in clinical and public health practice; however, no valid spirometry reference values were available for the general population in China. This study aimed to provide valid spirometry predictive equations for the general population in China, and to evaluate the predictive performance of previously used equations. METHODS: Data from the China National Health Survey 2012-2015 and the 'Generalized Additive Models for Location, Scale and Shape' statistical modelling method were used to establish spirometry predictive equations for forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC) and FEV1 /FVC. Paired t-tests were used to examine differences between spirometry measurements in this sample and predicted values of four previous spirometry predictive equations. RESULTS: This study included 3130 lifetime non-smokers (713 males and 2417 females) aged 7-80 years in China. Spirometry predictive equations with age and height as predictive variables plus age-specific splines were established separately by gender. Most previous spirometry predictive equations were found to significantly overestimate (maximum of 3.69% in FEV1 , 1.87% in FVC and 4.19% in FEV1 /FVC for males; 11.46% in FEV1 , 7.28% in FVC and 3.78% in FEV1 /FVC for females) or underestimate (maximum of 5.75% in FEV1 and 8.12% in FVC for males; 7.89% in FEV1 and 9.32% in FVC for females) lung function measurements when applied to this sample population. CONCLUSION: This study addressed the urgent need for valid and up-to-date spirometry reference values for the general population in China. Moreover, previous spirometry predictive equations showed unfavourable generalizability to this sample population.

[Study on the Effects of Ginsenoside Rb1 on DPPC Bilayers by Using Thermo-Raman Spectrum and DSC].

The research on the interactions between Ginsenosides and biomembranes plays a crucial role in thorough understanding the pharmacological activity and biologyical effect of Chinese medicine Panax ginseng. With the bilayer structure, DPPC often serves as an simulation model of the cell membrane to study the role of drug molecules and cell membranes. Ginsenoside Rb1, one of the most important components of Panaxginseng, playing the significant roles of pharmacological effects and biological properties. Raman and differential scanning calorimetry (DSC) are respectively a powerful tool for discussing the molecular interaction, and a kind of general technology by which researching the bilayer monomer structures and its interactions with drug molecules. However, rarely research reports on the interactions between drug molecules and biomembranes by means of both technologies above. In this paper, the influence of ginsenoside monomer Rb1 on DPPC membrane bilayers was investigated by thermo-Raman and DSC. In Raman spectra, the changes of DPPC molecule have been observed before and after interacted with ginsenoside Rb1, the data analysis indicates three aspects: the O-C-C-N+ polar head group skeleton, C-C stretching vibration area, and the C-H bond stretching vibrarion in terminated methyl group of alkyl chains. The results showed that ginsenoside Rb1 molecule with certain concentration has not changed the gauche conformation of the polar head backbone group in DPPC bilayers, the order of the internal molecular chain and the lateral chain-chain packing have been decreased as the temperature increased, the lateral disposed disorder has been increased. The changes of some thermodynamic constants obtained by DSC experiment such as phase transition temperature (Tm), the temperature at which the transition is half completed (ΔT1/2), and the transition enthalpy normalized per mol of DPPC (AH) have been showed further results of the thermo Raman experiments, with increasing the concentration of ginsenoside Rb1, the pre-transition temperature of DPPC bilayers dropped immediately with small amount of the Rb1 drug when the containtion was only 5 mol% and the whole system has been destructed at the same time, the main phase transition peak showed as a new little shoulder seam, however, both pre- and main transition peak disappeared completely until the drug concentration increased to 20 mol%, the phase transition temperature of DPPC has been reduced significantly, and the fluidity of bilayers has been increased. Both experiments indicated that the strong effects of ginsenoside Rb1 on DPPC.

[Raman and DSC spectroscopic studies on the interaction between ginsenosides and DMPC bilayer membranes].

Study the effect of drugs and biological membranes is of prime importance on understanding drugs' curative effects and improving their biological properties. In this article, Raman spectrum has been combined with differential thermal scanning technology to discuss the relationship between five categories of ginsenoside molecules and DMPC bilayer films. Raman results indicated that the saponin molecules have not altered the polarity conformation of O-C-C-N+ backbone in DMPC bilayers, and the polarity head still paralleled to the membrane surface. The order of the internal molecular chain and the lateral chain-chain packing have been decreased as the panaxadiol saponins Rb1 and Rh2 increased, and to the opposite, the panaxatriol saponins Re, Rf and Rg1 have showed weak effects on DMPC bilayers. The DSC showed further results that the strong effects of ginsenoside Rb1 and Rh2 on DMPC, which both have obviously reduced the DMPC molecular phase transition temperature, thus increasing the fluidity of bilayers. In addition, panaxatriol saponin Rf has displayed stronger disturbance effect on DMPC than Re and Rg1.

Tracking of lineage mass via quantitative phase imaging and confinement in low refractive index microwells.

Measurements of cell lineages are central to a variety of fundamental biological questions, ranging from developmental to cancer biology. However, accurate lineage tracing requires nearly perfect cell tracking, which can be challenging due to cell motion during imaging. Here we demonstrate the integration of microfabrication, imaging, and image processing approaches to demonstrate a platform for cell lineage tracing. We use quantitative phase imaging (QPI), a label-free imaging approach that quantifies cell mass. This gives an additional parameter, cell mass, that can be used to improve tracking accuracy. We confine lineages within microwells fabricated to reduce cell adhesion to sidewalls made of a low refractive index polymer. This also allows the microwells themselves to serve as references for QPI, enabling measurement of cell mass even in confluent microwells. We demonstrate application of this approach to immortalized adherent and nonadherent cell lines as well as stimulated primary B cells cultured ex vivo. Overall, our approach enables lineage tracking, or measurement of lineage mass, in a platform that can be customized to varied cell types.

FTO is Associated with Patient Prognosis and Immune Infiltrates in Gastric Cancer and Regulates TGF-ß Expression.

AIMS: This study aimed to examine the associations of FTO expression with prognosis, tumor microenvironment (TME), immune cell infiltration, immune checkpoint genes, and relevant signaling pathways in GC. Furthermore, the relationship between FTO and TGF-ß was studied in GC. METHODS: The mRNA expression and clinical survival data of GC samples were obtained from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD). TIMER2, TNM plot, and GEPIA database were used to analyze FTO expression. The associations of FTO with prognosis and clinicopathologic features were assessed using the Kaplan-Meier plotter and UALCAN database, respectively. The R software was employed to analyze its related signaling pathways and the associations with TME, immune cell infiltration, and immune checkpoint genes. GEPIA and ENCORI were used to examine the association of FTO with TGF-ß expression. The SRAMP website was utilized to predict m6A modification of TGF-ß. IHC, Western blot, and qPCR were used to analyze the expression levels of FTO and TGF-ß in clinical gastric cancer tissue samples or gastric cancer cell lines. In addition, a m6A RNA methylation assay kit was used to determine m6A levels in gastric cancer cells. RESULTS: FTO mRNA and protein levels were significantly elevated in GC compared to normal gastric tissues. Kaplan-Meier survival analysis suggested that upregulated FTO was associated with a worse prognosis in GC. Upregulated FTO was markedly correlated with differentiation degree, lymph node metastasis, and clinical TNM stage. GO and KEGG pathway analyses revealed that FTO-associated molecules were enriched in neuroactive ligand-receptor interaction, calcium signaling, PI3k-Akt signaling, cAMP signaling pathways, and TGF-ß signaling pathways, among others. The TME score was remarkably higher in the high-FTO group than in the low-FTO group. Furthermore, FTO expression had positive correlations with different types of immune cells and immune checkpoint genes. Moreover, FTO may regulate TGF-ß in an m6A RNA modification manner in GC. CONCLUSION: FTO may become an independent predictive prognostic biomarker correlating with TME, immune cell infiltration, and immune checkpoint genes in gastric cancer and might influence GC progression by regulating TGF-ß expression.

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.

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.

Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes.

Rationale: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. Objectives: Define high-risk COPD subtypes using both genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics. Methods: We defined high-risk groups based on PRS and TRS quantiles by maximizing differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing analyses between high-risk groups. Measurements and Main Results: We examined two high-risk omics-defined groups in non-overlapping test sets (n=1,133 NHW COPDGene, n=299 African American (AA) COPDGene, n=468 ECLIPSE). We defined "High activity" (low PRS/high TRS) and "severe risk" (high PRS/high TRS) subgroups. Participants in both subgroups had lower body-mass index (BMI), lower lung function, and alterations in metabolic, growth, and immune signaling processes compared to a low-risk (low PRS, low TRS) reference subgroup. "High activity" but not "severe risk" participants had greater prospective FEV 1 decline (COPDGene: -51 mL/year; ECLIPSE: - 40 mL/year) and their proteomic profiles were enriched in gene sets perturbed by treatment with 5-lipoxygenase inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Conclusions: Concomitant use of polygenic and transcriptional risk scores identified clinical and molecular heterogeneity amongst high-risk individuals. Proteomic and drug repurposing analysis identified subtype-specific enrichment for therapies and suggest prior drug repurposing failures may be explained by patient selection.

Glenoid articular conformity affects stress distributions in total shoulder arthroplasty.

BACKGROUND: The stress applied to the glenoid component in total shoulder arthroplasty (TSA) remains an important concern because of the risk of wear and loosening. The purpose of this study was to determine the stress pattern in the glenoid component with 3 different surface designs. METHODS: Computer models of 9 scapulae of patients scheduled for TSA were created from computerized tomography images. Each glenoid was virtually reamed, and 3 different glenoid component designs (conforming, nonconforming, and hybrid) were placed. Using finite element analysis, superior translation of the humeral head was modeled. Maximum stress and shear stress were measured at 3 different locations in the glenoid component: center, transition, and superior regions. RESULTS: All 3 designs showed a similar level of maximum stress at the center and transition regions, while the maximum stress at the superior periphery was significantly higher in the conforming design than in the other 2 designs (P = .0017). The conforming design showed significantly higher shear stress at the superior periphery (P < .0001). DISCUSSION: Stress from periphery loading is higher than from the center and transition region regardless of component design and is highest in the conforming design. The stress at the transition region of the hybrid design was not higher than the other 2 designs. The hybrid design has favorable characteristics based on its low stress at the periphery and greater contact area with the humeral head at the center. LEVEL OF EVIDENCE: Basic Science Study, Biomechanical Computer Simulation Study.

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.

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.