New labdane diterpenoids from Alpinia galanga: A new type of GLP-1 secretagogues targeting the PKA-CREB and PI3K-Akt signaling axes.

Glucagon-like peptide-1 (GLP-1) secretagogues are fascinating pharmacotherapies to overcome the defects of GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors in treating diabetes and obesity. To discover new GLP-1 secretagogues from natural sources, alpigalangols A-Q (1-17), 17 new labdane diterpenoids including four unusual nor-labdane and N-containing ones, were isolated from the fruits of Alpinia galanga. Most of the isolates showed GLP-1 promotive effects in NCl-H716 cells, of which compounds 3, 4, 12, and 14-17 were revealed with high promoting rates of 246.0%-413.8% at 50 µM. A mechanistic study manifested that the most effective compound 12 upregulated the mRNA expression of Gcg and Pcsk1, and the protein phosphorylation of PKA, CREB, and GSK3ß, but was inactive on GPBAR and GPR119 receptors. Network pharmacology analysis indicated that the PI3K-Akt pathway was involved in the GLP-1 stimulation of 12, which was highly associated with AKT1, CASP3, PPARG, and ICAM1 proteins. This study suggests that A. galanga is rich in diverse labdane diterpenoids with GLP-1 promoting effects, representing a new type of antidiabetic candidates from natural sources.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study.

CONTEXT: Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies. OBJECTIVE: To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk. METHODS: We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants. RESULTS: In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003). CONCLUSIONS: These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study.

Background: The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women. Methods: This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer. Results: Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87). Conclusion: The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case-control study.

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

Revelation of adhesive proteins affecting cellular contractility through reference-free traction force microscopy.

Over the past few decades, the critical role played by cellular contractility associated mechanotransduction in the regulation of cell functions has been revealed. In this case, numerous biomaterials have been chemically or structurally designed to manipulate cell behaviors through the regulation of cellular contractility. In particular, adhesive proteins including fibronectin, poly-L-lysine and collagen type I have been widely applied in various biomaterials to improve cell adhesion. Therefore, clarifying the effects of adhesive proteins on cellular contractility has been valuable for the development of biomaterial design. In this study, reference-free traction force microscopy with a well-organized microdot array was designed and prepared to investigate the relationship between adhesive proteins, cellular contractility, and mechanotransduction. The results showed that fibronectin and collagen type I were able to promote the assembly of focal adhesions and further enhance cellular contraction and YAP activity. In contrast, although poly-L-lysine supported cell spreading and elongation, it was inefficient at inducing cell contractility and activating YAP. Additionally, compared with cellular morphogenesis, cellular contraction was essential for YAP activation.

The Association between Educational Attainment and the Risk of Nonalcoholic Fatty Liver Disease among Chinese Adults: Findings from the REACTION Study.

Background/Aims: : Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: : A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: : Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions: : In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Expression of small nucleolar RNA SNORA51 and its clinical significance in hepatocellular carcinoma.

Small nucleolar RNA H/ACA Box 51 (SNORA51) is involved in progression of multiple cancers. However, its role in hepatocellular carcinoma (HCC) is still unclear. The aim of the present study was to analyze the expression of SNORA51 in HCC and its clinical significance. A total of 136 patients with HCC who underwent surgery from January 1, 2016 to December 31, 2018 were included. The expression of SNORA51 in cancer tissues and adjacent tissues was compared using reverse transcription-quantitative PCR and bioinformatics methods. Methylation of the SNORA51 promoter in cancer and adjacent tissues was compared using bioinformatics. The relationship between SNORA51 expression levels and clinicopathological characteristics of patients with HCC, in addition to prognosis, was analyzed. The expression of SNORA51 in HCC was significantly higher compared with that in adjacent tissues (P<0.05). starBase demonstrated that higher expression levels of SNORA51 were associated with a significantly worse prognosis of patients with HCC compared with those who had lower expression levels of SNORA51 (P<0.05). Bioinformatics analysis using The University of Alabama at Birmingham Cancer Data Analysis Portal demonstrated that methylation of the SNORA51 promoter region in HCC was significantly decreased compared with adjacent tissues (P<0.05). A high expression of SNORA51 was significantly associated with portal vein tumor thrombus, vascular invasion and TNM stage (P<0.05). The median survival time of patients with high SNORA51 expression was significantly lower compared with those who had low SNORA51 expression (P<0.05). Both uni- and multivariate Cox regression analysis demonstrated that SNORA51 expression was an independent risk factor that significantly worsened the prognosis of patients with HCC (P<0.05). The overexpression of SNORA51 in patients with HCC was significantly associated with a poor prognosis and may be related to the reduced methylation of the SNORA51 promoter region. Therefore, SNORA51 may be a promising biomarker for prediction of the prognosis of patients with HCC and may be a therapeutic target for the treatment of HCC in future.

Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults.

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease (CKD) risk, but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD. We included 104 538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study, with self-reported time of daily-life behavior. Using isotemporal substitution models, we found that substituting 1 h of sleeping with sitting, walking, or moderate-to-vigorous physical activity was associated with a lower CKD prevalence. Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population. In stratified analysis, a lower CKD prevalence related to substitution toward physical activity was found in long sleepers. More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes, and they benefited from other behavior substitutions toward a more active way. The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys, in which the pernicious link with oversleep could be reversed by time reallocation to physical activity. The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

Early adulthood weight change, midlife "Life's essential 8" health status and risk of cardiometabolic diseases: a chinese nationwide cohort study.

BACKGROUND: The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by "Life's Essential 8" has not been characterized. We aim to examine the associations of early adulthood weight change and midlife "Life's Essential 8" CVH status with cardiometabolic outcomes in a Chinese cohort. METHODS: The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in "Life's Essential 8" was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria. RESULTS: 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04-1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25-1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01-2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90-2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife. CONCLUSIONS: Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population.

Sesquiterpenoids from Alpinia oxyphylla with GLP-1 Stimulative Effects through Ca2+/CaMKII and PKA Pathways and Multiple-Enzyme Inhibition.

Six new sesquiterpenoids (1-6), a pair of enantiomers (7a and 7b), and six known ones (8-13) were isolated from the fruits of Alpinia oxyphylla. The structures of the new compounds were elucidated by extensive spectroscopic data and ECD calculations. The stereochemistry of 7a and 7b was reported for the first time. All compounds showed significant GLP-1 stimulation in NCI-H716 cells with promoting ratios ranging from 90.4 to 668.9% at 50 µM. Mechanism study indicated that compound 6 stimulated GLP-1 secretion mainly by regulating the transcription and the shearing process of proglucagon, while compound 13 exerted its effects through up-regulating prkaca levels. Interestingly, the GLP-1 stimulative effects of 6 and 13 were both closely related with Ca2+/CaMKII and PKA pathways but irrelevant to TGR5 and GPR119 receptors. Moreover, most compounds exhibited inhibitory activity against α-glucosidase and PTP1B at concentrations of 100 and 200 µM, while showing no activity against GPa. Compounds 3, 9, 11, and 13 could suppress α-glucosidase with IC50 values of 190.0, 204.0, 181.8, and 159.6 µM, equivalent to acarbose (IC50 = 212.0 µM). This study manifests that A. oxyphylla contains diverse sesquiterpenoids with multiple activities.

Silymarin suppresses proliferation of human hepatocellular carcinoma cells under hypoxia through downregulation of the HIF-1α/VEGF pathway.

BACKGROUND: Hypoxia is a significant feature of many solid tumors and can activate hypoxia-inducible factor 1α (HIF-1α)/vascular epidermal growth factor (VEGF) signaling pathway, which is closely related to the occurrence and development of primary liver cancer (PLC). Silymarin (SM) had been used as a traditional liver protective drug for decades. Recent studies have found that SM has chemopreventive and chemosensitizing effects on multiple cancers. In this study, we investigated the effects of SM on HIF-1α/VEGF signaling in human hepatocellular carcinoma cells under hypoxia conditions. METHODS: HepG2 and Hep3B cells were divided into different experimental groups according to different culture conditions (aerobic or anaerobic) and the concentration of SM in the culture medium. The cellular proliferation, migration, invasion, colony formation, and apoptosis were observed by using methyl thiazolyl tetrazolium (MTT) assay, cell migration assay, in vitro invasion assay, soft agar colony formation assay, and Annexin V apoptosis assay, respectively. The cellular expressions of HIF-1α and VEGF were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) analyses. RESULTS: SM reduced cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in HepG2 and Hep3B cells under hypoxia conditions. The half inhibitory concentrations (IC50) of SM on HepG2 and Hep3B cells were 58.46 and 75.13 umol/L, respectively. SM also suppressed cellular expressions of HIF-1α and VEGF in HepG2 and Hep3B cells under hypoxia conditions at the mRNA and protein levels. All these effects of SM were dose dependent. CONCLUSIONS: The inhibitory effect of SM on HepG2 and Hep3B cells under hypoxia is partially via downregulating HIF-1α/VEGF signaling, which may serve as a potential drug therapy target for liver cancer based on SM.

Association between the lean nonalcoholic fatty liver disease and risk of incident type 2 diabetes in a healthy population of Northwest China: a retrospective cohort study with a 2-year follow-up period.

Aims: We aimed to explore the metabolic features of lean nonalcoholic fatty liver disease (Lean-NAFLD) and its association with the risk of incident type 2 diabetes in young and middle-aged people. Methods: We conducted a retrospective cohort study of 3001 participants who were enrolled in a health check-up program from January 2018 to December 2020 in the Health Management Center of Karamay People's Hospital. The age, sex, height, weight, body mass index (BMI), blood pressure, waist circumference (WC), fasting plasma glucose (FPG), lipid profiles, serum uric acid and alanine aminotransferase (ALT) of the subjects were collected. The cutoff point of BMI for lean nonalcoholic fatty liver disease is <25 kg/m2. A COX proportional hazard regression model was used to analyze the risk ratio of lean nonalcoholic fatty liver disease to type 2 diabetes mellitus. Results: Lean NAFLD participants had many metabolic abnormalities, such as overweight and obesity with nonalcoholic fatty liver disease. Compared with lean participants without nonalcoholic fatty liver disease, the fully adjusted hazard ratio (HR) for lean participants with nonalcoholic fatty liver disease was 3.83 (95% CI 2.02-7.24, p<0.01). In the normal waist circumference group (man<90cm, woman<80 cm), compared with lean participants without NAFLD, the adjusted hazard ratios (HRs) of incident type 2 diabetes for lean participants with NAFLD and overweight or obese participants with NAFLD were 1.93 (95% CI 0.70-5.35, p>0.05) and 4.20 (95% CI 1.44-12.22, p<0.05), respectively. For excess waist circumference (man≥90 cm, woman ≥80 cm) compared with lean participants without NAFLD, the adjusted hazard ratios (HRs) of incident type 2 diabetes for lean participants with NAFLD and overweight or obese participants with NAFLD were 3.88 (95% CI 1.56-9.66, p<0.05) and 3.30 (95% CI 1.52-7.14, p<0.05), respectively. Conclusion: Abdominal obesity is the strongest risk factor for type 2 diabetes in lean nonalcoholic fatty liver disease.

Surface Properties of Global Land Surface Microwave Emissivity Derived from FY-3D/MWRI Measurements.

Land surface microwave emissivity is crucial to the accurate retrieval of surface and atmospheric parameters and the assimilation of microwave data into numerical models over land. The microwave radiation imager (MWRI) sensors aboard on Chinese FengYun-3 (FY-3) series satellites provide valuable measurements for the derivation of global microwave physical parameters. In this study, an approximated microwave radiation transfer equation was used to estimate land surface emissivity from MWRI by using brightness temperature observations along with corresponding land and atmospheric properties obtained from ERA-Interim reanalysis data. Surface microwave emissivity at the 10.65, 18.7, 23.8, 36.5, and 89 GHz vertical and horizontal polarizations was derived. Then, the global spatial distribution and spectrum characteristics of emissivity over different land cover types were investigated. The seasonal variations of emissivity for different surface properties were presented. Furthermore, the error source was also discussed in our emissivity derivation. The results showed that the estimated emissivity was able to capture the major large-scale features and contains a wealth of information regarding soil moisture and vegetation density. The emissivity increased with the increase in frequency. The smaller surface roughness and increased scattering effect may result in low emissivity. Desert regions showed high emissivity microwave polarization difference index (MPDI) values, which suggested the high contrast between vertical and horizontal microwave signals in this region. The emissivity of the deciduous needleleaf forest in summer was almost the greatest among different land cover types. There was a sharp decrease in the emissivity at 89 GHz in the winter, possibly due to the influence of deciduous leaves and snowfall. The land surface temperature, the radio-frequency interference, and the high-frequency channel under cloudy conditions may be the main error sources in this retrieval. This work showed the potential capabilities of providing continuous and comprehensive global surface microwave emissivity from FY-3 series satellites for a better understanding of its spatiotemporal variability and underlying processes.

Association of Spousal Diabetes Status and Ideal Cardiovascular Health Metrics With Risk of Incident Diabetes Among Chinese Adults.

Importance: Spouses share common socioeconomic, environmental, and lifestyle factors, and multiple studies have found that spousal diabetes status was associated with diabetes prevalence. But the association of spousal diabetes status and ideal cardiovascular health metrics (ICVHMs) assessed by the American Heart Association's Life's Essential 8 measures with incident diabetes has not been comprehensively characterized, especially in large-scale cohort studies. Objective: To explore the association of spousal diabetes status and cardiovascular health metrics with risk of incident diabetes in Chinese adults. Design, Setting, and Participants: This cohort study included individuals in the China Cardiovascular Disease and Cancer Cohort without diabetes who underwent baseline and follow-up glucose measurements and had spouses with baseline glucose measurements. The data were collected in January 2011 to December 2012 and March 2014 to December 2016. The spousal study had a mean (SD) follow-up of 3.6 (0.9) years (median [IQR], 3.2 [2.9-4.5] years). Statistical analysis was performed from July to November 2022. Exposure: Spousal diabetes status was diagnosed according to the 2010 American Diabetes Association (ADA) criteria. All participants provided detailed clinical, sociodemographic, and lifestyle information included in cardiovascular health metrics. Main Outcomes and Measures: Incident diabetes, diagnosed according to 2010 ADA criteria. Results: Overall, 34 821 individuals were included, with a mean (SD) age of 56.4 (8.3) years and 16 699 (48.0%) male participants. Spousal diabetes diagnosis was associated with an increased risk of incident diabetes (hazard ratio [HR], 1.15; 95% CI, 1.03-1.30). Furthermore, participants whose spouses had uncontrolled glycated hemoglobin (HbA1c) had a higher risk of diabetes (HR, 1.20; 95% CI, 1.04-1.39) but the risk of diabetes in participants whose spouses had controlled HbA1c did not increase significantly (HR, 1.10; 95% CI, 0.92-1.30). Moreover, this association varied with composite cardiovascular health status. Diabetes risk in individuals who had poor cardiovascular health status (<4 ICVHMs) was associated with spousal diabetes status (3 ICVHMs: HR, 1.50; 95% CI, 1.15-1.97), while diabetes risk in individuals who had intermediate to ideal cardiovascular health status (≥4 ICVHMs) was not associated with it (4 ICVHMs: HR, 1.01; 95% CI, 0.69-1.50). Conclusions and Relevance: In this study, spousal diabetes diagnosis with uncontrolled HbA1c level was associated with increased risk of incident diabetes, but strict management of spousal HbA1c level and improving ICVHM profiles may attenuate the association of spousal diabetes status with diabetes risk. These findings suggest the potential benefit of couple-based lifestyle or pharmaceutical interventions for diabetes.

A multimodal fusion enabled ensemble approach for human activity recognition in smart homes.

How to deal with multi-modality data from different types of devices is a challenging issue for accurate recognition of human activities in a smart environment. In this paper, we propose a multimodal fusion enabled ensemble approach. Firstly, useful features collected from Bluetooth beacons, binary sensors, and smart floor are extracted and presented by fuzzy logic based-method with variable-size temporal windows. Secondly, a group of support vector machine classifiers are used to perform the classification task. Finally, a weighted ensemble method is used to obtain the final prediction. Especially, by applying the geometric framework, we are able to obtain the optimal weights for the ensemble. The proposed approach is evaluated on the UJAmI dataset. The experimental results demonstrate the efficacy and robustness of the proposed method.

Diarylheptanoids with hypoglycemic potency from the rhizomes of Kaempferia galanga.

Five new diarylheptanoids, kaemgalangins A-E (1-5), and seven known ones were isolated from the rhizomes of Kaempferia galanga. The structures of new compounds were identified by spectroscopic analyses involving 1D and 2D NMR, HRESIMS, IR, UV, [α]D, ECD calculations, and chemical methods. All compounds were tested for their hypoglycemic effects against α-glucosidase, Gpa and PTP1B enzymes, and stimulative effects on GLP-1 secretion. Kaemgalangins A (1) and E (5) showed significant inhibition on α-glucosidase with IC50 values of 45.3 and 116.0 µM; renealtin B (8) showed inhibition on GPa with an IC50 value of 68.1 µM; whereas all compounds were inactive to PTP1B. Docking study manifested that 1 well located in the catalytic pocket of α-glucosidase and OH-4″ played important roles in maintaining activity. Moreover, all compounds showed obviously stimulative effects on GLP-1 with promoting rates of 826.9%-1738.3% in NCI-H716 cells. This study suggests that the diarylheptanoids in K. galanga have antidiabetic potency by inhibiting α-glucosidase and Gpa enzymes, and promoting GLP-1 secretion.

A global daily soil moisture dataset derived from Chinese FengYun Microwave Radiation Imager (MWRI)(2010-2019).

Surface soil moisture (SSM) is an important variable in drought monitoring, floods predicting, weather forecasting, etc. and plays a critical role in water and heat exchanges between land and atmosphere. SSM products from L-band observations, such as the Soil Moisture Active Passive (SMAP) Mission, have proven to be optimal global estimations. Although X-band has a lower sensitivity to soil moisture than that of L-band, Chinese FengYun-3 series satellites (FY-3A/B/C/D) have provided sustainable and daily multiple SSM products from X-band since 2008. This research developed a new global SSM product (NNsm-FY) from FY-3B MWRI from 2010 to 2019, transferred high accuracy of SMAP L-band to FY-3B X-band. The NNsm-FY shows good agreement with in-situ observations and SMAP product and has a higher accuracy than that of official FY-3B product. With this new dataset, Chinese FY-3 satellites may play a larger role and provide opportunities of sustainable and longer-term soil moisture data record for hydrological study.

Data-driven subgroups of prediabetes and the associations with outcomes in Chinese adults.

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic ß cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment.

Risk of cardiovascular disease, death, and renal progression in diabetes according to albuminuria and estimated glomerular filtration rate.

AIM: We aimed to examine risks of major cardiovascular events (MACEs), renal outcomes, and all-cause mortality in type 2 diabetes mellitus (T2DM) patients with different diabetic kidney disease (DKD) subtypes. METHODS: A total of 36,509 participants with T2DM recruited from 20 community sites across mainland China were followed up during 2011-2016. DKD subtypes were categorized based on albuminuria (urinary albumin-to-creatinine ratio, UACR ≥ 30 mg/g) and reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) as Alb-/eGFR-, Alb+/eGFR-, Alb-/eGFR+, and Alb+/eGFR+. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of developing clinical outcomes in DKD subtypes. RESULTS: More than half (53.5%) of participants with diabetes and reduced eGFR had normal UACR levels (Alb-/eGFR+), termed as non-albuminuria DKD. These patients had a modest increase in the risks of MACEs (hazard ratio, HR 1.42 [95% CI 1.08;1.88]) and mortality (HR 1.42 [1.04;1.92]) compared with patients without DKD, whereas CKD progression was not significantly increased (HR 0.97 [0.60;1.57]). Participants with albuminuria (Alb+/eGFR- or Alb+/eGFR+) had higher risks of clinical outcomes. Subgroup analysis revealed that the associations between non-albuminuria DKD and risks of MACEs and mortality were more evident in those aged <65 years. CONCLUSION: Non-albuminuria DKD accounts for more than half of DKD cases with low eGFR in Chinese diabetes patients. Diabetes patients with albuminuria are at higher risks of developing clinical outcomes and warrant early intervention, as well as patients with non-albuminuria DKD with age < 65 years.