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Abstract Cardiovascular disease (CVD) is a major chronic disease worldwide and its risk factors have long been investigating in epidemiological studies. Our study aims to develop a body composition-based risk score and integrate it into the Framingham Risk Score (FRS) to improve CVD prediction among well-functioning older adults. We included 1882 older adults from the Health, Aging and Body Composition (Health ABC) study to screen body composition variables obtained from the Dual-energy X-ray absorptiometry (DXA). Three models were developed and compared: the 4-DXA model, the refit FRS, and the refit FRS plus 4-DXA model. C-statistics were 0.62 (95% CI: 0.59, 0.65) for the refit FRS, 0.58 (95% CI: 0.55, 0.61) for the 4-DXA model, and 0.63 (95% CI: 0.60, 0.66) for the refit FRS plus 4-DXA model. Compared to the refit FRS, the refit FRS plus 4-DXA model slightly improved CVD outcome prediction as the discrimination slope, net reclassification index, and the integrated discrimination index were 0.053 (95% CI: 0.041, 0.066), 0.098 (95% CI = – 0.0033, 0.20) and 0.013 (95% CI: 0.0069–0.019). This study provides a model for more accurate risk stratification and draws more attention on DXA-based indices in the clinical setting. It also encourages further research in validating the developed risk score in more diverse population and in investigating a broader range of CVD risk factors.

Cholemic nephropathy （CN） is a disease with renal dysfunction as a major manifestation in patients with advanced chronic liver disease complicated with severe jaundice. Currently no effective non-invasive diagnostic modality is available for CN. Renal biopsy has been a gold standard for its clinical diagnosis. Furthermore, it is frequently misdiagnosed or confused with hepatorenal syndrome so that patient prognosis remains poor. The overall objective of clinical management is lowering a high level of bilirubin and blunting renal injury. If drug therapy fails, artificial liver systems may be employed for improving renal function. The underlying pathological mechanisms of CN have not been fully elucidated. However, recent studies implied that the development of disease was correlated closely with abnormal renal transporters, oxidative stress and inflammatory responses. Based upon previous studies, the authors summarized the latest researches on CN through focusing upon clinical diagnosis, potential pathogenesis and therapeutic strategies for providing theoretical rationales for advanced researches and clinical interventions of CN.

Summary: Despite the development of an increasing number of multi-kinase and immune checkpoint inhibitors for hepatocellular carcinoma (HCC), improvement in cancer survival remains limited due to their similar structures and targets. Natural products (NPs) maintain diverse structures and activities and are important sources of drug discovery. Currently, most of active NPs exhibit ambiguous binding targets and mechanisms. Herein, we proposed the CIPHEN (compound-protein interactions prediction based on the heterogeneous network) to predict potential antihepatoma NPs and their targets. The evaluation of canonical compound-protein interactions (CPIs) databases and independent test demonstrated the good ability of CPIHN to reveal known and unreported CPIs. Both prediction and experiment results indicated that CIPHEN could unveil relationships between actively antihepatoma sesquiterpenoid dimers (SDs) and anti-HCC targets. In conclusion, the CIPHEN provides a promising choice to investigate the mode of action of compounds, which will help to accelerate the process of drug research and development against HCC.

BackgroundAAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR.MethodsThis was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively.ResultsCompared with group A, patients in group B had higher midterm mortality (p

Cardiovascular disease (CVD) is a major chronic disease worldwide and its risk factors have long been investigating in epidemiological studies. Our study aims to develop a body composition-based risk score and integrate it into the Framingham Risk Score (FRS) to improve CVD prediction among well-functioning older adults. We included 1882 older adults from the Health, Aging and Body Composition (Health ABC) study to screen body composition variables obtained from the Dual-energy X-ray absorptiometry (DXA). Three models were developed and compared: the 4-DXA model, the refit FRS, and the refit FRS plus 4-DXA model. C-statistics were 0.62 (95% CI: 0.59, 0.65) for the refit FRS, 0.58 (95% CI: 0.55, 0.61) for the 4-DXA model, and 0.63 (95% CI: 0.60, 0.66) for the refit FRS plus 4-DXA model. Compared to the refit FRS, the refit FRS plus 4-DXA model slightly improved CVD outcome prediction as the discrimination slope, net reclassification index, and the integrated discrimination index were 0.053 (95% CI: 0.041, 0.066), 0.098 (95% CI = – 0.0033, 0.20) and 0.013 (95% CI: 0.0069–0.019). This study provides a model for more accurate risk stratification and draws more attention on DXA-based indices in the clinical setting. It also encourages further research in validating the developed risk score in more diverse population and in investigating a broader range of CVD risk factors. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Ten novel isocoumarins, including four pairs of enantiomers, were isolated from Artemisia dubia var. subdigitata (Asteraceae). Compounds 1, 2 and 3a/3b possessed a unique 6/6/6‐tricyclic system comprising an unusual 1‐(2‐methylcyclohexyl) propan‐1‐one moiety fused with isocoumarin core skeleton. Compounds 4a/4b were characterized as an unexpected 2,5‐dimethylcyclohexan‐1‐one scaffold, and compounds 5a/5b and 6a/6b were rare 1,2‐seco‐isocoumarin. Their structures and absolute configurations were elucidated through spectroscopic data, X‐ray crystallography, ECD and NMR calculations with DP4+ analyses. Plausible biosynthetic pathways were proposed from the naturally occurring isocoumarin. Network pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and PI3K‐Akt signaling pathway. The molecular docking revealed that compound 1 had high binding affinity with CDK2 (total score: 6.8717). Furthermore, compounds 1 and 2 exhibited inhibitory activity on three human hepatoma cell lines, with inhibitory ratios of 85.1% and 84.5% (HepG2), 88.2% and 87.3% (Huh7), and 69.2% and 69.1% (SK‐Hep‐1) at 200 μmol·L–1, respectively. [ABSTRACT FROM AUTHOR]

A catalytic asymmetric vinylogous aldol reaction between β,γ-unsaturated amides and isatins has been developed. In the presence of 10 mol% of tertiary amine-thiourea C7, the vinylogous reaction has been achieved in up to 98% yield and up to 99% ee (26 examples). This methodology provides an efficient approach to construct chiral multifunctional 3-hydroxy-2-oxindoles. Moreover, the transformations of the chiral products, including the esterification of amides, the hydrogenation of the C–C double bond and further conversion to spirolactones, have been investigated. [ABSTRACT FROM AUTHOR]

Under the double pressure of economic downturn and climate deterioration, the Chinese government needs to use the "double carbon" policy to drive the green transformation of the manufacturing industry. This article takes A-share manufacturing listed companies as the research object, constructs the enterprise digital economy investment index by text analysis and expert scoring method, and represents the degree of green transformation by enterprise green total factor productivity. At the theoretical level, the impact mechanism of the digital economy empowering green transformation in the manufacturing industry is hypothesized. The relevant hypotheses were tested through econometric empirical evidence, and the econometric model significantly passed the robustness test, proving that the digital economy empowers the development of green transformation in the manufacturing industry significantly. This article reveals that the digital economy promotes the green total factor productivity of enterprises by enhancing their innovation capability, improving the efficiency of production factor flow, and increasing their emission costs, but the factor intensity and the nature of enterprise owners will have different effects on the green transformation of the manufacturing industry enabled by the digital economy. This article explores the internal mechanism of green transformation development in the digital economy-enabled manufacturing industry and provides empirical evidence for enterprises to formulate development strategies and for governments to issue guiding policies. [ABSTRACT FROM AUTHOR]

The low carbon living of residents is important for China to achieve the "double carbon goal." This paper uses the natural language processing technique in machine learning to collect data from 2005 to 2020, constructs the government's "green will" index and residents' low-carbon life index, and conducts an empirical study through a static panel model and a dynamic panel model. The study shows that: (a) all cities in the Yangtze River Delta pay more and more attention to low-carbon publicity, but there are individual differences in the degree of attention; (b) in general, the government's willingness to go green does drive residents to develop a low-carbon life; (c) affluence and human capital growth are positively related to the effect of government low-carbon publicity. Accordingly, the following measures are proposed: increase the government's low-carbon publicity efforts, deepen education reform, attract high-end talents, strengthen scientific and technological innovation, promote new urbanization, and reduce the marginal cost of carbon emissions. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Nineteen new cadinane‐involving sesquiterpenoid dimers, artemordins A—S (1—19), together with 13 known SDs (20—32) were isolated from Artemisia ordosica. Their structures and absolute configurations were established by comprehensive spectral analyses, X‐ray single crystal diffraction, theoretical ECD, and NMR calculations. Chemically, artemordins A—F (1—6) were the first examples of two cadinane units constructed by unprecedented C‐3−C‐15′ or C‐3−C‐13′ single bond with an oxido‐rearranged 6/5/6/6 fused ring system; artemordins G—K (7—11) were biogenetically connected by [4 + 2] cycloaddition reaction and artemordins G—J (7—10) possessed a novel 5/6/6/6/6/6/5‐heptacyclic fused ring system. Artemordins L—S (12—19) were formed by esterification, which involved three different types of sesquiterpenoids. Antihepatoma assay suggested that the most active compounds, artemordins B and H (2 and 8), exhibited inhibitory activities on three hepatoma cell lines with IC50 values of 26.9 and 25.1 μmol/L (HepG2), 29.5 and 18.3 μmol/L (Huh7), 19.7 and 15.7 μmol/L (SK‐Hep‐1). [ABSTRACT FROM AUTHOR]

In the field of molecular nonequilibrium transports, physical mechanisms of multiple reaction dynamics of these systems are the core of deep understanding complex reactions and transport mechanisms. In order to explore related mechanisms, establishing multiple systems coupled with tremendous exit dynamics and studying their exit dynamics properties are quite vital. Beyond previous researches, new stochastic transport processes are emphasized here. Multiple new exit dynamic systems are established, which are motivated by the multiplicity of paths and products of real biochemical processes in organisms. In order to ensure research universality, core system modeling factors are fully considered. Countable parallel orbits, uniform connection with external sources, countable parallel orbits as subsystems in middle lattices and influences of all lattices on transport trajectories on dynamic properties are analyzed. Dynamic properties of different particles located in orbits are explored by deeply studying average exit time and time scale. Quantitative spatiotemporal impacts are extensively studied. The rationality of average exit time as a time scale in the universal exit dynamic system is proved. Main findings and fruitful results can not only serve as theoretical bases for broadening reaction path modeling, but also be helpful to support understanding nonequilibrium transport mechanisms, especially stochastic biochemical processes. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Eight new guaiane‐type sesquiterpenoid trimers, artemsieverolactones A—H, possessing unprecedented scaffolds via biocatalyzed [4+2] Diels−Alder cycloaddition reactions were identified from Artemisia sieversiana. Their structures were determined by comprehensive spectroscopic data, single‐crystal X‐ray diffraction analyses, and ECD calculations. In terms of structure, artemsieverolactones A—H are first examples of sesquiterpenoid trimers from guaiane‐type sesquiterpenoid through four different [4+2] Diels−Alder cycloaddition models. Antihepatic fibrosis assay suggested that five compounds exhibited activity against HSC‐LX2 with IC50 values ranging from 37.8 to 117.1 μmol/L. The most active artemsieverolactone B (2) displayed significant inhibitory activity against HSC‐LX2 with IC50 value of 37.8 μmol/L, which was 3 times more active than the positive drug silybin (IC50, 139.7 μmol/L). Preliminary mechanism study revealed that artemsieverolactone B could inhibit the deposition of human collagen type I (Col I), human hyaluronic acid (HA), and human laminin (HL) with IC50 values of 40.4 μmol/L (Col I), 55.1 μmol/L (HL), 47.3 μmol/L (HA), which was 2 to 3‐fold more potent than silybin. [ABSTRACT FROM AUTHOR]