We have rationally designed a new class of alkyne‐tethered oximes and applied them in an unprecedented iron‐catalyzed radical relay protocol for the rapid assembly of a wide array of structurally new ...and interesting fused pyridines. This method shows broad substrate scope and good functional‐group tolerance and enabled the synthesis of several biologically active molecules. Furthermore, the fused pyridines could be diversely functionalized through various simple transformations, such as cyclization, C−H alkylation, and a click reaction. DFT calculation studies indicate that the reactions involve cascade 1,5‐hydrogen atom transfer, 5‐exo‐dig radical addition, and cyclization processes. Moreover, preliminary biological investigations suggest that some of the fused pyridines exhibit good anti‐inflammatory activity by restoring the imbalance of inflammatory homeostasis of macrophages in a lipopolysaccharide‐induced model.
An efficient iron‐catalyzed radical relay protocol enabled the rapid assembly of a wide array of structurally interesting fused pyridines from alkyne‐tethered oximes and alkenes (see scheme). Preliminary biological investigations suggest that some of the fused pyridines exhibit good anti‐inflammatory activity by restoring the imbalance of inflammatory homeostasis of macrophages in a lipopolysaccharide‐induced model.
Despite the growing interest in the effects of neighborhood environments on cognitive function, most studies on older people are based on cross-sectional survey data from developed countries. This ...study examines the relationship between neighborhood environments and decline in cognitive function over time among middle-aged and older people in China and whether this relationship varies between rural and urban residents.
The three waves of China Health and Retirement Longitudinal Study (CHARLS 2011-2015) were used. The sample included 12,131 respondents living in 298 rural villages and 4,059 respondents living in 150 urban communities. Three-level linear growth curve models were estimated to track trajectories of cognitive change over a 4-year period.
Chinese older people who lived in neighborhoods with more handicap access, more bus lines, employment service, and higher socioeconomic status (SES) had slower cognitive decline. Neighborhood basic infrastructures, number of days that roads were unpassable, outdoor exercise facilities, and average social activity participation were associated with baseline cognitive function in both rural and urban areas, but neighborhood environments had more impact on cognitive decline among rural older adults than urban older adults.
Findings from this study call for increased infrastructure development and community building programs in rural China.
•Hurst exponent is an effective way for detecting variations in vegetation series.•Vegetation coverage and its response to climatic factors were detected.•NDVI values showed a very significant growth ...trend in the wet season.•Topographic affected spatiotemporal of patterns vegetation coverage.
Vegetation coverage is a critical factor in soil conservation and improving the ecological environment. As an important ecological corridor connecting China's southwest and Southeast Asia, the Red River Basin is characterized by vulnerable ecosystems and serious soil erosion. Identifying the heterogeneity in vegetation coverage and its response to climatic factors are critical for ecological protection and soil and water conservation. MOD13Q1 NDVI data with a spatial resolution of 250 m and 16 d temporal resolution were collected from 2000 to 2014. The maximum synthesis method, univariate linear regression, Hurst exponent, and partial correlation analysis were used to detect the spatiotemporal variation and sustainability of vegetation coverage and characterize the relationship between vegetation NDVI and climatic factors in the wet season in the Red River Basin. NDVI showed a rather significant increasing trend in the wet season. The “corridor-barrier” function of valleys and mountains affected the spatiotemporal patterns in the Longitudinal Range-Gorge Region. Areas of improved, degraded, and stable vegetation coverage accounted for 50.1%, 27.1%, and 22.8% of the total, respectively. The role of precipitation was higher than temperature in the interaction between NDVI and climatic factors. A time lag effect was found in the NDVI response to rainfall and temperature variation. Different vegetation types showed various spatiotemporal responses to climatic factors. Human activities, especially the implementation of the Grain for Green Project (GFGP), affected the spatial and temporal patterns of vegetation coverage.
Objectives: Characterized by infrequent contact, low emotional intensity, and limited intimacy, weak ties are found to be associated with better subjective well-being and other health outcomes. ...Drawing on the theory of weak ties and the convoy model of social relations, this paper aims to examine the association between weak ties and cognitive function among older adults in China.
Methods: We used multilevel growth modeling to analyze panel data for adults aged 60 years and over (N = 2,650) selected from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015). Weak ties were measured based on the frequency of social activity participation and the number of social activities.
Results: Weekly or irregular social activity participation in at least one social activity was significantly associated with better mental status and memory. The number of participated social activities was also significantly and positively associated with mental status and memory. After controlling for age, gender, marital status, educational attainment, geographic residence, household expenditures, and health conditions (i.e., depressive symptoms and self-reported health), we found that participation in a greater number of social activities protected memory from declining by 4% for every 2 years (p < 0.001).
Conclusion: These findings suggest that social interactions with peripheral members of a diverse social network may help prevent cognitive decline for older Chinese adults. Greater attention on weak ties might yield practical implications for non-pharmacological dementia prevention and health promotion for the general older population.
Major depressive disorder (MDD) is a debilitating psychiatric illness. However, there is currently no objective laboratory-based diagnostic tests for this disorder. Although, perturbations in ...multiple neurotransmitter systems have been implicated in MDD, the biochemical changes underlying the disorder remain unclear, and a comprehensive global evaluation of neurotransmitters in MDD has not yet been performed. Here, using a GC-MS coupled with LC-MS/MS-based targeted metabolomics approach, we simultaneously quantified the levels of 19 plasma metabolites involved in GABAergic, catecholaminergic, and serotonergic neurotransmitter systems in 50 first-episode, antidepressant drug-naïve MDD subjects and 50 healthy controls to identify potential metabolite biomarkers for MDD (training set). Moreover, an independent sample cohort comprising 49 MDD patients, 30 bipolar disorder (BD) patients and 40 healthy controls (testing set) was further used to validate diagnostic generalizability and specificity of these candidate biomarkers. Among the 19 plasma neurotransmitter metabolites examined, nine were significantly changed in MDD subjects. These metabolites were mainly involved in GABAergic, catecholaminergic and serotonergic systems. The GABAergic and catecholaminergic had better diagnostic value than serotonergic pathway. A panel of four candidate plasma metabolite biomarkers (GABA, dopamine, tyramine, kynurenine) could distinguish MDD subjects from health controls with an AUC of 0.968 and 0.953 in the training and testing set, respectively. Furthermore, this panel distinguished MDD subjects from BD subjects with high accuracy. This study is the first to globally evaluate multiple neurotransmitters in MDD plasma. The altered plasma neurotransmitter metabolite profile has potential differential diagnostic value for MDD.
Diet is intimately associated with the risk of type 2 diabetes (T2D). Recently, attention has focused on the contributions of individual nutrients, food groups and eating patterns to the outcome of ...T2D. High consumption of coffee, whole grains, fruits and vegetables, and nuts are each independently associated with the reduced risk of T2D in high risk, glucose intolerant individuals. Experimental and clinical trials have given insight to the diverse mechanisms that may be responsible for the observed protective effects of certain foods on T2D, including nutrients, phytochemicals and dietary fiber, weight control, enhanced satiety and improvement in glucose tolerance and insulin sensitivity in diabetic patients. Elevated consumption of refined grains and sugar‐sweetened beverages has shown to significantly elevate the risk of incident T2D. An overall healthy diet primarily comprising whole plant‐based foods, together with regular physical activity and weight manage, could significantly reduce the risk of T2D. The present review consolidates current research and delineates major food groups shown to significantly influence risk of T2D. Documenting and quantifying the effects of diet on the outcome of T2D are of great scientific and public health importance as there is urgent need to implement dietary strategies to prevent and manage the outcome of T2D.
Diet is closely associated with the risk of type 2 diabetes (T2D). High consumption of coffee, whole grains, fruits and vegetables, and nuts are associated with a reduced risk of T2D. High consumption of refined grains and sugar‐sweetened beverages significantly increases the risk of T2D. An overall healthy diet primarily comprising whole plant‐based foods, together with regular physical activity and weight management could significantly reduce the risk of T2D. The present review consolidates current research and delineates major food groups shown to significantly influence risk of T2D.
In situ-growth of 1T/2H-MoS2 nanosheets on the CFC, ultra-small SnS2 nanoparticles are anchored on the surface of MoS2 nanosheets unifromly. When the SnS2/MoS2/CFC composites applied as a binder-free ...flexible anode, it exhibits excellent performances. A highly flexible full cell was fabricated, demonstrating remarkable flexibility and cycling stability.
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•In-situ growth SnS2/MoS2 on CFC by a hydrothermal method and water bath process.•SnS2/MoS2 shows a capacity of 1294 mA h g−1 at 0.1 A g−1 after 120 cycles.•The distribution of SnS2 on 1T/2H-MoS2 can enhance electrochemical properties.•A full cell is fabricated, showing high flexibility and electrochemical properties.
Flexible lithium ion batteries are important for wearable electronic devices. Herein, 1T/2H phase MoS2 nanosheets are grown on carbon fiber cloth, and the ultra-small SnS2 nanoparticles are anchored in the surface of MoS2 nanosheets uniformly. We fabricate the hierarchical nanostructures via a hydrothermal method then water bath process. During in-situ growth of 1T/2H phase MoS2, urea is used as the surfactant and NH4+ (produced by urea and ammonium molybdate tetrahydrate) is acted as insertion guest ions to stabilize 1T phase MoS2. The synergistic effects between MoS2 nanosheets and SnS2 nanoparticles can improve structural stability of the electrode and significant enhance the transport of Li ions and electrons, thereby ameliorate the electrochemical properties. When applied as a binder-free, flexible Li-ion battery anode, it exhibits admirable cycling stability and excellent rate performance. Due to the presence of 1T phase MoS2 and uniform distribution of ultra-small SnS2 nanoparticles on MoS2 nanosheets, the SnS2/MoS2/carbon fiber cloth composites maintain 1294 mA h g−1 when cycling at 100 mA g−1 after 120 cycles. A highly flexible battery based on SnS2/MoS2/carbon fiber cloth and LiCoO2 is fabricated, demonstrating excellent mechanical flexibility and cycling stability.
Adipocytes play important roles in regulating cardiovascular health and disease. However, the molecular mechanism underlying the endocrine role of brown adipose tissue (BAT) in pathological cardiac ...remodeling remains unknown. Herein we show that adenosine A2A receptor (A2AR) knockout (A2ARKO) causes interscapular BAT (iBAT) dysfunction, leading to accelerated cardiac remodeling in hypertension compared with wild-type (WT) mice. Surgical iBAT depletion induces dramatic cardiac remodeling in WT but not in A2ARKO hypertensive mice. AMPK/PGC1α signaling-induced fibroblast growth factor 21 (FGF21) in brown adipocytes is required for A2AR-mediated inhibition of hypertensive cardiac remodeling. Recombinant FGF21 administration improves cardiac remodeling in iBAT-depleted hypertensive mice. More importantly, brown adipocyte-specific A2ARKO inhibits FGF21 production and accelerates cardiac damage in hypertension. Consistently, brown adipocyte-specific FGF21 knockout abolishes the effects of A2AR agonism in attenuating hypertensive cardiac remodeling. Our findings reveal a distinctive endocrine role of BAT in hypertensive cardiac remodeling via activating A2AR/FGF21 pathway.
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•Brown adipocyte is a direct target of A2AR in hypertension•A2AR activation promotes FGF21 in brown adipocytes•A2AR/FGF21 axis provides a link between brown adipocyte and cardiac remodeling
Ruan et al. uncover a direct crosstalk between brown adipose tissue (BAT) and the heart. Adenosine A2A receptor (A2AR) signaling in BAT mediates the release of the batokine, FGF21, which prevents hypertension-related cardiac damage.
The nuclear receptor farnesoid-X-receptor (FXR) plays an essential role in bile acid, glucose, and lipid homeostasis. In the last two decades, several diseases, such as obesity, type 2 diabetes, ...nonalcoholic fatty liver disease, cholestasis, and chronic inflammatory diseases of the liver and intestine, have been revealed to be associated with alterations in FXR functions. FXR has become a promising therapeutic drug target, particularly for enterohepatic diseases. Despite the large number of FXR modulators reported, only obeticholic acid (OCA) has been approved for primary biliary cholangitis (PBC) therapy as FXR modulator. In this review, we summarize the structure and function of FXR, the development of FXR modulators, and the structure-activity relationships of FXR modulators. Based on the structural analysis, we discuss potential strategies for developing future therapeutic FXR modulators to overcome current limitations, providing new perspectives for enterohepatic and metabolic diseases treatment.
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