The proposition that "xungu tong yili" (an exegetical tradition leading to Confucian teachings) expresses the core idea of traditional Chinese philology, which threads throughout the Han and Song ...dynasties and reached its historical acme in the form of the Qian-Jia school. The overemphasis of scholars from this school on exegesis led to the division between Hanxue (Qing scholarship in the Han dynasty tradition) and Songxue (Qing scholarship in the Song dynasty tradition) and a disconnection between "xungu (Chinese exegetical tradition exegesis) and yili (Confucian teachings)." The modern "linguistized" shift has seen the slow death of the xunguxue tradition (the theory and practice of xungu as a discipline), under which "xungu tong yili." At the same time, modern xunguxue has clarified its own disciplinary orientation and has made great progress in both theory and practice, laying a reliable foundation for the renewed process of working out meanings through xungu. The heights of modern xunguxue allow the scholarly development of the meanings behind the classic texts in five respects: semantic verification, context representation, validation of themes, history of xungu interpretation, and pursuit of imagery. In the cross-disciplinary collision centered on Chinese hermeneutics, the modern approach to the proposition that "xungu tong yili" has shown abundant vitality.
General circulation model (GCM) biases are one of the important sources of biases and uncertainty in dynamic downscaling–based simulations. The ability of regional climate models to simulate tropical ...cyclones (TCs) is strongly affected by the ability of GCMs to simulate the large-scale environmental field. Thus, in this work, we employ a recently developed multivariable integrated evaluation method to assess the performance of 33 CMIP6 (phase 6 of the Coupled Model Intercomparison Project) models in simulating multiple fields in terms of their climatology. The CMIP6 models are quantitatively evaluated against two reanalysis datasets over five ocean areas. The results show that most of the CMIP6 models overestimate the mid-level humidity in almost all tropical oceans. The multi-model ensemble mean overestimates the vertical shear of the horizontal winds in the Northeast Pacific and North Atlantic. An increase in model horizontal resolution appears to be helpful in improving the model simulations. For example, there are 6–8 models with higher resolution among the top 10 models in terms of overall model performance in simulating the climatology and interannual variability of multiple variables. Similarly, there are 7–8 models with lower resolution among the bottom 10 models. The model skill varies depending on the region and variable being evaluated. Although no model performs best in all regions and for all variables, some models do show relatively good capability in simulating the large-scale environmental field of TCs.
Brown fat activates uncoupled respiration in response to cold temperature and contributes to systemic metabolic homeostasis. To date, the metabolic action of brown fat has been primarily attributed ...to its role in fuel oxidation and uncoupling protein 1 (UCP1)-mediated thermogenesis. Whether brown fat engages other tissues through secreted factors remains largely unexplored. Here we show that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family of extracellular ligands, is highly expressed in adipose tissues, enriched in brown fat and markedly increased during brown adipocyte differentiation. Adipose tissue Nrg4 expression was reduced in rodent and human obesity. Gain- and loss-of-function studies in mice demonstrated that Nrg4 protects against diet-induced insulin resistance and hepatic steatosis through attenuating hepatic lipogenic signaling. Mechanistically, Nrg4 activates ErbB3 and ErbB4 signaling in hepatocytes and negatively regulates de novo lipogenesis mediated by LXR and SREBP1c in a cell-autonomous manner. These results establish Nrg4 as a brown fat-enriched endocrine factor with therapeutic potential for the treatment of obesity-associated disorders, including type 2 diabetes and nonalcoholic fatty liver disease (NAFLD).
Background
Nonalcoholic fatty liver disease (NAFLD), whose pathogenesis remains unelucidated, has become an increasingly prevalent disease globally requiring novel treatment strategies. This study ...aims to explore the role of leukocyte cell‐derived chemotaxin 2 (LECT2), one of the known hepatokines, in the development of NAFLD.
Methods
The serum LECT2 level was evaluated in patients with NAFLD and male C57BL/6 mice fed a high‐fat diet (HFD) for 8 weeks. Tail intravenous injection of adeno‐associated virus that contained Lect2 short hairpin RNA or Lect2 overexpression plasmid was administered to mice to inhibit or increase hepatic Lect2 expression. Hepatic steatosis was evaluated by histological staining with haematoxylin and eosin and Oil Red O, and also by quantitative hepatic triglyceride measurements. RNA‐seq was performed to discover the specific targets of LECT2 on NAFLD.
Results
Serum and hepatic LECT2 levels were elevated in NAFLD patients and HFD‐fed mice. Inhibition of hepatic Lect2 expression alleviated HFD‐induced hepatic steatosis and inflammation, whereas hepatic overexpression of Lect2 aggravated HFD‐induced hepatic steatosis and inflammation. RNA‐seq and bioinformatical analysis suggested that the signal transducers and activators of transcription‐1 (STAT‐1) pathway might play an indispensable role in the interaction between LECT2 and NAFLD. A STAT‐1 inhibitor could reverse the accumulation of hepatic lipids caused by Lect2 overexpression.
Conclusion
LECT2 expression is significantly elevated in NAFLD. LECT2 induces the occurrence and development of NAFLD through the STAT‐1 pathway. LECT2 may be a potential therapeutic target for NAFLD.
When photovoltaic (PV) array is operated under partially shaded condition (PSC), power-voltage curve will show multiply peaks. This causes the inability of conventional maximum power point tracking ...(MPPT) methods such as hill climbing (HC). To deal with this problem, this paper proposes a new MPPT method based on a modified cat swarm optimization (MCSO) to achieve global maximum power point (GMPP) tracking. To assess the performance of proposed method, different simulations and experiments have been carried out. The proposed method can successfully track GMPP under different PSCs. Furthermore, MCSO based MPPT method shows a high tracking accuracy and convergence speed as compared with other MPPT methods.
•A modified cat swarm optimization (MCSO) is proposed to realize global MPPT for PV system.•Proposed method can effectively deal with the partial shading problem of PV system.•Proposed method shows a high MPPT performance in terms of accuracy and speed.
Insulin resistance and β-cell dysfunction are two main molecular bases yet to be further elucidated for type 2 diabetes (T2D). Accumulating evidence indicates that stimulator of interferon genes ...(STING) plays an important role in regulating insulin sensitivity. However, its function in β-cells remains unknown. Herein, using global STING knockout (STING
) and β-cell-specific STING knockout (STING-βKO) mouse models, we revealed a distinct role of STING in the regulation of glucose homeostasis through peripheral tissues and β-cells. Specially, although STING
beneficially alleviated insulin resistance and glucose intolerance induced by high-fat diet, it surprisingly impaired islet glucose-stimulated insulin secretion (GSIS). Importantly, STING is decreased in islets of db/db mice and patients with T2D, suggesting a possible role of STING in β-cell dysfunction. Indeed, STING-βKO caused glucose intolerance due to impaired GSIS, indicating that STING is required for normal β-cell function. Islet transcriptome analysis showed that STING deficiency decreased expression of β-cell function-related genes, including Glut2, Kcnj11, and Abcc8, contributing to impaired GSIS. Mechanistically, the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and cleavage under targets and tagmentation (CUT&Tag) analyses suggested that Pax6 was the transcription factor that might be associated with defective GSIS in STING-βKO mice. Indeed, Pax6 messenger RNA and protein levels were down-regulated and its nuclear localization was lost in STING-βKO β-cells. Together, these data revealed a function of STING in the regulation of insulin secretion and established pathophysiological significance of fine-tuned STING within β-cells and insulin target tissues for maintaining glucose homeostasis.
Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders ...adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.
Long-range communication between intestinal symbiotic bacteria and extra-intestinal organs can occur through circulating bacterial signal molecules, through neural circuits, or through cytokines or ...hormones from host cells. Here we report that Nod1 ligands derived from intestinal bacteria act as signal molecules and directly modulate insulin trafficking in pancreatic beta cells. The cytosolic peptidoglycan receptor Nod1 and its downstream adapter Rip2 are required for insulin trafficking in beta cells in a cell-autonomous manner. Mechanistically, upon recognizing cognate ligands, Nod1 and Rip2 localize to insulin vesicles, recruiting Rab1a to direct insulin trafficking through the cytoplasm. Importantly, intestinal lysozyme liberates Nod1 ligands into the circulation, thus enabling long-range communication between intestinal microbes and islets. The intestine-islet crosstalk bridged by Nod1 ligands modulates host glucose tolerance. Our study defines a new type of inter-organ communication based on circulating bacterial signal molecules, which has broad implications for understanding the mutualistic relationship between microbes and host.
The initiation and development of diabetes are mainly ascribed to the loss of functional β-cells. Therapies designed to regenerate β-cells provide great potential for controlling glucose levels and ...thereby preventing the devastating complications associated with diabetes. This requires detailed knowledge of the molecular events and underlying mechanisms in this disorder. Here, we report that expression of microRNA-223 (miR-223) is up-regulated in islets from diabetic mice and humans, as well as in murine Min6 β-cells exposed to tumor necrosis factor α (TNFα) or high glucose. Interestingly, miR-223 knockout (KO) mice exhibit impaired glucose tolerance and insulin resistance. Further analysis reveals that miR-223 deficiency dramatically suppresses β-cell proliferation and insulin secretion. Mechanistically, using luciferase reporter gene assays, histological analysis, and immunoblotting, we demonstrate that miR-223 inhibits both forkhead box O1 (FOXO1) and SRY-box 6 (SOX6) signaling, a unique bipartite mechanism that modulates expression of several β-cell markers (pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1), and urocortin 3 (UCN3)) and cell cycle–related genes (cyclin D1, cyclin E1, and cyclin-dependent kinase inhibitor P27 (P27)). Importantly, miR-223 overexpression in β-cells could promote β-cell proliferation and improve β-cell function. Taken together, our results suggest that miR-223 is a critical factor for maintaining functional β-cell mass and adaptation during metabolic stress.
Single-screw extruders and injection molding machines are essential equipment in polymer processing. It is of great importance for the optimization of operating parameters and the design of extrusion ...screw to predict the throughput of an extruder and the metering time of an injection molding machine according to the geometric parameters of the screw, operating parameters, and the rheological behavior of materials. Most polymer melts exhibit non-Newtonian behavior. The lattice Boltzmann method has many advantages in simulating the flow of non-Newtonian fluids. Herein, the dimensionless velocity profiles and dimensionless volumetric flow rate of generalized Newtonian fluids in a screw channel have been studied using the two-relaxation-time lattice Boltzmann method (TRT–LBM). The numerical results of power-law fluids are in good agreement with the analytical solutions, which verifies the validity of TRT–LBM. Through research, the change rule of the dimensionless volumetric flow rate of Bingham fluids with dimensionless pressure gradient has been obtained. It was found that the rheological properties of polymer melts and the dimensionless pressure gradient significantly affect the dimensionless velocity profiles and dimensionless volumetric flow rate. The dimensionless volume flow rate has some unexpected changes with the increase of the dimensionless pressure gradient. This study can provide theoretical guidance for the optimization of operating parameters and the design of extrusion screws.
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