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result(s) for
"Wan, Yanjun"
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Trimethylamine N-oxide impairs β-cell function and glucose tolerance
2024
β-Cell dysfunction and β-cell loss are hallmarks of type 2 diabetes (T2D). Here, we found that trimethylamine N-oxide (TMAO) at a similar concentration to that found in diabetes could directly decrease glucose-stimulated insulin secretion (GSIS) in MIN6 cells and primary islets from mice or humans. Elevation of TMAO levels impairs GSIS, β-cell proportion, and glucose tolerance in male C57BL/6 J mice. TMAO inhibits calcium transients through NLRP3 inflammasome-related cytokines and induced Serca2 loss, and a Serca2 agonist reversed the effect of TMAO on β-cell function in vitro and in vivo. Additionally, long-term TMAO exposure promotes β-cell ER stress, dedifferentiation, and apoptosis and inhibits β-cell transcriptional identity. Inhibition of TMAO production improves β-cell GSIS, β-cell proportion, and glucose tolerance in both male
db/db
and choline diet-fed mice. These observations identify a role for TMAO in β-cell dysfunction and maintenance, and inhibition of TMAO could be an approach for the treatment of T2D.
β-Cell dysfunction is a hallmark of type 2 diabetes. Here, the authors show that trimethylamine N-oxide (TMAO (a microbiota metabolite)) induces β-cell dysfunction and type 2 diabetes in mice through NLRP3 inflammasome activation and calcium transients.
Journal Article
Galectin-3 impairs calcium transients and β-cell function
2024
In diabetes, macrophages and inflammation are increased in the islets, along with β-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic
db/db
mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in β-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS. β-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD-fed and
db/db
mice. All animal findings are applicable to male mice. Here we show a role of Gal3 in pancreatic β-cell dysfunction, and Gal3 could be a therapeutic target for the treatment of type 2 diabetes.
Galectin-3, mainly produced and secreted by macrophages, is elevated in diabetes. Here, the authors show that galectin-3 directly interacts with voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and blocks calcium transients and subsequent insulin secretion.
Journal Article
Hydrocyclization/Defluorination of CF3‐Substituted Acrylamides: Insights from Kinetics of Hydrogen Atom Transfer
2025
The introduction of F‐containing groups into organic molecules can significantly alter their physical and chemical properties. Particularly, gem‐difluoroalkenes serve as versatile precursors for a broad variety of organofluorine compounds, commonly used in agrochemicals, pharmaceuticals, and materials science. Based on the kinetics of H• transfer to acrylamide (kH = 2.28 × 10−4 M−1 s−1 at 300 K in toluene), the study describes a nickel‐hydride‐(or Li[BEt3H]) initiated hydrocyclization/defluorination of CF3‐substituted acrylamides, offering alternative access to 4‐fluorovinyl‐substituted 2‐pyrrolidones (Seletracetam derivatives that are antiepileptic drug candidates). This process proceeds with high yields and remarkable chemo‐ and regioselectivity. The hydrocyclization/defluorination can be initiated by either H• or H– transfer, followed by a 5‐exo‐trig cyclization and subsequent fluorine elimination. The strategy has been applied in the late‐stage functionalization of drug molecules, providing a valuable tool in the synthesis of pharmaceutical compounds. The study develops a H•/H– transfer strategy enabling efficient hydrocyclization/defluorination of CF3‐acrylamides to synthesize Seletracetam derivatives with gem‐difluoroalkenes. Mechanistic studies reveal distinct pathways: the NiII‐H/PhSiH3 system operates through a hydrogen atom transfer process, while the 1,4‐Michael addition of H– appears to be responsible for the Li[BEt3H] system.
Journal Article
Prolonged glucagon exposure rewires lipid oxidation and drives diabetic kidney disease progression
2025
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Tubular abnormalities may precede glomerular pathology and indicate functional progression of DKD. Here, we find glucagon injection exacerbates lipid accumulation and renal injury, in addition to causing morphological changes in proximal tubules, podocytes, and mitochondria in the early phase of DKD in mice. However, the specific knockdown or knockout of
Gcgr
in renal tubular epithelial cells almost completely halts DKD development. In contrast to the effect of short-term glucagon stimulation, long-term glucagon exposure leads to the reversal of glucagon action (glucagon reversal) in proximal tubular epithelial cells (PTECs), which is characterized by reduced energy production and an increase in lipogenesis through Gcgr-PKA-Creb-mTORC1 pathway. Accordingly, anti-GCGR antibody treatment strongly blocks the pathogenesis of DKD induced by both type 2 and type 1 diabetes. Thus, our results highlight a previously unrecognized role of glucagon/Gcgr signaling in PTEC lipogenesis and DKD.
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney failure. This study shows that prolonged glucagon exacerbates lipid accumulation, promoting renal injury in early DKD, rather than lipid oxidation. Targeting glucagon signaling significantly inhibits DKD progression.
Journal Article
Macrophage Derived Galectin‐3 Promotes Renal Fibrosis and Diabetic Kidney Disease by Enhancing TGFβ1 Signaling
2025
Over 30% of patients with type 2 diabetes develop diabetic kidney disease (DKD), which has emerged as a major contributor to end stage renal disease. Renal fibrosis represents the final pathological outcome of most chronic kidney disease, particularly DKD. This study demonstrates elevated levels of Galectin‐3 (Gal3), a lectin associated with inflammatory and fibrotic conditions, in the plasma and kidneys of DKD mice. Positive correlations between Gal3 expression and renal fibrosis are observed in both DKD patients and mice. Macrophage‐derived Gal3 is found to promote Transforming growth factor beta 1 (TGFβ1) signaling activation and renal fibrogenesis. Genetic ablation of Gal3 globally or specifically in macrophages, as well as pharmacological inhibition of Gal3, significantly attenuated kidney fibrosis in diabetic mice. Mechanistically, macrophage‐derived Gal3 interacted with TGFβ receptor2 (TGFBR2) and Pro‐TGFβ1, preventing TGFBR2 proteasomal degradation in fibroblasts and increasing TGFβ1 levels in the diabetic kidney. These events enhances TGFβ1 signaling activation and ultimately facilitated kidney fibrosis. The findings of this study suggest Gal3 as a potential therapeutic target for renal fibrosis and DKD. Macrophage‐derived Galectin‐3 amplifies TGFβ1 signaling to drive diabetic kidney fibrosis: a novel therapeutic target.
Journal Article
Being Effective or Not? A Study on the Association Between China’s COVID-19 Lockdown Policy and City-Level Gross Regional Product Growth Rate
2024
The COVID-19 pandemic has severely impacted the globe from 2020 to 2022. Among a wide range of negative economic growth in the three years, China has survived with a positive GDP growth rate, incurring a closer look at how China managed to deal with the disease. This study focuses on the potential association between the unique lockdown policy implemented by local governments and the city-level annual Gross Regional Product (GRP) growth rate. The research narrows the gap in the current literature review by innovatively combining the three parts of COVID-19 disease, lockdown policy, and cities’ economic resilience to construct an integrated conceptual framework. By using panel data from 289 Chinese prefecture-level cities in the years 2020 and 2021, this study uses both OLS and state and time fixed effects regression to analyze the correlation between the key independent variable lockdown policy, and the city-level GRP growth rate. Cities that enacted the lockdown policy are on average 6.17% lower in their annual GRP growth rate than cities that did not implement the policy during the pandemic, holding all other variables constant. The statistically significant results turn out to be persuasive and help the government to distinguish the actual effect of the lockdown policy that could be taken into consideration in case of a future resurgence of the disease. The analysis also extends to future potential topics related to the lockdown policy that are conducive to the nation’s development and social well-being.
Dissertation
Fly Ash-Based Zeolite-Complexed Polyethylene-Glycol on an Interdigitated Electrode Surface for High-Performance Determination of Diabetes Mellitus
2020
Background: Diabetes is a complex metabolic disorder known to induce a high blood glucose level that fluctuates outside the normal range. Diabetes affects and damages the organs in the body and causes heart issues, blindness and kidney failure. Continuous monitoring is mandatory to keep the blood glucose level within a healthy range. Materials and Methods: This research was focused on diagnosing diabetes mellitus on zeolite nanoparticle-polyethylene glycol complex-immobilized interdigitated electrode sensor (IDE) surfaces. Zeolite nanoparticles were extracted from the fly ash of a thermal power plant by alkaline extraction. The surface morphology of the synthesized nanoparticles was observed by field-emission scanning electron microscopy and transmission electron microscopy, and the presence of certain elements and the particle size were determined by energydispersive X-ray spectroscopy and particle size analysis, respectively. Results: The crystalline PEG-zeolite nanoparticles were synthesized with a size of 40[+ or -]10 nm according to high-resolution microscopy. A particle size analyzer revealed the sizes of the fly ash and PEG-zeolite particles as 60[+ or -]10 [micro]m and 50[+ or -]10 nm, respectively. The IDE surface was evaluated for its ability to display antifouling properties and sense glucose levels on the abovementioned nanoparticle-modified surface. Glucose oxidase was probed on the PEG-zeolite-modified IDE surface, and glucose was detected. PEG zeolite performed well with excellent antifouling properties on the IDE sensor surface and improved the glucose detection limit to 0.03 mg/mL from 0.08 mg/mL, as determined by linear regressions [y = 5.365x - 6.803; [R.sup.2] = 0.9035 (zeolite surface) and y = 5.498x + 5.914[R.sup.2] = 0.9061 (PEGzeolite surface)]. This enhancement was ~3-fold, and sensitivities were found to be 0.03 and 0.06 mg/mL glucose for the PEG-zeolite- and zeolite-modified surfaces, respectively, showing a 2-fold difference. Conclusion: The excellent biocompatible surface modified by PEG zeolite exhibited high performance and is useful for medical diagnosis. Keywords: blood glucose, dielectric sensor, biosensor, nanomaterial, nanoparticle
Journal Article
Hydrocyclization/Defluorination of CF 3 ‐Substituted Acrylamides: Insights from Kinetics of Hydrogen Atom Transfer
2025
The introduction of F‐containing groups into organic molecules can significantly alter their physical and chemical properties. Particularly, gem ‐difluoroalkenes serve as versatile precursors for a broad variety of organofluorine compounds, commonly used in agrochemicals, pharmaceuticals, and materials science. Based on the kinetics of H• transfer to acrylamide ( k H = 2.28 × 10 −4 M −1 s −1 at 300 K in toluene), the study describes a nickel‐hydride‐(or Li[BEt 3 H]) initiated hydrocyclization/defluorination of CF 3 ‐substituted acrylamides, offering alternative access to 4‐fluorovinyl‐substituted 2‐pyrrolidones (Seletracetam derivatives that are antiepileptic drug candidates). This process proceeds with high yields and remarkable chemo‐ and regioselectivity. The hydrocyclization/defluorination can be initiated by either H• or H – transfer, followed by a 5‐exo‐trig cyclization and subsequent fluorine elimination. The strategy has been applied in the late‐stage functionalization of drug molecules, providing a valuable tool in the synthesis of pharmaceutical compounds.
Journal Article
Lightweight and Flexible Carbon-based Materials for High-Efficiency Electromagnetic Interference Shielding
2018
Electromagnetic pollution and electromagnetic interference (EMI) caused by electrical and electronic equipment have increased substantially with the rapid development of information technology. Electronics and their components with higher power, smaller size and faster operative speed emit the unwanted electromagnetic waves, which not only lead to malfunctioning and degradation of electronics but also threaten human health and the surrounding environment. EMI shielding has become the effective method and key technology to protect human and environment from the negative effects, which is of great importance in both fields of the civil and military. The aim of this study is to develop lightweight and flexible EMI shielding materials, and various carbon-based materials have been synthesized and their EMI shielding properties have been investigated. This dissertation includes six chapters. The first chapter gives an overview of EMI shielding with focuses on the introduction of electromagnetic (EM) waves, and EMI shielding, including the shielding phenomenon, shielding theory, and measurement for EMI shielding and typical shielding materials. Chapters 2 to 5 involve preparation, microstructures and properties of the materials for EMI shielding developed in this thesis work. The second chapter introduces the three-dimensional (3D) graphene aerogel/epoxy composites. The pore size of 3D aerogel on EMI effectiveness (SE) and mechanical properties are investigated and discussed. The third chapter focuses on the lightweight and super elastic graphene/cellulose hybrid aerogel with high efficiency shielding effectiveness. The aerogel with 5 mm thickness exhibits high EMI SE of ~47.8 dB after annealing at 1000 °C with 5% hydrogen-argon mixture atmosphere. The density of CF/RGO aerogel is as low as 2.83 mg/cm3, leading to ultrahigh specific shielding effectiveness (up to 33780 dB cm2/g). To decrease the thickness of the shield, in the fourth chapter, large-sized graphene sheets (LG) and doping strategy are employed to fabricate lightweight and flexible graphene paper. LG with fewer defects and more conjugated carbon domain size as well as better alignment result in higher electrical conductivity and strength of graphene paper. The iodine doping further improves the carrier density of LG by formation of tri-iodide and penta-iodide through charge transfer process without deteriorating the mechanical property, thus leading to superior EMI SE. The EMI SE of iodine doped LG film with thickness of 12.5 μm is up to ~52.2 dB at 8.2 GHz. The fifth chapter introduces the metal/carbon hybrid sponge. Lightweight, flexible and anticorrosive silver nanowire wrapped carbon hybrid sponge is employed as ultra-high efficiency EMI shielding material. The hybrid sponges provide an effective way for electron transport, leading to a remarkable conductivity of 363.1 S/m and superb EMI shielding effectiveness of around 70.1 dB in the frequency range of 8.2-18 GHz, while, the density is as low as 0.00382 g/cm3, which are among the best performances for electrically conductive sponges/aerogels/foams by far. More importantly, the Ag@C sponge surprisingly exhibits super-hydrophobicity and strong corrosion resistance. In addition, the hybrid sponges possess excellent mechanical resilience even with a large strain (90% reversible compressibility) and an outstanding cycling stability. The last chapter gives a summary for this thesis and future research work that needs further investigation is prospected.
Dissertation
Optimized design of battery pole control system based on dual-chip architecture
2022
At present, the global demand for lithium batteries is still in a high growth state, and the traditional lithium battery pole mill control system is still dominated by ARM (Artificial Intelligence Enhanced Computing), DSP (Digital Signal Processing), and other single-chip control methods. There are problems such as poor anti-interference ability and insufficient real-time online analysis of production data. This paper adopts the dual-chip control system architecture based on \"ARM+DSP\", starting from the mechanical characteristics and operating signal features of the pole mill. The hardware system adopts a three-unit joint control hardware structure, which separates the control unit from the data processing unit and improves the operation of the system. The software system adopts fuzzy PID algorithm to realize deflection control and tension control, and verifies that the Fuzzy PID (Proportion Integration Differentiation) control algorithm can effectively improve the anti-interference ability of the deflection system and tension system. The results show that the data loss rate is low with the SPI communication between DSP and ARM. The tension error of the \"ARM+DSP\" control system does not exceed 5%, and the deviation of the correction band is within ±4mm. The dedicated dual-chip hardware architecture effectively improves the robustness and operation efficiency of the pole mill, solves the problem of low tension control accuracy, and provides a theoretical basis for the application of the dual-roll mill.
Journal Article