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3,741 result(s) for "Tan, Hua"
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Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or spatiotemporal profiles of MAPK activities. Hence, DUSPs need to be properly controlled. Protein post-translational modifications, such as ubiquitination, phosphorylation, methylation, and acetylation, play important roles in the regulation of protein stability and activity. Ubiquitination is critical for controlling protein degradation, activation, and interaction. For DUSPs, ubiquitination induces degradation of eight DUSPs, namely, DUSP1, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, and DUSP16. In addition, protein stability of DUSP2 and DUSP10 is enhanced by phosphorylation. Methylation-induced ubiquitination of DUSP14 stimulates its phosphatase activity. In this review, we summarize the knowledge of the regulation of DUSP stability and ubiquitination through post-translational modifications.
Can Syntactic Complexity Distinguish Translator Style?—A Novel Stylometric Analysis of Hongloumeng with Dependency Grammar
The present study is likely the first to investigate translation style through the lens of dependency distance. While translator style has been explored using various indicators—such as STTR, LR, MSL, and typical language patterns like reporting verbs and loan words—prior research has rarely accounted for syntactic structures, particularly syntactic complexity, which has been widely discussed in fields like second language acquisition. Dependency distance is considered a valid measure of syntactic complexity, and studies have demonstrated that its ability to differentiate between translational and original English. Given this, it can be hypothesized that translation style could also be distinguished by dependency distance. Accordingly, this study examines the translator styles of four English versions of the Chinese classic novel Hongloumeng. The results support the hypothesis, showing that dependency distance can effectively distinguish translator styles. Moreover, the findings suggest that dependency direction should also be considered when analyzing translator style.
Antimicrobial Gold Nanoclusters: Recent Developments and Future Perspectives
Bacterial infections have caused serious threats to public health due to the antimicrobial resistance in bacteria. Recently, gold nanoclusters (AuNCs) have been extensively investigated for biomedical applications because of their superior structural and optical properties. Great efforts have demonstrated that AuNCs conjugated with various surface ligands are promising antimicrobial agents owing to their high biocompatibility, polyvalent effect, easy modification and photothermal stability. In this review, we have highlighted the recent achievements for the utilizations of AuNCs as the antimicrobial agents. We have classified the antimicrobial AuNCs by their surface ligands including small molecules (<900 Daltons) and macromolecules (>900 Daltons). Moreover, the antimicrobial activities and mechanisms of AuNCs have been introduced into two main categories of small molecules and macromolecules, respectively. In accordance with the advancements of antimicrobial AuNCs, we further provided conclusions of current challenges and recommendations of future perspectives of antimicrobial AuNCs for fundamental researches and clinical applications.
COX-2/sEH Dual Inhibitor Alleviates Hepatocyte Senescence in NAFLD Mice by Restoring Autophagy through Sirt1/PI3K/AKT/mTOR
We previously found that the disorder of soluble epoxide hydrolase (sEH)/cyclooxygenase-2 (COX-2)-mediated arachidonic acid (ARA) metabolism contributes to the pathogenesis of the non-alcoholic fatty liver disease (NAFLD) in mice. However, the exact mechanism has not been elucidated. Accumulating evidence points to the essential role of cellular senescence in NAFLD. Herein, we investigated whether restoring the balance of sEH/COX-2-mediated ARA metabolism attenuated NAFLD via hepatocyte senescence. A promised dual inhibitor of sEH and COX-2, PTUPB, was used in our study to restore the balance of sEH/COX-2-mediated ARA metabolism. In vivo, NAFLD was induced by a high-fat diet (HFD) using C57BL/6J mice. In vitro, mouse hepatocytes (AML12) and mouse hepatic astrocytes (JS1) were used to investigate the effects of PTUPB on palmitic acid (PA)-induced hepatocyte senescence and its mechanism. PTUPB alleviated liver injury, decreased collagen and lipid accumulation, restored glucose tolerance, and reduced hepatic triglyceride levels in HFD-induced NAFLD mice. Importantly, PTUPB significantly reduced the expression of liver senescence-related molecules p16, p53, and p21 in HFD mice. In vitro, the protein levels of γH2AX, p53, p21, COX-2, and sEH were increased in AML12 hepatocytes treated with PA, while Ki67 and PCNA were significantly decreased. PTUPB decreased the lipid content, the number of β-gal positive cells, and the expression of p53, p21, and γH2AX proteins in AML12 cells. Meanwhile, PTUPB reduced the activation of hepatic astrocytes JS1 by slowing the senescence of AML12 cells in a co-culture system. It was further observed that PTUPB enhanced the ratio of autophagy-related protein LC3II/I in AML12 cells, up-regulated the expression of Fundc1 protein, reduced p62 protein, and suppressed hepatocyte senescence. In addition, PTUPB enhanced hepatocyte autophagy by inhibiting the PI3K/AKT/mTOR pathway through Sirt1, contributing to the suppression of senescence. PTUPB inhibits the PI3K/AKT/mTOR pathway through Sirt1, improves autophagy, slows down the senescence of hepatocytes, and alleviates NAFLD.
Pt-O bond as an active site superior to Pt0 in hydrogen evolution reaction
The oxidized platinum (Pt) can exhibit better electrocatalytic activity than metallic Pt 0 in the hydrogen evolution reaction (HER), which has aroused great interest in exploring the role of oxygen in Pt-based catalysts. Herein, we select two structurally well-defined polyoxometalates Na 5 [H 3 Pt (IV) W 6 O 24 ] (PtW 6 O 24 ) and Na 3 K 5 [Pt (II) 2 (W 5 O 18 ) 2 ] (Pt 2 (W 5 O 18 ) 2 ) as the platinum oxide model to investigate the HER performance. Electrocatalytic experiments show the mass activities of PtW 6 O 24 /C and Pt 2 (W 5 O 18 ) 2 /C are 20.175 A mg −1 and 10.976 A mg −1 at 77 mV, respectively, which are better than that of commercial 20% Pt/C (0.398 A mg −1 ). The in situ synchrotron radiation experiments and DFT calculations suggest that the elongated Pt-O bond acts as the active site during the HER process, which can accelerate the coupling of proton and electron and the rapid release of H 2 . This work complements the knowledge boundary of Pt-based electrocatalytic HER, and suggests another way to update the state-of-the-art electrocatalyst. While converting water to H 2 with a catalyst offers a renewable means to produce carbon-neutral fuels, understanding the catalytic active sites has proven challenging. Here, authors show a structurally well-defined model complex with Pt-O bonding to enable efficient H 2 evolution electrocatalysis.
ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification
Angiotensin-converting enzyme 2 (ACE2), a counter regulator of the renin-angiotensin system, provides protection against several chronic diseases. Besides chronic diseases, ACE2 is the host receptor for SARS-CoV or SARS-CoV-2 virus, mediating the first step of virus infection. ACE2 levels are regulated by transcriptional, post-transcriptional, and post-translational regulation or modification. ACE2 transcription is enhanced by transcription factors including Ikaros, HNFs, GATA6, STAT3 or SIRT1, whereas ACE2 transcription is reduced by the transcription factor Brg1-FoxM1 complex or ERRα. ACE2 levels are also regulated by histone modification or miRNA-induced destabilization. The protein kinase AMPK, CK1α, or MAP4K3 phosphorylates ACE2 protein and induces ACE2 protein levels by decreasing its ubiquitination. The ubiquitination of ACE2 is induced by the E3 ubiquitin ligase MDM2 or UBR4 and decreased by the deubiquitinase UCHL1 or USP50. ACE2 protein levels are also increased by the E3 ligase PIAS4-mediated SUMOylation or the methyltransferase PRMT5-mediated ACE2 methylation, whereas ACE2 protein levels are decreased by AP2-mediated lysosomal degradation. ACE2 is downregulated in several human chronic diseases like diabetes, hypertension, or lung injury. In contrast, SARS-CoV-2 upregulates ACE2 levels, enhancing host cell susceptibility to virus infection. Moreover, soluble ACE2 protein and exosomal ACE2 protein facilitate SARS-CoV-2 infection into host cells. In this review, we summarize the gene regulation and post-translational modification of ACE2 in chronic disease and COVID-19. Understanding the regulation and modification of ACE2 may help to develop prevention or treatment strategies for ACE2-mediated diseases.
Highly efficient pure-blue organic light-emitting diodes based on rationally designed heterocyclic phenophosphazinine-containing emitters
Multi-resonance thermally activated delayed fluorophores have been actively studied for high-resolution photonic applications due to their exceptional color purity. However, these compounds encounter challenges associated with the inefficient spin-flip process, compromising device performance. Herein, we report two pure-blue emitters based on an organoboron multi-resonance core, incorporating a conformationally flexible donor, 10-phenyl-5 H -phenophosphazinine 10-oxide (or sulfide). This design concept selectively modifies the orbital type of high-lying excited states to a charge transfer configuration while simultaneously providing the necessary conformational freedom to enhance the density of excited states without sacrificing color purity. We show that the different embedded phosphorus motifs (phosphine oxide/sulfide) of the donor can finely tune the electronic structure and conformational freedom, resulting in an accelerated spin-flip process through intense spin-vibronic coupling, achieving over a 20-fold increase in the reverse intersystem crossing rate compared to the parent multi-resonance emitter. Utilizing these emitters, we achieve high-performance pure-blue organic light-emitting diodes, showcasing a top-tier external quantum efficiency of 37.6% with reduced efficiency roll-offs. This proposed strategy not only challenges the conventional notion that flexible electron-donors are undesirable for constructing narrowband emitters but also offer a pathway for designing efficient narrow-spectrum blue organic light-emitting diodes. The inefficient spin-flip process of multi-resonance emitters could compromise the device performance of light-emitting diodes. Here, the authors incorporate conformationally flexible donor to enhance the density of excited states, achieving 20-fold increase in reverse intersystem crossing rate.
Ligand effect on switching the rate-determining step of water oxidation in atomically precise metal nanoclusters
The ligand effects of atomically precise metal nanoclusters on electrocatalysis kinetics have been rarely revealed. Herein, we employ atomically precise Au 25 nanoclusters with different ligands (i.e., para-mercaptobenzoic acid, 6-mercaptohexanoic acid, and homocysteine) as paradigm electrocatalysts to demonstrate oxygen evolution reaction rate-determining step switching through ligand engineering. Au 25 nanoclusters capped by para-mercaptobenzoic acid exhibit a better performance with nearly 4 times higher than that of Au 25 NCs capped by other two ligands. We deduce that para-mercaptobenzoic acid with a stronger electron-withdrawing ability establishes more partial positive charges on Au(I) (i.e., active sites) for facilitating feasible adsorption of OH – in alkaline media. X-ray photo-electron spectroscopy and theoretical study indicate a profound electron transfer from Au(I) to para-mercaptobenzoic acid. The Tafel slope and in situ Raman spectroscopy suggest different ligands trigger different rate-determining step for these Au 25 nanoclusters. The mechanistic insights reported here can add to the acceptance of atomically precise metal nanoclusters as effective electrocatalysts. Surface modification using organic molecules is crucial for tailoring the physicochemical properties of electrocatalysts. In this study, we employ atomically precise Au25 nanoclusters with different ligands to identify the ligand effect on switching rate-limiting steps of oxygen evolution reaction.
Rhubarb Protect Against Tubulointerstitial Fibrosis by Inhibiting TGF-β/Smad Pathway and Improving Abnormal Metabolome in Chronic Kidney Disease
Tubulointerstitial fibrosis is the final common pathway for all kidney diseases leading to chronic kidney disease (CKD). TGF-β/Smad signaling pathway plays a key role in renal fibrosis. Previous studies have revealed that rhubarb extracts attenuated the increase of transforming growth factor-β 1 (TGF-β1) in CKD rats. To gain an in-depth insight into the mechanism of the anti-fibrotic activities of the rhubarb extracts, we investigated the influence of rhubarb extracts on TGF-β/Smad signaling pathway and the influence on metabolome in a rat model of CKD with adenine-induced chronic tubulointerstitial nephropathy. Male Sprague-Dawley rats were divided into four groups, including control, CKD, CKD + petroleum ether extract, CKD + ethyl acetate extract, and CKD + -butanol extract groups. Kidneys harvested on the week three were evaluated for renal fibrosis, the expression of proteins in TGF-β/Smad signaling pathway and metabolomic study. We found rhubarb extracts suppressed TGF-β/Smad3-mediated renal fibrosis by reducing the TGF-β1, transforming growth factor-β receptor I (TGF-β RI), transforming growth factor-β receptor II (TGF-β RII), Smad2, p-Smad2, Smad3, p-Smad3, and Smad4, meanwhile increased Smad7. In addition, rhubarb extracts mitigated renal injury and dysfunction, and either fully or partially reversed the abnormalities of tissue metabolites. Thus, rebalancing the disorder of TGF-β/Smad signaling and metabolic dysfunction by treatment with rhubarb extracts may represent as an effective therapy for CKD associated with fibrosis.