Effects of tenofovir disoproxil fumarate on intrahepatic viral burden and liver immune microenvironment in patients with chronic hepatitis B.

BACKGROUND: The impact of nucleos(t)ide analogues on intrahepatic viral burden and immune microenvironment in patients with chronic hepatitis B (CHB) is not clear. OBJECTIVE: We aimed to characterise the effects of tenofovir disoproxil fumarate (TDF) on intrahepatic viral burden and the liver immune microenvironment in patients with CHB. DESIGN: Core liver biopsies were collected at baseline and year 3 from patients with CHB with minimally raised serum alanine aminotransferase in a double-blind placebo-controlled trial (NCT01522625). Paired biopsies were analysed by RNA-sequencing (n=119 pairs), a custom multiplex immunofluorescence assay (n=30 pairs), and HBV-targeted long-read DNA sequencing (n=49 pairs). RESULTS: Both non-integrated and integrated HBV DNA were present in all patients at baseline, with >65% having interchromosomal translocations. Treatment significantly reduced the frequency of HBV core+ hepatocytes and intrahepatic (integrated and non-integrated) HBV DNA, but had no effect on HBsAg+ hepatocytes. Clonally expanded integrations were enriched for HBsAg coding regions and showed dysregulation of nearby genes. At baseline, there was significant enrichment of intrahepatic CD8+ T cell proximity to HBV core+ hepatocytes, but not to HBsAg+ cells. The densities of T cells and B cells were significantly reduced by TDF. Transcriptomic analyses found TDF induced widespread downregulation of immune-related genes including inhibitory and regulatory genes. CONCLUSION: TDF significantly reduced intrahepatic integrated and non-integrated HBV DNA, exerting disparate effects on HBV core+ and HBsAg+ cells and on different immune cell subsets. Our data suggest there may be differential cytotoxic T cell-mediated killing of HBV core+ versus HBsAg+ hepatocytes, providing insights for HBV cure strategies.

Thermally Stable High-Entropy Layered Double Hydroxides for Advanced Catalysis.

Layered double hydroxides (LDHs), especially high-entropy LDHs (HE-LDHs), have gained increasing attention. However, HE-LDHs often possess poor thermal stability, restricting their applications in thermo-catalysis. Herein, a novel complexing nucleation method is proposed for engineering HE-LDHs with enhanced thermal stability. This approach precisely controls the nucleation of metal ions with different solubility products, achieving homogeneous nucleation and effectively mitigating phase segregation and transformation at elevated temperatures. The prepared HE-LDH sample demonstrated exceptional thermal stability at temperatures up to 300 °C, outperforming all previously reported LDHs. Importantly, these HE-LDHs preserve both Lewis and Brønsted acidic sites, enabling the 100% removal of aromatic sulfides and alkaline nitrogen compounds from fuel oils in thermo-catalytic oxidation reactions. Experimental and characterization findings reveal that the metal-hydroxide bonds in the prepared HE-LDHs are strengthened by associated hydroxyl groups, inducing negative thermal expansion and augmenting the presence of acidic sites, thereby ensuring structural stability and enhancing catalytic activity. This study not only proposes a strategy for engineering HE-LDHs with remarkable thermal stability but also highlights potential applications of LDHs in thermo-catalysis.

Identification and virus-induced gene silencing (VIGS) analysis of methyltransferase affecting tomato (Solanum lycopersicum) fruit ripening.

MAIN CONCLUSION: Six methyltransferase genes affecting tomato fruit ripening were identified through genome-wide screening, VIGS assay, and expression pattern analysis. The data provide the basis for understanding new mechanisms of methyltransferases. Fruit ripening is a critical stage for the formation of edible quality and seed maturation, which is finely modulated by kinds of factors, including genetic regulators, hormones, external signals, etc. Methyltransferases (MTases), important genetic regulators, play vital roles in plant development through epigenetic regulation, post-translational modification, or other mechanisms. However, the regulatory functions of numerous MTases except DNA methylation in fruit ripening remain limited so far. Here, six MTases, which act on different types of substrates, were identified to affect tomato fruit ripening. First, 35 MTase genes with relatively high expression at breaker (Br) stage of tomato fruit were screened from the tomato MTase gene database encompassing 421 genes totally. Thereafter, six MTase genes were identified as potential regulators of fruit ripening via virus-induced gene silencing (VIGS), including four genes with a positive regulatory role and two genes with a negative regulatory role, respectively. The expression of these six MTase genes exhibited diverse patterns during the fruit ripening process, and responded to various external ripening-related factors, including ethylene, 1-methylcyclopropene (1-MCP), temperature, and light exposure. These results help to further elaborate the biological mechanisms of MTase genes in tomato fruit ripening and enrich the understanding of the regulatory mechanisms of fruit ripening involving MTases, despite of DNA MTases.

Liraglutide ameliorates inflammation and fibrosis by downregulating the TLR4/MyD88/NF-κB pathway in diabetic kidney disease.

Inflammation and fibrosis play important roles in diabetic kidney disease (DKD). Previous studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists had renal protective effects. However, the mechanisms are not clear. The present study explored the effect of liraglutide (LR), a GLP-1R agonist, on the downregulation of glomerular inflammation and fibrosis in DKD by regulating the Toll-like receptor (TLR)4/myeloid differentiation marker 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in mesangial cells (MCs). In vitro, rat MCs were cultured in high glucose (HG). We found that liraglutide treatment significantly reduced the HG-mediated activation of the TLR4/MYD88/NF-κB signaling pathway, extracellular matrix (ECM)-related proteins, and inflammatory factors. A combination of TLR4 inhibitor (TAK242) and liraglutide did not synergistically inhibit inflammatory factors and ECM proteins. Furthermore, in the presence of TLR4 siRNA, liraglutide significantly blunted HG-induced expression of fibronectin protein and inflammatory factors. Importantly, TLR4 selective agonist LPS or TLR4 overexpression eliminated the improvement effects of liraglutide on the HG-induced response. In vivo, administration of liraglutide for 8 wk significantly improved the glomerular damage in streptozotocin-induced diabetic mice and reduced the expression of TLR4/MYD88/NF-κB signaling proteins, ECM protein, and inflammatory factors in renal cortex. TLR4-/- diabetic mice showed significant amelioration in urine protein excretion rate, glomerular pathological damage, inflammation, and fibrosis. Liraglutide attenuated glomerular hypertrophy, renal fibrosis, and inflammatory response in TLR4-/- diabetic mice. Taken together, our findings suggest that TLR4/MYD88/NF-κB signaling is involved in the regulation of inflammatory response and ECM protein proliferation in DKD. Liraglutide alleviates inflammation and fibrosis by downregulating the TLR4/MYD88/NF-κB signaling pathway in MCs.NEW & NOTEWORTHY Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has renoprotective effect in diabetic kidney disease (DKD). In DKD, TLR4/MYD88/NF-κB signaling is involved in the regulation of inflammatory responses and extracellular matrix (ECM) protein proliferation. Liraglutide attenuates renal inflammation and overexpression of ECM proteins by inhibiting TLR4/MYD88/NF-κB signaling pathway. Therefore, we have identified a new mechanism that contributes to the renal protection of GLP-1RA, thus helping to design innovative treatment strategies for diabetic patients with various complications.

Modulating the Reaction Pathway of Ni2P/Al2O3 by Introducing Different Noble Metals for Hydrodesulfurization of Diesel.

Regulating the reaction pathway of a hydrodesulfurization (HDS) catalyst to achieve ultradeep desulfurization of diesel is a low-energy-consumption yet effective strategy but remains a tricky challenge. Herein, we present a Ni2P/Al2O3 catalyst with mesoporous properties synthesized by a facile hydrothermal-temperature-programmed reduction and normal impregnation (TPRI) method, and then different precious metals with similar loadings were introduced to prepare M-Ni2P/Al2O3 (M = Pt, Pd) catalysts through incipient wetness impregnation. Their structures were analyzed by a series of characterization methods, and their catalytic performances were examined for 4,6-dimethyldibenzothiophene (4,6-DMDBT) HDS. The correlation characterization results revealed that the kind of precious metals significantly affected the surface acidity and then the metal-support interaction (MSI) between Ni2P and Al2O3. Among them, the Pt-Ni2P/Al2O3 catalyst exhibits superior HDS activity with 88.5% 4,6-DMDBT conversion to Pd-Ni2P/Al2O3 (76.3%) and pristine Ni2P/Al2O3 (58.6%) catalysts under reaction conditions of 3.4 MPa, 340 °C, and LHSV = 4.8 h-1. This should be due to the introduction of Pt, which significantly facilitates the dissociation rate of H2 and the subsequent generation of more active hydrogen species than Pd, thereby promoting the formation of Brønsted acid sites, remarkably facilitating the isomerization (ISO) pathway, and markedly enhancing the 4,6-DMDBT HDS conversion of Pt-Ni2P/Al2O3. This work provides an efficient protocol to tame the reaction pathway and thereafter the catalytic performance of the HDS catalyst in the future.

Betel-quid addictive use disorders and Oral potentially malignant disorders and Oral cancer in south, southeast, and East Asia: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide a comprehensive assessment of the measurement and prevalence of betel-quid (BQ) abuse, dependence, and BQ use disorder (BUD), as well as to evaluate the impact of BQ addiction on oral malignant diseases. METHODS: We used the PRISMA guidelines to perform a systematic review and meta-analysis. We searched for relevant publications up to April 2024 in PubMed, Web of Science, and Embase. The articles were evaluated for BQ addiction and its relationship with oral potentially malignant disorders (OPMD) and oral cancer. RESULTS: The prevalence of BQ abuse, dependence, and BUD in South, Southeast, and East Asia varied between 0.8%-46.3%, 0.4%-43.5%, and 4.7%-39.2%, respectively. Among BQ chewers, the corresponding proportions of these disorders ranged from 40.5%-99.6%, 20.9%-99.6%, and 55.2%-99.3%. The pooled risks of OPMD associated with BQ abuse, dependence, and BUD were 16.3, 18.7, and 9.6-35.5, respectively. The risk of oral cancer for mild, moderate, and severe BUD was 8.5, 8.2, and 42.3, respectively. CONCLUSIONS: BUD mediates the link between BQ use and an increased risk of oral malignant disorders. Addressing and treating BQ addiction is an important component of comprehensive OPMD and oral cancer preventive and intervention programs that go beyond simple cessation efforts.

Multiple Physiological and Biochemical Functions of Ascorbic Acid in Plant Growth, Development, and Abiotic Stress Response.

Ascorbic acid (AsA) is an important nutrient for human health and disease cures, and it is also a crucial indicator for the quality of fruit and vegetables. As a reductant, AsA plays a pivotal role in maintaining the intracellular redox balance throughout all the stages of plant growth and development, fruit ripening, and abiotic stress responses. In recent years, the de novo synthesis and regulation at the transcriptional level and post-transcriptional level of AsA in plants have been studied relatively thoroughly. However, a comprehensive and systematic summary about AsA-involved biochemical pathways, as well as AsA's physiological functions in plants, is still lacking. In this review, we summarize and discuss the multiple physiological and biochemical functions of AsA in plants, including its involvement as a cofactor, substrate, antioxidant, and pro-oxidant. This review will help to facilitate a better understanding of the multiple functions of AsA in plant cells, as well as provide information on how to utilize AsA more efficiently by using modern molecular biology methods.

Identifying the Risk Factors for Orbital Complications in Isolated Sphenoid Rhinosinusitis.

Background and Objectives: Isolated sphenoid rhinosinusitis may have devastating consequences such as orbital complications due to its anatomical contiguity with vital structures. This study aimed to identify patients with isolated sphenoid inflammatory diseases at high risk for developing orbital complications and requiring aggressive management through investigation of the clinical and computed tomography (CT) characteristics of patients with isolated sphenoid rhinosinusitis. Materials and Methods: The medical records of patients who underwent endoscopic sinus surgery between 2005 and 2022 were retrospectively reviewed. Patients with isolated sphenoid rhinosinusitis were identified based on a manual review of the clinical and histopathological findings. Participants' clinical and CT features were reviewed. Results: Among the 118 patients with isolated sphenoid rhinosinusitis, 15 (12.7%) developed orbital complications, including diplopia, extraocular motility limitation, ptosis, and visual impairment. Headaches and facial pain occurred significantly more frequently in patients with orbital complications than in those without orbital complications (p < 0.001). Patients with diabetes mellitus or malignant neoplasms were more likely to develop orbital complications than those without these comorbidities (p < 0.05). Bony dehiscence on CT images was significantly more common in patients with orbital complications than in those without. In the regression analysis, diabetes mellitus (OR, 4.62), malignant neoplasm (OR, 4.32), and bony dehiscence (OR, 4.87) were significant predictors of orbital complications (p < 0.05). Conclusions: Headaches and facial pain are the most common symptoms of isolated sphenoid rhinosinusitis. Orbital complications of isolated sphenoid rhinosinusitis are more common in patients with comorbidities such as diabetes mellitus or malignancy or in those with bony dehiscence on CT images.

Single Mo Atoms Stabilized on High-Entropy Perovskite Oxide: A Frontier for Aerobic Oxidative Desulfurization.

The design and preparation of catalysts with both excellent stability and maximum exposure of catalytic active sites is highly desirable; however, it remains challenging in heterogeneous catalysis. Herein, a entropy-stabilized single-site Mo catalyst via a high-entropy perovskite oxide LaMn0.2Fe0.2Co0.2Ni0.2Cu0.2O3 (HEPO) with abundant mesoporous structures was initiated by a sacrificial-template strategy. The presence of electrostatic interaction between graphene oxide and metal precursors effectively inhibits the agglomeration of precursor nanoparticles in a high-temperature calcination process, thereby endowing the atomically dispersed Mo6+ coordinated with four O atoms on the defective sites of HEPO. The unique structure of single-site Mo atoms' random distribution with an atomic scale greatly enriches the oxygen vacancy and increases surface exposure of the catalytic active sites on the Mo/HEPO-SAC catalyst. As a result, the obtained Mo/HEPO-SAC exhibits robust recycling stability and ultra-high oxidation activity (turnover frequency = 3.28 × 10-2) for the catalytic removal of dibenzothiophene (DBT) with air as the oxidant, which represents the top level and is strikingly higher than the state-of-the-art oxidation desulfurization catalysts reported previously under the same or similar reaction conditions. Therefore, the finding here for the first time expands the application of single-atom Mo-supported HEPO materials into the field of ultra-deep oxidative desulfurization.

Adsorption behavior of hierarchical porous biochar from shrimp shell for tris(2-chloroethyl) phosphate (TCEP): Sorption experiments and DFT calculations.

Tris(2-chloroethyl) phosphate (TCEP) as a new type of flame retardant exists in various water environments, causing great risks to humans and the environment. In this study, shrimp shell was used to prepare an economical and environmental-friendly adsorbent for the efficient removal of TCEP. The systematic studies including characterization, removal performance, and adsorption mechanism of shrimp shell biochar toward TCEP were carried out. Adsorption kinetics and thermodynamics showed that fast equilibrium reached within 30 min, the maximum adsorption capacity qm was 108 µmol g-1 at 298 K, and the adsorption process is spontaneous and exothermic. The environmental factor, such as temperature, pH, inorganic anions and organic matter hardly affected the adsorption performance. Structural characterization indicated that the hierarchical porous structure of shrimp shell biochar is the key to excellent adsorption performance. The adsorption mechanisms were further revealed using density functional theory (DFT) calculations, and the hydrogen bond, van der Waals interactions, Cl-H interactions, and pi-H interactions were identified as potential interaction mechanisms between TCEP and specific biochar structures. The calculated binding energy between TCEP and simplified biochar structure suggested that oxygen-containing groups especially carboxyl, hydroxyl and aldehyde facilitate the adsorption. Our work not only provides a novel strategy for the quick remediation of organophosphate-contaminated water environments but also offers new opportunities for crustacean waste biomass valorization.

Phosphoribosyltransferases and Their Roles in Plant Development and Abiotic Stress Response.

Glycosylation is a widespread glycosyl modification that regulates gene expression and metabolite bioactivity in all life processes of plants. Phosphoribosylation is a special glycosyl modification catalyzed by phosphoribosyltransferase (PRTase), which functions as a key step in the biosynthesis pathway of purine and pyrimidine nucleotides, histidine, tryptophan, and coenzyme NAD(P)+ to control the production of these essential metabolites. Studies in the past decades have reported that PRTases are indispensable for plant survival and thriving, whereas the complicated physiological role of PRTases in plant life and their crosstalk is not well understood. Here, we comprehensively overview and critically discuss the recent findings on PRTases, including their classification, as well as the function and crosstalk in regulating plant development, abiotic stress response, and the balance of growth and stress responses. This review aims to increase the understanding of the role of plant PRTase and also contribute to future research on the trade-off between plant growth and stress response.

Prognostic Significance of Prognostic Nutritional Index in Esophageal Squamous Cell Carcinoma Patients Undergoing Radical Radiotherapy: A Propensity Score Matching Analysis.

BACKGROUND: The preoperative prognostic nutritional index (PNI) is associated with postoperative complications and long-term survival of various cancers. However, its role in esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of this study was to identify the prognostic value of PNI in predicting survival in ESCC patients undergoing radical radiotherapy. METHODS: We retrospectively reviewed 354 ESCC patients undergoing radical radiotherapy. The time-dependent receiver operating characteristics was used to determine the optimal cutoff value. The association between PNI and survival was determined by Kaplan-Meier method and Cox regression model. Propensity score matching was applied to balance the baseline characteristics. RESULTS: PNI was positively correlated with hemoglobin (P < 0.001) and prealbumin (P < 0.001). The optimal cutoff value of PNI was set at 50.5. The 5-year overall survival (OS) in low PNI group and high PNI group were 20.8% and 34.0%, respectively (P < 0.001). The 5-year progression free survival in patients with low PNI and high PNI were 15.2% and 28.5%, respectively (P = 0.001). Multivariate analysis showed that PNI was a significant predictor for OS (P = 0.038). In the PSM analysis, PNI still remained an independent predictor for OS (P = 0.015). CONCLUSIONS: The PNI is a significant and independent predictor for OS of ESCC patients undergoing radical radiotherapy.

Heteroatom Bridging Strategy in Carbon-Based Catalysts for Enhanced Oxidative Desulfurization Performance.

Carbon-based catalysts are found to be promising metal-free species for aerobic oxidative desulfurization of fuel oil. Thus, a proper approach to promote their catalytic performances is very much in demand. In this contribution, a heteroatom bridging strategy is proposed to enhance the catalytic activities of carbon-based catalysts. As proof of the strategy, a series of boron (B)-doped graphite catalysts were synthesized. Detailed characterizations showed that the hetero-B atoms were uniformly dispersed in graphite. More importantly, it was found that the doped B atoms functioned as a bridge for electron transfer. With the existence of the heteroatom bridge, the activation of oxygen by graphite during the catalytic oxidation process was enhanced remarkably, leading to an ultradeep oxidative desulfurization performance. Moreover, the catalyst can be readily recycled five times without a significant decrease in desulfurization performance.

Biosynthesis and the Roles of Plant Sterols in Development and Stress Responses.

Plant sterols are important components of the cell membrane and lipid rafts, which play a crucial role in various physiological and biochemical processes during development and stress resistance in plants. In recent years, many studies in higher plants have been reported in the biosynthesis pathway of plant sterols, whereas the knowledge about the regulation and accumulation of sterols is not well understood. In this review, we summarize and discuss the recent findings in the field of plant sterols, including their biosynthesis, regulation, functions, as well as the mechanism involved in abiotic stress responses. These studies provide better knowledge on the synthesis and regulation of sterols, and the review also aimed to provide new insights for the global role of sterols, which is liable to benefit future research on the development and abiotic stress tolerance in plant.

Contribution of insulin resistance to the relationship between sugar-sweetened beverage intake and a constellation of cardiometabolic abnormalities in adolescents.

BACKGROUND: Insulin resistance (IR) is a pathophysiological construct that derives a series of metabolic disturbances that promote cardiometabolic dysfunction. This study evaluated mediating and modifying effects of homeostatic model assessment-based IR (HOMA-IR) on the association between sugar-sweetened beverage (SSB) consumption and a constellation of adolescent cardiometabolic abnormalities. METHODS: Comprehensive data on sociodemographics, diet, physical activity, and anthropometric and biochemical parameters for 1454 adolescents were obtained from a large-scale representative study for adolescent metabolic syndrome (MetS) conducted in Taiwan. The original (HOMA1-IR) and updated nonlinear (HOMA2-IR) HOMA-IR indicators were used as IR biomarkers. Principal component (PC) analysis was employed to create reduced groups of variables and risk scores for retained PCs. RESULTS: Higher SSB intake was associated with higher levels of HOMA1-IR and HOMA2-IR, and the two IR biomarkers were positively correlated with metabolic dysfunction clustering. Compared with SSB nondrinkers, adolescents who consumed >500 mL/day of hand-shaken high-fructose corn syrup beverages (HHB) had a 0.22 increase in the number of abnormal MetS components, and HOMA-IR mediation explained 33.9-37.9% of the effect. IR biomarkers accounted for 26.5-31.0% of the relationship between >500 mL/day of SSB consumption and bodyweight-enhanced PC scores. The effects of HOMA-IR indicators on all bodyweight-related factors were consistently intensified among >350 mL/day HHB drinkers (all Pinteraction < 0.05). CONCLUSIONS: Fructose-rich SSB intake correlates with a constellation of cardiometabolic abnormalities in adolescents, and this association may be partly mediated by HOMA-IR levels. The adverse effects of HOMA-IR on bodyweight-associated cardiometabolic risk factors depend on the type of SSB consumption, with enhanced risks observed in the intake of high amounts of HFCS-containing SSBs.

Tissue microbiota in nasopharyngeal adenoid and its association with pneumococcal carriage.

The microbial colonization in the nasopharynx is a prerequisite for the onset of infectious diseases. For successful infection, pathogens should overcome host defenses as well as compete effectively with the resident microbiota. Hence, elucidating the richness and diversity of the microbiome at the site of pathogen colonization is pivotal. Here, we investigated the adenoidal tissue microbiota collected through adenoidectomy to evaluate the impact of Streptococcus pneumoniae. Prospectively, children with sleep-disordered breathing (SDB) and otitis media with effusion (OME) were enrolled. During adenoidectomy, the nasopharyngeal swab and adenoid tissues were collected to determine the pneumococcal carriage and tissue microbiota, using multiplex PCR and 16S ribosomal RNA (16S rRNA) pyrosequencing. A total of 66 pediatric patients comprising 38 children with SDB and 28 children with OME were enrolled. There was no difference between the bacterial cultures from the surface of the nasopharyngeal adenoid in the SDB and OME groups. Thirty-four samples (17 SDB and 17 OME) underwent 16S rRNA pyrosequencing and fulfilled the criteria for further analysis. The Shannon diversity index for the samples from the SDB patients was found to be higher than that observed for the samples from OME patients, although the difference was not significant (p = 0.095). The Shannon diversity index for the samples negative for the pneumococcal carriage was significantly higher than that for the samples positive for pneumococcal carriage (p = 0.038). Alloprevotella, Staphylococcus, Moraxella, and Neisseriaceae were significantly dominant in the samples positive for the pneumococcal carriage. Dialister was significantly less present in the adenoid tissue positive for the pneumococcal carriage. Streptococcus pneumoniae, one of the most common pathogens of the airway, significantly influences the composition and diversity of the microbiota in the nasopharyngeal adenoid. Thus, bacterial community analysis based on 16S rRNA pyrosequencing allows for better understanding of the relationship between the adenoidal microbial communities.

Oral tongue leukoplakia: analysis of clinicopathological characteristics, treatment outcomes, and factors related to recurrence and malignant transformation.

OBJECTIVES: The tongue is identified as a high-risk site for oral leukoplakia and malignant transformation. The purpose of this study is to investigate the clinicopathological characteristics and treatment outcomes of tongue leukoplakia and assess the factors related to recurrence and malignant transformation. MATERIALS AND METHODS: One hundred and forty-four patients who received carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were analyzed statistically. RESULTS: The follow-up period was 54.90 ± 54.41 months. Thirty patients showed postoperative recurrence (20.83%), and 12 patients developed malignant transformation (8.33%). The annual transformation rate was 2.28%. Univariate analysis showed that a history of head and neck cancer, size of lesion area, clinical appearance, and pathology were significant factors for both recurrence and malignant transformation. In the multivariate logistic regression, a history of head and neck cancer and size of lesion area were independent prognostic factors for recurrence, and a history of head and neck cancer was the only independent factor for postoperative malignant change. CONCLUSIONS: Clinicians should adopt more aggressive strategies for tongue leukoplakia patients with a history of head and neck cancer. CLINICAL RELEVANCE: These results may help clinicians gain a better understanding of oral tongue leukoplakia.

Liraglutide suppresses production of extracellular matrix proteins and ameliorates renal injury of diabetic nephropathy by enhancing Wnt/ß-catenin signaling.

The Wnt/ß-catenin signaling pathway is involved in production of the extracellular matrix (ECM) by mesangial cells (MCs). Recent studies by us and others have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have protective effects against diabetic nephropathy. The purpose of the present study was to investigate whether the Wnt/ß-catenin signaling in MCs contributes to GLP-1RA-induced inhibition of ECM accumulation and mitigation of glomerular injury in diabetic nephropathy. In cultured human mesangial cells, liraglutide (a GLP-1RA) treatment significantly reduced high glucose (HG)-stimulated production of fibronectin, collagen type IV, and α-smooth muscle actin, and the liraglutide effects were significantly attenuated by XAV-939, a selective inhibitor of Wnt/ß-catenin signaling. Furthermore, HG treatment significantly decreased protein abundance of Wnt4, Wnt5a, phospho-glycogen synthase kinase-3ß, and ß-catenin. These HG effects on Wnt/ß-catenin signaling proteins were significantly blunted by liraglutide treatment. For in vivo experiments, we administered liraglutide (200 µg·kg-1·12 h-1) by subcutaneous injection to streptozocin-induced type 1 diabetic rats for 8 wk. Administration of liraglutide significantly improved elevated blood urine nitrogen, serum creatinine, and urinary albumin excretion rate and alleviated renal hypertrophy, mesangial expansion, and glomerular fibrosis in type 1 diabetic rats, whereas blood glucose level and body weight did not have significant changes. Consistent with the in vitro experiments, liraglutide treatment significantly reduced the diabetes-induced increases in glomerular fibronectin, collagen type IV, and α-smooth muscle actin and decreases in glomerular Wnt/ß-catenin signaling proteins. These results suggest that liraglutide alleviated glomerular ECM accumulation and renal injury in diabetic nephropathy by enhancing Wnt/ß-catenin signaling.

Functional characterization of T3SS C-ring component VscQ and evaluation of its mutant as a live attenuated vaccine in zebrafish (Danio rerio) model.

Vibrio alginolyticus, a Gram-negative bacterium, has been recognized as an opportunistic pathogen in marine animals as well as humans. Type III secretion system (T3SS) is critical for pathogen virulence and disease development. However, no more information is known about the C-ring component VscQ and its physiological role. In this study, gene vscQ was cloned from V. alginolyticus wild-type strain HY9901 and the mutant strain HY9901ΔvscQ was constructed by the in-frame deletion method. The HY9901ΔvscQ mutant showed an attenuated swarming phenotype and a closely 4.6-fold decrease in the virulence to Danio rerio. However, the HY9901ΔvscQ mutant showed no difference in growth, biofilm formation and ECPase activity. HY9901ΔvscQ reduces the release of LDH, NO and caspase-3 activity of infected FHM cell, which are involved in fish cell apoptosis. Deletion of gene vscQ downregulates the expression level of T3SS-related genes including vscL, vopB, hop, vscO, vscK, vopD, vcrV and vopS and flagellum-related genes (flaA and fliG). And Danio rerio vaccinated via i.m injection with HY9901ΔvscQ induced a relative percent survival (RPS) value of 71% after challenging with the wild-type HY9901. Real-time PCR assays showed that vaccination with HY9901ΔvscQ enhanced the expression of immune-related genes, including TNF-α, TLR5, IL-6R, IgM and c/ebpß in liver and spleen after vaccination, indicating that it is able to induce humoral and cell-mediated immune response in zebrafish. These results demonstrate that the HY9901ΔvscQ mutant could be used as an effective live vaccine to combat V. alginolyticus infection.

Radical Chemistry and Reaction Mechanisms of Propane Oxidative Dehydrogenation over Hexagonal Boron Nitride Catalysts.

Although hexagonal boron nitride (h-BN) has recently been identified as a highly efficient catalyst for the oxidative dehydrogenation of propane (ODHP) reaction, the reaction mechanisms, especially regarding radical chemistry of this system, remain elusive. Now, the first direct experimental evidence of gas-phase methyl radicals (CH3 . ) in the ODHP reaction over boron-based catalysts is achieved by using online synchrotron vacuum ultraviolet photoionization mass spectroscopy (SVUV-PIMS), which uncovers the existence of gas-phase radical pathways. Combined with density functional theory (DFT) calculations, the results demonstrate that propene is mainly generated on the catalyst surface from the C-H activation of propane, while C2 and C1 products can be formed via both surface-mediated and gas-phase pathways. These observations provide new insights towards understanding the ODHP reaction mechanisms over boron-based catalysts.