4-Oxo-2-Nonenal- and Agitation-Induced Aggregates of α-Synuclein and Phosphorylated α-Synuclein with Distinct Biophysical Properties and Biomedical Applications.

α-Synuclein (α-syn) can form oligomers, protofibrils, and fibrils, which are associated with the pathogenesis of Parkinson's disease and other synucleinopathies. Both the lipid peroxidation product 4-oxo-2-nonenal (ONE) and agitation can induce aggregation of α-syn and phosphorylated α-syn. Thus, clarification of the characteristics of different α-syn species could help to select suitable aggregates for diagnosis and elucidate the pathogenesis of diseases. Here, we characterized ONE-induced wild-type (WT) α-syn aggregates (OW), ONE-induced phosphorylated α-syn (p-α-syn) aggregates (OP), agitation-induced α-syn preformed fibrils (PFF), and agitation-induced p-α-syn preformed fibrils (pPFF). Thioflavin T (ThT) dying demonstrated that OW and OP had fewer fibrils than the PFF and pPFF. Transmission electron microscopy revealed that the lengths of PFF and pPFF were similar, but the diameters differed. OW and OP had more compact structures than PFF and pPFF. Aggregation of p-α-syn was significantly faster than WT α-syn. Furthermore, OW and OP were more sodium dodecyl sulfate-stable and proteinase K-resistant, suggesting greater stability and compactness, while aggregates of PFF and pPFF were more sensitive to proteinase K treatment. Both ONE- and agitation-induced aggregates were cytotoxic when added exogenously to SH-SY5Y cells with increasing incubation times, but the agitation-induced aggregates caused cell toxicity in a shorter time and more p-α-syn inclusions. Similarly, p-proteins were more cytotoxic than non-p-proteins. Finally, all four aggregates were used as standard antigens to establish sandwich enzyme-linked immunosorbent assay (ELISA). The results showed that the recognition efficiency of OW and OP was more sensitive than that of PFF and pPFF. The OW- and OP-specific ELISA for detection of p-α-syn and α-syn in plasma samples of Thy1-α-syn transgenic mice showed that the content of aggregates could reflect the extent of disease. ONE and agitation induced the formation of α-syn aggregates with distinct biophysical properties and biomedical applications.

[The auxiliary diagnostic value of ECP and MPO expression in nasal secretions in different types of rhinitis].

Objective:To evaluate the expression of eosinophil cationic protein and myeloperoxidase in nasal secretions in different types of rhinitis, and to explore their values in the differential diagnosis of different types of rhinitis. Methods:Six hundred and eighty-four subjects were selected, including 62 subjects in the acute rhinitis group, 378 subjects in the allergic rhinitis group, 94 subjects in the vasomotor rhinitis group, 70 subjects in the eosinophilic non-allergic rhinitis group, and 80 subjects in the control group. Nasal secretion samples were collected from the five groups, and the percentages of inflammatory cells were counted by Rachel's staining, and the expression of ECP/MPO was detected by colloidal gold assay. The correlation between the clinical diagnosis, the inflammatory cells in the nasal secretions and the expression of ECP/MPO was analyzed. Results:Nasal cytological smears showed that compared with the control group, the percentage of eosinophils in the AR and NARES groups were significantly higher （P<0.05）, while the percentage of neutrophils was not different （P>0.05）; the percentage of neutrophils was significantly higher in the acute rhinitis group compared with the control group （P<0.05）, while the percentage of eosinophils was not statistically different （P>0.05）; in vasomotor rhinitis group, the eosinophils and neutrophils were not statistically different compared with the control group（P> 0.05）. The colloidal gold results showed that there were differences in the expression of ECP/MPO in different types of rhinitis, among which 49 cases （79.0%） in the acute rhinitis group expressed ECP+/MPO+; 267 cases （70.6%） in the AR group and 56 cases （75.7%） in the NARES group expressed ECP+/MPO-; 80 cases （85.1%） in the vasomotor rhinitis group and 69 cases （86.3%） in the control group expressed ECP-/MPO-. Conclusion:The differences in ECP and MPO expression between different types of rhinitis have certain reference value for the differential diagnosis of different types of rhinitis and the selection of treatment programs.

Exploration of YBX1 role in the prognostic value and immune characteristics by single-cell and bulk sequencing analysis for liver hepatocellular carcinoma.

BACKGROUND: Y-box binding protein 1 (YBX1) plays a variety of roles in progression of multiple tumors. However, the role of YBX1 in prognostic value and immune regulation for liver hepatocellular carcinoma (LIHC) remains unclear. The present study aimed to examine the effect of YBX1 on the regulation of tumor immunity and survival prediction in LIHC patients. METHODS: YBX1-related expression profiles and single-cell and bulk sequencing analysis were performed using online databases. YBX1 expression was validated by a quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. Univariate/multivariate Cox regression analysis was performed to determine independent predictors of overall survival (OS). The ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis were used to assess the relationships between YBX1 and LIHC immunity. RESULTS: YBX1 was over-expressed in LIHC tissues and cell lines. High YBX1 expression was significantly associated with poor OS. Univariate/multivariate Cox regression analysis revealed that YBX1 was an independent prognostic factor for LIHC. Gene set enrichment analysis revealed that YBX1 was associated with multiple signaling pathways correlated to LIHC. Additionally, YBX1 was expressed in multiple immune cells and was significantly correlated with immune cells, immune checkpoint markers and tumor immune microenvironment. The TIDE analysis demonstrated that LIHC patients with high YBX1 expression showed a higher T-cell dysfunction score and a higher exclusion score, as well as poorer immunotherapy response. CONCLUSIONS: YBX1 plays crucial oncogenic roles in LIHC and is closely associated with the immune defense system. YBX1 inhibition may serve as a potential treatment for LIHC.

TM-search: An Efficient and Effective Tool for Protein Structure Database Search.

The quickly increasing size of the Protein Data Bank is challenging biologists to develop a more scalable protein structure alignment tool for fast structure database search. Although many protein structure search algorithms and programs have been designed and implemented for this purpose, most require a large amount of computational time. We propose a novel protein structure search approach, TM-search, which is based on the pairwise structure alignment program TM-align and a new iterative clustering algorithm. Benchmark tests demonstrate that TM-search is 27 times faster than a TM-align full database search while still being able to identify ∼90% of all high TM-score hits, which is 2-10 times more than other existing programs such as Foldseek, Dali, and PSI-BLAST.

Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice.

BACKGROUND: Some patients show persistent cognitive decline for weeks, months or even years after surgery, which seriously affects their long-term prognosis and quality of life. However, most previous basic studies have focused mainly on the mechanisms of early postoperative cognitive decline, whereas cognitive decline in the longer term after surgery is less well-understood. The subgranular zone of the dentate gyrus exhibits life-long neurogenesis, supporting hippocampus-dependent learning and memory. MAIN TEXT: The aim of this study was to investigate whether adult hippocampal neurogenesis (AHN) involves in cognitive decline later following surgery and to further explore the roles of CD8 + T lymphocytes infiltrating the hippocampal parenchyma after surgery in this pathological process. Cognitive function was examined in adult mice that underwent laparotomy combined with partial hepatectomy, and the results showed that cognitive decline persisted in mice who underwent surgery during the first postoperative month, even though there was a trend toward continuous improvement over time. Significantly decreased numbers of DCX + cells, BrdU + cells, and BrdU + /DCX + cells were observed on day 8 after surgery, and a significantly decreased number of NeuN + /BrdU + cells was observed on day 28 after surgery, which indicated inhibition of AHN. After surgery, T lymphocytes, the majority of which were CD8 + T cells, infiltrated the hippocampus and secreted Interferon-γ (IFN-γ). Depletion of CD8 + T cells could inhibit the increase of IFN-γ synthesis, improve hippocampal neurogenesis, and improve postoperative cognitive function. Hippocampal microinjection of IFN-γ neutralizing antibody or adeno-associated virus to knock down IFN-γ receptor 1 (IFNGR1) could also partially attenuate the inhibition of AHN and improve postoperative cognitive function. CONCLUSIONS: These results demonstrate that postoperative infiltration of CD8 + T cells into the hippocampus and subsequent secretion of IFN-γ contribute to the inhibition of AHN and cognitive decline later following surgery.

Escherichia coli Promotes Endothelial to Mesenchymal Transformation of Liver Sinusoidal Endothelial Cells and Exacerbates Nonalcoholic Fatty Liver Disease Via Its Flagellin.

BACKGROUND＆AIMS: Gut bacteria translocate into the liver through a disrupted gut vascular barrier, which is an early and common event in the development of nonalcoholic fatty liver disease (NAFLD). Liver sinusoidal endothelial cells (LSECs) are directly exposed to translocated gut microbiota in portal vein blood. Escherichia coli, a commensal gut bacterium with flagella, is markedly enriched in the gut microbiota of patients with NAFLD. However, the impact of E coli on NAFLD progression and its underlying mechanisms remains unclear. METHODS: The abundance of E coli was analyzed by using 16S ribosomal RNA sequencing in a cohort of patients with NAFLD and healthy controls. The role of E coli was assessed in NAFLD mice after 16 weeks of administration, and the features of NAFLD were evaluated. Endothelial to mesenchymal transition (EndMT) in LSECs induced by E coli was analyzed through Western blotting and immunofluorescence. RESULTS: The abundance of gut Enterobacteriaceae increased in NAFLD patients with severe fat deposition and fibrosis. Importantly, translocated E coli in the liver aggravated hepatic steatosis, inflammation, and fibrosis in NAFLD mice. Mechanistically, E coli induced EndMT in LSECs through the TLR5/MYD88/TWIST1 pathway during NAFLD development. The toll-like receptor 5 inhibitor attenuated E coli-induced EndMT in LSECs and liver injury in NAFLD mice. Interestingly, flagellin-deficient E coli promoted less EndMT in LSECs and liver injury in NAFLD mice. CONCLUSIONS: E coli promoted the development of NAFLD and promoted EndMT in LSECs through toll-like receptor 5/nuclear factor kappa B-dependent activation of TWIST1 mediated by flagellin. Therapeutic interventions targeting E coli and/or flagellin may represent a promising candidate for NAFLD treatment.

Overexpression of IGF2 affects mouse weight and glycolipid metabolism and IGF2 is positively related to macrosomia.

Objective: To investigate the effects of insulin-like growth factor 2 (IGF2) on growth and glycolipid metabolism, as well as the underlying mechanism. Methods: A mouse model of IGF2 overexpression was constructed to measure weight gain before adulthood, to obtain the values of adult glycolipid metabolism indicators in the peripheral blood and to detect the expression of genes in the IGF2 signaling pathway in different mouse tissues. The present study also explored the independent association between the IGF2 gene and macrosomia by detecting and comparing the expression levels of IGF2 mRNA/H19 RNA in maternal peripheral blood and fetal cord blood of 26 human pregnancies. Results: In the mouse model, weights of the IGF2-overexpressing mice were significantly higher than those of the control mice at the age of 5-10 weeks. The glucose concentration, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels of IGF2-overexpressing mice were significantly lower than those of wild-type (WT) mice. Compared with the WT mice, the expression of H19 was significantly decreased in the pancreas and IGF1R was significantly decreased in the muscle of mice with IGF2 overexpression. The expression levels of STAT3 and AKT2 showed significant decrease in liver, muscle and increase in muscle of IGF2-overexpressing mice, respectively. GLUT2 expression showed significant increase in liver, kidney, muscle and decrease in pancreas of mice with IGF2 overexpression. This study also found that in normal mothers with the similar clinical characteristics, IGF2 expression in the maternal peripheral blood and fetal cord blood is an independent factor influencing macrosomia. Conclusion: IGF2 expression was independently correlated with the occurrence of macrosomia, and overexpression of IGF2 significantly increased the weights of mice at the age of 5-10 weeks and significantly affected the values of adult glycolipid metabolism indicators, which might be the result of changes in the IGF2-IGF1R-STAT3/AKT2-GLUT2/GLUT4 pathway. These findings might suggest that IGF2 plays an important role in growth and glycolipid metabolism during both pregnancy and postnatal development.

A Europium Nanosphere-Based Time-Resolved Fluorescent Immunochromatographic Assay for the Rapid Screening of 4,4'-Dinitrocarbanilide: Aiming at Improving Strip Method Performance.

Considering that the strip method is simple and convenient for users, a Europium nanosphere-based time-resolved fluorescent immunochromatographic assay (TRFICA) for the rapid screening of 4,4'-dinitrocarbanilide (DNC) was developed to improve the performance of strip assays. After optimization, TRFICA showed IC50, the limit of detection, and cut-off values of 0.4, 0.07, and 5.0 ng mL-1, respectively. No significant cross-reactivity (CR < 0.1%) with 15 DNC analogs was observed in the developed method. TRFICA was validated for DNC detection in spiked chicken homogenates, and recoveries ranged from 77.3% to 92.7%, with coefficients of variation of <14.9%. Moreover, the time needed for the detection procedure, including the sample pre-treatment, was less than 30 min for TRFICA, which had never been achieved before in other immunoassays. The newly developed strip test is a rapid, sensitive, quantitative, and cost-effective on-site screening technique for DNC analysis in chicken muscle.

Microglial priming induced by loss of Mef2C contributes to postoperative cognitive dysfunction in aged mice.

Postoperative cognitive dysfunction (POCD) is a common postoperative central nervous system (CNS) complication with a higher occurrence among aged individuals than among young individuals. The aim of this study was to explore the mechanisms by which POCD preferentially affects older individuals. We found here that exploratory laparotomy induced cognitive function decline in aged mice but not in young mice and that this decline was accompanied by inflammatory activation of microglia in the hippocampus. Furthermore, microglial depletion by feeding of a standard diet containing a colony stimulating factor 1 receptor (CSF1R) inhibitor (PLX5622) markedly protected aged mice from POCD. Notably, the expression of myocyte-specific enhancer 2C (Mef2C), an immune checkpoint that limits overactivation of microglia, was downregulated in aged microglia. Knocking down Mef2C induced a microglial priming phenotype in young mice, resulting in postoperative increases in the hippocampal levels of the inflammatory factors IL1-ß, IL-6 and TNF-α that could impair cognition; these findings were consistent with the observations in aged mice. In vitro, BV2 cells lacking Mef2C released higher levels of inflammatory cytokines upon stimulation with lipopolysaccharide (LPS, a bacterial toxin) than Mef2C-sufficient cells. Moreover, upregulation of Mef2C in aged mice restrained postoperative microglial activation, attenuating the neuroinflammatory response and cognitive impairment. These results reveal that during aging, loss of Mef2C leads to microglial priming, amplifying postsurgical neuroinflammation and contributing to the vulnerability of elderly patients to POCD. Thus, targeting the immune checkpoint Mef2C in microglia may be a potential strategy for the prevention and treatment of POCD in aged individuals.

Time-Resolved Spectroscopic Study of a Photoinduced Intramolecular Chloride Exchange Reaction of 3',5'-Dimethoxybenzoin Chloride.

Photoremovable protecting groups are of great importance due to their remote control over the liberation of diverse reactive species temporally and spatially, including biologically active compounds and functional groups. Here, an in-depth investigation on the heterolysis-solvolysis reaction mechanisms of a photoremovable protecting group, 3',5'-dimethoxybenzoin (DMB) chloride, has been accomplished. With the aid of transient absorption and time-resolved resonance Raman spectroscopies, the features of the intermediates that emerged from the photolysis process were directly observed. Elaborate optical and theoretical studies on DMB chloride have suggested a long-lived α-keto cation intermediate (0.9 ms) exists as a key intermediate, unlike the radical intermediates that are typically generated in such photocyclization reactions. After undergoing nucleophilic addition and isomerization, the intermediate species eventually leads to the formation of the final product(s).

A Preliminary Study in Immune Response of BALB/c and C57BL/6 Mice with a Locally Allergic Rhinitis Model.

BACKGROUND: BALB/c and C57BL/6 mouse strains are commonly used in allergy research. The current study investigated the immunological differences between these two mouse strains with a locally allergic rhinitis model. METHODS: Eighteen BALB/c and eighteen C57BL/6 mice received different doses of ovalbumin (OVA) intranasally for eight weeks (each mouse strain has three subgroups, 25 mg/mL group, 0.25 mg/mL group, and the PBS group). The allergic symptoms, OVA-specific serum antibody (IgE, IgG1, IgG2a), cytokines (IL-4, IFN-γ, IL-10) in the splenic culture supernatant, infiltrating eosinophils and goblet cells in local nasal mucosa were measured. RNA-seq technology was applied to detect differential gene expression in the local nasal mucosa. RESULTS: With the same dose of OVA stimulation, the exacerbation of allergic symptoms was more pronounced in C57BL/6 than in BALB/c. BALB/c serum IgE, IgG1, and IgG2a gradually increased, and C57BL/6 produced fewer serum antibodies IgE and IgG1, while IgG2a never increased. BALB/c spleen cell culture supernatant IL-4 and IL-10 increased with increasing dose, and IFN-γ increased significantly in the intermediate dose group, while IL-4, IL-10, and IFN-γ did not increase in C57BL/6. The infiltration of eosinophils and goblet cells in both mice was proportional to the dose, while C57BL/6 was elevated more than BALB/c. RNA-seq suggested that the innate immune response, immune system process function, Jun kinase (JNK) pathway, and MAPKK pathway were upregulated in C57BL/6 compared to BALB/c. The core genes responsible for the differential immune response in both mice with allergic rhinitis were Kng2, Kng1, Gnb3, Lpar3, Lpar1, Pik3r1, Pf4, Apob, Rps9, and Fbxo2. CONCLUSION: There are significant differences in the immunologic responses between BALB/c mice and C57BL/6 mice. BALB/c mice developed mild local allergic inflammatory reactions and strong systemic immune responses. In contrast, C57BL/6 mice had stronger local allergic inflammatory responses and relatively mild systemic immune responses. Different mice strains can be selected according to the research purpose.

North-south regional differential decomposition and spatiotemporal dynamic evolution of China's industrial green total factor productivity.

"Green development" has become the way for countries around the world to strengthen industries, and it is an important part of China's high-quality economic development. The key for China to strike a balance between economic growth and environmental management is to optimize green total factor productivity (GTFP). This paper measures the GTFP of industry in 30 provinces of China from 2003 to 2019, based on the perspective of energy and carbon emission constraints. It empirically examines the spatial disequilibrium and dynamic evolution of industrial GTFP in China using Dagum Gini coefficients, Kernel density estimation, and Markov chain analysis. The study finds that, (1) although China's industrial GTFP is not high, it shows an increasing trend. The industrial GTFP in the southern region is higher than that in the northern region. (2) Technical efficiency is the shortcoming of China's industrial GTFP improvement. Technological progress is the main driving force of China's industrial GTFP improvement. (3) The relative and absolute differences in China'' industrial GTFP, technical efficiency, and technological progress have all shown a widening trend. Regional differences between the southern and northern regions are the main source of relative differences in industrial GTFP, technical efficiency, and technological progress. (4) China's industrial GTFP shows a clear "club convergence" phenomenon and the "Matthew effect." However, after the introduction of the spatial factor, the "club convergence" phenomenon and the "Matthew effect" have weakened. The driving effect of industrial GTFP on neighboring provinces is stronger in the south than in the north. This paper enriches the analysis of industrial GTFP and provides an important basis for the coordinated regional development of Chinese industry.

Changes of the microbial community in kiwifruit during storage after postharvest application of Wickerhamomyces anomalus.

High-throughput sequencing techniques can provide important information for understanding the interaction between exogenous microbial agents and fruit microbial communities, and explain how it controls postharvest fungal diseases. In this study, we found that Wickerhamomyces anomalus could control the postharvest disease of kiwifruit. Meanwhile, high-throughput sequencing technology results showed that the composition and structure changes of the fungal community in microbial flora were significantly greater than those of bacteria after W. anomalus treated. W. anomalus could colonize inside the fruit and regulate the community composition of bacteria to reduce the abundance of pathogens and eventually maintain the healthy state of the fruit. The dominant genus in the microbiota of kiwifruit after application of W. anomalus showed an increased ability to interact. Some fungi or bacteria are positively associated with yeast in the epiphytic and endophytic sample communities, guiding the synthesis of compound biocontrol strains for kiwifruit postharvest diseases.

Exosomes derived from hepatitis B virus-infected hepatocytes promote liver fibrosis via miR-222/TFRC axis.

Exosomal miRNAs activates hepatic stellate cell (HSC) and promote fibrosis. miR-222 was found to be increased in hepatitis B virus (HBV)-infected hepatocytes, and ferroptosis was reported to ameliorate liver fibrosis (LF). Although miR-222 and ferroptosis have been implicated in LF, the association between miR-222 and ferroptosis and how they coordinate to regulate LF are still not explicit. This study investigates the roles of miR-222 and transferrin receptor (TFRC) in LF. Lipid reactive oxygen species (ROS) level was analyzed by flow cytometry. FerroOrange staining was used to measure intracellular iron level. Luciferase reporter assay was adopted to confirm the binding of miR-222 and TFRC. Real-time quantitative PCR and immunoblots were applied to analyze gene and protein expression. The results showed that supplementation of exosomes derived from HBV-infected LO2 cells remarkably enhanced LX-2 cell activation, evidenced by elevated hydroxyprolin (Hyp) secretion and α-SMA and COL1A2 expression. miR-222 was significantly increased in HBV-Exo. Overexpressing miR-222 upregulated cell viability, secretion of Hpy, and expression of α-SMA and COL1A2, which were all blocked by overexpression of TFRC. Further study showed that TFRC was a target of miR-222, and miR-222 promoted LX-2 cell activation through suppressing TFRC-induced ferroptosis in LX-2 cells. Exosomal miR-222 derived from HBV-infected hepatocytes promoted LF through inhibiting TFRC and TFRC-induced ferroptosis. This study emphasizes the significance of miR-222/TFRC axis in LF and suggests new insights in clinical decision making while treating LF. Exosomes derived from HBV-infected LO2 cells promote LX-2 cell activation and liver fibrosis in mouse Exosomal miR-222 derived from HBV-infected LO2 cells promotes LX-2 cell activation TFRC is a target of miR-222 and inhibits LX-2 cell activation induced by miR-222 miR-222 promotes LX-2 cell activation through inhibiting TFRC-induced ferroptosis.

[Establishment of local allergic rhinitis tolerance in mouse model].

Objective:To establish a mouse model of local allergic rhinitis tolerance by intranasal infusion of allergen, and study its immunological indexes and characteristics. Methods:The mice were given ovalbumin（OVA） and phosphate buffer solution（PBS） daily, and their allergic symptoms were recorded. OVA-specific antibodies（IgE, IgG1, IgG2a） in serum and cytokine（IL-4, IL-10, IFN-γ） in splenic culture supernatant were detected. The infiltration of eosinophils and goblet cells in nasal mucosa were observed, and the changes in local nasal mucosa genes were analyzed by RNA-seq technique. Results:Mice first showed aggravation of allergic symptoms when stimulated with OVA. The serum OVA-specific antibodies IgE, IgG1, IgG2a and the cytokine（IL-4, IL-10, IFN-γ） Iin splenic culture supernatant were increased, the eosinophils and goblet cells in nasal mucosa were significantly increased. The expression of encoding IL-10, TGF-ß gene and eosinophils activation gene in nasal mucosa were up-regulated. As the duration of nasal dripping increased, the allergic symptoms gradually decreased, serum OVA-specific antibodies IgE, IgG1, IgG2a continued to increase. Splenic culture supernatant IL-4 decreased, IL-10 increased, IFN-γ had a downward trend. In nasal mucosa, goblet cells decreased significantly. Genes involved in eosinophils activation were significantly down-regulated. The encoding tolerance genes such as IL-10 and TGF-ß genes remained highly expressed. Ten core genes associated with immune tolerance in localized allergic rhinitis were screened, Rps27a, Uba52, Kng2, Gnal, C3, Rtp4, Reep1, Rtp2, Rtp1, Reep5. Conclusion:The mice first develop an allergy and then develop immune tolerance by continuous local drops of the allergen. The generation of immune tolerance may be induced by the continuous action of allergens, which induced systemic and local immune tolerance effects.

Recent advances in supported acid/base ionic liquids as catalysts for biodiesel production.

Biodiesel is considered a potential substitute for fossil diesel because of its unique environmentally friendly and renewable advantages. The efficient and durable heterogeneous catalysts are vital to greenly and efficiently drive the biodiesel production process. The ionic liquid-functionalized materials, possessing the characteristics of both homogeneous and heterogeneous catalysts, are one of the promising substitutions for conventional homogeneous acid/base catalysts for producing biodiesel. This mini-review focuses on recent advances in supported acid/base ionic liquids to synthesize ionic liquid-functionalized materials for producing biodiesel. The methods of immobilizing ionic liquids on supports were summarized. The merits and demerits of various supports were discussed. The catalytic activities of the ionic liquid-functionalized materials for biodiesel production were reviewed. Finally, we proposed the challenges and future development direction in this area.

Loss of YB-1 alleviates liver fibrosis by suppressing epithelial-mesenchymal transition in hepatic progenitor cells.

Previously, we reported that the nuclear translocation of Y-box binding protein 1 (YB-1) is induced by transforming growth factor-ß (TGF-ß) and promotes hepatic progenitor cells (HPCs) expansion. Here, we explored the mechanisms underlying YB-1 translocation and the impact of YB-1 on the epithelial-mesenchymal transition (EMT) in HPCs. YB-1flox/floxcre+/- (YB-1f/fcre+/-) mice and YB-1f/fcre-/- mice were fed with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or a choline-deficient, ethionine-supplemented (CDE) diet. Liver injury and fibrosis were assessed by performing hematoxylin and eosin (HE) and Masson staining. The expression of collagen and EMT-related markers (E-cadherin, N-cadherin, and Snail) was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence analyses. Protein kinase B (AKT) expression in HPCs was silenced via RNA interference. Nuclear YB-1 expression in HPCs was detected via western blotting and immunofluorescence analyses. HPC proliferation was detected by immunofluorescence. Our results indicate that YB-1 transcriptionally regulated the biological behavior of HPCs. HPC-specific YB-1 knockout alleviated liver fibrosis in mice fed with DDC or CDE diet. YB-1 nuclear translocation promoted matrix metallopeptidase 9 transcription. YB-1 depletion in HPCs significantly dampened the EMT and inhibited AKT phosphorylation in vitro and in vivo. AKT knockdown compromised TGF-ß-induced YB-1 nuclear translocation, thereby inhibiting the EMT and HPC proliferation. EMT and AKT were highly activated in HPCs in cirrhotic livers. Collectively, our findings indicate that the loss of YB-1 suppressed EMT in HPCs and alleviated liver fibrosis in mice, and that AKT was essential for TGF-ß-induced YB-1 nuclear translocation and HPC proliferation.

Association between use of liraglutide and liver fibrosis in patients with type 2 diabetes.

Objective: Patients with type 2 diabetes have a high risk of non-alcoholic fatty liver disease (NAFLD) and related liver fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated efficacy in improving NAFLD, while their effectiveness on liver fibrosis is limited in type 2 diabetic patients. Materials/Methods: A prospective cohort study was performed in type 2 diabetic patients. The study subjects were divided into two groups based on the use of liraglutide or not, and propensity score matching (PSM) was also conducted. After 12 months follow-up, liver fibrosis was assessed by NAFLD fibrosis score (NFS) fibrosis-4 (FIB-4), and liver stiffness measurement (LSM). The association between liraglutide use and liver fibrosis was analyzed by multivariable linear regression. Results: In the current study, a total of 1,765 type 2 diabetic patients were enrolled. 262 patients were liraglutide user and 1,503 were nouser. After 12 months follow-up, liraglutide use tended to be associated with reduced prevalence of advanced fibrosis (3.1% vs. 6.1%, P = 0.218). After adjustment for confounding factors, multivariable linear regression revealed that liraglutide use was negatively associated with decreased NFS (ß= -0.34, P = 0.043), FIB4 (ß= -0.26, P = 0.044) and LSM (ß= -4.95, P = 0.007) in type 2 diabetics. The results after PSM were similar to those before PSM. Conclusions: Liraglutide treatment is associated with decreased liver fibrosis in type 2 diabetic subjects.

Simvastatin-Loaded Lipid Emulsion Nanoparticles: Characterizations and Applications.

Simvastatin (SIM) is a diet drug to treat high lipid levels in the blood. It has the drawback of being metabolized in humans' gastrointestinal tract (GIT) when taken in an oral dosage form. To enhance the role of SIM in treating hyperlipidemias and bypassing its metabolism in GIT, a biodegradable nanocarrier as a SIM-loaded lipid emulsion nanoparticle via the solvent injection method was designed. Cholesterol acts as a lipid core, and Tween 80 was utilized to stabilize the core. The optimized nanoformulation was characterized for its particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. Furthermore, the transdermal hydrogel was characterized by physical appearance, rheology, pH, and spreadability. In vitro assays were executed to gauge the potential of LENPs and olive oil for transdermal delivery. The mean particle size and zeta potential of the optimized nanoparticles were 174 nm and -22.5 mV 0.127, respectively. Crystallinity studies and Fourier transform infrared analyses revealed no molecular interactions. Hydrogels showed a sustained release compared to SIM-loaded LENPs that can be proposed as a better delivery system for SIM. We encourage further investigations to explore the effect of reported formulations for transdermal delivery by in vivo experiments.

The necrosis-inducing protein (NIP) gene contributes to Penicillium expansum virulence during postharvest pear infection.

Penicillium expansum is the causative fungus of blue mold decay in postharvest pears resulting in substantial economic losses. Investigating P. expansum-pear fruit interactions is necessary to help develop P. expansum control strategies for effective and safe pear production. Investigating the P. expansum gene expression alterations and essential gene functions during the infection process is indispensable. Based on our results, the necrosis-inducing protein (NIP) gene was closely associated with genes related to plant cell wall degrading enzymes (CWDEs) and involved in P. expansum virulence. The NIP has high homology with other already-known fungal NIPs. To evidence the role of NIP in P. expansum virulence, NIP mutant (including knockout (ΔNIP) and complementation mutant (cNIP)) P. expansum were generated. Despite the NIP deletion did not affect the basic morphology and structure of P. expansum, it slowed down the fungal growth and hyphal production, thus reducing P. expansum's sporulation and patulin (PAT) accumulation. Furthermore, the deletion of NIP reduced the pathogenicity of P. expansum in pear. The complementation of NIP (cNIP) restored the growth, conidia production, PAT accumulation, and virulence of ΔNIP to the level of wild-type P. expansum. In addition, PAT can cause decay and aggravate the disease severity of wild-type P. expansum and ΔNIP on pears. Our results confirmed NIP plays a crucial role in P. expansum's growth, hyphal production, and pathogenicity in pears.