Benefit of aerosol reduction to winter wheat during China's clean air action: A case study of Henan Province.

A strongly declining aerosol radiative effect has been observed in China since 2013 after implementing the clean air action, yet its impact on wheat (Triticum aestivum L.) production remains unclear. We use satellite measures and a biophysical crop model to assess the impact of aerosol-induced radiative perturbations on winter wheat production in the agricultural belt of Henan province from 2013 to 2018. After calibrating parameters with the extended Fourier Amplitude Sensitivity Test (EFAST) and the generalized likelihood uncertainty estimation (GLUE) method, the DSSAT CERES-Wheat model was able to simulate crop biomass and yield more accurately. We found that the aerosol negatively impacted wheat biomass by 21.87% and yield by 22.48% from 2006 to 2018, and the biomass effects from planting to anthesis were more significant compared to anthesis to maturity. Due to the strict clean air action, under all-sky conditions, the surface solar shortwave radiation (SSR) in 2018 increased by about 7.08% over 2006-2013 during the wheat growing seasons. As a result of the improvement of crop photosynthesis, winter wheat biomass and yield increased by an average of 5.46% and 2.9%, respectively. Our findings show that crop carbon uptake and yield will benefit from the clean air action in China, helping to ensure national food and health security.

Vitamin D receptor inhibits EMT via regulation of the epithelial mitochondrial function in intestinal fibrosis.

We previously showed that the vitamin D receptor (VDR) plays a crucial role in acute inflammatory bowel disease and that intestinal fibrosis is a common complication of Crohn's disease (CD). Epithelial-mesenchymal transition (EMT) is an important hallmark of fibrogenesis through which epithelial cells lose their epithelial phenotype and transform into mesenchymal cells. It is known that the VDR plays an essential role in epithelial integrity and mitochondrial function, but its role in intestinal fibrosis remains unknown. Here, we investigated whether the VDR is involved in epithelial mitochondrial dysfunction that results in EMT in intestinal fibrosis. Using human CD samples, intestine-specific VDR-KO mice, and fibroblast cellular models, we showed that the expression of the VDR was significantly lower in intestinal stenotic areas than in nonstenotic areas in patients with chronic CD. Genetic deletion of the VDR in the intestinal epithelium exacerbated intestinal fibrosis in mice administered with dextran sulfate sodium or 2,4,6-trinitrobenzene sulfonic acid, two experimental colitis inducers. In addition, we found that vitamin D dietary intervention regulated intestinal fibrosis by modulating the intestinal expression of the VDR. Mechanistically, knocking down the VDR in both CCD-18Co cells and human primary colonic fibroblasts promoted fibroblast activation, whereas VDR overexpression or VDR agonist administration inhibited fibroblast activation. Further analysis illustrated that the VDR inhibited EMT in the HT29 cell model and that mitochondrial dysfunction mediated epithelial integrity and barrier function in VDR-deficient epithelial cells. Together, our data for the first time demonstrate that VDR activation alleviates intestinal fibrosis by inhibiting fibroblast activation and epithelial mitochondria-mediated EMT.

The DEAD-box helicase DDX3x ameliorates non-alcoholic fatty liver disease via mTORC1 signalling pathway.

BACKGROUND & AIMS: The DEAD (Asp-Glu-Ala-Asp)-box helicase family member DDX3x has been proven to involve in hepatic lipid disruption during HCV infection. However, the role of DDX3x in non-alcoholic fatty liver disease (NAFLD), in which lipid homeostasis is severely disrupted, remains unclear. Here, we aimed to illustrate the potential role of DDX3x in NAFLD. METHODS: DDX3x protein levels were evaluated in NAFLD patients and NAFLD models via immunohistochemistry or western blotting. In vivo ubiquitin assay was performed to identify the ubiquitination levels of DDX3x in the progression of steatosis. DDX3x protein levels in mice livers were manipulated by adeno-associated virus-containing DDX3x short hairpin RNA or DDX3x overexpression plasmid. Hepatic or serum triglyceride and total cholesterol were evaluated and hepatic steatosis was confirmed by haematoxylin and eosin staining and oil red o staining. Western blotting was performed to identify the underlying mechanisms of DDX3x involving in the progression of NAFLD. RESULTS: DDX3x protein levels were significantly decreased in NAFLD patients and NAFLD models. DDX3x protein might be degraded via ubiquitin-proteasome system in the progression of steatosis. Knockdown of hepatic DDX3x exacerbated HFD-induced hepatic steatosis in mice, while overexpression of hepatic DDX3x alleviated HFD-induced hepatic steatosis in mice. Further explorative experiments revealed that knockdown of DDX3x could lead to the overactivation of mTORC1 signalling pathway which exacerbates NAFLD. CONCLUSIONS: DDX3x involved in the progression of NAFLD via affecting the mTORC1 signalling pathway. DDX3x might be a potential target for NAFLD treatment.

Recombinant invasive Lactobacillus plantarum expressing the J subgroup avian leukosis virus Gp85 protein induces protection against avian leukosis in chickens.

Avian leukosis, caused by avian leukosis virus (ALV), is an infectious tumor disease and severely hinders the development of the poultry industry. The use of Lactobacillus plantarum (L. plantarum) could effectively alleviate viremia in the early period of J subgroup ALV (ALV-J) infection. In this study, an invasive L. plantarum NC8 expressing Gp85 protein of ALV-J was constructed. After chickens were orally administered the recombinant invasive NC8, the levels of expression of CD4+ and CD8+ T lymphocytes in peripheral blood and spleen by flow cytometry and the proliferation ability of splenocytes by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were examined, and the contents of cytokines, the anti-ALV-J antibody in serum, and mucosal antibody sIgA in intestinal lavage fluid were detected by enzyme-linked immunosorbent assay (ELISA). The immunoprotective efficiency was evaluated by monitoring the infection rate, the percent of cloacal swabs and survival, body weight gain, the organ indexes, and relative virus loads after challenge with ALV-J. The results showed that the recombinant invasive strain (FnBPA-gp85) could promote the expression levels of the CD8+T cells in peripheral blood and spleen, the proliferation of splenocytes, the secretions of cytokines interleukin 2 (IL-2) and γ-interferon (IFN-γ), and the production of IgG and sIgA compared with the PBS and FnBPA control groups in chickens. The FnBPA-gp85 group was exhibited the highest immune protection against ALV-J infection. The above results indicated that the recombinant invasive NC8 could promote the cellular immunity, humoral immunity, and mucosal immunity responses in chicken and provide a new method for exploring the live vaccine against ALV-J.Key points• The FnBPA-gp85 strain could enhance cellular immunity response.• The FnBPA-gp85 strain could improve the immune protection against ALV-J infection.

Vitamin D receptor targets hepatocyte nuclear factor 4α and mediates protective effects of vitamin D in nonalcoholic fatty liver disease.

Epidemiological studies have suggested a link between vitamin D deficiency and increased risk for nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms have remained unclear. Here, using both clinical samples and experimental rodent models along with several biochemical approaches, we explored the specific effects and mechanisms of vitamin D deficiency in NAFLD pathology. Serum vitamin D levels were significantly lower in individuals with NAFLD and in high-fat diet (HFD)-fed mice than in healthy controls and chow-fed mice, respectively. Vitamin D supplementation ameliorated HFD-induced hepatic steatosis and insulin resistance in mice. Hepatic expression of vitamin D receptor (VDR) was up-regulated in three models of NAFLD, including HFD-fed mice, methionine/choline-deficient diet (MCD)-fed mice, and genetically obese (ob/ob) mice. Liver-specific VDR deletion significantly exacerbated HFD- or MCD-induced hepatic steatosis and insulin resistance and also diminished the protective effect of vitamin D supplementation on NAFLD. Mechanistic experiments revealed that VDR interacted with hepatocyte nuclear factor 4 α (HNF4α) and that overexpression of HNF4α improved HFD-induced NAFLD and metabolic abnormalities in liver-specific VDR-knockout mice. These results suggest that vitamin D ameliorates NAFLD and metabolic abnormalities by activating hepatic VDR, leading to its interaction with HNF4α. Our findings highlight a potential value of using vitamin D for preventing and managing NAFLD by targeting VDR.

SeP is elevated in NAFLD and participates in NAFLD pathogenesis through AMPK/ACC pathway.

Nonalcoholic fatty liver disease (NAFLD) is prevalent chronic liver diseases with unknown mechanism and no curative treatment. Hepatokines have demonstrated importance in NAFLD but, role of selenoprotein P (SeP) in NAFLD is unknown. A total of 79 patients with NAFLD and 79 healthy controls were included in this case-control study. SeP is elevated in patients with NAFLD. With elevating level of SeP, NAFLD prevalence, and detecting rate increases. As NAFLD aggravated, serum SeP increases. Correlation analysis demonstrates that SeP is positively associated with NAFLD risk factors including body mass index, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and serum uric acid. Both NAFLD in vivo and in vitro models, SeP protein level is higher in liver. Small interfering RNA of SEPP1 inhibited TG accumulation by activating adenosine monophosphate activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC), and overexpression of SEPP1 aggravated lipid accumulation and inhibited AMPK/ACC phosphorylation. SeP expression is activated in NAFLD and exacerbated NAFLD through AMPK/ACC, providing insight into new diagnostic, therapeutic target in NAFLD.

GCSF deficiency attenuates nonalcoholic fatty liver disease through regulating GCSFR-SOCS3-JAK-STAT3 pathway and immune cells infiltration.

Granulocyte colony stimulating factor (GCSF) is a cytokine with immunomodulation effects. However, little is known about its role in metabolic diseases. In the current study, we aimed to explore the role of GCSF in nonalcoholic fatty liver disease (NAFLD). Male GCSF-/- mice were used to investigate the function of GCSF in vivo after high-fat diet (HFD). Primary hepatocytes were used for evaluating the function of GCSF in vitro. Liver immune cells were isolated and analyzed by flow cytometry. Our results showed that GCSF administration significantly increased serum triglyceride (TG) levels in patients. Circulating GCSF was markedly elevated in HFD-fed mice. GCSF-/- mice exhibited alleviated HFD-induced obesity, insulin resistance, and hepatic steatosis. Extra administration of GCSF significantly aggravated palmitic acid (PA)-induced lipid accumulation in primary hepatocytes. Mechanically, GCSF could bind to granulocyte colony stimulating factor receptor (GCSFR) and regulate suppressors of cytokine signaling 3, Janus kinase, signal transducer and activator of transcription 3 (SOCS3-JAK-STAT3) pathway. GCSF also enhanced hepatic neutrophils and macrophages infiltration, thereby modulating NAFLD. These findings suggest that GCSF plays an important regulatory role in NAFLD and may be a potential therapeutic target for NAFLD.NEW & NOTEWORTHY We found GCSF was involved in lipid metabolism and NAFLD development. GCSF administration increased serum triglyceride levels in patients. GCSF deficiency alleviated HFD-induced insulin resistance and hepatic steatosis in mice. GCSF could directly act on hepatocytes through GCSFR-SOCS3-JAK-STAT3 pathway, and regulate the infiltration of immune cells into the liver to indirectly modulate NAFLD. Our finding indicates that GCSF may provide new strategies for the treatment of NAFLD.

The efficacy of Helicobacter pylori eradication in diabetics and its effect on glycemic control: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Previous studies have revealed the association between Helicobacter pylori (H. pylori) and diabetes mellitus, but conflicts still exist. The present study tried to investigate the underlying link between these two diseases by making comprehensive analyses of the impact of diabetes on H. pylori eradication and the influence of H. pylori eradication on diabetes. METHODS: We systematically searched relevant studies from PubMed, Cochrane Library, Web of Science, and Embase updated to April 23, 2020. Studies examining the association between H. pylori eradication and diabetes were included. Pooled odds ratio (OR) and weighted mean differences (WMD) were calculated for different results. RESULTS: Among the 2125 retrieved studies, 36 studies were included. Patients with type 2 diabetes mellitus (T2DM) have higher risk of H. pylori eradication failure than the non-diabetic one (OR = 2.59, 95% CI 1.82-3.70). Body mass index (BMI) was identified as a major factor affecting the efficacy of H. pylori eradication in diabetics, and better glycemic control was also found in eradication succeed patients (WMD: 0.51, 95% CI 0.20-0.81). Moreover, after eradication of H. pylori, improvement of HbA1c was proved (WMD = -0.33, 95% CI -0.65 to -0.02) in T2DM. CONCLUSION: A higher risk of H. pylori eradication failure in T2DM was confirmed, and it was associated with BMI and glycemic control. Moreover, we also provided evidence that H. pylori eradication could improve glycemic control in patients with T2DM, which indirectly reflect the interaction between H. pylori and the diabetes.

Insulin-like growth factor binding protein 1 ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Insulin-like growth factor binding protein 1 (IGFBP1) is recently proved to be associated with glucose regulation and insulin resistance. However, little is known about its direct impact on nonalcoholic fatty liver disease (NAFLD). This study aims to investigate the effect and potential mechanism of IGFBP1 in NAFLD. METHODS: We first measured the expression level of IGFBP1 in NAFLD patients, mice, and cells. Then in in vivo study, C57BL/6 mice were fed with a methionine/choline-deficient (MCD) diet for 4 weeks to establish the model of NAFLD. And for the last 2 weeks, the mice were injected intraperitoneally with vehicle or recombinant mouse IGFBP1 0.015 mg/kg/d. The L02 cells were treated with free fatty acids (FFA) or palmitate acids (PA) and recombinant IGFBP1 for 48 h. Integrin-linked kinase (ILK) inhibitor and small interfering RNA were used to explore the potential interactions between IGFBP1 and integrin ß1 (ITGB1). RESULTS: The expression of IGFBP1 was increased in NAFLD patients, mice, and cells. IGFBP1 treatment significantly ameliorated lipid accumulation and hepatic injury in MCD-fed mice. IGFBP1 downregulated hepatic lipogenesis and upregulated lipid ß-oxidation. In addition, IGFBP1 attenuated the nuclear factor-kappa B (NF-κB) and extracellular regulated protein kinases (ERK) signaling pathways. In vitro, we proved that IGFBP1 relieved FFA-induced lipid accumulation via interacting with ITGB1 and alleviated inflammation by inhibiting NF-κB and ERK signaling pathways. CONCLUSIONS: IGFBP1 treatment significantly ameliorated hepatic steatosis by interacting with ITGB1 and suppressed inflammation by inhibiting NF-κB and ERK signaling pathways. Therefore, IGFBP1 might be a potential therapeutic target for NAFLD.

Long noncoding RNA FLRL2 alleviated nonalcoholic fatty liver disease through Arntl-Sirt1 pathway.

Nonalcoholic fatty liver disease (NAFLD), which has an unknown pathogenesis and lacks a curative treatment, is becoming more prevalent. A previous long noncoding RNA (lncRNA) profiling analysis revealed a potential role for fatty liver-related lncRNA 2 (FLRL2) in the pathogenesis of NAFLD. To further understand the role of FLRL2 in NAFLD and explore its therapeutic value, both in vivo and in vitro NAFLD models were constructed. Small interfering RNA and small hairpin RNA interference and adenovirus transfection were adopted to manipulate the expressions of FLRL2, aryl-hydrocarbon receptor nuclear translocator-like (Arntl), and sirtuin 1 (Sirt1) expression. Steatosis was evaluated through histologic staining with hematoxylin and eosin and oil red O and also by quantitative triglyceride measurements. FLRL2 is a widely distributed nuclear lncRNA that is down-regulated in NAFLD. Overexpression of FLRL2 resolved steatosis, lipogenesis, inflammation, and endoplasmic reticulum (ER) stress in NAFLD, and down-regulation of FLRL2 resulted in the opposite effects. Sequence analysis demonstrated that FLRL2 was located in the intronic region of the Arntl gene, and a luciferase assay showed transcriptional activation of the Arntl gene upon FLRL2 overexpression. A similar expression pattern and synergistic effect of Arntl manipulation was observed in NAFLD in vitro. Inhibition of Arntl partially reversed the steatosis amelioration induced by FLRL2 overexpression. Downstream Sirt1 was also inhibited in NAFLD and influenced by both FLRL2 and Arntl. In NAFLD mice, FLRL2 enhancement alleviated steatosis, activated the Arntl-Sirt1 axis, and inhibited lipogenesis, ER stress, and inflammation, providing preliminary evidence of the benefits of FLRL2-mediated gene therapy in NAFLD.-Chen, Y., Chen, X., Gao, J., Xu, C., Xu, P., Li, Y., Zhu, Y., Yu, C. Long noncoding RNA FLRL2 alleviated nonalcoholic fatty liver disease through Arntl-Sirt1 pathway.

Regio- and Enantioselective Friedel-Crafts Benzhydrylation of Indoles in Carbocyclic Ring with ortho-Quinomethanes: Access to Chiral Diarylindolylmethanes.

The functionalization of indoles in the carbocyclic ring has been achieved via organocatalytic enantioselective Friedel-Crafts benzhydrylation of hydroxyindoles with in situ generated ortho-quinomethanes in oil-water biphases, allowing an efficient access to varied diarylindolylmethanes with a wide substrate scope. The high yields, excellent stereoselectivities, mild conditions, low catalyst loading, and easy scalability also demonstrated the interest of this novel methodology.

Regioselective catalytic asymmetric N-alkylation of isoxazol-5-ones with para-quinone methides.

A highly regioselective and enantioselective N-alkylation of isoxazol-5-ones with para-quinone methides promoted by bi-functional squaramide catalysts was developed. This unexpected asymmetric N-addition of isoxazolinones afforded a series of enantioenriched N-diarylmethane substituted isoxazolinones with high yields and enantioselectivities (up to 97 : 3 er). This reaction not only provides a useful approach for intermolecular chiral C-N bond formation but also demonstrates the immense potential of isoxazol-5-ones as N-nucleophiles in catalytic asymmetric reactions.

Identification and characterization of a novel natural recombinant avian leucosis virus from Chinese indigenous chicken flock.

Avian leukosis virus (ALV) caused tremendous economic losses to poultry industry all over the world, especially in China. One natural recombinant ALV strain, designated as HB2015032, was isolated from indigenous chickens with neoplastic diseases in Hubei, China. The complete proviral genome of HB2015032 is 7703 bp in length. Sequence analysis showed that the Env of HB2015032 exhibited 99.3% similarity with that of a ALV subgroup K (ALV-K) isolate JS11C1 at amino acid level. Phylogenetic analysis revealed that both gp85 and gp37 of HB2015032 were clustered in the same branch with JS11C1 and other ALV-K strains isolated from Chinese indigenous chickens in recent years. However, the pol gene, the 3' untranslated region (3' UTR), and the 3' long terminal repeat (3' LTR) of HB2015032 were more closely related to ALV-J prototype HPRS-103, and clustered in the same branch with ALV-J strains. Furthermore, the pol gene of HB2015032 contained a premature stop codon that resulted in a truncated Pol protein with 22 amino acid residues missing, which was a unique feature of the pol gene of ALV-J. 3'UTR of HB2015032 containing entire DR1, E element and U3. E element of HB2015032 contained one base deletion, which resulted in a c-Ets-1 binding site. In addition, U3 region of HB2015032 contains most of the transcription regulatory elements of ALV-J, including two CAAT boxes, Y boxes, CArG boxes, PRE boxes, NFAP-1 boxes, and one TATA box. These results suggest that isolate HB2015032 was a novel recombinant ALV-K containing the ALV-K env gene and the ALV-J backbone and exhibiting high pathogenicity.

The relationship of antioxidant components and antioxidant activity of sesame seed oil.

Although sesame seed oil contains high levels of unsaturated fatty acids and even a small amount of free fatty acids in its unrefined flavored form, it shows markedly greater stability than other dietary vegetable oils. The good stability of sesame seed oil against autoxidation has been ascribed not only to its inherent lignans and tocopherols but also to browning reaction products generated when sesame seeds are roasted. Also, there is a strong synergistic effect among these components. The lignans in sesame seed oil can be categorized into two types, i.e. inherent lignans (sesamin, sesamolin) and lignans mainly formed during the oil production process (sesamol, sesamolinol, etc.). The most abundant tocopherol in sesame seed oil is γ-tocopherol. This article reviews the antioxidant activities of lignans and tocopherols as well as the browning reaction and its products in sesame seed and/or its oil. It is concluded that the composition and structure of browning reaction products and their impacts on sesame ingredients need to be further studied to better explain the remaining mysteries of sesame oil.

Contrasting effects of river inflow and seawater intrusion on zooplankton community structure in Jiaozhou bay, the Yellow Sea.

Environmental changes associated with river inflow and seawater intrusion are known to affect zooplankton communities in coastal systems, but how zooplankton respond to these environmental changes remains unclear at present. Here we explored the effects of river inflow and seawater intrusion on zooplankton community structure in Jiaozhou Bay. The results showed that the river inflow and seawater intrusion are key in driving zooplankton dynamics, but with contrasting effects. According to the distinct hydrographic conditions, the sampling area could be geographically divided into the river inflow area with low-salinity and high-nutrient conditions (i.e., EIZ) and the seawater intrusion zone with high-salinity and low-nutrient conditions (i.e., SIZ). There were significant differences in zooplankton communities (e.g., abundance and species composition) between the two regions with seasonal changes. For example, the zooplankton abundance was significantly higher in the SIZ than in the EIZ during spring, whereas an opposite pattern was observed for the summer season. In contrast, the species richness was higher in the EIZ than in the SIZ in spring, while an opposite variation trend was observed during summer. These results together suggested that the river inflow and seawater intrusion had contrasting effects on zooplankton community structure in different seasons. According to the canonical correspondence analysis, we observed that the zooplankton community structure was mainly driven by temperature, chlorophyll a (Chl a), and nutrients in the EIZ, but it was largely affected by salinity in the SIZ. The implication is that changes in temperature, Chl a, and nutrients as a result of river inflow and changes in salinity as a consequence of seawater intrusion are key in driving the dynamics of zooplankton communities in Jiaozhou Bay.

Key determinants controlling the seasonal variation of coastal zooplankton communities: A case study along the Yellow Sea.

Zooplankton play key top-down and bottom-up regulatory roles in aquatic food webs, and are also ecologically indicative in marine ecosystems. However, there are relatively limited data on the effects of environmental changes on natural zooplankton communities, especially in coastal ecosystems. In the present study, we systematically evaluated the potential effects of various environmental variables, such as temperature, salinity, and nutrients, on the zooplankton communities along the coastal Yellow Sea during spring, summer, and fall. The results showed that the average abundance of zooplankton decreased in general from spring to autumn, but the biomass exhibited a different seasonal variation trend, with the highest in summer and the lowest in fall. Throughout the three seasons, copepods were the most dominant species within the zooplankton communities, followed by Pelagic larvae and Hydromedusae. However, Noctiluca miliaris accounted for a large proportion of zooplankton abundance during spring. Moreover, the correlation analysis was applied to explore the potential effects of environmental factors on the seasonal variation of zooplankton communities. The results showed that chlorophyll a (Chl a) and salinity were significantly correlated with zooplankton abundance and biomass during spring. The implication is that high phytoplankton biomass (expressed as Chl a) and salinity would benefit the growth of zooplankton in spring. During summer and fall, the effects of dissolved inorganic phosphate (DIP) on the zooplankton abundance and biomass showed a significant positive correlation, indicating that zooplankton were better able to tolerate high DIP during summer and fall. Taken together, Chl a, salinity, and DIP may be the key determinants controlling the seasonal dynamics of zooplankton communities in the coastal Yellow Sea.

Diffusion Depth and Efficacy of Different Infiltration Times for Rose Bengal/Green Light Corneal Cross-linking in Rabbit Eyes.

PURPOSE: To explore the diffusion depth and green light corneal cross-linking efficacy of different rose bengal (Rb) infiltration times in rabbit eyes. METHODS: Twenty-eight fresh rabbit eyes were deepithelialized and infiltrated in 0.1% Rb solution for 2 to 30 minutes. Corneal frozen sections were cut and Rb diffusion depth was observed under the confocal microscope. A further 36 rabbits were randomly divided into eight groups according to the type of treatment (control, Rb infiltration only without irradiation, rose bengal/green light [RGX] for different infiltration times, or riboflavin/ultraviolet radiation [UVX]). The corneas' resistance to keratolysis and biomechanical properties were measured after treatment. RESULTS: After 2, 10, 20, and 30 minutes of infiltration, Rb penetration depths in the corneal stroma were 100, 150, 200, and 270 µm, respectively. The times for complete digestion of the RGX 10 minutes (14.0 ± 1.4 hours), RGX 20 minutes (18.8 ± 1.1 hours), and UVX (51.2 ± 7.2 hours) groups were statistically greater than that of the control group (7.2 ± 1.1 hours). At 10% extension, the Young's modulus of the RGX 20 minutes (36.59 ± 4.90 MPa) and UVX (40.89 ± 2.57 MPa) groups was statistically greater than that of the control group (21.76 ± 5.69 MPa). CONCLUSIONS: The diffusion depth of Rb in corneal stroma increased by prolonging the infiltration time. The longer the infiltration time, the better the RGX effect. RGX for 20 minutes showed the best cross-linking efficacy among all RGX groups, albeit not as good as UVX. [J Refract Surg. 2023;39(9):620-626.].

A20 Enhances the Expression of the Proto-Oncogene C-Myc by Downregulating TRAF6 Ubiquitination after ALV-A Infection.

Hens infected with avian leukosis virus subgroup A (ALV-A) experience stunted growth, immunosuppression, and potentially, lymphoma development. According to past research, A20 can both promote and inhibit tumor growth. In this study, DF-1 cells were infected with ALV-A rHB2015012, and Gp85 expression was measured at various time points. A recombinant plasmid encoding the chicken A20 gene and short hairpin RNA targeting chicken A20 (A20-shRNA) was constructed and transfected into DF-1 cells to determine the effect on ALV-A replication. The potential signaling pathways of A20 were explored using bioinformatics prediction, co-immunoprecipitation, and other techniques. The results demonstrate that A20 and ALV-A promoted each other after ALV-A infection of DF-1 cells, upregulated A20, inhibited TRAF6 ubiquitination, and promoted STAT3 phosphorylation. The phosphorylated-STAT3 (p-STAT3) promoted the expression of proto-oncogene c-myc, which may lead to tumorigenesis. This study will help to further understand the tumorigenic process of ALV-A and provide a reference for preventing and controlling ALV.

Enhanced pathogenicity by up-regulation of A20 after avian leukemia subgroup a virus infection.

Avian leukemia virus subgroup A (ALV-A) infection slows chicken growth, immunosuppression, and tumor occurrence, causing economic loss to the poultry industry. According to previous findings, A20 has a dual role in promoting and inhibiting tumor formation but has rarely been studied in avians. In this study, A20 overexpression and shRNA interference recombinant adenoviruses were constructed and inoculated into chicken embryos, and ALV-A (rHB2015012) was inoculated into 1-day-old chicks. Analysis of body weight, organ index, detoxification, antibody production, organ toxin load, and Pathological observation revealed that A20 overexpression could enhance ALV-A pathogenicity. This study lays the foundation for subsequent exploration of the A20-mediated tumorigenic mechanism of ALV-A.

Caveolin-1 Alleviates Crohn's Disease-induced Intestinal Fibrosis by Inhibiting Fibroblasts Autophagy Through Modulating Sequestosome 1.

BACKGROUND: Intestinal fibrosis is a common complication of Crohn's disease (CD) and is characterized by the excessive accumulation of extracellular matrix produced by activated myofibroblasts. Caveolin-1 (CAV1) inhibits fibrosis. However, limited data show that CAV1 affects intestinal fibrosis. METHODS: Human CD tissue samples were gained from patients with CD who underwent surgical resection of the intestine and were defined as stenotic or nonstenotic areas. A dextran sodium sulfate-induced mouse model of intestinal fibrosis was established. For in vitro experiments, we purchased CCD-18Co intestinal fibrosis cells and isolated and cultured human primary colonic fibroblasts. These fibroblasts were activated by transforming growth factor ß administration for 48 hours. In the functional experiments, a specific small interfering RNA or overexpression plasmid was transfected into fibroblasts. The messenger RNA levels of fibrosis markers, such as α-smooth muscle actin, fibronectin, connective tissue growth factor, and collagen I1α, were determined using quantitative polymerase chain reaction. Western blot analysis was applied to detect the expression of CAV1, SQSTM1/p62 (sequestosome 1), and other fibrosis markers. RESULTS: In human CD samples and the dextran sodium sulfate-induced mouse model of intestinal fibrosis, we observed a downregulation of CAV1 in fibrosis-activated areas. Mechanistically, CAV1 knockdown in both human primary colonic fibroblasts and CCD-18Co cells promoted fibroblast activation, while CAV1 overexpression inhibited fibroblast activation in vitro. We found that SQSTM1/p62 positively correlated with CAV1 expression levels in patients with CD and that it was indirectly modulated by CAV1 expression. Rescue experiments showed that CAV1 decreased primary human intestinal fibroblast activation by inhibiting fibroblast autophagy through the modulation of SQSTM1/p62. CONCLUSIONS: Our data demonstrate that CAV1 deficiency induces fibroblast activation by indirectly regulating SQSTM1/p62 to promote fibroblast autophagy. CAV1 or SQSTM1/p62 may be potential therapeutic targets for intestinal fibrosis.

Intestinal fibrosis is a common complication of Crohn's disease. In human Crohn's disease samples and a mouse model of intestinal fibrosis, we observed a downregulation of caveolin-1 (CAV1) in fibrosis-activated areas. Mechanistically, CAV1 deficiency induces fibroblast activation by indirectly regulating SQSTM1/p62 (sequestosome 1) to promote fibroblast autophagy. CAV1 or SQSTM1/p62 may be potential therapeutic targets for intestinal fibrosis.