Current knowledge on the epidemiology and prevention of Avian leukosis virus in China.

Avian leukosis virus (ALV) is an enveloped retrovirus with a single-stranded RNA genome, belonging to the genus Alpharetrovirus within the family Retroviridae. The disease (Avian leukosis, AL) caused by ALV is mainly characterized by tumor development and immunosuppression in chickens, which increases susceptibility to other pathogens and leads to significant economic losses in the Chinese poultry industry. The government and poultry industry have made lots of efforts to eradicate ALV, but the threat of which remains not vanished. This review provides a summary of the updated understanding of ALV in China, which mainly focuses on genetic and molecular biology, epidemiology, and diagnostic methods. Additionally, promising antiviral agents and ALV eradication strategies performed in China are also included.

SIRT1 silencing promotes EMT and Crizotinib resistance by regulating autophagy through AMPK/mTOR/S6K signaling pathway in EML4-ALK L1196M and EML4-ALK G1202R mutant non-small cell lung cancer cells.

Most EML4-ALK rearrangement non-small cell lung cancer (NSCLC) patients inevitably develop acquired drug resistance after treatment. The main mechanism of drug resistance is the acquired secondary mutation of ALK kinase domain. L1196M and G1202R are classical mutation sites. We urgently need to understand the underlying molecular mechanism of drug resistance to study the therapeutic targets of mutant drug-resistant NSCLC cells. The silent information regulator sirtuin1 (SIRT1) can regulate the normal energy metabolism of cells, but its role in cancer is still unclear. In our report, it was found that the SIRT1 in EML4-ALK G1202R and EML4-ALK L1196M mutant drug-resistant cells was downregulated compared with EML4-ALK NSCLC cells. The high expression of SIRT1 was related to the longer survival time of patients with lung cancer. Activation of SIRT1 induced autophagy and suppressed the invasion and migration of mutant cells. Further experiments indicated that the activation of SIRT1 inhibited the phosphorylation level of mTOR and S6K by upregulating the expression of AMPK, thus activating autophagy. SIRT1 can significantly enhanced the sensitivity of mutant cells to crizotinib, improved its ability to promote apoptosis of mutant cells, and inhibited cell proliferation. In conclusion, SIRT1 is a key regulator of drug resistant in EML4-ALK L1196M and G1202R mutant cells. SIRT1 may be a novel therapeutic target for EML4-ALK drug resistant NSCLC.

Efficacy and safety of esketamine combined with propofol for curative endoscopic resection in colorectum: a prospective, randomized controlled trial.

BACKGROUND: Curative endoscopic resection is widely used to treat colonic polyps and early stage cancers. The anesthetic strategy commonly involves the use of propofol combined with a small dose of opioids for sedation. Adverse respiratory or cardiovascular events such as hypotension often occur when attempting to achieve the necessary level of sedation. Several studies have suggested its advantages owing to the anesthetic, analgesic, and sympathomimetic properties of esketamine. However, there are no reports on curative colorectal endoscopic resection. We designed this randomized controlled trial to assess the efficacy and safety of esketamine combined with propofol for sedation in patients undergoing curative colorectal endoscopic resection. METHODS: A total of 166 patients who underwent curative colorectal endoscopic resection were randomly assigned to groups A (propofol + fentanyl) or E (propofol + esketamine). Ideal sedation was assessed using the MOAA/S scale and was achieved using TCI-propofol with different doses of fentanyl and esketamine. The propofol consumption and vasoactive drug dosages were recorded. Sedation-related times, adverse events, and satisfaction were recorded. RESULTS: Of the 160 patients, the total propofol consumption was significantly lower in group E (n = 81) (300 mg) than in group A (n = 79) (350 mg). Hypotension and bradycardia were significantly lower in Group E than in Group A. The groups showed no significant differences in other adverse events, induction time, recovery time, or patient or endoscopist satisfaction. CONCLUSION: Compared to fentanyl, esketamine helps decrease propofol consumption and increases cardiovascular stability during curative colorectal endoscopic resection in American Society of Anesthesiologists Class I-III patients without affecting anesthesia, patient and endoscopist satisfaction, or other adverse events. TRIAL REGISTRATION: The study was retrospectively registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; registration number: ChiCTR2300069014 on 03/03/2023).

UBE2J1 promotes ALV-A proviral DNA synthesis through the STAT3/IRF1 signaling pathway.

The ubiquitin-binding enzyme E2J1 is located on the endoplasmic reticulum membrane. It plays a role in transport throughout the process of ubiquitination. In mammals, UBE2J1 can promote RNA virus replication. However, the biological function of chicken UBE2J1 is unclear. In this study, chicken UBE2J1 was cloned for the first time, and UBE2J1 overexpression and shRNA knockdown plasmids were constructed. In chicken embryo fibroblasts, overexpression of UBE2J1 promoted the replication of subtype A avian leukosis virus, while knockdown of UBE2J1 inhibited the replication of ALV-A virus. In addition, we divided virus replication into virus adsorption and invasion into DF-1 cells, synthesis of proviral DNA, and release of viral particles. UBE2J1 promoted the replication of ALV-A virus by promoting the synthesis of proviral DNA. This result was caused by UBE2J1 inhibiting the production of interferon by inhibiting the STAT3/IRF1 pathway. We mutated ser at position 184 of UBE2J1 to Gly and found that this site plays a role as the phosphorylation site of UBE2J1. We confirmed that UBE2J1 promotes ALV-A replication in chicken embryo fibroblasts by inhibiting the STAT3/IRF1 pathway. This study provides new ideas and insights into ubiquitin-related proteins and antiviral immunity.

Metabolomic analysis reveals biogenic selenium nanoparticles improve the meat quality of thigh muscle in heat-stressed broilers is related to the regulation of ferroptosis pathway.

Heat stress (HS) causes oxidative damage and abnormal metabolism of muscle, thus impairing the meat quality in broilers. Selenium is an indispensable element for enhancing antioxidant systems. In our previous study, we synthesized a novel type of biogenic selenium nanoparticles synthesized with alginate oligosaccharides (SeNPs-AOS), and found that the particle size of Se is 80 nm and the Se content is 8% in the SeNPs-AOS; and dietary 5 mg/kg SeNPs-AOS has been shown to be effective against HS in broilers. However, whether SeNPs-AOS can mitigate HS-induced the impairment of thigh muscle quality in broilers is still unclear. Therefore, the purpose of this study was to investigate the protective effects of dietary SeNPs-AOS on meat quality, antioxidant capacity, and metabolomics of thigh muscle in broilers under HS. A total of 192 twenty-one-day-old Arbor Acres broilers were randomly divided into 4 groups with 6 replicates per group (8 broilers per replicate) according to a 2 × 2 experimental design: thermoneutral group (TN, broilers raised under 23±1.5°C); TN+SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (broilers raised under 33 ± 2°C for 10 h/d); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). The results showed that HS increased the freezing loss, cooking loss, and malondialdehyde (MDA) content of thigh muscle, whereas decreased the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, as well as downregulated the mRNA expression of SOD2, CAT, GPX3, nuclear factor erythroid 2-related factor 2 (Nrf2), selenoprotein S (SELENOS), solute carrier family 7 member 11 (SLC7A11), GPX4, and ferroportin 1 (Fpn1) of thigh muscle (P < 0.05). Dietary SeNPS-AOS reduced the b* value, elevated the pH0min value and the activities of T-SOD, GSH-Px, glutathione S-transferase (GST) and the mRNA expression levels of GSTT1, GSTA3, GPX1, GPX3, ferritin heavy polypeptide-1 (FTH1), and Fpn1 of thigh muscle in broilers under HS (P < 0.05). Nontargeted metabolomics analysis identified a total of 79 metabolites with significant differences among the four groups, and the differential metabolites were mainly enriched in 8 metabolic pathways including glutathione metabolism and ferroptosis (P < 0.05). In summary, dietary 5 mg/kg SeNPs-AOS (Se content of 8%) could alleviate HS-induced impairment of meat quality by improving the oxidative damage, metabolic disorders and ferroptosis of thigh muscle in broilers challenged with HS. Suggesting that the SeNPs-AOS may be used as a novel nano-modifier for meat quality in broilers raised in thermal environment.

Lipocalin 2-A bone-derived anorexigenic and ß-cell promoting signal: From mice to humans.

The skeleton is traditionally known for its structural support, organ protection, movement, and maintenance of mineral homeostasis. Over the last 10 years, bone has emerged as an endocrine organ with diverse physiological functions. The two key molecules in this context are fibroblast growth factor 23 (FGF23), secreted by osteocytes, and osteocalcin, a hormone produced by osteoblasts. FGF23 affects mineral homeostasis through its actions on the kidneys, and osteocalcin has beneficial effects in improving glucose homeostasis, muscle function, brain development, cognition, and male fertility. In addition, another osteoblast-derived hormone, lipocalin 2 (LCN2) has emerged into the researchers' field of vision. In this review, we mainly focus on LCN2's role in appetite regulation and glucose metabolism and also briefly introduce its effects in other pathophysiological conditions, such as nonalcoholic fatty liver disease, sarcopenic obesity, and cancer-induced cachexia.

Biogenic Selenium Nanoparticles Synthesized Using Alginate Oligosaccharides Attenuate Heat Stress-Induced Impairment of Breast Meat Quality via Regulating Oxidative Stress, Metabolome and Ferroptosis in Broilers.

Selenium (Se) is an indispensable trace element with versatile functions in antioxidant defense in poultry. In our previous study, we synthesized a novel type of biogenic selenium nanoparticle based on alginate oligosaccharides (SeNPs-AOS), and found that the particles are sized around 80 nm with an 8% Se content, and the dietary addition of 5 mg/kg of SeNPs-AOS could effectively alleviate the deleterious effects of heat stress (HS) in broilers, but it is still unclear whether SeNPs-AOS can improve the meat quality. Therefore, the aim of this study was to evaluate the protective effects of SeNPs-AOS on breast meat quality in heat-stressed broilers, and explore the relevant mechanisms. Birds at the age of 21 days were randomly divided into four groups with six replicates per group (eight broilers per replicate) according to a 2 × 2 experimental design, using HS (33 ± 2 °C, 10 h/day vs. thermoneutral, TN, under 23 ± 1.5 °C) and SeNPs-AOS (5 mg/kg feed vs. no inclusion) as variables. The results showed that dietary SeNPs-AOS decreased the cooking loss (p < 0.05), freezing loss (p < 0.001), and shear force (p < 0.01) of breast muscle in heat-stressed broilers. The non-targeted metabolomics analysis of the breast muscle identified 78 differential metabolites between the HS and HS + SeNPs-AOS groups, mainly enriched in the arginine and proline metabolism, ß-alanine metabolism, D-arginine and D-ornithine metabolism, pantothenate, and CoA biosynthesis pathways (p < 0.05). Meanwhile, supplementation with SeNPs-AOS increased the levels of the total antioxidant capacity (T-AOC), the activities of catalase (CAT) and glutathione peroxidase (GSH-Px), and decreased the content of malondialdehyde (MDA) in the breast muscle (p < 0.05) in broilers under HS exposure. Additionally, SeNPs-AOS upregulated the mRNA expression of CAT, GPX1, GPX3, heme oxygenase-1 (HO-1), masculoaponeurotic fibrosarcoma G (MafG), MafK, selenoprotein W (SELENOW), SELENOK, ferritin heavy polypeptide-1 (FTH1), Ferroportin 1 (Fpn1), and nuclear factor erythroid 2-related factor 2 (Nrf2) (p < 0.05), while it downregulated Kelch-like ECH-associated pro-36 tein 1 (Keap1) and prostaglandin-endoperoxide Synthase 2 (PTGS2) expression (p < 0.05) in broilers under HS. These findings demonstrated that the dietary addition of SeNPs-AOS mitigated HS-induced oxidative damage and metabolite changes in the breast muscle of broilers, which may be related to the regulation of the Nrf2 signaling pathway and selenoprotein synthesis. In addition, SeNPs-AOS upregulated the breast muscle gene expression of anti-ferroptosis-related molecules in broilers under HS, suggesting that SeNPs-AOS can be used as novel Se supplements against HS in broilers.

Endothelial progenitor cell-derived exosomes promote anti-inflammatory macrophages via SOCS3/JAK2/STAT3 axis and improve the outcome of spinal cord injury.

BACKGROUND: Macrophage in the spinal cord injury (SCI) area imparts a chronic pro-inflammation effect that challenges the recovery of SCI. Previously, endothelial progenitor cell-produced exosomes (EPC-EXOs) have been noticed to facilitate revascularization and inflammation control after SCI. However, their effects on macrophage polarization remained unclear. This study aimed to investigate the EPC-EXOs' role in macrophage polarization and reveal its underlying mechanism. METHODS: We extracted the macrophages and EPC from the bone marrow suspension of C57BL/L mice by centrifugation. After cell identification, the EPC-EXOs were collected by ultra-high-speed centrifugation and exosome extraction kits and identified by transmission electron microscopy and nanoparticle tracking analysis. Then, macrophages were cultured with EPC-EXOs in different concentrations. We labeled the exosome to confirm its internalization by macrophage and detected the macrophage polarization marker level both in vitro and in vivo. We further estimated EPC-EXOs' protective effects on SCI by mice spinal cord tissue H&E staining and motor behavior evaluation. Finally, we performed RT-qPCR to identify the upregulated miRNA in EPC-EXOs and manipulate its expression to estimate its role in macrophage polarization, SOCS3/JAK2/STAT3 pathway activation, and motor behavior improvement. RESULTS: We found that EPC-EXOs decreased the macrophages' pro-inflammatory marker expression and increased their anti-inflammatory marker expression on the 7 and 14 days after SCI. The spinal cord H&E staining results showed that EPC-EXOs raised the tissue-sparing area rate significantly after 28 days of SCI and the motor behavior evaluation indicated an increased BMS score and motor-evoked potential by EPC-EXOs treatment after SCI. The RT-qPCR assay identified that miR-222-3P upregulated in EPC-EXOs and its miRNA-mimic also decreased the pro-inflammatory macrophages and increased the anti-inflammatory macrophages. Additionally, miR-222-3P mimic activated the SOCS3/JAK2/STAT3 pathway, and SOCS3/JAK2/STAT3 pathway inhibition blocked miR-2223P's effects on macrophage polarization and mouse motor behavior. CONCLUSION: Comprehensively, we discovered that EPC-EXOs-derived miR-222-3p affected macrophage polarization via SOCS3/JAK2/STAT3 pathway and promoted mouse functional repair after SCI, which reveals EPC-EXOs' role in modulation of macrophage phenotype and will provide a novel interventional strategy to induce post-SCI recovery.

Natural Chlorogenic Acid Planted Nanohybrids with Steerable Hyperthermia for Osteosarcoma Suppression and Bone Regeneration.

Surgical resection is the most common approach for the treatment of osteosarcoma. However, two major complications, including residual tumor cells and large bone defects, often arise from the surgical resection of osteosarcoma. Discovering new strategies for programmatically solving the two above-mentioned puzzles has become a worldwide challenge. Herein, a novel one-step strategy is reported for natural phenolic acid planted nanohybrids with desired physicochemical properties and steerable photothermal effects for efficacious osteosarcoma suppression and bone healing. Nanohybrids are prepared based on the self-assembly of chlorogenic acid and gold nanorods through robust Au-catechol interface actions, featuring precise nanostructures, great water solubility, good stability, and adjustable hyperthermia generating capacity. As expected, on the one hand, these integrated nanohybrids can severely trigger apoptosis and suppress tumor growth with strong hyperthermia. On the other hand, with controllable mild NIR irradiation, the nanohybrids promote the expression of heat shock proteins and induce prominent osteogenic differentiation. This work initiates a brand-new strategy for assisting osteosarcoma surgical excision to resolve the blockage of residual tumor cells elimination and bone regeneration.

Effects of Fecal Occult Blood Immunoassay Screening for Colorectal Cancer-Experience from a Hospital in Central Taiwan.

Background and Objectives: In 2004, the Health Administration of Taiwan began to promote a hospital-based cancer screening quality improvement program, under the principle that "prevention is better than therapy". The aim of this study was to evaluate the effectiveness of colorectal cancer (CRC) screening in patients who received a fecal immunochemical test (FIT) at a hospital in central Taiwan. Materials and Methods: This was a retrospective study. Results: Fecal occult blood immunoassays for CRC screening were conducted in 58,891 participants, of whom 6533 were positive (positive detection rate 11.10%). The positive patients then underwent colonoscopy, and the detection rates of polyps and CRC accounted for 53.6% and 2.4% of all colonoscopy-confirmed diagnoses (3607), respectively. We further enrolled data from patients diagnosed with CRC at our hospital from 2010 to 2018. The patients with CRC were divided into two groups according to whether or not they had received fecal occult blood screening. Among the 88 patients with CRC by screening, 54 had detailed medical records including cancer stage. Of these 54 patients, 1 (1.8%) had pre-stage, 11 (20.4%) had stage I, 24 (44.4%) had stage II, 10 (18.5%) had stage III, and 8 (14.8%) had stage IV CRC. The early cancer detection rates of the screening and non-screening groups were 66.7% and 52.7%, respectively, and the difference was significant (p = 0.00130). Conclusions: In this study, screening with FIT significantly increased the early detection of CRC. The main advantage of FIT is the non-invasiveness and low cost. It is hoped that the further adoption of early screening can increase the detection rates of colorectal polyps or early cancer to improve survival, reduce the high cost of subsequent cancer treatment, and reduce the burden on the patient and healthcare system.

Highly Active Hydrogen-rich Photothermal Reverse Water Gas Shift Reaction on Ni/LaInO3 Perovskite Catalysts with Near-unity Selectivity.

Photo-assisted reverse water gas shift (RWGS) reaction is regarded green and promising in controlling the reaction gas ratio in Fischer Tropsch synthesis. But it is inclined to produce more byproducts in high H2 concentration condition. Herein, LaInO3 loaded with Ni-nanoparticles (Ni NPs) was designed to obtain an efficient photothermal RWGS reaction rate, where LaInO3 was enriched with oxygen vacancies to roundly adsorbing CO2 and the strong interaction with Ni NPs endowed the catalysts with powerful H2 activity. The optimized catalyst performed a large CO yield rate (1314 mmol gNi -1 h-1 ) and ≈100 % selectivity. In situ characterizations demonstrated a COOH* pathway of the reaction and photoinduced charge transfer process for reducing the RWGS reaction active energy. Our work provides valuable insights on the construction of catalysts concerning products selectivity and photoelectronic activating mechanism on CO2 hydrogenation.

The effects of vitamin B6 on the nutritional support of BCAAs-enriched amino acids formula in rats with partial gastrectomy.

BACKGROUND: Total parenteral nutrition with the formula of amino acids enriched branched-chain amino acids (BCAAs) could promote patients' recovery after gastrointestinal surgery. Previous studies reported that vitamin B6 could promote amino acid metabolism and enhance protein synthesis. The aim of this study was to determine if the addition of vitamin B6 to BCAAs-enriched formula can enhance postoperative nutritional status and intestinal function in rats undergoing partial gastrectomy, and the appropriate compatibility concentration of vitamin B6. METHODS: Fifty-six male rats were randomly divided into seven groups (n = 8 per group): (I) Control, (II) BCAAs-enriched formula group (BCAA), (III) BCAA plus vitamin B6 (50 mg/L), (IV) BCAA plus vitamin B6 (100 mg/L), (V) BCAA plus vitamin B6 (200 mg/L), (VI) BCAA plus vitamin B6 (500 mg/L), and (VII) BCAA plus vitamin B6 (1000 mg/L). All animals were performed partial gastrectomy and placed a jugular vein catheter. During enteral nutrition, blood and urine samples were repeatedly collected. Gastrocnemius muscle and small intestine were also collected at the end of experiment. RESULTS: The addition of vitamin B6 to BCAAs-enriched formula improved negative nitrogen balance after gastrectomy compared to the BCAAs-enriched formula group at POD1 (first postoperative day) and POD3 (third postoperative day), and 100 mg/L was an appropriate concentration of vitamin B6 to enhance the effects of BCAAs-enriched formula. The 3-methylhistidine/creatinine in BCAA plus vitamin B6 groups were significantly lower than that in the BCAA group at POD3. Moreover, BCAA plus vitamin B6 group significantly increased the cross-sectional area of the muscle fibers compared to the BCAA group. Transcriptome sequencing, GO and KEGG enhancement analysis also showed that BCAA plus vitamin B6 group showed muscle organ development and PI3K/AKT pathway enhancement compared to BCAA group. Moreover, AKT/mTOR/4EBP1 pathway was activated in BCAA plus vitamin B6 group. In addition, the results also showed that BCAA plus vitamin B6 decreased D-lactate, and exerted synergistic effects on intestinal morphology. CONCLUSION: The addition of vitamin B6 to BCAAs-enriched formula could improve nitrogen balance, promote muscle protein synthesis through AKT/mTOR/4EBP1 pathway, and alleviate intestinal mucosa damage after partial gastrectomy in rats. Overall, the results from this pre-clinical study support the use of vitamin B6 as an ingredient to BCAAs-enriched formula, and 100 mg/L may be an optimal concentration for rats.

ZYY-B-2, a novel ALK inhibitor, overcomes resistance to ceritinib by inhibiting P-gp function and induces apoptosis through mitochondrial pathway in ceritinib-resistant H2228 cells.

Targeting the Echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) fusion gene is a promising therapeutic strategy for non-small-cell lung cancer (NSCLC) patients. With the advent of the first- and second-generation ALK inhibitors, the mortality rate of lung cancer has shown a downward trend, but almost inevitably, patients will eventually develop resistance, which severely limits the clinical application. Hence, developing new ALK inhibitors which can overcome resistance is essential. Here, we synthesized a novel ALK inhibitor 1-[4-[[5-Chloro-4-[[2-[(1-methylethyl)sulfonyl]phenyl]amino]-2-pyrimidinyl]amino]-3-methoxyphenyl]-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-imidazolidinone (ZYY-B-2) based on the structure of the second-generation ALK inhibitor ceritinib. ZYY-B-2 exhibited impressive anti-proliferative effect in the EML4-ALK positive H2228 cells and ceritinib-resistant H2228 (H2228/Cer) cells. Meanwhile, ZYY-B-2 inhibited the activation of p-ALK in a concentration-dependent manner, and inactivated its downstream target proteins p-AKT and p-ERK to inhibit cell proliferation. Subsequently, we found that ZYY-B-2 blocked H2228 cells and H2228/Cer cells in G0/G1 phase and induced cells to undergo apoptosis through the mitochondrial pathway. The ability of its anti-proliferation and pro-apoptosis was significantly stronger than the second generation ALK inhibitor ceritinib. In addition, high expression of P-gp was found in H2228/Cer cells compared with H2228 cells. ZYY-B-2 could inhibit the expression of P-gp in a dose-dependent manner to overcome ceritinib resistance, and the suppression effect of ZYY-B-2 on P-gp might be related to its inhibition of PI3K/AKT signaling pathway. In summary, ZYY-B-2, a promising ALK inhibitor, shows potent activity against ceritinib-resistant cells, which provides experimental and theoretical basis for the further development of new ALK inhibitors.

Machine learning-based model for predicting the esophagogastric variceal bleeding risk in liver cirrhosis patients.

BACKGROUND: Liver cirrhosis patients are at risk for esophagogastric variceal bleeding (EGVB). Herein, we aimed to estimate the EGVB risk in patients with liver cirrhosis using an artificial neural network (ANN). METHODS: We included 999 liver cirrhosis patients hospitalized at the Beijing Ditan Hospital, Capital Medical University in the training cohort and 101 patients from Shuguang Hospital in the validation cohort. The factors independently affecting EGVB occurrence were determined via univariate analysis and used to develop an ANN model. RESULTS: The 1-year cumulative EGVB incidence rates were 11.9 and 11.9% in the training and validation groups, respectively. A total of 12 independent risk factors, including gender, drinking and smoking history, decompensation, ascites, location and size of varices, alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), hematocrit (HCT) and neutrophil-lymphocyte ratio (NLR) levels as well as red blood cell (RBC) count were evaluated and used to establish the ANN model, which estimated the 1-year EGVB risk. The ANN model had an area under the curve (AUC) of 0.959, which was significantly higher than the AUC for the North Italian Endoscopic Club (NIEC) (0.669) and revised North Italian Endoscopic Club (Rev-NIEC) indices (0.725) (all P <  0.001). Decision curve analyses revealed improved net benefits of the ANN compared to the NIEC and Rev-NIEC indices. CONCLUSIONS: The ANN model accurately predicted the 1-year risk for EGVB in liver cirrhosis patients and might be used as a basis for risk-based EGVB surveillance strategies.

A polypeptide coating for preventing biofilm on implants by inhibiting antibiotic resistance genes.

Aging population has been boosting the need for orthopedic implants. However, biofilm has been a major obstacle for orthopedic implants due to its insensitivity to antibiotics and tendency to drive antimicrobial resistance. Herein, an antibacterial polypeptide coating with excellent in vivo adhesive capacity was prepared to prevent implants from forming biofilms and inducing acquired antibiotic resistance. A peptide-based copolymer, poly[phenylalanine10-stat-lysine12]-block-3,4-dihydroxy-l-phenylalanine [Poly(Phe10-stat-Lys12)-DOPA] was modularly designed, where poly(Phe10-stat-Lys12) is antibacterial polypeptide with high antibacterial activity, and DOPA provides strong adhesion in both wet and dry microenvironments. Meanwhile, compared to traditional "graft-onto" methods, this antibacterial coating can be facilely achieved by immersing Titanium substrates into antibacterial polypeptide solution for 5 min at room temperature. The poly(Phe10-stat-Lys12)-DOPA polymer showed good antibacterial activity with minimum inhibitory concentrations against S. aureus and E. coli of 32 and 400 µg/mL, respectively. Compared to obvious antimicrobial resistance of S. aureus after continuous treatment with vancomycin, this antibacterial coating doesn't drive antimicrobial resistance upon long-term utilization. Transcriptome sequencing and qPCR tests further confirmed that the antibacterial coating was able to inhibit the expression of multiple peptide resistance factor (mprF) and lipoteichoic acid modification D-alanylation genes (dltB and dltC) that can increase the net positive charge of bacterial cell wall to induce the resistance to cationic antimicrobial peptides. In vivo experiments confirmed that this poly(Phe10-stat-Lys12)-DOPA coating can both effectively prevent biofilm formation through surface contact sterilization and avoid local and systemic infections. Overall, we proposed a facile method for preparing antibacterial orthopedic implants with longer indwelling time and without inducing antimicrobial resistance by coating a polypeptide-based polymer on the implants.

FAT4 activation inhibits epithelial-mesenchymal transition (EMT) by promoting autophagy in H2228/Cer cells.

As a tumor suppressor in lung cancer, FAT atypical cadherin 4 (FAT4) has a critical role in epithelial-mesenchymal transition (EMT). However, the role of FAT4 in ceritinib-resistant anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) EMT has not been reported. It is necessary to discuss the role of FAT4 in this process and its potential mechanism of interaction. We found that the expression level of FAT4 was downregulated markedly in ceritinib-resistant NCI-H2228 (H2228/Cer) cells. Jujuboside A, a FAT4 activator, diminished EMT and metastasis of H2228/Cer cells. Importantly, autophagy inhibition inverted the inhibitory effect of FAT4 activation on EMT. Furthermore, we found the regulatory action of FAT4 on autophagy was related to proteasome 26S subunit ubiquitin receptor and non-ATPase 4 (PSMD4) and proteasome 20S subunit beta 4 (PSMB4), and the inhibitory effect of autophagy on EMT might be related to ROS/NF-κB/IκB-α and Wnt/ß-catenin pathways. In conclusion, FAT4 activation can inhibit the process of EMT in H2228/Cer cells by promoting autophagy, which provides a potential target for ceritinib-resistant ALK positive NSCLC therapy.

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.

Network-based pharmacology and molecular docking exploring the "Bupleuri Radix-Scutellariae Radix" mechanism of action in the viral hepatitis B treatment.

Viral hepatitis B is caused by the hepatitis B virus, which is characterized by liver lesions. Bupleuri Radix and Scutellariae Radix are the main traditional medicine pairs with remarkable efficacy in hepatitis B. However, their molecular mechanisms are incompletely understood. The main active components of Bupleuri Radix and Scutellariae Radix, as well as therapeutic targets for the treatment of hepatitis B, were identified through network pharmacology techniques. We identified viral hepatitis B targets using the GeneCards, online mendelian inheritance in man, and therapeutic target databases. We discovered the active components of Bupleuri Radix and Scutellariae Radix as well as therapeutic targets using the encyclopedia of traditional Chinese medicine, HERB, traditional Chinese medicine systems pharmacology database, and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. VENNY obtained the intersections. Cytoscape and STRING were used to create the "active ingredient-potential target" network and protein interaction network. The DAVID database was used to enrich GO and KEGG pathways. The results were confirmed using the molecular docking method. There were 1827 viral hepatitis B targets, and 37 active ingredients for Bupleuri and Scutellariae Radix, with the main components being quercetin, wogonin, baicalein, and kaempferol. Tumor necrosis factor (TNF), mitogen-activated protein kinase 3 (MAPK3), interleukin-6 (IL-6), vascular endothelial growth factor A, cysteinyl aspartate specific proteinase 3, transcription factor AP-1 (JUN), RAC-alpha serine/threonine-protein kinase, and cellular tumor antigen p53 are among the 78 common targets of Bupleuri Radix and Scutellariae Radix intervention in viral hepatitis B. KEGG enrichment resulted in 107 pathways, including cancer, hepatitis B, and TNF signaling pathways. According to the molecular docking technique, quercetin, wogonin, baicalein, and kaempferol had strong binding activities with TNF, MAPK3, and IL-6. In this study, we initially identified various molecular targets and multiple pathways involved in hepatitis B treatment with Bupleuri Radix and Scutellariae Radix.

Isolation and characterization of avian leukosis virus subgroup J associated with hemangioma and myelocytoma in layer chickens in China.

A strain of avian leukosis virus (ALV) belonging to a new envelope subgroup J (ALV-J) emerged in 1988 as a new subgroup of ALV and spread rapidly throughout the world. Due to the infection and spread of ALV-J, the global poultry industry experienced a significant loss. Although the disease had been prevented and controlled effectively by culling domestic chickens in the infected zone, a few field cases of ALV-J infection were reported in China in recent years. This study was conducted to characterize the genome and analyze the lesions and histopathology of the ALV-J strain named HB2020, which was isolated from layer chickens in Hubei Province, China. The full-length proviral genome sequence analysis of ALV-J HB2020 revealed that it was a recombinant strain of ev-1 and HPRS-103 in the gag gene in comparison to ALV-J prototype HPRS-103. In the 3'-untranslated region (3'UTR) of the nucleotide sequence, there were found 205-base pairs (bp) deletion, of which 175 were detected in the redundant transmembrane (rTM) region. Besides, the surface glycoprotein gene gp85 had five mutations in a conservative site, whereas the transmembrane protein gene gp37 was relatively conserved. The animal experiments conducted later on this strain have shown that HB2020 can cause various neoplastic lesions in chickens, including enlarged livers with hemangiomas and spleens with white nodules. Additionally, as the exposure time increased, the number of tumor cells that resembled myelocytes in the blood smears of infected chickens gradually increased. These results indicated that HB2020 on recombination with ALV subgroup E (ALV-E) and ALV-J could induce severe hemangiomas and myelocytomas. This inference might provide a molecular basis for further research about the pathogenicity of ALV and emphasize the need for control and prevention of avian leukosis.

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.