Complexes Based on Zinc and Cadmium for Visible Light-Driven Hydrogen Production.

Photocatalytic water decomposition using solar energy is one of the most effective hydrogen production technologies. The development of a structurally stable photocatalyst for hydrogen production without cocatalysts and photosensitizers remains a great challenge. In this paper, complex photocatalyst compounds 1 and 2 with different crystal structures were designed and obtained by connecting the 4'-(2,4-disulfophenyl)-4,2':6',4″-terpyridine organic ligands with Zn(Ac)2·2H2O and CdCO3. These products were used for photocatalytic hydrogen production separately, and the hydrogen production rates of compounds 1 and 2 were 0.66 mol·mol-1·h-1 and 0.12 mol·mol-1·h-1, respectively, without the addition of any cocatalysts and photosensitizers, and their charge separation and transfer processes were verified by PL, time-resolved PL, and photocurrent. Compound 1 was tested in 6 cycles over 18 h and showed high stability and reproducibility.

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

BACKGROUND: Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. METHODS: The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. RESULTS: NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712-0.896), sensitivity of 0.892 (95% CI: 0.856-0.923) and specificity of 0.564 (95% CI: 0.512-0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724-0.861), sensitivity of 0.874 (95% CI: 0.843-0.905) and specificity of 0.534 (95% CI: 0.512-0.556). Lymphatic metastasis ([95% CI: 1.435-5.461], [95% CI: 1.336-4.281], depth of invasion ([95% CI: 1.281-3.546], [95% CI: 1.183-3.359]) and tumour size ([95% CI: 1.129-3.451], [95% CI: 1.129-3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. CONCLUSION: NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy were retrospectively analysed. Receiver operating characteristic curves showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly associated with the therapeutic effects of neoadjuvant therapy. Univariate and multivariate regression analysis revealed that lymphatic metastasis, depth of invasion and tumour size were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR and PLR in the peripheral blood before treatment may predict the DFS of patients with stage IB2-IIB cervical cancer.

M2 macrophages regulate KDM6B/PFKFB2 metabolic reprogramming of cervical squamous cell carcinoma through CXCL1.

Macrophages in the tumor microenvironment can polarize into M1 or M2 forms, with M2 macrophages (M2φ) promoting tumor growth and metastasis in cervical squamous cell carcinoma (CESC). This study explored the effects of M2φ on CESC metabolic reprogramming both in vitro and in vivo. Results showed that M2φ secreted CXCL1, which significantly increased CESC migration and metabolic regulation. Further experiments revealed that CXCL1 upregulated KDM6B to enhance PFKFB2 transcriptional activity, thus regulating CESC glucose metabolism. Transcriptome sequencing screened 5 upregulated genes related to glycolysis, with PFKFB2 showing the most significant increase in cells treated with rCXCL1. Dual-luciferase reporter assay confirmed that rCXCL1 enhances PFKFB2 transcriptional activity. Bioinformatics analysis revealed a high correlation between expressions of KDM6B and PFKFB2 in CESC. Mechanistic experiments demonstrated that KDM6B inhibited H3K27me3 modification to activate PFKFB2 transcriptional expression. In conclusion, M2φ secreted CXCL1 to promote CESC cell migration and invasion, and CXCL1 activated KDM6B expression in CESC cells, inhibiting H3K27 protein methylation modification, and enhanced PFKFB2 transcriptional activity to regulate CESC glucose metabolism. These results provided new insights into the complex interplay between the immune system and cancer metabolism, which may have broader implications for understanding and treating other types of cancer.

Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer.

Inter- and intra-tumor heterogeneity is a major hurdle in primary liver cancer (PLC) precision therapy. Here, we establish a PLC biobank, consisting of 399 tumor organoids derived from 144 patients, which recapitulates histopathology and genomic landscape of parental tumors, and is reliable for drug sensitivity screening, as evidenced by both in vivo models and patient response. Integrative analysis dissects PLC heterogeneity, regarding genomic/transcriptomic characteristics and sensitivity to seven clinically relevant drugs, as well as clinical associations. Pharmacogenomic analysis identifies and validates multi-gene expression signatures predicting drug response for better patient stratification. Furthermore, we reveal c-Jun as a major mediator of lenvatinib resistance through JNK and ß-catenin signaling. A compound (PKUF-01) comprising moieties of lenvatinib and veratramine (c-Jun inhibitor) is synthesized and screened, exhibiting a marked synergistic effect. Together, our study characterizes the landscape of PLC heterogeneity, develops predictive biomarker panels, and identifies a lenvatinib-resistant mechanism for combination therapy.

DctViT: Discrete Cosine Transform meet vision transformers.

Vision transformers (ViTs) have become one of the dominant frameworks for vision tasks in recent years because of their ability to efficiently capture long-range dependencies in image recognition tasks using self-attention. In fact, both CNNs and ViTs have advantages and disadvantages in vision tasks, and some studies suggest that the use of both may be an effective way to balance performance and computational cost. In this paper, we propose a new hybrid network based on CNN and transformer, using CNN to extract local features and transformer to capture long-distance dependencies. We also proposed a new feature map resolution reduction based on Discrete Cosine Transform and self-attention, named DCT-Attention Down-sample (DAD). Our DctViT-L achieves 84.8% top-1 accuracy on ImageNet 1K, far outperforming CMT, Next-ViT, SpectFormer and other state-of-the-art models, with lower computational costs. Using DctViT-B as the backbone, RetinaNet can achieve 46.8% mAP on COCO val2017, which improves mAP by 2.5% and 1.1% with less calculation cost compared with CMT-S and SpectFormer as the backbone.

Complete genome sequence of a porcine circovirus type 2 strain, PCV2/CN/GD/2018/10, obtained in Guangdong, China, in 2018.

Porcine circovirus type 2 (PCV2) poses significant issue for the global swine industry. We conducted a comprehensive analysis of the complete genome sequence of a Chinese PCV2 strain belonging to genotype PCV2a, which was designated as PCV2/CN/GD/2018/10. Our findings provide insights into the prevalence of PCV2 in China.

Saxagliptin reduces the injury of Alzheimer's disease cell model by down-regulating the expression of miR-483-5p.

This study aimed to investigate the effect of saxagliptin on the injury of Alzheimer's disease (AD) cell model and its possible mechanism. SK-N-SH cells were cultured in vitro and divided into CON group, AD group, AD+L-SAX group, AD+M-SAX group, AD+H-SAX group, AD+anti-miR-NC group, AD+anti-miR-483-5p group, AD+SAX+miR-NC group and AD+SAX+miR-483-5p group. Then the levels of MDA, SOD and GSH-Px in each group were detected by ELISA method; cell apoptosis was detected by flow cytometry; the protein expression levels of Bax and Bcl-2 were detected by Western Blot; the expression level of miR-483-5p was detected by RT-qPCR. Compared with the control group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p increased in the AD group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein decreased (P<0.05). Compared with the AD group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p decreased in the AD+L-SAX group, AD+M-SAX group and AD+H-SAX group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein increased (P<0.05). Compared with AD+anti-miR-NC group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p decreased in the AD+anti-miR-483-5p group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein increased (P<0.05). Compared with AD+SAX+miR-NC group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p increased in the AD+SAX+miR-483-5p group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein decreased (P<0.05). Saxagliptin may reduce the injury of Alzheimer's disease cell model by down-regulating the expression of miR-483-5p.

The Prevalence and Genetic Diversity of Porcine Circoviruses (PCVs) during 2017-2023 in Guangdong Province, China.

Porcine circovirus disease poses a significant threat to the pig farming industry. Globally, four genotypes of porcine circovirus are circulating, with porcine circovirus type 2 and 3 (PCV2 and PCV3) being most strongly associated with clinical manifestations. The recently discovered porcine circovirus type 4 (PCV4) exhibits clinical symptoms resembling porcine dermatitis nephropathy syndrome. This study aimed to assess the prevalence and genetic characteristics of PCVs in Guangdong province, China. A comprehensive analysis was conducted on 193 samples collected from 83 distinct pig farms during the period of 2017-2023. A conventional PCR was employed to investigate the presence of PCV2, PCV3, and PCV4. Among the samples, 56.48%, 8.81%, and 8.81% tested positive for PCV2, PCV3, and PCV2/3 co-infection, respectively. Interestingly, PCV4 was not detected. Whole-genome sequencing was performed on 80 PCV2 isolates and 7 PCV3 isolates. A phylo-genetic analysis revealed that 12 strains belonged to PCV2a, 8 strains belonged to PCV2b, and 60 strains belonged to PCV2d, indicating the prevailing presence of PCV2d in Guangdong province, China. Furthermore, two PCV3 isolates were classified as PCV3a and five strains as PCV3b. Notably, an in-depth analysis of the Cap protein sequence of the PCV2 and PCV3 isolates identified high-frequency mutation sites located in predicted epitope regions. Overall, this study provides valuable insights into the prevalence and evolution of PCV2 and PCV3 during the period of 2017-2023 in Guangdong province, China, thereby contributing to the development of effective prevention and control measures.

Medicine Targeting Epithelial-Mesenchymal Transition to Treat Airway Remodeling and Pulmonary Fibrosis Progression.

Objective. Dysregulation of epithelial-mesenchymal transition (EMT) in the airway epithelium is associated with airway remodeling and the progression of pulmonary fibrosis. Many treatments have been shown to inhibit airway remodeling and pulmonary fibrosis progression in asthma and chronic obstructive pulmonary disease (COPD) by regulating EMT and have few side effects. This review aimed to describe the development of airway remodeling through the EMT pathway, as well as the potential therapeutic targets in these pathways. Furthermore, this study aimed to review the current research on drugs to treat airway remodeling and their effects on the EMT pathway. Findings. The dysregulation of EMT was associated with airway remodeling in various respiratory diseases. The cytokines released during inflammation may induce EMT and subsequent airway remodeling. Various drugs, including herbal formulations, specific herbal compounds, cytokines, amino acid or protein inhibitors, microRNAs, and vitamins, may suppress airway remodeling by inhibiting EMT-related pathways.

Safety of entecavir antiviral therapyduring an accidental pregnancy in patients with chronic hepatitis B.

The present study aimed to investigate the effects of accidental pregnancy CHB patients' reproductive age on their offspring during entecavir (ETV) antiviral therapy. A total of 112 couples were retrospectively enrolled, and they were divided into an observational and control group. A total of 53 couples who had accidental pregnancies while receiving long-term ETV antiviral medication were recruited for the observational group. The control group consisted of 59 couples who became pregnant accidentally while receiving long-term tenofovir disoproxil fumarate (TDF) antiviral treatment. All mothers persisted in their pregnancies in the observational group, and ETV was promptly replaced with TDF. Every mother remained pregnant and continued to use TDF in the control group. The maternal and baby safety profiles, including the prevalence of congenital disabilities, were comparable across the observational and control groups at delivery. In addition, no unusual indications or symptoms of the newborns were noted during the follow-up intervals of 28, 48, and 96 weeks postpartum. Initiating ETV or TDF in early and middle pregnancy seems safe for mothers and infants. Important data from the present study support using ETV in early-mid gestational accidental pregnancies and the prompt substitution of TDF antiviral medication for ETV.

Efficacy evaluation of direct antiviral drugs against hepatitis B virus in improving the degree of liver fibrosis.

Introduction: The aim of the study was to find an ideal index reflecting inflammation and fibrosis for patients after antiviral treatment, and compare it with imaging examination (liver stiffness measurement - LSM) and traditional liver fibrosis models (APRI and FIB-4). Material and methods: A total of 77 chronic hepatitis B (CHB) patients who achieved a sustained virological response (SVR) after entecavir (ETV) treatment were included, and the changes of various clinical indicators before and after treatment were compared. Results: After 78 weeks of ETV treatment, WBC and PLT of 77 patients were significantly increased, while ALT, AST and total bilirubin were significantly decreased (p < 0.05). There was no significant difference in serum creatinine (Cr) or blood urea nitrogen (BUN) compared to the values before treatment (p > 0.05). The three non-invasive liver fibrosis indexes, namely, LSM, APRI and FIB-4, were significantly decreased in 77 patients compared to the values before treatment (p < 0.001). Conclusions: Acoustic radiation force impulse (ARFI), fibrosis-4 (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI) have a high consistency with the grading of liver fibrosis, and can be used to evaluate the severity of liver fibrosis. Among them, ARFI has good diagnostic value for the classification of different degrees of liver fibrosis and the best diagnostic accuracy.

Lycopene alleviates food allergy by modulating the PI3K/AKT pathway in peanut-sensitized BALB/c mice.

Food allergies, which lead to life-threatening acute symptoms, are considered an important public health problem. Therefore, it is essential to develop efficient preventive and treatment measures. We developed a crude peanut protein extract (PPE)-induced allergy mouse model to investigate the effects of lycopene on peanut allergy. Mice were divided into four groups: 5 mg/kg lycopene, 20 mg/kg lycopene, no treatment, and control groups. Serum inflammatory factors were detected using enzyme-linked immunosorbent assay. In addition, pathology and immunohistochemistry analyses were used to examine the small intestine of mice. We found that lycopene decreased PPE-specific immunoglobulin E (IgE) and IL-13 levels in the serum, relieved small intestine inflammation, attenuated the production of histamine and mouse mast cell protease-1, and downregulated PI3K and AKT1 expression in the small intestine tissues of mice allergic to peanuts. Our results suggest that lycopene can ameliorate allergy by attenuating the PI3K/AKT pathway and the anaphylactic reactions mediated by PPE-specific IgE.

ReProMSig: an integrative platform for development and application of reproducible multivariable models for cancer prognosis supporting guideline-based transparent reporting.

Adequate reporting is essential for evaluating the performance and clinical utility of a prognostic prediction model. Previous studies indicated a prevalence of incomplete or suboptimal reporting in translational and clinical studies involving development of multivariable prediction models for prognosis, which limited the potential applications of these models. While reporting templates introduced by the established guidelines provide an invaluable framework for reporting prognostic studies uniformly, there is a widespread lack of qualified adherence, which may be due to miscellaneous challenges in manual reporting of extensive model details, especially in the era of precision medicine. Here, we present ReProMSig (Reproducible Prognosis Molecular Signature), a web-based integrative platform providing the analysis framework for development, validation and application of a multivariable prediction model for cancer prognosis, using clinicopathological features and/or molecular profiles. ReProMSig platform supports transparent reporting by presenting both methodology details and analysis results in a strictly structured reporting file, following the guideline checklist with minimal manual input needed. The generated reporting file can be published together with a developed prediction model, to allow thorough interrogation and external validation, as well as online application for prospective cases. We demonstrated the utilities of ReProMSig by development of prognostic molecular signatures for stage II and III colorectal cancer respectively, in comparison with a published signature reproduced by ReProMSig. Together, ReProMSig provides an integrated framework for development, evaluation and application of prognostic/predictive biomarkers for cancer in a more transparent and reproducible way, which would be a useful resource for health care professionals and biomedical researchers.

Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment.

Introduction: The clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir. Methods: A total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development. Results: Of the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment. Discussion: In conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578).

A Novel PMVK Variant Associated with Familial Porokeratosis.

BACKGROUND: Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis. OBJECTIVES: The aim of the study was to identify the causative gene variant of porokeratosis in a Chinese family and investigate its population frequency and pathogenicity. METHOD: In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated by polymerase chain reaction-restriction fragment length polymorphism in 4 patients and three normal individuals as well as in 100 normal unrelated controls; finally, the pathogenicity of the mutation and the associated structural changes were predicted. RESULTS: We identified a novel heterozygous missense variant, c.207G>T (p. Lys69Asn) in the PMVK gene. This variant was found in all patients but not in the normal individuals in this family or in the 100 controls. In silico analysis indicated that the variant was pathogenic; p.Lys69Asn changed the length of the α-helix and the hydrogen bond pattern compared with the wild-type protein. CONCLUSIONS: The novel variant c.207G>T (p. Lys69Asn) in the PMVK gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.

Construction of tea tree oil/salicylic acid/palygorskite hybrids for advanced antibacterial and anti-inflammatory performance.

This study describes the construction of a tailor-made clay-based hybrid with advanced dermocompatibility, antibacterial and anti-inflammatory performance by incorporating tunable ratios of tea tree oil (TTO) and salicylic acid (SA) into the naturally occurring porous structure of palygorskite (Pal). Among the three TTO/SA/Pal (TSP) systems constructed, TSP-1 with a TTO : SA ratio of 1 : 3 demonstrated the lowest 3T3 NRU predicted acute oral toxicity and dermal HaCaT cytotoxicity as well as the most pronounced antibacterial activity with a selective inhibitory action against the pathogens (E. coli, P. acnes and S. aureus) over the beneficial (S. epdermidis) species inhabiting on the human skin. Also noticeable is that exposure of these skin commensal bacteria to TSP-1 prevented the antimicrobial resistance evolution compared to the conventional antibiotic ciprofloxacin. Mechanistic investigation of its antibacterial modes of action revealed a synergy between the TTO and SA loadings on the Pal supports in reactive oxygen production, causing oxidative damage to bacterial cell membranes and increased leakage of intracellular compounds. Additionally, TSP-1 significantly decreased the proinflammatory cytokines of IL-1ß, IL-6, IL-8, and TNF-α in a bacterial lipopolysaccharide-stimulated differentiated THP-1 macrophage model, showing the potential to inhibit inflammatory responses in bacterial infections. Overall, this is the first report exploring the potential of constructing clay-based organic-inorganic hybrids as alternatives to antibiotics to combat bacterial resistance with advanced compatibility and anti-inflammatory benefits that are desired for the development of topically applied biopharmaceuticals.

The hub genes and their potential regulatory mechanisms in chronic spontaneous urticaria revealed by integrated transcriptional expression analysis.

Chronic spontaneous urticaria (CSU) is a recurrent disease characterized by wheals and or angioedema, and its pathogenesis is still unclear. The microarray datasets of skin tissue from CSU patients and healthy controls were integrated and analysed in Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the NetworkAnalyst tool. Then, the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Subsequently, a protein-protein interaction (PPI) network of DEGs was constructed by STRING and the related hub genes were identified through the MOCDE tool. The potential miRNAs targeting hub genes were predicted based on the intersection of three online databases, namely TargetScanHuman, TargetBase and miRNet. Differentially expressed lncRNAs (DElncRNAs) was performed using the GEO2R tool. The potential miRNAs targeting DElncRNAs were predicted through miRNet. Finally, the shared miRNAs targeting both hub genes and DElncRNAs were used to construct an mRNA/miRNA/lncRNA regulatory network. A total of 296 DEGs were obtained, which were mainly enriched in inflammatory and immune responses. Further, 14 hub genes were identified by the PPI network of DEGs. Clinical correlation analysis showed that the mRNA expressions of S100A7, S100A8, S100A9, S100A12, IL6 and SOCS3 in CSU were positively correlated with the 7-day urticaria activity score (UAS7), and their potential diagnostic value was supported by the receiver operating characteristic curve (ROC) analysis. Five up-regulated lncRNAs in the cytoplasm were obtained by DElncRNAs analysis. The ROC analysis showed that PVT1, SNHG3 and ZBTB20 - AS1 was of potential diagnostic value for CSU. Eight shared miRNAs targeting both hub genes and DElncRNAs were identified and used to construct a competing endogenous RNA (ceRNA) network. It was found that the IL-6/miR - 149 - 5p/ZBTB20 - AS1 axis might play an important role in the activation of mast cells in CSU. IL-6 and its related regulatory molecules may be used as potential diagnostic markers and therapeutic targets for CSU.

Deep-learning based approach to identify substrates of human E3 ubiquitin ligases and deubiquitinases.

E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) play key roles in protein degradation. However, a large number of E3 substrate interactions (ESIs) and DUB substrate interactions (DSIs) remain elusive. Here, we present DeepUSI, a deep learning-based framework to identify ESIs and DSIs using the rich information present in protein sequences. Utilizing the collected golden standard dataset, key hyperparameters in the process of model training, including the ones relevant to data sampling and number of epochs, have been systematically assessed. The performance of DeepUSI was thoroughly evaluated by multiple metrics, based on internal and external validation. Application of DeepUSI to cancer-associated E3 and DUB genes identified a list of druggable substrates with functional implications, warranting further investigation. Together, DeepUSI presents a new framework for predicting substrates of E3 ubiquitin ligases and deubiquitinates.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.