PhyloVelo enhances transcriptomic velocity field mapping using monotonically expressed genes.

Single-cell RNA sequencing (scRNA-seq) is a powerful approach for studying cellular differentiation, but accurately tracking cell fate transitions can be challenging, especially in disease conditions. Here we introduce PhyloVelo, a computational framework that estimates the velocity of transcriptomic dynamics by using monotonically expressed genes (MEGs) or genes with expression patterns that either increase or decrease, but do not cycle, through phylogenetic time. Through integration of scRNA-seq data with lineage information, PhyloVelo identifies MEGs and reconstructs a transcriptomic velocity field. We validate PhyloVelo using simulated data and Caenorhabditis elegans ground truth data, successfully recovering linear, bifurcated and convergent differentiations. Applying PhyloVelo to seven lineage-traced scRNA-seq datasets, generated using CRISPR-Cas9 editing, lentiviral barcoding or immune repertoire profiling, demonstrates its high accuracy and robustness in inferring complex lineage trajectories while outperforming RNA velocity. Additionally, we discovered that MEGs across tissues and organisms share similar functions in translation and ribosome biogenesis.

Relationship between the Level of Serum Golgi Protein 73 and the Risk of Short-term Death in Patients with ALD-ACLF.

Background and Aims: As a hepatocellular carcinoma biomarker, serum Golgi protein 73 (GP73) is reportedly related to inflammation. Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation. In this study, we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF (ALD-ACLF). Methods: This retrospective cohort study involved 126 Chinese adults with ALD-ACLF. Baseline serum GP73 level was measured using enzyme-linked immunosorbent assay. Patients were followed-up for 90 d and outcomes were assessed. Data were analyzed using multivariate Cox regression and piecewise linear regression analyses. The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves. Results: The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF. Compared with the lowest tertile, the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model [at 28 days: hazard ratio (HR): 4.29 (0.99-18.54), p=0.0511; at 90 days: HR: 3.52 (1.15-10.79), p=0.0276]. Further analysis revealed a positive linear association. GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score, model for end-stage liver disease score, and model for end-stage liver disease-sodium score in predicting short-time prognosis of patients with ALD-ACLF. Conclusions: The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF. GP73 improved the predictive value of classic prognostic scores.

Reappraisal of the diagnostic value of alpha-fetoprotein for surveillance of HBV-related hepatocellular carcinoma in the era of antiviral therapy.

This study was designed to explore if antiviral treatment influences the performance of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) among the high-risk chronic HBV-infected patients. A total of 5936 patients who had evidence of chronic HBV infection were enrolled from four independent centres in this retrospective study, including 1721 chronic hepatitis B (CHB), 2286 liver cirrhosis (LC), 798 HCC within Milan criteria and 1131 HCC beyond Milan criteria patients. Stratified by whether they received treatment or not, the patients were further divided into antiviral and non-antiviral groups. Then, the performance of AFP for discriminating HCC was evaluated. Patients receiving antivirals had significantly lower median levels of AFP compared with the non-antiviral patients (P < .001), and there were significantly less patients with abnormal AFP levels in antiviral groups (P < .001). Antiviral therapy improved the AUROCs of AFP for discriminating HCC within Milan criteria. When setting the cut-off values at 20 ng/mL and 100 ng/mL as surveillance and confirmatory tests respectively for HCC among patients receiving antiviral treatment, AFP exhibited a significantly higher sensitivity than those of 200 ng/mL and 400 ng/mL, which are currently recommended by some guidelines, without compromising specificity. Further analysis in antiviral patients revealed that serum AFP had better performance for discriminating HCC within Milan criteria in ALT ≤ 1ULN patients than that in ALT > 1ULN patients. In conclusion, in the era of antiviral therapy, serum AFP's surveillance performance was substantially improved for HCC within Milan criteria among the high-risk population of CHB and LC patients.

Altered Brain Functional Network in Parkinson Disease With Rapid Eye Movement Sleep Behavior Disorder.

Background and Objective: Parkinson disease (PD) with rapid eye movement (REM) sleep behavior disorder (PD-RBD) tend to be a distinct phenotype with more severe clinical characteristics and pathological lesion when compared with PD without RBD (PD-nRBD). However, the pathological mechanism underlying PD-RBD remains unclear. We aim to use the resting-state functional magnetic resonance imaging (rs-fMRI) to explore the mechanism of PD-RBD from the perspective of internal connectivity networks. Materials and Methods: A total of 92 PD patients and 20 age and sex matched normal controls (NC) were included. All participants underwent rs-fMRI scan and clinical assessment. According to the RBD screening questionnaire (RBDSQ), PD patients were divided into two groups: PD with probable RBD (PD-pRBD) and PD without probable RBD (PD-npRBD). The whole brain was divided into 90 regions using automated anatomic labeling atlas. Functional network of each subject was constructed according to the correlation of rs-fMRI blood oxygenation level dependent signals in any two brain regions and network metrics were analyzed using graph theory approaches. Network properties among three groups were compared and correlation analysis was made using distinguishing network metrics and RBDSQ scores. Results: We found both PD-pRBD and PD-npRBD patients existed small-world characteristics. PD-pRBD showed a wider range of nodal property changes in neocortex and limbic system than PD-npRBD patients when compared with NC. Besides, PD-pRBD showed significant enhanced nodal efficiency in the bilateral thalamus and betweenness centrality in the left insula, but, reduced betweenness centrality in the right dorsolateral superior frontal gyrus when compared with PD-npRBD. Moreover, nodal efficiency in the bilateral thalamus were positively correlated with RBDSQ scores. Conclusions: Both NC and PD patients displayed small-world properties and indiscriminate global measure but PD-pRBD showed more extensive changes of nodal properties than PD-npRBD. The increased centrality role in the bilateral thalamus and the left insula, and disruption in the right dorsolateral superior frontal gyrus may play as a key role in underlying pathogenesis of PD-RBD.

Nonalcoholic fatty liver disease is associated with lower hepatitis B viral load and antiviral response in pediatric population.

BACKGROUND: The interaction between nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B infection (CBI) was unclear. We aimed to investigate the association between NAFLD and CBI and the effect of NAFLD on response to antiviral therapy in pediatric population. METHODS: All children aged 0-18 years with liver biopsy-proven NAFLD, CBI, and co-existing NAFLD and CBI were consecutively collected. Children with co-existing CBI and NAFLD were considered as cases and n:m matched with simple NAFLD and simple CBI patients in the same cohort, respectively. In longitude study, the role of NAFLD in antiviral response was further analyzed in children with CBI who received antiviral treatment. Logistic or Cox regression models were used appropriately for analysis. RESULTS: 765 subjects were finally enrolled with 62 co-existing patients, 560 CBI patients, and 143 NAFLD patients. Multivariate analysis showed that HBV DNA level was negatively associated with NAFLD in CBI children (OR 0.376, 95% CI 0.173-0.818). Conversely, the severity of steatosis and levels of serum lipid profile were found to be inversely associated with CBI in NAFLD subjects. Then, in longitude study, we found that HBsAg loss at 96 weeks of antiviral treatment was independently associated with NAFLD (aHR 3.245, 95% CI 1.288-8.176). CONCLUSIONS: An inverse association between CBI and NAFLD reciprocally existed in pediatric population. In longitude study, HBsAg loss was associated with NAFLD at week 96 of antiviral therapy.

[Expression of GFP gene in mouse early embryo produced by sperm-mediated gene transfer].

The efficiency of the exogenous DNA transfecting mouse sperm was studied by the DIG end labeled and immunohistochemistry technology. The results suggested that: the efficiency of transfecting positive rate of individual mouse sperm was distinct difference (P < 0.01), and the average rate was 13%. The acrosomal reaction was evaluated using the technology of Coomassie brilliant blue stained, and the appropriate in vitro fertilization (IVF) medium TYH was elected. Mouse sperms were transferred with GFP gene in vitro, and the mature oocytes were fertilized using IVF, and then the zygotes were cultured in vitro. The embryos were observed using the fluorescence microscopy, and the transgenic rate was 4.7%. The results suggested that sperm mediated gene transfer (SMGT) was an effective and feasible method.