Virus classification for viral genomic fragments using PhaGCN2.

Viruses are the most ubiquitous and diverse entities in the biome. Due to the rapid growth of newly identified viruses, there is an urgent need for accurate and comprehensive virus classification, particularly for novel viruses. Here, we present PhaGCN2, which can rapidly classify the taxonomy of viral sequences at the family level and supports the visualization of the associations of all families. We evaluate the performance of PhaGCN2 and compare it with the state-of-the-art virus classification tools, such as vConTACT2, CAT and VPF-Class, using the widely accepted metrics. The results show that PhaGCN2 largely improves the precision and recall of virus classification, increases the number of classifiable virus sequences in the Global Ocean Virome dataset (v2.0) by four times and classifies more than 90% of the Gut Phage Database. PhaGCN2 makes it possible to conduct high-throughput and automatic expansion of the database of the International Committee on Taxonomy of Viruses. The source code is freely available at https://github.com/KennthShang/PhaGCN2.0.

Clinical characteristics and effects of inhaled corticosteroid in patients with post-COVID-19 chronic cough during the Omicron variant outbreak.

BACKGROUND: Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. METHODS: An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. RESULTS: A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P < 0.05), and the improvement in the FEV1/FVC was significantly greater than that in the NICS group (P = 0.003) after 60 days. CONCLUSIONS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may contribute to the pathogenesis of asthma, which could be the underlying cause of persistent cough post-COVID-19 infection. Post-COVID-19 chronic cough during the Omicron era was often accompanied by sputum, dyspnea, and airway hyperresponsiveness. ICS treatment did not have a significant impact on symptom management of post-COVID-19 chronic cough; however, it can improve impaired lung function in in these individuals.

A cycloartenol synthase from the steroidal saponin biosynthesis pathway of Paris polyphylla.

Steroidal saponins named polyphyllin are the major active components of Paris polyphylla. Cycloartenol synthase (CAS) is a key enzyme that catalyzes the formation of the sterol scaffold. In this study, we cloned a putative CAS gene from Paris polyphylla. Heterologous expression in yeast indicated that PpCAS can convert 2,3-oxidosqualene into cycloartenol. qRT-PCR analysis showed that the expression of PpCAS was highest in leaves and lowest in roots. To our best knowledge, this is the first report of the functional characterization of cycloartenol synthase from Paris polyphylla, which lays the foundation for further analysis of the biosynthesis pathway of polyphyllins.[Formula: see text].

A discussion of RNA virus taxonomy based on the 2020 International Committee on Taxonomy of Viruses report.

RNA viruses have a higher mutation rate than DNA viruses; however, RNA viruses are insufficiently studied outside disease settings. The International Committee on Taxonomy of Viruses (ICTV) is an organization set up by virologists to standardize virus classification. To better understand ICTV taxonomy and the characteristics and rules of different RNA virus families, we analyzed the 3,529 RNA viruses included in the 2020 ICTV report using five widely used metrics: length, host, GC content, number of predicted ORFs, and sequence similarity. The results show that host type has a significant influence on viral genome length and GC content. The genome lengths of virus members within the same genus are quite similar: 98.28% of the genome length differences within any particular genus are less than 20%. The species within those genera containing segmented viruses also have a similar length and number of segments. The number of predicted ORFs in the RNA viral genomes also shows a strong, statistically significant correlation with genome length. We suggest that due to the high mutation rate of RNA virus genomes, current RNA virus classification should mainly rely on protein similarities rather than nucleic acid similarities.

Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression.

AIM: To investigate whether telmisartan (Telm) pretreatment attenuates isoproterenol (Iso)-induced postinfarction remodeling (PIR) in rats, and whether the effect of Telm is associated with cardiac expression of adiponectin. METHODS: PIR was induced in male Wistar rats with two consecutive injections of Iso (80 mg/kg, sc) at an interval of 24 h. Primary culture of ventricular myocytes from neonatal rats was prepared. Iso-induced cardiomyocyte injury was assessed based on cell growth and lactate dehydrogenase (LDH) activity. Cardiac adiponectin expression was measured using qRT-PCR and immunoblot analysis. RESULTS: In the rats with PIR, Telm (10 mg·kg(-1)·d(-1), po for 65 d) suppressed Iso-induced increases in gravimetric parameters, cardiomyocyte diameter and collagen volume fraction, but had no effect on Iso-induced myocardial hypertrophy and interstitial fibrosis. The protective effect of Telm was associated with enhanced protein expression of cardiac adiponectin. In cultured cardiomyocytes, Telm (5-20 µmol/L) inhibited the cell death and LDH release induced by Iso (10 µmol/L), and reversed Iso-induced reduction in adiponectin protein expression. In cardiomyocytes exposed to Iso (20 µmol/L), GW9662 (30 µmol/L), a selective antagonist of PPAR-γ, blocked the effects of Telm pretreatment on adiponectin protein expression, as well as the protective effects of Telm on Iso-induced cell injury. CONCLUSION: Telm attenuates Iso-induced cardiac remodeling and cell injury, which is associated with induction of cardiac adiponectin expression.

[Changes of ocular higher order aberration in keratoconus eyes wearing rigid gas-permeable contact lens].

OBJECTIVE: To compare the wavefront characteristics of normal and keratoconus eyes with and without rigid gas-permeable contact lens (RGPCL), and to evaluate the visual quality in keratoconus eyes corrected by RGPCL. METHODS: Retrospective study. Higher order aberrations (HOAs) of 90 eyes in 56 keratoconus patients and 30 eyes of 17 subjects with refractive errors were quantified with a Bausch&Lomb Zywave Wavefront Analyzer. The keratoconus eyes were divided into mild (28 eyes), moderate (33 eyes) and severe (29 eyes) groups. Zernike's polynomial was used to describe the wavefront measurements. Root mean square (RMS) values of the total HOAs, S3, S4, S5, total coma (T. Coma) and total spherical aberrations (T. Sph) were obtained in the same eye with and without contact lenses. We used paired sample t-test and independent-samples t-test to analyze the data. RESULTS: Mean RMS values for High (F = 72.12, P(1) = 0.00), S3 (F = 68.15, P = 0.00), S4 (F = 24.95, P(1) = 0.00), T. Coma (F = 44.67, P = 0.00), T. Sph (F = 28.90, P = 0.01) increased significantly from mild to sever keratoconus eyes RMS values of the total HOAs (t = 4.83), S3 (t = 4.39), total coma (t = 3.71) of refractive error eyes decreased significantly after fitting with RGPCL (P < 0.05). RMS values of the total HOAs (t = 8.27), S3 (t = 8.14), S4 (t = 2.29), total coma (t = 4.38) of mild keratoconus eyes decreased significantly after fitting with RGPCL (P < 0.05) RMS values of the total HOAs (t = 8.03), S3 (t = 7.22), s4 (t = 4.38), S5 (t = 4.53), total coma (t = 5.26) and total spherical (t = 2.77) of moderate keratoconus eyes decreased significantly after fitting with RGPCL (P < 0.05). Every high front-wave aberration of mild keratoconus eyes decreased to refractive error eyes'level after RGPCL fitting. Moderate (t(HOAs) = 0.63, t(s3) = 0.31, t(s4) = 1.70, t(s5) = 0.95, t(coma) = 0.06, t(spherical) = 1.99) and sever keratoconus eyes' higher order aberrations decreased significantly after RGPCL fitting (t(HOAs) = 7.50, t(s3) = 5.25, t(s4) = 5.50, t(s5) = 3.02, t(coma) = 5.90, t(spherical) = 4.60), but they still degrade compared with refractive error eyes (P < 0.05). CONCLUSIONS: RGPCL could reduce high aberrations and improve optical quality in keratoconus eyes. But the visual performance in moderate and severe keratoconus eyes with a RGPCLs is still poorer than that of normal eyes even if the corrected visual acuity is good.

Effects of chain length of saturated fatty acids on Aß generation in SH-SY5Y cells.

Many studies have shown that saturated fat diet increases the risk of AD. Recently saturated very long chain fatty acids (VLCFAs) have been found be accumulated in AD patients. The variety of saturated fatty acids are found in the diets and human bodies. However, it is not clear which one or more fatty acids are involved in AD pathogenesis. This study investigated the effects of three saturated fatty acids with different carbon chain length (C16:0, C20:0, and C26:0) on amyloid precursor protein (APP) processing and amyloid-ß peptide (Aß) generation. Here, SH-SY5Y cells were treated with vehicle, C16:0, C20:0, and C26:0 (10 µmol/L, 24 h). Compared to the vehicle, C16:0 did not cause any significantly change in APP processing and Aß generation. C20:0 and C26:0 increased Aß levels and the expressions of APP, ß- and γ-secretase and decreased the expression of α-secretase, and C26:0 had the strongest effects among three fatty acids. Moreover, C20:0 and C26:0 significantly increased reactive oxygen species (ROS), and C16:0 had no such effect. These data indicate that saturated fatty acids with different carbon chain length (C16:0, C20:0 and C26:0) have different effects on the process of Aß generation, and fatty acids with longer chain (C20:0 and C26:0) have more potential to promote Aß production and an underlying mechanism of fatty acids action may be related to the elevated oxidative stress. This work supports saturated very long chain fatty acids may play a potential role in the pathogenesis of AD.

Correlation between hepatitis B virus genotypes and clinical outcomes.

Hepatitis B virus (HBV) has been classified into 10 genotypes (A-J) according to genome sequence divergence. HBV genotypes have a distinct geographical distribution. As chronic HBV infection is endemic in the Asian region, genotypes B and C prevail there, and genotypes A and D are mainly found in the western world and Europe. Genotypes A, B, C, and D have been studied most extensively. In Europe and Asia, most patients with genotypes A and B have acute hepatitis B; however, some mutants may tend to cause fulminant hepatitis B. Many studies have indicated that the severity and outcomes of chronic hepatitis B infections are more serious in patients with genotypes C and D than in those with genotypes A and B. Cirrhosis and hepatocellular carcinoma (HCC) are more frequently diagnosed in carriers of genotypes C and D than in those of genotypes A and B. Accumulating evidence indicated that higher plasma HBV DNA levels, infection with HBV genotype C, as well as mutations at 1653T, 1753V, and A1762T/G1764A are independently associated with the risk of HCC in Asian men. However, the therapeutic responses differ with regard to the different HBV genotypes. For example, the response to interferon-α treatment in patients with genotypes A and B was better than that in patients with genotypes C, D, and mixed genotypes. Some studies have shown seroconversion after treatment, i.e., genotypes A and C may switch to genotypes D and B, respectively. Some reports indicated a correlation between the emergence of the hepatitis B e antigen-negative variant in patients with genotypes C and D and worsening of liver injury without sustained response. In order to provide better treatment options for these poorly responding patients, further studies, e.g, novel immunomodulatory therapies, are required. Many studies have shown that HBV genotypes have remarkable clinical and epidemical differences; however, HBV sub-genotypes, mixed genotype infections, and the effect of different genotypes on the treatment of HBV infections require further studies.

Molecular characteristics and stages of chronic hepatitis B virus infection.

Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our understanding of the natural stages of chronic HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. Knowledge of the HBV genome organization and replication cycle can unravel HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. Most HBV infections are spontaneously resolved in immunocompetent adults, whereas they become chronic in most neonates and infants at a great risk of developing complications such as cirrhosis and hepatocellular carcinoma (HCC). Those with chronic HBV infection may present in one of the four phases of infection: immune tolerance, immune clearance [hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB)], inactive carrier state, and reactivation (HBeAg-negative CHB). Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers. Long-term monitoring and optimal timing of antiviral therapy for chronic HBV infection help to prevent progression of HBV-related liver disease to its later stage, particularly in patients with higher risk markers of HCC, such as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes, and pre-core or core mutants.