The role of lysosomes as intermediates in betacoronavirus PHEV egress from nerve cells.

IMPORTANCE: Betacoronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and mouse hepatitis virus (MHV), exploit the lysosomal exocytosis pathway for egress. However, whether all betacoronaviruses members use the same pathway to exit cells remains unknown. Here, we demonstrated that porcine hemagglutinating encephalomyelitis virus (PHEV) egress occurs by Arl8b-dependent lysosomal exocytosis, a cellular egress mechanism shared by SARS-CoV-2 and MHV. Notably, PHEV acidifies lysosomes and activates lysosomal degradative enzymes, while SARS-CoV-2 and MHV deacidify lysosomes and limit the activation of lysosomal degradative enzymes. In addition, PHEV release depends on V-ATPase-mediated lysosomal pH. Furthermore, this is the first study to evaluate ßCoV using lysosome for spreading through the body, and we have found that lysosome played a critical role in PHEV neural transmission and brain damage caused by virus infection in the central nervous system. Taken together, different betacoronaviruses could disrupt lysosomal function differently to exit cells.

Age at menarche and its association with blood pressure in adult women of developing countries: a systematic review and meta-analysis.

CONTEXT: Evidence about the effect of age at menarche (AAM) on blood pressure (BP) has largely been drawn from studies in developed countries. Studies in developing countries are expanding recently but have not been summarised. OBJECTIVE: To systematically explore the association between AAM and BP and the potential modifiers in developing countries. METHODS: We searched PubMed, Embase, and Web of Science for publications until March 2022. A random-effects model was used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). RESULTS: Twenty studies were eligible. In studies with participants' mean age at BP assessment <55 years, women in the oldest group as compared with the middle or the youngest group of AAM had a higher risk of hypertension in those studies without adjustment for confounders (RR 1.79, 95% CI 1.41-2.28, I2=97.0%), those with adjustment for confounders excluding adiposity (1.25,1.04-1.51, I2=84.8%), and those with adjustment for confounders including adiposity (1.38,1.03-1.86, I2=91.8%). In studies with participants' mean age at BP assessment ≥55 years, no significant differences were found for studies without adjustment for confounders (RR 1.07, 95% CI 0.78-1.47, I2=90.3%), studies with adjustment for confounders excluding adiposity (0.85, 0.78-0.92, I2=12.3%), or studies with adjustment for confounders including adiposity (0.95, 0.80-1.11, I2=45.5%). A similar association was observed between AAM and baseline systolic BP and diabolic BP. CONCLUSION: Late menarche was associated with a higher risk of BP and this association was modified by age and adiposity in developing countries.

Pneumococcal vaccination coverage and willingness in mainland China.

OBJECTIVES: To estimate the coverage and willingness of pneumococcal vaccination and further explore the influencing factors of vaccination willingness among people in mainland China. METHODS: Literature searches were conducted independently by two researchers in English- and Chinese-language databases from database inception to 6 October 2021. A random-effects meta-analysis model was used to derive summary vaccination coverage and willingness. Predefined subgroup analysis and meta-regression were performed to explore the sources of heterogeneity. RESULTS: A total of 97 studies were included in this meta-analysis. The summary vaccination coverage in 76 included studies was 21.7% (95% confidence interval [CI]: 17.2%-26.5%). Subgroup analysis shows that the summary coverage was 29.0% (95% CI, 20.4%-39.1%) among the permanent residents and 20.7% (95% CI, 12.4%-35.9%) among the floating residents. The eastern and central regions presented higher coverage than the western region. Notable differences were observed between the various study populations. A total of 27 studies provided an estimation of vaccination willingness, with a summary willingness of 51.2% (95% CI, 40.4%-61.9%). In subgroup analysis, the summary willingness was 57.9% (95% CI, 48.3%-67.2%) in urban areas and 52.3% (95% CI, 40.8%-63.8%) in rural areas. Parents with children and people with a history of pneumonia were more willing to be vaccinated than the elderly. Recommendations by family members and physicians, previous pneumococcal and influenza vaccination, perceived vaccination effectiveness and severity of disease and a history of pneumonia contributed to vaccination willingness. CONCLUSIONS: Compared to global estimates and other countries, pneumococcal vaccination coverage and willingness are at a lower level in mainland China. Recommendations for vaccination by family members and doctors, a history of vaccination and the perception of pneumonia and vaccination are associated with greater willingness to be vaccinated.

Suppression of porcine hemagglutinating encephalomyelitis virus replication by resveratrol.

BACKGROUND: Porcine hemagglutinating encephalomyelitis virus (PHEV), a member of the genus Betacoronavirus, is the causative agent of neurological disease in pigs. No effective therapeutics are currently available for PHEV infection. Resveratrol has been shown to exert neuroprotective and antiviral effects. Here resveratrol was investigated for its ability to inhibit PHEV replication in nerve cells and central nervous system tissues. METHODS: Anti-PHEV effect of resveratrol was evaluated using an in vitro cell-based PHEV infection model and employing a mouse PHEV infection model. The collected cells or tissues were used for quantitative PCR analysis, western blot analysis, or indirect immunofluorescence assay. The supernatants were collected to quantify viral loads by TCID50 assay in vitro. EC50 and CC50 were determined by dose-response experiments, and the ratio (EC50/CC50) was used as a selectivity index (SI) to measure the antiviral versus cytotoxic activity. RESULTS: Our results showed that resveratrol treatment reduced PHEV titer in a dose-dependent manner, with a 50% inhibition concentration of 6.24 µM. A reduction of > 70% of viral protein expression and mRNA copy number and a 19-fold reduction of virus titer were achieved when infected cells were treated with 10 µM resveratrol in a pre-treatment assay. Quantitative PCR analysis and TCID50 assay results revealed that the addition of 10 µM resveratrol to cells after adsorption of PHEV significantly reduced 56% PHEV mRNA copy number and eightfold virus titer. 10 µM resveratrol treatment reduced 46% PHEV mRNA copy number and fourfold virus titer in virus inactivation assay. Moreover, the in vivo data obtained in this work also demonstrated that resveratrol inhibited PHEV replication, and anti-PHEV activities of resveratrol treatment via intranasal installation displayed better than oral gavage. CONCLUSION: These results indicated that resveratrol exerted antiviral effects under various drug treatment and virus infection conditions in vitro and holds promise as a treatment for PHEV infection in vivo.

Potential Antiviral Strategy Exploiting Dependence of SARS-CoV-2 Replication on Lysosome-Based Pathway.

The recent novel coronavirus (SARS-CoV-2) disease (COVID-19) outbreak created a severe public health burden worldwide. Unfortunately, the SARS-CoV-2 variant is still spreading at an unprecedented speed in many countries and regions. There is still a lack of effective treatment for moderate and severe COVID-19 patients, due to a lack of understanding of the SARS-CoV-2 life cycle. Lysosomes, which act as "garbage disposals" for nearly all types of eukaryotic cells, were shown in numerous studies to support SARS-CoV-2 replication. Lysosome-associated pathways are required for virus entry and exit during replication. In this review, we summarize experimental evidence demonstrating a correlation between lysosomal function and SARS-CoV-2 replication, and the development of lysosomal perturbation drugs as anti-SARS-CoV-2 agents.

A multiplex TaqMan real-time PCR for detection and differentiation of four antigenic types of canine parvovirus in China.

Canine parvovirus (CPV) is an important pathogen in domestic dogs, and the original antigenic types CPV-2 and its variants, CPV-2a, 2b and 2c, are prevalent worldwide. A multiplex TaqMan real-time PCR method was developed for the detection and differentiation of four antigenic types of CPV. A set of primers and probes, CPV-305F/CPV-305R and CPV-2-305P (for CPV-2)/CPV-2a-305P (for CPV-2a, 2b and 2c), was able to differentiate CPV-2 and its variants (CPV-2a, 2b and 2c). Another set of primers and probes, CPV-426F/CPV-426R and CPV-2-426P (for CPV-2 and 2a)/CPV-2b-426P (for CPV-2b)/CPV-2c-426P (for CPV-2c), was able to differentiate CPV-2a (2), CPV-2b, and CPV-2c. With these primers and probes, the multiplex TaqMan real-time PCR assay detected effectively and differentiated CPV-2, 2a, 2b and 2c by two separate real-time PCRs. No cross reactivity was observed with canine distemper virus, canine adenovirus, and canine coronavirus. The detection limit of the assay is 101 genome copies/µL for CPV-2, CPV-2a, CPV-2b, and 102 copies/µL for CPV-2c. The multiplex real-time PCR has 100% agreement with DNA sequencing. We provide a sensitive assay that simultaneously detects and differentiate four antigenic types of CPV and the method was also used for quantification of CPVs viral genome.

Gene-expression patterns in the cerebral cortex of mice infected with porcine haemagglutinating encephalomyelitis virus detected using microarray.

Porcine haemagglutinating encephalomyelitis virus (PHEV) is the main causative agent of porcine coronavirus-associated disease, which is characterized by encephalomyelitis and involves the central nervous system. Little is known about the molecular mechanisms of brain injury caused by PHEV. To gain insight into the interaction between the virus and host cells, changes in global gene expression in the cerebral cortex of PHEV- or mock-infected mice were investigated using DNA microarray analysis and quantitative real-time PCR. The results of the microarray analysis showed that 365 genes on day 3 post-infection (p.i.) and 781 genes on day 5 p.i. were differentially expressed in response to PHEV infection in the cerebral cortex. The upregulated genes were mainly involved in immune system processes, antigen processing and presentation, the Jak-STAT signalling pathway, the RIG-I-like receptor signalling pathway, Toll-like receptor signalling and apoptosis-related proteases. Significantly downregulated genes were mainly involved in nervous-system development, synaptic transmission, neuron-projection development, the transmission of nerve impulses and negative regulation of glial cell differentiation. The differential expression of these genes suggests a strong antiviral host response, but may also contribute to the pathogenesis of PHEV resulting in encephalomyelitis.

Identification and characterization of improved nitrogen efficiency in interspecific hybridized new-type Brassica napus.

BACKGROUND AND AIMS: Oilseed rape (Brassica napus) is an important oil crop worldwide. The aim of this study was to identify the variation in nitrogen (N) efficiency of new-type B. napus (genome A(r)A(r)C(c)C(c)) genotypes, and to characterize some critical physiological and molecular mechanisms in response to N limitation. METHODS: Two genotypes with contrasting N efficiency (D4-15 and D1-1) were identified from 150 new-type B. napus lines, and hydroponic and pot experiments were conducted. Root morphology, plant biomass, N uptake parameters and seed yield of D4-15 and D1-1 were investigated. Two traditional B. napus (genome A(n)A(n)C(n)C(n)) genotypes, QY10 and NY7, were also cultivated. Introgression of exotic genomic components in D4-15 and D1-1 was evaluated with molecular markers. KEY RESULTS: Large genetic variation existed among traits contributing to the N efficiency of new-type B. napus. Under low N levels at the seedling stage, the N-efficient new-type D4-15 showed higher values than the N-inefficient D1-1 line and the traditional B. napus QY10 and NY7 genotypes with respect to several traits, including root and shoot biomass, root morphology, N accumulation, N utilization efficiency (NutE), N uptake efficiency (NupE), activities of nitrate reductase (NR) and glutamine synthetase (GS), and expression levels of N transporter genes and genes that are involved in N assimilation. Higher yield was produced by the N-efficient D4-15 line compared with the N-inefficient D1-1 at maturity. More exotic genome components were introgressed into the genome of D4-15 (64·97 %) compared with D1-1 (32·23 %). CONCLUSIONS: The N-efficient new-type B. napus identified in this research had higher N efficiency (and tolerance to low-N stress) than traditional B. napus cultivars, and thus could have important potential for use in breeding N-efficient B. napus cultivars in the field.

In vitro RNA interference targeting the DNA polymerase gene inhibits orf virus replication in primary ovine fetal turbinate cells.

Orf, which is caused by orf virus (ORFV), is distributed worldwide and is endemic in most sheep- and/or goat-raising countries. RNA interference (RNAi) pathways have emerged as important regulators of virus-host cell interactions. In this study, the specific effect of RNAi on the replication of ORFV was explored. The application of RNA interference (RNAi) inhibited the replication of ORFV in cell culture by targeting the ORF025 gene of ORFV, which encodes the viral polymerase. Three small interfering RNA (siRNA) (named siRNA704, siRNA1017 and siRNA1388) were prepared by in vitro transcription. The siRNAs were evaluated for antiviral activity against the ORFV Jilin isolate by the observation of cytopathic effects (CPE), virus titration, and real-time PCR. After 48 h of infection, siRNA704, siRNA1017 and siRNA1388 reduced virus titers by 59- to 199-fold and reduced the level of viral replication by 73-89 %. These results suggest that these three siRNAs can efficiently inhibit ORFV genome replication and infectious virus production. RNAi targeting of the DNA polymerase gene is therefore potentially useful for studying the replication of ORFV and may have potential therapeutic applications.

Development and evaluation of inactivated vaccines incorporating a novel Senecavirus A strain-based Immunogen and various adjuvants in mice.

Porcine idiopathic vesicular disease (PIVD), one of several clinically indistinguishable vesicular diseases of pigs, is caused by the emerging pathogen Senecavirus A (SVA). Despite the widespread prevalence of porcine SVA infection, no effective commercial vaccines for PIVD prevention and control are available, due to high costs associated with vaccine testing in pigs, considerable SVA diversity, and SVA rapid evolution. In this study, SVA CH/JL/2022 (OP562896), a novel mutant SVA strain derived from an isolate obtained from a pig farm in Jilin Province, China, was inactivated then combined with four adjuvants, MONTANIDETM GEL02 PR (GEL 02), MONTANIDETM ISA 201 VG (ISA 201), MONTANIDETM IMG 1313 VG N (IMS1313), or Rehydragel LV (LV). The resulting inactivated SVA CH/JL/2022 vaccines were assessed for efficacy in mice and found to induce robust in vivo lymphocyte proliferation responses and strong IgG1, IgG2a, and neutralizing antibody responses with IgG2a/IgG1 ratios of <1. Furthermore, all vaccinated groups exhibited significantly higher levels of serum cytokines IL-2, IL-4, IL-6, and IFN as compared to unvaccinated mice. These results indicate that all vaccines elicited both Th1 and Th2 responses, with Th2 responses predominating. Moreover, vaccinated mice exhibited enhanced resistance to SVA infection, as evidenced by reduced viral RNA levels and SVA infection-induced histopathological changes. Collectively, our results demonstrate that the SVA-GEL vaccine induced more robust immunological responses in mice than did the other three vaccines, thus highlighting the potential of SVA-GEL to serve an effective tool for preventing and controlling SVA infection.

Rapid detection of orf virus by loop-mediated isothermal amplification based on the DNA polymerase gene.

At present, there are no effective antiviral treatments available for contagious ecthyma, and rapid diagnosis is therefore critical for effective control of the disease. Recently, the invention of a novel LAMP technique that can rapidly amplify nucleic acids with high specificity and sensitivity under isothermal conditions has overcome some of the deficiencies of nucleic acid-based diagnostic tests and has made on-site diagnosis possible. To establish a flexible loop-mediated isothermal amplification (LAMP) assay for the rapid detection of orf virus, two pairs of primers, including outer primers F3/B3 and inner primers FIP/BIP, were designed to amplify the DNA polymerase gene. Optimal time and temperature conditions for LAMP were found to be 45 min and 62 °C, respectively. The LAMP assay was shown to be specific, with no cross-reactivity with sheeppox virus, goatpox virus, avian molluscum roup virus or vesicular stomatitis virus. Additionally, the sensitivity of the LAMP method was similar to that of real-time PCR and demonstrated greater sensitivity than a conventional polymerase chain reaction (PCR) assay. To assess the utility of LAMP in the detection of orf virus in clinical samples, a total of 35 samples collected from orf virus-infected sheep and goats were tested using the optimized LAMP assay, real-time PCR, and conventional PCR. Of the samples, 26 were found to be positive by LAMP, and 25 (74.3 %) were positive by real-time PCR, whereas only 18 (51.4 %) were positive by conventional PCR. Our results have shown that the LAMP assay developed in this study can be used for the rapid detection of orf virus.

Age-related changes for the predictors of benign prostatic hyperplasia in Chinese men aged 40 years or older.

A cross-sectional study was conducted to estimate the age-stratified normal levels and age-related changes in the risk predictors of benign prostatic hyperplasia (BPH) progression. A total of 4706 male participants aged 40 years or older in Zhengzhou (China) were enrolled. The values of the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), prostate volume (PV), and postvoid residual urine volume (PVR) significantly increased with age. Nonlinear relationships between age and IPSS scores ≥8 (P for nonlinearity = 0.046), PSA level ≥1.6 ng ml-1, PV ≥31 ml, or PVR ≥39 ml (all P for nonlinearity <0.001) were observed. After the age of 61 years, the risk indicators related to BPH progression were positively correlated with age (odds ratio [OR] >1), regardless of the predictors of the IPSS score, PSA level, PV, or PVR; and the OR values increased gradually. Therefore, after the age of 61 years, the risk predictors related to BPH progression were positively correlated with age.

The Mediating Role of Body Mass Index in the Association Between Age at First Childbirth and Lung Function Among Chinese Postmenopausal Women.

Objective: Little is known about the effect of age at first childbirth on lung function. We aimed to investigate the association between age at first childbirth and lung function in Chinese women and further test whether this association is mediated by body mass index (BMI). Methods: This cross-sectional study is a partial survey of the China Kadoorie Biobank (CKB) which was conducted in Xinxiang City, Henan Province between 2004 and 2008. A total of 16,584 postmenopausal women aged 30-79 years were enrolled. Multiple linear and logistic regression were used to investigate the association between age at first childbirth and lung function and overweight/obesity. The mediation analysis was performed using the PROCESS procedure for SPSS. Results: The mean (SD) age at first childbirth was 23.1 (2.7) years. Women with first childbirth aged ≤19 years and 20-22 years had lower lung function than women who gave first childbirth aged 23-25 years. Per 1-year increase in the age at first childbirth was associated with a 3.31 mL increase in FEV1 (95% CI = 1.27-5.35), 3.91 mL increase in FVC (95% CI = 1.63-6.18), 0.15% increase in FEV1, % predicted (95% CI = 0.05-0.24) and 0.14% increase in FVC, % predicted (95% CI = 0.05-0.22). There was no clear association between age at first childbirth and FEV1/FVC ratio. BMI played a contribution to the association between age at first childbirth and FEV1 and the proportion was 16.4% (indirect effect: ß = 0.65, 95% CI = 0.46-0.89; total effect: ß = 3.96, 95% CI = 1.92-5.99). Similarly, the proportion to FVC, FEV1, % predicted, and FVC, % predicted was 25.0%, 16.6%, and 25.0%, respectively. Conclusion: Early age at first childbirth was associated with lower lung function and BMI mediated the association. It is important to test lung function and popularize the knowledge of weight control in women who gave first childbirth at an early age.

In vitro inhibition of porcine hemagglutinating encephalomyelitis virus replication with siRNAs targeting the spike glycoprotein and replicase polyprotein genes.

OBJECTIVE: The specific effect of rna interference on the replication of porcine hemagglutinating encephalomyelitis virus (phe-cov) was explored. METHODS: Four species of small interfering RNA (siRNA), targeting different regions of the PHE-CoV spike glycoprotein and replicase polyprotein genes, were prepared by in vitro transcription. After transfection of PK-15 cells with each of the siRNAs followed by infection with PHE-CoV, the cytopathic effect (CPE) was examined by phase-contrast microscope, and viral proliferation within cells was examined by indirect immunofluorescence microscopy, hemagglutination (HA) test, TCID(50) assay and real-time RT-PCR. RESULTS: Examination of CPE demonstrated that the four siRNAs were capable of protecting cells against PHE-CoV invasion with very high specificity and efficiency. At 48 h post-infection, only a few siRNA-treated cells were positive for viral antigen staining, whereas most untreated virus-infected cells were positive. Transfection with siRNAs also suppressed the production of infectious virus by up to 18- to 32-fold as assessed by a HA test and 93- to 494-fold as assessed by TCID(50) assay. Furthermore, treatment with siRNAs caused a 53-91% reduction in the viral genome copy number as assessed by real-time RT-PCR. CONCLUSION: These results suggested that the four species of siRNAs can efficiently inhibit PHE-CoV genome replication and infectious virus production.

Using a two-sample mendelian randomization analysis to explore the relationship between physical activity and Alzheimer's disease.

Evidence from previous epidemiological studies on the effect of physical activity on the risk of Alzheimer's disease (AD) is conflicting. We performed a two-sample Mendelian randomization analysis to verify whether physical activity is causally associated with AD. This study used two-sample Mendelian randomization (MR) analysis to estimate the association between physical activity (including overall activity, sedentary behavior, walking, and moderate-intensity activity) and AD. Genetic instruments for physical activity were obtained from published genome-wide association studies (GWAS) including 91,105 individuals from UK Biobank. Summary-level GWAS data were extracted from the International Genomics of Alzheimer's Project IGAP (21,982 patients with AD and 41,944 controls). Inverse Variance Weighted (IVW) was used to estimate the effect of physical activity on AD. Sensitivity analyses including weighted median, MR-Egger, MR-PRESSO, and leave-one-out analysis were used to estimate pleiotropy and heterogeneity. Mendelian randomization evidences suggested a protective relationship between walking and AD (odds ratio (OR) = 0.30, 95% confidence interval (CI), 0.13-0.68, P = 0.0039). Genetically predicted overall activity, sedentary behavior, and moderate-intensity activity were not associated with AD. In summary, this study provided evidence that genetically predicted walking might associate with a reduced risk of AD. Further research into the causal association between physical activity and AD could help to explore the real relationship and provide more measures to reduce AD risk.

Real-world effectiveness of COVID-19 vaccines: a literature review and meta-analysis.

OBJECTIVE: To estimate the coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) against concerned outcomes in real-world settings. METHODS: Studies reporting COVID-19 VE from August 6, 2020 to October 6, 2021 were included. The summary VE (with 95% confidence intervals (95% CI)) against disease related to COVID-19 was estimated. The results were presented in forest plots. Predefined subgroup analyses and sensitivity analyses were also performed. RESULTS: A total of 51 records were included in this meta-analysis. In fully vaccinated populations, the VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19-related hospitalization, admission to the intensive care unit, and death was 89.1% (95% CI 85.6-92.6%), 97.2% (95% CI 96.1-98.3%), 97.4% (95% CI 96.0-98.8%), and 99.0% (95% CI 98.5-99.6%), respectively. The VE against infection in the general population aged ≥16 years, the elderly, and healthcare workers was 86.1% (95% CI 77.8-94.4%), 83.8% (95% CI 77.1-90.6%), and 95.3% (95% CI 92.0-98.6%), respectively. For those fully vaccinated against infection, the observed effectiveness of the Pfizer-BioNTech vaccine was 91.2% and of the Moderna vaccine was 98.1%, while the effectiveness of the CoronaVac vaccine was found to be 65.7%. CONCLUSIONS: The COVID-19 vaccines are highly protective against SARS-CoV-2-related diseases in real-world settings.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern in real-world: a literature review and meta-analysis.

Knowing vaccine effectiveness (VE) against variants of concern (VOCs) in the real-world setting is essential for public health decision-making. A systematic landscape of the VE against a series of clinical outcomes caused by the VOCs in the real-world setting is needed. We systematically searched for studies that evaluated VE against VOCs in the real-world setting and collected individual data. We identified 113 studies meeting the eligibility criteria. We found full vaccination provided strong protection against each clinical outcome with summary VE ranging from 86.8% to 96.0% Alpha, moderate protection against infection caused by Beta, Gamma and Delta with summary VE ranging from 70.9% to 72.8%, strong protection against severe disease caused by Delta with summary VE ranging from 84.9% to 90.3%, limited protection with summary VE of 23.5% (95% CI, 17.0-29.5) against infection and moderate protection with summary VE ranging from 56.5% to 82.4% against severe diseases caused by Omicron. Booster vaccination can provide a substantial improvement in protection against Delta and Omicron, but not as much as the Delta. The meta-regression analysis showed that the VE against the Omicron wanned over time, and the VE against hospitalization declined relatively slowly, compared to against infection. Those findings supported the need for public health measures, increasing booster vaccination coverage in response to current and new infectious waves driven by variants and developing broadly protective vaccines to confront virus evolution.

Association between sleep status and lower urinary tract symptoms among men aged 40 or older in Zhengzhou.

A cross-sectional study based on the community was conducted to explore the association between sleep status and LUTS among middle and old-aged men. Male residents in Zhengzhou aged 40 or older were recruited. Participants received the Pittsburgh Sleep Quality Index questionnaire and the International Prostate Symptom Score questionnaire to evaluate sleep status and the severity of lower urinary tract symptoms (LUTS), respectively. Logistic regression analyses and linear regression analyses were performed to evaluate the relationship between sleep quality and sleep duration and LUTS. A total of 5785 participants were enrolled. Multivariable analyses showed a positive relationship between sleep quality and LUTS (ß 0.716, 95% CI 0.647-0.784), and poor sleepers were significantly associated with moderate or severe LUTS (OR 2.486, 95% CI 2.095-2.950). U-shaped dose-response relationship revealed that sleeping less than 5.8 h/day and more than 7.9 h/day was related to moderate or severe LUTS and more than 7.9 h/day of sleep duration was associated with poor voiding and storage symptoms (P for nonlinearity < 0.001). Similar relationship was observed between sleep status and nocturia. It showed a significantly positive relationship between sleep quality and LUTS. U-shaped dose-response relationships between sleep duration and LUTS were observed.

Integrated Analysis of miRNA-mRNA Expression in Mink Lung Epithelial Cells Infected With Canine Distemper Virus.

Canine distemper (CD) caused by canine distemper virus (CDV) is one of the major infectious diseases in minks, bringing serious economic losses to the mink breeding industry. By an integrated analysis of microRNA (miRNA)-messenger RNA (mRNA), the present study analyzed the changes in the mink transcriptome upon CDV infection in mink lung epithelial cells (Mv. l. Lu cells) for the first time. A total of 4,734 differentially expressed mRNAs (2,691 upregulated and 2,043 downregulated) with |log2(FoldChange) |>1 and P-adj<0.05 and 181 differentially expressed miRNAs (152 upregulated and 29 downregulated) with |log2(FoldChange) |>2 and P-adj<0.05 were identified. Gene Ontology (GO) enrichment indicated that differentially expressed genes (DEGs) were associated with various biological processes and molecular function, such as response to stimulus, cell communication, signaling, cytokine activity, transmembrane signaling receptor activity and signaling receptor activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the combination of miRNA and mRNA was done for immune and inflammatory responses, such as Janus kinase (JAK)-signal transducer and activator (STAT) signaling pathway and nuclear factor (NF)-kappa B signaling pathway. The enrichment analysis of target mRNA of differentially expressed miRNA revealed that mir-140-5p and mir-378-12 targeted corresponding genes to regulate NF-kappa B signaling pathway. JAK-STAT signaling pathway could be modulated by mir-425-2, mir-139-4, mir-140-6, mir-145-3, mir-140-5p and mir-204-2. This study compared the influence of miRNA-mRNA expression in Mv. l. Lu cells before and after CDV infection by integrated analysis of miRNA-mRNA and analyzed the complex network interaction between virus and host cells. The results can help understand the molecular mechanism of the natural immune response induced by CDV infection in host cells.

Antiviral effect of lysosomotropic disaccharide trehalose on porcine hemagglutinating encephalomyelitis virus, a highly neurotropic betacoronavirus.

Many members of the genus Betacoronavirus are neurotropic viruses that frequently cause serious harm to humans or animals, including highly neurotropic porcine hemagglutinating encephalomyelitis virus (PHEV). Nevertheless, very few approved treatments exist to combat these viruses. Lysosomotropic trehalose, a widely used, nontoxic, natural disaccharide that can traverse the blood-brain barrier, has been proposed as a potential antiviral agent for use in prevention or treatment of betacoronavirus-associated infections. The purpose of this study was to determine if trehalose could inhibit PHEV infection of cells of a mouse central nervous system-derived neuroblastoma cell line in vitro or brain cells in vivo. Our results demonstrated that treatment of PHEV-infected mouse neuroblastoma cells and mice with trehalose reduced viral replication and that these trehalose antiviral effects were dependent on expression of lysosomal protein progranulin. Collectively, these results indicated that trehalose holds promise as a new antiviral agent for use in controlling neurotropic betacoronavirus infections.