Electrochemical epitaxial PbTe nanowires photodetector for NIR response.

Lead telluride nanowires deposited by electrochemical atomic layers have broad application prospects in the field of photodetectors. In this work, using the method of electrochemical atomic layer deposition, we obtained different morphologies of lead telluride materials by controlling the deposition parameters, such as deposition time, temperature, and potential, and characterized them using SEM, TEM, XPS, and other techniques. A lead telluride nanowire detector with good performance was prepared. The photoresponsivity of the detector is 102 mA W-1, the detectivity is 2.1 × 108Jones, and the response time and recovery time are 0.52 s and 0.54 s respectively at 2.7µm wavelength laser irradiation.

A Comparative Study of Associated Microbiota Between Pig Farm and Pig Slaughterhouse in Guangdong, China.

The goal of this study was to compare the microbiota in different pig-present settings in China. Bioaerosol samples from pig farms and slaughterhouses and nasal samples from pig farmers and slaughterhouse workers were collected in Guangdong, southern China. The bacterial genomic DNA was isolated and subjected to 16S sequencing. The data were analyzed using QIIME2 with the DADA2 pipeline. A total of 14,923,551 clean reads and 2785 operational taxonomic units (OTUs) were obtained, which were mostly grouped into 4 phyla (Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria) and 220 families. The microbiota richness of nasal samples in pig-present workers was higher than that of bioaerosols collected in the vicinity of the pig enclosures. There were 31.7% (620/1954) shared OTUs between pig farm bioaerosols and pig farmers which was higher than that between pig slaughterhouses and slaughterhouse workers (23.4%, 364/1553) (p < 0.001). Acinetobacter and Pseudomonas were the most abundant in pig-present bioaerosols, and Staphylococcus, Pseudomonas, and Corynebacterium were dominant bacterial genus in pig farmers. The bacterial patterns are also specific to the location of sample collected. The results suggest that bioaerosol microbiota interact with human nasal microbes in the vicinity of the pig farm enclosures, providing the basis for further analysis of microbial transmission across hosts in pig-present settings.

Prevalence of human alveolar echinococcosis in China: a systematic review and meta-analysis.

BACKGROUND: Human alveolar echinococcosis (HAE), caused by the larvae of Echinococcus multilocularis, is a severe parasitic disease that is a major public health concern. New HAE cases in China account for 91% of the global HAE burden every year. Although there are a few studies and systematic reviews (SRs) on the prevalence of HAE in China, trends in the prevalence have not been estimated. This study aims to describe the overall variation in the trend of HAE prevalence in China, and provide evidence for preventive measures in the future. METHODS: Thirty-five eligible studies were retrieved from PubMed, Web of Science, EMBASE, CNKI, Wanfang Data, and VIP, and included in the SR and meta-analysis. An adjusted Agency for Healthcare Research and Quality checklist was used to evaluate study quality. The arcsine transformation was used to adjust the individual reported prevalence, and the pooled HAE prevalence was calculated. Heterogeneity was evaluated using the chi-square test and I2 statistic. Forest plots were generated for the meta-analysis, and publication bias of the studies was assessed using the Egger's test and funnel plots. We conducted subgroup analyses, sensitivity analyses, and meta-regression analyses to analyze the source of heterogeneity and factors potentially influencing the prevalence of HAE. RESULTS: The meta-analysis indicated that the pooled HAE prevalence in China was 0.96% (95% CI: 0.71 to 1.25%). Factors potentially influencing HAE prevalence were female sex (OR = 1.60, 95% CI: 1.35 to 1.91, P<0.01), being ≥30 years old (OR = 4.72, 95% CI: 2.29 to 9.75, P<0.01), and being farmers and/or herdsmen (OR = 2.54, 95% CI: 1.60 to 4.02, P<0.01). The results of the meta-regression analysis (R2 = 38.11%, P < 0.01) indicated that HAE prevalence is on a downward trend. CONCLUSIONS: HAE prevalence has decreased over time and maintained low levels after 2005 in China. This decline was influenced by the utilization of One Health strategies as intervention measures. Therefore, these One Health strategies should be used as references to formulate future programs for HAE control. More high-quality epidemiological investigations and surveillance programs should be conducted in order to improve HAE control in the future.

ATP-binding cassette transporters and sterol O-acyltransferases interact at membrane microdomains to modulate sterol uptake and esterification.

A key component of eukaryotic lipid homeostasis is the esterification of sterols with fatty acids by sterol O-acyltransferases (SOATs). The esterification reactions are allosterically activated by their sterol substrates, the majority of which accumulate at the plasma membrane. We demonstrate that in yeast, sterol transport from the plasma membrane to the site of esterification is associated with the physical interaction of the major SOAT, acyl-coenzyme A:cholesterol acyltransferase (ACAT)-related enzyme (Are)2p, with 2 plasma membrane ATP-binding cassette (ABC) transporters: Aus1p and Pdr11p. Are2p, Aus1p, and Pdr11p, unlike the minor acyltransferase, Are1p, colocalize to sterol and sphingolipid-enriched, detergent-resistant microdomains (DRMs). Deletion of either ABC transporter results in Are2p relocalization to detergent-soluble membrane domains and a significant decrease (53-36%) in esterification of exogenous sterol. Similarly, in murine tissues, the SOAT1/Acat1 enzyme and activity localize to DRMs. This subcellular localization is diminished upon deletion of murine ABC transporters, such as Abcg1, which itself is DRM associated. We propose that the close proximity of sterol esterification and transport proteins to each other combined with their residence in lipid-enriched membrane microdomains facilitates rapid, high-capacity sterol transport and esterification, obviating any requirement for soluble intermediary proteins.

A preliminary analysis of microRNA as potential clinical biomarker for schizophrenia.

MicroRNAs (miRNA, miR) have been implicated as promising blood-based biomarkers for schizophrenia patients. This study aimed to clinically validate miRNA as potential schizophrenia biomarkers. Plasma levels of 10 miRNAs were analyzed using qPCR in a cohort of 61 schizophrenia patients and 62 normal controls, as well as 25 patients particularly selected for a six-week antipsychotic treatment course. Positive And Negative Syndrome Scale (PANSS), Global Assessment Scale (GAS) and Clinical Global Impression (CGI) were administered to assess the clinical symptoms. The results demonstrated that a panel of miRNAs consisting of miR-30e, miR-181b, miR-34a, miR-346 and miR-7 had significantly increased expression levels with significant combined diagnostic value (AUC:0.713; sensitivity:35.5%; specificity:90.2%). In response to pharmacological treatment, expression levels of miR-132, miR-181b, miR-432 and miR-30e were significantly decreased. In addition, the improvement of clinical symptomatology was significantly correlated with the changes of miR-132, miR-181b, miR-212 and miR-30e expression levels. Furthermore, the decreases of plasma levels of miR-132 and miR-432 were significantly greater in high-effect subgroup than those in low-effect subgroup after six-week treatment course. We conclude that miR-30e, miR-181b, miR-34a, miR-346 and miR-7 combined as a panel are potentially useful non-invasive biomarkers for schizophrenia diagnosis. Markers miR-132, miR-181b, miR-30e and miR-432 are potential indicators for symptomatology improvements, treatment responses and prognosis for schizophrenia patients.

SERPINB2 down-regulation contributes to chemoresistance in head and neck cancer.

Resistance to cisplatin-based chemotherapy is responsible for the majority of deaths from head and neck squamous cell carcinoma (HNSCC). In this study, using genome-wide gene expression analysis to investigate potential molecular mediators of HNSCC chemoresistance, we identified SERPINB2, a known inhibitor of extracellular serine proteinase urokinase-type plasminogen activator (uPA), as an important candidate. Whereas SERPINB2 is known to function as a suppressor of uPA molecular cascades, many of which play important roles in tumor invasion and metastasis, a role for SERPINB2 in cancer drug resistance has not been examined. By using quantitative real-time PCR and Western blot analysis, we determined that SERPINB2 mRNA and protein levels correlated with chemoresistance in HNSCC cell lines, and significantly lower SERPINB2 expression levels were observed in two cisplatin resistant HNSCC subclones compared to their isogenic drug-sensitive parental lines. Immunohistochemical analysis of HNSCC tumor tissues from patients treated with neoadjuvant cisplatin-based chemotherapy (n = 67 cases) revealed a significant association between SERPINB2 protein levels, tumor differentiation and patient relapse. Moreover, SERPINB2 down-regulation was a strong predictor of reduced overall survival in patients with HNSCC who received cisplatin-based chemotherapy (P = 0.001, log rank test). Studies using either siRNA-mediated down-regulation or forced over-expression of SERPINB2 in HNSCC cell lines confirmed a functional role for SERPINB2 in drug resistance. The findings were further supported using chemical inhibitors of STAT3 activity (a downstream effecter of uPAR signaling pathway), showing that STAT3 suppression altered HNSCC cell line cisplatin sensitivity. This is the first report on a role for SERPINB2 in acquired resistance to cisplatin in patients with HNSCC.

Schottky infrared detectors with optically tunable barriers beyond the internal photoemission limit.

Internal photoemission is a prominent branch of the photoelectric effect and has emerged as a viable method for detecting photons with energies below the semiconductor bandgap. This breakthrough has played a significant role in accelerating the development of infrared imaging in one chip with state-of-the-art silicon techniques. However, the performance of these Schottky infrared detectors is currently hindered by the limit of internal photoemission; specifically, a low Schottky barrier height is inevitable for the detection of low-energy infrared photons. Herein, a distinct paradigm of Schottky infrared detectors is proposed to overcome the internal photoemission limit by introducing an optically tunable barrier. This device uses an infrared absorbing material-sensitized Schottky diode, assisted by the highly adjustable Fermi level of graphene, which subtly decouples the photon energy from the Schottky barrier height. Correspondingly, a broadband photoresponse spanning from ultraviolet to mid-wave infrared is achieved, with a high specific detectivity of 9.83 × 1010 cm Hz1/2 W-1 at 2,700 nm and an excellent specific detectivity of 7.2 × 109 cm Hz1/2 W-1 at room temperature under blackbody radiation. These results address a key challenge in internal photoemission and hold great promise for the development of the Schottky infrared detector with high sensitivity and room temperature operation.

Convolutional neural network-assisted diagnosis of midpalatal suture maturation stage in cone-beam computed tomography.

OBJECTIVES: The selection of treatment for maxillary expansion is closely related to the calcification degree of the midpalatal suture. A classification method for individual assessment of the morphology of midpalatal suture in cone-beam computed tomography (CBCT) is useful for evaluating the calcification degree. Currently, convolutional neural networks (CNNs) have been introduced into the field of oral and maxillofacial imaging diagnosis. This study validated the ability of CNN models in assessing the maturation stage of the midpalatal suture. METHODS: The existing CNN model ResNet50 was trained to locate the CBCT transverse plane which contained a complete midpalatal suture. ResNet18, ResNet50, RessNet101, Inception-v3, and Efficientnetv2-s models were trained to evaluate the midpalatal suture maturation stage. Multi-class classification metrics, accuracy, recall, precision, F1-score, and area under the curve values from the receiver operating characteristic curve were used to evaluate the performance of the models, and gradient-weighted class activation map technology was utilised to visualise five midpalatal suture maturation stages for each model. RESULTS: Resnet50 demonstrated an accuracy of 99.74 % in identifying the transverse plane that contained the complete midpalatal suture. The highest accuracies achieved on the two-stage, three-stage, and five-stage maturation classification tests were 95.15, 88.06, and 75.37 %, all of which exceeded the average accuracy of three experienced orthodontists. CONCLUSIONS: The CNN model can locate the plane of the midpalatal suture in CBCT images and can assist clinicians in assessing the maturation stage of the midpalatal suture to select the means of maxillary expansion. CLINICAL SIGNIFICANCE: The application of artificial intelligence on CBCT midpalatal suture plane localisation and maturation stage evaluation enhances diagnostic and treatment efficiency and accuracy of individual assessment of midpalatal suture calcification degree. Additionally, it assists the clinical palatal expansion technique in achieving ideal results.

A meta-transcriptomic study of mosquito virome and blood feeding patterns at the human-animal-environment interface in Guangdong Province, China.

Mosquitoes are a formidable reservoir of viruses and important vectors of zoonotic pathogens. Blood-fed mosquitoes have been utilized to determine host infection status, overcoming the difficulties associated with sampling from human and animal populations. Comprehensive surveillance of potential pathogens at the interface of humans, animals, and the environment is currently an accredited method to provide an early warning of emerging or re-emerging infectious diseases and to proactively respond to them. Herein we performed comprehensive sampling of mosquitoes from seven habitats (residential areas, hospital, airplane, harbor, zoo, domestic sheds, and forest park) across five cities in Guangdong Province, China. Our aim was to characterize the viral communities and blood feeding patterns at the human-animal-environment interface and analyze the potential risk of cross-species transmission using meta-transcriptomic sequencing. 1898 female adult mosquitoes were collected, including 1062 Aedes and 836 Culex mosquitoes, of which approximately 12% (n = 226) were satiated with blood. Consequently, 101 putative viruses were identified, which included DNA and RNA viruses, and positive-stranded RNA viruses (+ssRNA) were the most abundant. According to viral diversity analysis, the composition of the viral structure was highly dependent on host species, and Culex mosquitoes showed richer viral diversity than Aedes mosquitoes. Although the virome of mosquitoes from different sampling habitats showed an overlap of 39.6%, multiple viruses were specific to certain habitats, particularly at the human-animal interface. Blood meal analysis found four mammals and one bird bloodmeal source, including humans, dogs, cats, poultry, and rats. Further, the blood feeding patterns of mosquitoes were found to be habitat dependent, and mosquitoes at the human-animal interface and from forests had a wider choice of hosts, including humans, domesticated animals, and wildlife, which in turn considerably increases the risk of spillover of potential zoonotic pathogens. To summarize, we are the first to investigate the virome of mosquitoes from multiple interfaces based on the One Health concept. The characteristics of viral community and blood feeding patterns of mosquitoes at the human-animal-environment interface were determined. Our findings should support surveillance activities to identify known and potential pathogens that are pathogenic to vertebrates.

Subcutaneous 5-azacitidine treatment of naturally occurring canine urothelial carcinoma: a novel epigenetic approach to human urothelial carcinoma drug development.

PURPOSE: We determined the efficacy, biological activity, pharmacokinetics and safety of the hypomethylating agent 5-azacitidine (Celgene Corp., Summit, New Jersey) in dogs with naturally occurring invasive urothelial carcinoma. MATERIALS AND METHODS: We performed a preclinical phase I trial in dogs with naturally occurring invasive urothelial carcinoma to examine once daily subcutaneous administration of 5-azacitidine in 28-day cycles at doses of 0.10 to 0.30 mg/kg per day according to 2 dose schedules, including days 1 to 5 (28-day cohort) or days 1 to 5 and 15 to 19 (14-day cohort). Clinical efficacy was assessed by serial cystosonography, radiography and cystoscopy. Urinary 5-azacitidine pharmacokinetic analysis was also done. Pretreatment and posttreatment peripheral blood mononuclear cell and invasive urothelial carcinoma DNA, respectively, was analyzed for global and gene specific [CDKN2A (p14ARF)] methylation changes. RESULTS: Enrolled in the study were 19 dogs with naturally occurring invasive urothelial carcinoma. In the 28-day cohort the maximum tolerated dose was 0.20 mg/kg per day with higher doses resulting in grade 3 or 4 neutropenia in 4 of 6 dogs. In the 14-day cohort the maximum tolerated dose was 0.10 mg/kg per day with grade 3 or 4 neutropenia seen in 2 of 3 dogs treated at higher doses. No grade 3 or 4 nonhematological toxicity was observed during either dosing schedule. Of 18 dogs evaluable for tumor response partial remission, stable disease and progressive disease were observed in 4 (22.2%), 9 (50.0%) and 4 (22.2%), respectively. Consistent 5-azacitidine levels (205 to 857 ng/ml) were detected in urine. Pretreatment and posttreatment methylation analysis revealed no significant correlation with clinical response. CONCLUSIONS: Subcutaneous 5-azacitidine showed promising clinical activity in a canine invasive urothelial carcinoma model, thus meriting further development in humans with urothelial carcinoma.

P-ResUnet: Segmentation of brain tissue with Purified Residual Unet.

Brain tissue of Magnetic Resonance Imaging is precisely segmented and quantified, which aids in the diagnosis of neurological diseases such as epilepsy, Alzheimer's, and multiple sclerosis. Recently, UNet-like architectures are widely used for medical image segmentation, which achieved promising performance by using the skip connection to fuse the low-level and high-level information. However, In the process of integrating the low-level and high-level information, the non-object information (noise) will be added, which reduces the accuracy of medical image segmentation. Likewise, the same problem also exists in the residual unit. Since the output and input of the residual unit are fused, the non-object information (noise) of the input of the residual unit will be in the integration. To address this challenging problem, in this paper we propose a Purified Residual U-net for the segmentation of brain tissue. This model encodes the image to obtain deep semantic information and purifies the information of low-level features and the residual unit from the image, and acquires the result through a decoder at last. We use the Dilated Pyramid Separate Block (DPSB) as the first block to purify the features for each layer in the encoder without the first layer, which expands the receptive field of the convolution kernel with only a few parameters added. In the first layer, we have explored the best performance achieved with DPB. We find the most non-object information (noise) in the initial image, so it is good for the accuracy to exchange the information to the max degree. We have conducted experiments with the widely used IBSR-18 dataset composed of T-1 weighted MRI volumes from 18 subjects. The results show that compared with some of the cutting-edge methods, our method enhances segmentation performance with the mean dice score reaching 91.093% and the mean Hausdorff distance decreasing to 3.2606.

Effects of COVID-19 Non-Pharmacological Interventions on Dengue Infection: A Systematic Review and Meta-Analysis.

Non-pharmacological interventions (NPIs) implemented during the coronavirus disease 2019 (COVID-19) pandemic have demonstrated significant positive effects on other communicable diseases. Nevertheless, the response for dengue fever has been mixed. To illustrate the real implications of NPIs on dengue transmission and to determine the effective measures for preventing and controlling dengue, we performed a systematic review and meta-analysis of the available global data to summarize the effects comprehensively. We searched Embase, PubMed, and Web of Science in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines from December 31, 2019, to March 30, 2022, for studies of NPI efficacy on dengue infection. We obtained the annual reported dengue cases from highly dengue-endemic countries in 2015-2021 from the European Centre for Disease Prevention and Control to determine the actual change in dengue cases in 2020 and 2021, respectively. A random-effects estimate of the pooled odds was generated with the Mantel-Haenszel method. Between-study heterogeneity was assessed using the inconsistency index (I2 ) and subgroup analysis according to country (dengue-endemic or non-endemic) was conducted. This review was registered with PROSPERO (CRD42021291487). A total of 17 articles covering 32 countries or regions were included in the review. Meta-analysis estimated a pooled relative risk of 0.39 (95% CI: 0.28-0.55), and subgroup revealed 0.06 (95% CI: 0.02-0.25) and 0.55 (95% CI: 0.44-0.68) in dengue non-endemic areas and dengue-endemic countries, respectively, in 2020. The majority of highly dengue-endemic countries in Asia and Americas reported 0-100% reductions in dengue cases in 2020 compared to previous years, while some countries (4/20) reported a dramatic increase, resulting in an overall increase of 11%. In contrast, there was an obvious reduction in dengue cases in 2021 in almost all countries (18/20) studied, with an overall 40% reduction rate. The overall effectiveness of NPIs on dengue varied with region and time due to multiple factors, but most countries reported significant reductions. Travel-related interventions demonstrated great effectiveness for reducing imported cases of dengue fever. Internal movement restrictions of constantly varying intensity and range are more likely to mitigate the entire level of dengue transmission by reducing the spread of dengue fever between regions within a country, which is useful for developing a more comprehensive and sustainable strategy for preventing and controlling dengue fever in the future.

An occupational risk of hepatitis E virus infection in the workers along the meat supply chains in Guangzhou, China.

Hepatitis E virus (HEV) causes infections in humans and animals. HEV have been identified in pig farms, markets and swine workers, but studies with parallel observations along the poultry and pork supply chains remains limited. This study aimed to characterize HEV infection risks in workers along the meat supply chain. Two rounds of cross-sectional surveys were performed among swine and poultry workers in pig and poultry farms, slaughterhouses, wholesale and retail live poultry markets, live pig markets and pork markets. Human sera from the workers and the general population were collected and tested for HEV specific IgM/IgG antibodies by commercial indirect-ELISA test kits. Risk factors of HEV seropositivity associated with different occupational settings were identified using logistic regression. 47.0% (156/332) of the swine workers and 40.2% (119/296) of the poultry workers were seropositive, compared to 26.1% (35/134) in the general population. Multivariable analysis showed that human HEV infection risk increased along the pork supply chain, with the highest risk at pig slaughterhouses (adjusted OR = 3.19, 95% CI = 1.49-6.88) and pork markets (adjusted OR = 2.02, 95% CI = 1.04-3.97), but no significant higher risk was observed among poultry workers. Swine occupational exposure is associated with HEV infection, especially in workers in pig slaughterhouses and pork markets. Strengthening control measures in these settings is important for HEV control and long term HEV elimination.

Inhibition of Chikungunya virus early replication by intracellular nanoantibodies targeting nsP2 Epitope Rich Region.

Chikungunya fever, caused by Chikungunya virus (CHIKV), is an Aedes mosquito-borne disease present worldwide, and millions of CHIKV infections have been reported. Treatment for CHIKV includes supportive care and anti-inflammatory medications, but there are currently no antiviral treatments or vaccines. Nonstructural protein 2 (nsP2) of CHIKV is the most important functional protein mediating virus replication and amplification, making it an ideal antiviral target for CHIKV. In this study, we determined the CHIKV nsP2 Epitope Rich Region, expressed recombinant nsP2 protein, and isolated 5 nsP2-specific nanobodies (Nb-A2, Nb-A9, Nb-D7, Nb-D12 and Nb-E12) from a phage display library comprising variable domains of Camellidae heavy chain-only antibodies (VHH). We subsequently established a stable Nbs-expressing HEK293T cell line to explore antiviral function. The results showed that Nb-A9 inhibited CHIKV replication at the early stage of CHIKV infection in HEK293T cells, and protected cells against CHIKV-induced cytopathic effect (CPE). This is possibly the first report of an Nbs-based strategy against CHIKV nsP2, Nb-A9 has great potential for developing a novel antiviral drug to treat CHIKV infection. The acquisition of antibodies has laid a foundation for further research on the function of CHIKV nsP2 and the development of therapeutic drugs.

CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.

Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the glycosylphosphatidylinositol (GPI) anchoring pathway), as the only gene whose expression was affected by the translocation. CDC91L1 was amplified and overexpressed in about one-third of bladder cancer cell lines and primary tumors, as well as in oncogenic uroepithelial cells transformed with human papillomavirus (HPV) E7. Forced overexpression of CDC91L1 malignantly transformed NIH3T3 cells in vitro and in vivo. Overexpression of CDC91L1 also resulted in upregulation of the urokinase receptor (uPAR), a GPI-anchored protein, and in turn increased STAT-3 phosphorylation in bladder cancer cells. Our findings suggest that CDC91L1 is an oncogene in bladder cancer, and implicate the GPI anchoring system as a potential oncogenic pathway and therapeutic target in human cancers.

Genomic characterization of Wenzhou mammarenavirus detected in wild rodents in Guangzhou City, China.

Wenzhou mammarenavirus (WENV) is a zoonotic pathogen newly discovered in east and southeast Asia. WENV has been found in wild rodent animals around the world while its standing is barely understood in Guangzhou city, where is known as a region of outbreak hotspot for zoonotic emerging infectious diseases. To investigate the prevalence and genomic characteristics of mammarenavirus in Guangzhou City, lung tissue samples from wild rodent species were collected from five districts of Guangzhou City in the year 2015 and 2016. The viral RNA was extracted and then subjected to mammarenavirus-specific PCR. The result revealed approximately 1.0% (3/306) nucleic acid positivity for lung tissue samples obtained from three rodent species: Mus musculus, Rattus flavipectus, and Rattus norvegicus. Viral metagenomic sequencing of three samples was then carried out and two full segment L and three full segment S sequences were obtained. Phylogenetics analysis indicated the sequences of the new mammarenavirus strain have 76.2% - 94.4% similarity to known WENV encoded genes, with the highest similarity to the WENV 9-24 strain. Population structure analysis grouped all known WENV into seven lineages, and this WENV Guangzhou strain was grouped with WENV 9-24 as well. Though the seroprevalence result was not available, our data provides the first nucleic acid evidence of circulating WENV in Guangzhou city, and it suggested WENV had a broader host tropism than previously known.

Pre-Existing Cross-Reactive Antibody Responses Do Not Significantly Impact Inactivated COVID-19 Vaccine-Induced Neutralization.

Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against severe acute respiratory syndrome CoV 2 (SARS-CoV-2). However, previous studies have produced divergent results regarding protective or damaging immunity induced by prior sCoV exposure. It remains unknown whether pre-existing humoral immunity plays a role in vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera samples from 36 healthy volunteers before and after immunization with inactivated whole-virion SARS-CoV-2 vaccines for COVID-19, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level pre-vaccination as well as the relationship between pre-existing sCoV immunity and vaccine-induced neutralization. We observed large amounts of pre-existing cross-reactive antibodies in the conserved regions among sCoVs, especially the S2 subunit. Excep t for a few peptides, the IgG and IgM fluorescence intensities against S, M and N peptides did not differ significantly between pre-vaccination and post-vaccination sera of vaccinees who developed a neutralization inhibition rate (%inhibition) <40 and %inhibition ≥40 after two doses of the COVID-19 vaccine. Participants with strong and weak pre-existing cross-reactive antibodies (strong pre-CRA; weak pre-CRA) had similar %inhibition pre-vaccination (10.9% ± 2.9% vs. 12.0% ± 2.2%, P=0.990) and post-vaccination (43.8% ± 25.1% vs. 44.6% ± 21.5%, P=0.997). Overall, the strong pre-CRA group did not show a significantly greater increase in antibody responses to the S protein linear peptides post-vaccination compared with the weak pre-CRA group. Therefore, we found no evidence for a significant impact of pre-existing antibody responses on inactivated vaccine-induced neutralization and antibody responses. Our research provides an important basis for inactivated SARS-CoV-2 vaccine use in the context of high sCoV seroprevalence.

Distribution of the COVID-19 epidemic and correlation with population emigration from Wuhan, China.

BACKGROUND: The ongoing new coronavirus pneumonia (Corona Virus Disease 2019, COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks. METHODS: The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed. RESULTS: The COVID-19 confirmed and death cases in Hubei province accounted for 59.91% (5806/9692) and 95.77% (204/213) of the total cases in China, respectively. Hot spot provinces included Sichuan and Yunnan, which are adjacent to Hubei. The time risk of Hubei province on the following day was 1.960 times that on the previous day. The number of cases in some cities was relatively low, but the time risk appeared to be continuously rising. The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943. The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases. CONCLUSIONS: The population that emigrated from Wuhan was the main infection source in other cities and provinces. Some cities with a low number of cases showed a rapid increase in case load. Owing to the upcoming Spring Festival return wave, understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.

Dynamic regulation of endothelial NOS mediated by competitive interaction with alpha-actinin-4 and calmodulin.

Alpha-actinins are critical components of the actin cytoskeleton. Here we show that alpha-actinins serve another important biological function by binding to and competitively inhibiting calcium-dependent activation of endothelial NOS (eNOS). Alpha-actinin-2 was found to associate with eNOS in a yeast two-hybrid screen. In vascular endothelial cells, which only express alpha-actinin-1 and -4, alpha-actinin-4 interacted and colocalized with eNOS. Addition of alpha-actinin-4 directly inhibited eNOS recombinant protein, and overexpression of alpha-actinin-4 inhibited eNOS activity in eNOS-transfected COS-7 cells and bovine aortic endothelial cells (BAECs). In contrast, knockdown of alpha-actinin-4 by siRNA increased eNOS activity in BAECs. The alpha-actinin-4-binding site on eNOS was mapped to a central region comprising the calmodulin-binding domain, and the eNOS-binding site on alpha-actinin-4 was mapped to the fourth spectrin-like rod domain, R4. Treatment of endothelial cells with a calcium ionophore, A23187, decreased alpha-actinin-4-eNOS interaction, leading to translocation of alpha-actinin-4 from plasma membrane to cytoplasm. Indeed, addition of calmodulin displaced alpha-actinin-4 binding to eNOS and increased eNOS activity. These findings indicate that eNOS activity in vascular endothelial cells is tonically and dynamically regulated by competitive interaction with alpha-actinin-4 and calmodulin.

LOXL1 and LOXL4 are epigenetically silenced and can inhibit ras/extracellular signal-regulated kinase signaling pathway in human bladder cancer.

Promoter hypermethylation is one of the common mechanisms leading to gene silencing in various human cancers. Using a combination of pharmacologic unmasking and microarray techniques, we identified 59 candidate hypermethylated genes, including LOXL1, a lysyl oxidase-like gene, in human bladder cancer cells. We further showed that LOXL1 and LOXL4 are commonly silenced genes in human bladder cancer cells, and this silence is predominantly related to promoter methylation. We also found LOXL1 and LOXL4 gene methylation and loss of expression in primary bladder tumors. In addition, somatic mutations were identified in LOXL4, but not in LOXL1 in bladder cancer. Moreover, reintroduction of LOXL1 and LOXL4 genes into human bladder cancer cells leads to a decrease of colony formation ability. Further studies indicated that the overexpression of LOXL1 and LOXL4 could antagonize Ras in activating the extracellular signal-regulated kinase (ERK) signaling pathway. Thus, our current study suggests for the first time that lysyl oxidase-like genes can act as tumor suppressor genes and exert their functions through the inhibition of the Ras/ERK signaling pathway in human bladder cancer.