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Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.
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Variación Genética/genética , Enfermedades por Picaduras de Garrapatas/microbiología , Garrapatas/genética , Animales , Línea Celular , Vectores de Enfermedades , Especificidad del Huésped/genéticaRESUMEN
The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.
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Genoma Viral , Filogenia , Infecciones del Sistema Respiratorio , Humanos , China/epidemiología , Genoma Viral/genética , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Sistema Respiratorio/virología , Preescolar , Adulto , Niño , ARN Viral/genética , Persona de Mediana EdadRESUMEN
BACKGROUND: Malaria remains a significant public health concern in Niger, with the number of cases increasing from 592,334 in 2000 to 3,138,696 in 2010. In response, a concerted campaign against the disease has been initiated. However, the implementation of these malaria interventions and their association with epidemiological behaviour remains unclear. METHODS: A time-series study was conducted in Niger from 2010 to 2019. Multiple data sources concerning malaria were integrated, encompassing national surveillance data, Statistic Yearbook, targeted malaria control interventions, and meteorological data. Incidence rate, mortality rate, and case fatality ratio (CFR) by different regions and age groups were analysed. Joinpoint regression models were used to estimate annual changes in malaria. The changes in coverage of malaria interventions were evaluated. RESULTS: Between 2010 to 2019, the incidence rate of malaria decreased from 249.43 to 187.00 cases per 1,000 population in Niger. Niamey had a high annual mean incidence rate and the lowest CFR, while Agadez was on the contrary. Joinpoint regression analysis revealed a declining trend in malaria incidence for all age groups except the 10-24 years group, and the mortality rate and the CFR initially decreased followed by an increase in all age groups. Niger has implemented a series of malaria interventions, with the major ones being scaled up to larger populations during the study period. CONCLUSIONS: The scale-up of multi-interventions in Niger has significantly reduced malaria incidence, but the rise in mortality rate and CFR addresses the challenges in malaria control and elimination. Malaria endemic countries should enhance surveillance of malaria cases and drug resistance in Plasmodium, improve diagnosis and treatment, expand the population coverage of insecticide-treated bed nets and seasonal malaria chemoprevention, and strengthen the management of severe malaria cases.
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Mosquiteros Tratados con Insecticida , Malaria , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Niger/epidemiología , Malaria/epidemiología , Malaria/prevención & control , Proyectos de Investigación , IncidenciaRESUMEN
BACKGROUND: Heart failure (HF) is a rapidly growing global disease burden with high mortality rates. We aimed to utilize mendelian randomization (MR) analyses to investigate the association between educational attainment (EA) and HF, and to evaluate the contribution of modifiable risk factors as mediators. METHODS: We applied a two-sample MR approach based on the largest genome-wide association studies (GWAS) to investigate the causal relationship between EA and HF. Data collection was conducted in July 2023. We then conducted mediation analyses to explore whether body mass index (BMI), blood pressure, and type 2 diabetes mellitus (T2DM) mediate the effect of EA on HF, and utilized multivariable MR to estimate the proportion of mediation attributed to these factors. RESULTS: Genetically predicted 3.4 years of additional education was associated with a decrease in the risk of HF (OR 0.76 for each 3.4 years of schooling; 95% CI 0.72, 0.81). BMI, T2DM, systolic blood pressure, and diastolic blood pressure mediated 40.82% (95% CI: 28.86%, 52.77%), 18.00% (95% CI: 12.10%, 23.90%), 11.60% (95% CI: 7.63%, 15.56%), and 7.80% (95% CI: 4.63%, 10.96%) of the EA-HF association, respectively. All risk factors combined were estimated to mediate 63.81% (95% CI: 45.91%, 81.71%) of the effect of EA on HF. CONCLUSION: Higher EA has a protective effect against the risk of HF, and potential mechanisms may include regulation of BMI, blood pressure, and blood glucose. Further research is needed to understand whether interventions targeting these factors could influence the association between EA and HF risk.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Escolaridad , Estudio de Asociación del Genoma Completo , Insuficiencia Cardíaca , Análisis de la Aleatorización Mendeliana , Humanos , Diabetes Mellitus Tipo 2/genética , Factores de Riesgo , Presión Sanguínea , Masculino , Femenino , Factores Socioeconómicos , Persona de Mediana EdadRESUMEN
Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.
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Genómica , Cabras , Animales , Humanos , Prevalencia , Filogenia , Anaplasma/genética , China/epidemiologíaRESUMEN
The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.
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Coronavirus Humano 229E , Coronavirus Humano NL63 , Coronavirus Humano OC43 , Humanos , Estaciones del Año , Betacoronavirus , China , Coronavirus Humano OC43/genéticaRESUMEN
BACKGROUND: The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. METHODS: In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. RESULTS: In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ2 test for trend, P < 0.0001). Urban areas had a significantly higher ID than rural areas, with a relative risk of 1.25 (95% CI 1.23-1.27). Adolescents aged 10-19 years had the highest ID of varicella, women aged 20-39 years had significantly higher IDs of syphilis and trichomoniasis, and people aged ≥ 60 years had significantly higher IDs of zoster and viral conjunctivitis (all P < 0.05). CONCLUSIONS: Infectious diseases remain a substantial public health problem, and non-notifiable diseases should not be neglected. Multi-source-based big data are beneficial to better understand the profile and dynamics of infectious diseases.
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Enfermedades Transmisibles , Sífilis , Adolescente , Adulto , Macrodatos , Niño , China/epidemiología , Enfermedades Transmisibles/epidemiología , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: The ongoing pandemic of novel coronavirus disease 2019 (COVID-19) is challenging the global public health system. Sex differences in infectious diseases are a common but neglected problem. METHODS: We used the national surveillance database of COVID-19 in mainland China to compare gender differences in attack rate (AR), proportion of severe and critical cases (PSCC), and case fatality rate (CFR) in relation to age, affected province, and onset-to-diagnosis interval. RESULTS: The overall AR was significantly higher in females than in males (63.9 vs 60.5 per 1 million persons; P Ë .001). In contrast, PSCC and CFR were significantly lower among females (16.9% and 4.0%) than among males (19.5% and 7.2%), with odds ratios of 0.87 and 0.57, respectively (both P Ë .001). The female-to-male differences were age dependent, and were significant among people aged 50-69 years for AR and in patients aged 30 years or older for both PSCC and CFR (all P ≤ .001). The AR, PSCC, and CFR varied greatly from province to province. However, female-to-male differences in AR, PSCC, and CFR were significant in the epicenter, Hubei province, where 82.2% confirmed cases and 97.4% deaths occurred. After adjusting for age, affected province, and onset-to-diagnosis interval, the female-to-male difference in AR, PSCC, and CFR remained significant in multivariate logistic regression analyses. CONCLUSIONS: We elucidate an age-dependent gender dimorphism for COVID-19, in which females have higher susceptibility but lower severity and fatality. Further epidemiological and biological investigations are required to better understand the sex-specific differences for effective interventions.
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Factores de Edad , COVID-19/epidemiología , Vigilancia de la Población , SARS-CoV-2 , Factores Sexuales , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución por SexoAsunto(s)
Genoma de los Insectos/genética , Ixodidae/genética , Filogeografía , Fiebre Maculosa de las Montañas Rocosas/transmisión , Animales , China , Humanos , Ixodidae/clasificación , Ixodidae/patogenicidad , Anotación de Secuencia Molecular , Nueva Zelanda , Rickettsia rickettsii/genética , Rickettsia rickettsii/patogenicidad , Fiebre Maculosa de las Montañas Rocosas/genéticaRESUMEN
BACKGROUND: A model developed specifically for stable coronary artery disease (SCAD) patients to predict perioperative major adverse cardiovascular events (MACE) has not been previously reported. METHODS: The derivation cohort consisted of 5780 patients with SCAD undergoing noncardiac surgery at the First Affiliated Hospital of Zhejiang University School of Medicine, from January 1, 2013 until May 31, 2021. The validation cohort consisted of 2677 similar patients from June 1, 2021 to May 31, 2023. The primary outcome was a composite of MACEs (death, resuscitated cardiac arrest, myocardial infarction, heart failure, and stroke) intraoperatively or during hospitalization postoperatively. RESULTS: Six predictors, including Creatinine >90 µmol/L, Hemoglobin <110 g/L, Albumin <40 g/L, Leukocyte >10 ×109/L, high-risk Surgery (general abdominal or vascular), and American Society of Anesthesiologists (ASA) class (III or IV), were selected in the final model (CHALSA score). Each patient was assigned a CHALSA score of 0, 1, 2, 3, or > 3 according to the number of predictors present. The incidence of perioperative MACEs increased steadily across the CHALSA score groups in both the derivation (0.5%, 1.4%, 2.9%, 6.8%, and 23.4%, respectively; p < 0.001) and validation (0.3%, 1.5%, 4.1%, 9.2%, and 29.2%, respectively; p < 0.001) cohorts. The CHALSA score had a higher discriminatory ability than the revised cardiac risk index (C statistic: 0.827 vs. 0.695 in the validation dataset; p < 0.001). CONCLUSIONS: The CHALSA score showed good validity in an external dataset and will be a valuable bedside tool to guide the perioperative management of patients with SCAD undergoing noncardiac surgery.
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Enfermedad de la Arteria Coronaria , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/epidemiología , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Estudios de Cohortes , Valor Predictivo de las Pruebas , Procedimientos Quirúrgicos Operativos/efectos adversos , Medición de Riesgo/métodos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Rift valley fever (RVF) is listed as one of prioritized diseases by WHO. This study aims to describe RVF virus' landscape distribution globally, and to insight dynamics change of its evolution, prevalence, and outbreaks in the process of breaking geographical barriers. METHODS: A systematic literature review and meta-analyses was conducted to estimate RVF prevalence by hosts using a random-effect model. Molecular clock-based phylogenetic analyses were performed to estimate RVF virus nucleotide substitution rates using nucleotide sequences in NCBI database. RVF virus prevalence, nucleotide substitution rates, and outbreaks were compared before and after breaking geographical barriers twice, respectively. RESULTS: RVF virus was reported from 26 kinds of hosts covering 48 countries from 1930 to 2022. Since RVF broke geographical barriers, (1) nucleotide substitution rates significantly increased after firstly spreading out of Africa in 2000, (2) prevalence in humans significantly increased from 1.92 % (95 % CI: 0.86-3.25 %) to 3.03 % (95 % CI: 2.09-4.12 %) after it broke Sahara Desert geographical barriers in 1977, and to 5.24 % (95 % CI: 3.81-6.82 %) after 2000, (3) RVF outbreaks in humans and the number of wildlife hosts presented increasing trends. RVF virus spillover may exist between bats and humans, and accelerate viral substitution rates in humans. During outbreaks, the RVF virus substitution rates accelerated in humans. 60.00 % RVF outbreaks occurred 0-2 months after floods and (or) heavy rainfall. CONCLUSION: RVF has the increasing risk to cause pandemics, and global collaboration on "One Health" is needed to prevent potential pandemics.
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Brotes de Enfermedades , Fiebre del Valle del Rift , Virus de la Fiebre del Valle del Rift , Fiebre del Valle del Rift/epidemiología , Virus de la Fiebre del Valle del Rift/genética , Humanos , Animales , Prevalencia , FilogeniaRESUMEN
The emergence of Anaplasma bovis or A. bovis-like infection in humans from China and the United States of America has raised concern about the public health importance of this pathogen. Although A. bovis has been detected in a wide range of ticks and mammals in the world, no genome of the pathogen is available up to now, which has prohibited us from better understanding the genetic basis for its pathogenicity. Here we describe an A. bovis genome from metagenomic sequencing of an infected goat in China. Anaplasma bovis had the smallest genome of the genus Anaplasma, and relatively lower GC content. Phylogenetic analysis of single-copy orthologue sequence showed that A. bovis was closely related to A. platys and A. phagocytophilum, but relatively far from intraerythrocytic Anaplasma species. Anaplasma bovis had 116 unique orthogroups and lacked 51 orthogroups in comparison to other Anaplasma species. The virulence factors of A. bovis were significantly less than those of A. phagocytophilum, suggesting less pathogenicity of A. bovis. When tested by specific PCR assays, A. bovis was detected in 23 of 29 goats, with an infection rate up to 79.3% (95% CI: 64.6% â¼94.1%). The phylogenetic analyses based on partial 16S rRNA, gltA and groEL genes indicated that A. bovis had high genetic diversity. The findings of this study lay a foundation for further understanding of the biological characteristics and genetic diversity of A. bovis, and will facilitate the formulation of prevention and control strategies.
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Anaplasma , Genómica , Humanos , Animales , Filogenia , ARN Ribosómico 16S/genética , Anaplasma/genética , China/epidemiología , Cabras , Variación GenéticaRESUMEN
BACKGROUND: Haemaphysalis concinna, carrying multiple pathogens, has attracted increasing attention because of its expanded geographical range and significant role in disease transmission. This study aimed to identify the potential public health risks posed by H. concinna and H. concinna-associated pathogens. METHODS: A comprehensive database integrating a field survey, literature review, reference book, and relevant websites was developed. The geographical distribution of H. concinna and its associated pathogens was illustrated using ArcGIS. Meta-analysis was performed to estimate the prevalence of H. concinna-associated microbes. Phylogenetic and geographical methods were used to investigate the role of birds in the transmission of H. concinna-associated microbes. The potential global distribution of H. concinna was predicted by ecological niche modeling. RESULTS: Haemaphysalis concinna was distributed in 34 countries across the Eurasian continent, predominantly in China, Russia, and Central Europe. The tick species carried at least 40 human pathogens, including six species in the Anaplasmataceae family, five species of Babesia, four genospecies in the complex Borrelia burgdorferi sensu lato, ten species of spotted fever group rickettsiae, ten species of viruses, as well as Francisella, Coxiella, and other bacteria. Haemaphysalis concinna could parasitize 119 host species, with nearly half of them being birds, which played a crucial role in the long-distance transmission of tick-borne microbes. Our predictive modeling suggested that H. concinna could potentially survive in regions where the tick has never been previously recorded such as central North America, southern South America, southeast Oceania, and southern Africa. CONCLUSIONS: Our study revealed the wide distribution, broad host range, and pathogen diversity of H. concinna. Authorities, healthcare professionals, and the entire community should address the growing threat of H. concinna and associated pathogens. Tick monitoring and control, pathogen identification, diagnostic tools, and continuous research should be enhanced.
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Babesia , Ixodes , Garrapatas , Animales , Europa (Continente) , Ixodidae/microbiología , Filogenia , Garrapatas/microbiologíaRESUMEN
AIMS: Circular RNAs (circRNAs) are considered important regulators of biological processes, but their impact on atherosclerosis development, a key factor in coronary artery disease (CAD), has not been fully elucidated. We aimed to investigate their potential use in patients with CAD and the pathogenesis of atherosclerosis. METHODS AND RESULTS: Patients with stable angina (SA) or acute coronary syndrome (ACS) and controls were selected for transcriptomic screening and quantification of circRNAs in blood cells. We stained carotid plaque samples for circRNAs and performed gain- and loss-of-function studies in vitro. Western blots, protein interaction analysis, and molecular approaches were used to perform the mechanistic study. ApoE-/- mouse models were employed in functional studies with adeno-associated virus-mediated genetic intervention. We demonstrated elevated circARCN1 expression in peripheral blood mononuclear cells from patients with SA or ACS, especially in those with ACS. Furthermore, higher circARCN1 levels were associated with a higher risk of developing SA and ACS. We also observed elevated expression of circARCN1 in carotid artery plaques. Further analysis indicated that circARCN1 was mainly expressed in monocytes and macrophages, which was also confirmed in atherosclerotic plaques. Our in vitro studies provided evidence that circARCN1 affected the interaction between HuR and ubiquitin-specific peptidase 31 (USP31) mRNA, resulting in attenuated USP31-mediated NF-κB activation. Interestingly, macrophage accumulation and inflammation in atherosclerotic plaques were markedly decreased when circARCN1 was knocked down with adeno-associated virus in macrophages of ApoE-/- mice, while circARCN1 overexpression in the model exacerbated atherosclerotic lesions. CONCLUSIONS: Our findings provide solid evidence macrophagic-expressed circARCN1 plays a role in atherosclerosis development by regulating HuR-mediated USP31 mRNA stability and NF-κB activation, suggesting that circARCN1 may serve as a factor for atherosclerotic lesion formation.
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The continual emergence of tick-borne rickettsioses has garnered widespread global attention. Candidatus Rickettsia barbariae (Candidatus R. barbariae), which emerged in Italy in 2008, has been detected in humans from northwestern China. However, the lack of Candidatus R. barbariae genome and isolated strains limits the understanding of its biological characteristics and genomic features. Here, we isolated the Rickettsia for the first time from eggs of Rhipicephalus turanicus in northwestern China, and assembled its whole genome after next-generation sequencing, so we modified the proposed name to Rickettsia barbariae (R. barbariae) to conform to the International Code of Nomenclature of Prokaryotes. Phylogenetic analysis based on the whole genome revealed that it was most closely related to the pathogenic Rickettsia parkeri and Rickettsia africae. All virulence factors, present in the pathogenic spotted fever group rickettsiae, were identified in the R. barbariae isolate. These findings highlight the pathogenic potential of R. barbariae and the necessity for enhanced surveillance of the emerging Rickettsia in the human population.
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Genoma Bacteriano , Filogenia , Rickettsia , Rickettsia/genética , Rickettsia/aislamiento & purificación , Rickettsia/clasificación , Animales , China , Rhipicephalus/microbiología , Humanos , Infecciones por Rickettsia/microbiología , Factores de Virulencia/genética , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Secuenciación Completa del Genoma , Óvulo/microbiologíaRESUMEN
Ticks are important vectors of zoonotic pathogens, and represent an increasing threat for human and animal health. Considering the complex natural environments of Ningxia Hui Autonomous Region, China, we expect the diverse tick species in this region. Here, we conduct a field survey on parasitic and host-seeking ticks. A total of 10,419 ticks were collected, which belonged to nine species of four genera. There were significant differences in terms of vegetation index, altitude, and seven climatic factors among the four tick genera -Hyalomma, Dermacentor, Haemaphysalis, and Ixodes, except between Haemaphysalis and Ixodes, where no significant differences were observed in these factors. The ecological niche modelling revealed that the suitable habitats for Hyalomma asiaticum was in the northwest Ningxia, with annual ground surface temperature as the most important factor. The suitable area for Dermacentor nuttalli was in the southwest and eastern regions of Ningxia with elevation as the highest contribution. D. silvarum was best suited to the southern Ningxia also with elevation as the most important factor. The four tick species including Haemaphysalis longicornis, Hae. qinghaiensis, Hae. japonica, and Ixodes persulcatus were best suited to the southernmost Ningxia with annual precipitation as the main factors for Hae. longicornis and elevation for the other three ticks. The results of predicted potential distribution of different tick species provide a scientific basis for the prevention and control of ticks and tick-borne diseases in the region. Furthermore, the subsequent impacts of the Greening Program to regain forests and grasslands from former agricultural lands in Ningxia on tick population dynamics deserve further investigation.
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We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.
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Infecciones por Coronavirus , Coronavirus , Pangolines , Animales , Femenino , Humanos , Ratones , China , Quirópteros , Citocinas , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Ratones Transgénicos , Pangolines/virologíaRESUMEN
Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.
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Enzima Convertidora de Angiotensina 2 , Betacoronavirus , Pangolines , Animales , Humanos , Ratones , Enzima Convertidora de Angiotensina 2/metabolismo , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidad , Chlorocebus aethiops , Pulmón/virología , Pulmón/patología , Ratones Transgénicos , Pangolines/virología , SARS-CoV-2/patogenicidad , SARS-CoV-2/genética , Células Vero , Replicación ViralRESUMEN
BACKGROUND: Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. RESULTS: We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. CONCLUSIONS: These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.
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Ixodidae , Phlebovirus , Garrapatas , Animales , Humanos , Ixodidae/genética , Haemaphysalis longicornis , Viroma/genética , Filogenia , Phlebovirus/genéticaRESUMEN
The development of hydrogen evolution reaction (HER) technology that operates stably in a wide potential of hydrogen (pH) range of electrolytes is particular important for large-scale hydrogen production. However, the rational design of low-cost and pH-universal electrocatalyst with high catalytic performance remains a huge challenge. Herein, Co2P nanoparticles strongly coupled with P-modified NiMoO4 nanorods are directly grown on nickel foam (NF) substrates through carbon layer encapsulation (denoted as C-Co2P@P-NiMoO4/NF) by hydrothermal, deposition, and phosphating processes. This novel kind of hierarchical heterojunction has abundant heterogeneous interfaces, strong electronic interactions, and optimized reaction kinetics, representing the highly-active pH-universal electrodes for HER. Remarkably, the C-Co2P@P-NiMoO4/NF catalyst shows excellent HER properties in acidic and basic electrolytes, where the overpotentials of 105 mV and 107 mV are applied to drive the current density of 100 mA cm-2. In addition, a low overpotential of 177 mV at 100 mA cm-2 along with high stability is realized in 1 M phosphate buffer solution (PBS), which is close to the state-of-the-art non-precious metal electrocatalysts. Our work not only provides a class of robust pH-universal electrocatalyst but also offers a novel way for the rational design of other heterogeneous materials bythe interface regulation strategy.