RVdb: a comprehensive resource and analysis platform for rhinovirus research.

Rhinovirus (RV), a prominent causative agent of both upper and lower respiratory diseases, ranks among the most prevalent human respiratory viruses. RV infections are associated with various illnesses, including colds, asthma exacerbations, croup and pneumonia, imposing significant and extended societal burdens. Characterized by a high mutation rate and genomic diversity, RV displays a diverse serological landscape, encompassing a total of 174 serotypes identified to date. Understanding RV genetic diversity is crucial for epidemiological surveillance and investigation of respiratory diseases. This study introduces a comprehensive and high-quality RV data resource, designated RVdb (http://rvdb.mgc.ac.cn), covering 26 909 currently identified RV strains, along with RV-related sequences, 3D protein structures and publications. Furthermore, this resource features a suite of web-based utilities optimized for easy browsing and searching, as well as automatic sequence annotation, multiple sequence alignment (MSA), phylogenetic tree construction, RVdb BLAST and a serotyping pipeline. Equipped with a user-friendly interface and integrated online bioinformatics tools, RVdb provides a convenient and powerful platform on which to analyse the genetic characteristics of RVs. Additionally, RVdb also supports the efforts of virologists and epidemiologists to monitor and trace both existing and emerging RV-related infectious conditions in a public health context.

ZOVER: the database of zoonotic and vector-borne viruses.

Emerging infectious diseases significantly threaten global public health and socioeconomic security. The majority of emerging infectious disease outbreaks are caused by zoonotic/vector-borne viruses. Bats and rodents are the two most important reservoir hosts of many zoonotic viruses that can cross species barriers to infect humans, whereas mosquitos and ticks are well-established major vectors of many arboviral diseases. Moreover, some emerging zoonotic diseases require a vector to spread or are intrinsically vector-borne and zoonotically transmitted. In this study, we present a newly upgraded database of zoonotic and vector-borne viruses designated ZOVER (http://www.mgc.ac.cn/ZOVER). It incorporates two previously released databases, DBatVir and DRodVir, for bat- and rodent-associated viruses, respectively, and further collects up-to-date knowledge on mosquito- and tick-associated viruses to establish a comprehensive online resource for zoonotic and vector-borne viruses. Additionally, it integrates a set of online visualization tools for convenient comparative analyses to facilitate the discovery of potential patterns of virome diversity and ecological characteristics between/within different viral hosts/vectors. The ZOVER database will be a valuable resource for virologists, zoologists and epidemiologists to better understand the diversity and dynamics of zoonotic and vector-borne viruses and conduct effective surveillance to monitor potential interspecies spillover for efficient prevention and control of future emerging zoonotic diseases.

4E-BP2-dependent translation in parvalbumin neurons controls epileptic seizure threshold.

The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals to regulate critical cellular processes such as mRNA translation, lipid biogenesis, and autophagy. Germline and somatic mutations in mTOR and genes upstream of mTORC1, such as PTEN, TSC1/2, AKT3, PIK3CA, and components of GATOR1 and KICSTOR complexes, are associated with various epileptic disorders. Increased mTORC1 activity is linked to the pathophysiology of epilepsy in both humans and animal models, and mTORC1 inhibition suppresses epileptogenesis in humans with tuberous sclerosis and animal models with elevated mTORC1 activity. However, the role of mTORC1-dependent translation and the neuronal cell types mediating the effect of enhanced mTORC1 activity in seizures remain unknown. The eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and 2 (4E-BP2) are translational repressors downstream of mTORC1. Here we show that the ablation of 4E-BP2, but not 4E-BP1, in mice increases the sensitivity to pentylenetetrazole (PTZ)- and kainic acid (KA)-induced seizures. We demonstrate that the deletion of 4E-BP2 in inhibitory, but not excitatory neurons, causes an increase in the susceptibility to PTZ-induced seizures. Moreover, mice lacking 4E-BP2 in parvalbumin, but not somatostatin or VIP inhibitory neurons exhibit a lowered threshold for seizure induction and reduced number of parvalbumin neurons. A mouse model harboring a human PIK3CA mutation that enhances the activity of the PI3K-AKT pathway (Pik3caH1047R-Pvalb ) selectively in parvalbumin neurons shows susceptibility to PTZ-induced seizures. Our data identify 4E-BP2 as a regulator of epileptogenesis and highlight the central role of increased mTORC1-dependent translation in parvalbumin neurons in the pathophysiology of epilepsy.

Discovery and characterization of novel paramyxoviruses from bat samples in China.

Many paramyxoviruses are responsible for a variety of mild to severe human and animal diseases. Based on the novel discoveries over the past several decades, the family Paramyxoviridae infecting various hosts across the world includes 4 subfamilies, 17 classified genera and 78 species now. However, no systematic surveys of bat paramyxoviruses are available from the Chinese mainland. In this study, 13,064 samples from 54 bat species were collected and a comprehensive paramyxovirus survey was conducted. We obtained 94 new genome sequences distributed across paramyxoviruses from 22 bat species in seven provinces. Bayesian phylodynamic and phylogenetic analyses showed that there were four different lineages in the Jeilongvirus genus. Based on available data, results of host and region switches showed that the bat colony was partial to interior, whereas the rodent colony was exported, and the felines and hedgehogs were most likely the intermediate hosts from Scotophilus spp. rather than rodents. Based on the evolutionary trend, genus Jeilongvirus may have originated from Mus spp. in Australia, then transmitted to bats and rodents in Africa, Asia and Europe, and finally to bats and rodents in America.

A comprehensive dataset of animal-associated sarbecoviruses.

Zoonotic spillover of sarbecoviruses (SarbeCoVs) from non-human animals to humans under natural conditions has led to two large-scale pandemics, the severe acute respiratory syndrome (SARS) pandemic in 2003 and the ongoing COVID-19 pandemic. Knowledge of the genetic diversity, geographical distribution, and host specificity of SarbeCoVs is therefore of interest for pandemic surveillance and origin tracing of SARS-CoV and SARS-CoV-2. This study presents a comprehensive repository of publicly available animal-associated SarbeCoVs, covering 1,535 viruses identified from 63 animal species distributed in 43 countries worldwide (as of February 14,2023). Relevant meta-information, such as host species, sampling time and location, was manually curated and included in the dataset to facilitate further research on the potential patterns of viral diversity and ecological characteristics. In addition, the dataset also provides well-annotated sequence sets of receptor-binding domains (RBDs) and receptor-binding motifs (RBMs) for the scientific community to highlight the potential determinants of successful cross-species transmission that could be aid in risk estimation and strategic design for future emerging infectious disease control and prevention.

Panoramic analysis of coronaviruses carried by representative bat species in Southern China to better understand the coronavirus sphere.

Bats, recognized as considerable reservoirs for coronaviruses (CoVs), serve as natural hosts for several highly pathogenic CoVs, including SARS-CoV and SARS-CoV-2. Investigating the bat CoV community provides insights into the origin for highly pathogenic CoVs and highlights bat CoVs with potential spillover risks. This study probes the evolution, recombination, host range, geographical distribution, and cross-species transmission characteristics of bat CoVs across China and its associated CoVs in other regions. Through detailed research on 13,064 bat samples from 14 provinces of China, 1141 CoV strains are found across 10 subgenera and one unclassified Alpha-CoV, generating 399 complete genome sequences. Within bat CoVs, 11 new CoV species are identified and 425 recombination events are detected. Bats in southern China, particularly in Yunnan province, exhibit a pronounced diversity of CoVs. Limited sampling and low detection rates exist for CoVs in Myotacovirus, Nyctacovirus, Hibecovirus, Nobecovirus in China. The genus Myotis is highlighted as a potential ancestral host for Alpha-CoV, with the genus Hipposideros suggested as a likely progenitor host for bat-associated Beta-CoV, indicating the complexity of cross-species transmission dynamics. Through the comprehensive analysis, this study enriches the understanding of bat CoVs and offers a valuable resource for future research.

A comprehensive survey of bat sarbecoviruses across China in relation to the origins of SARS-CoV and SARS-CoV-2.

SARS-CoV and SARS-CoV-2 have been thought to originate from bats. In this study, we screened pharyngeal and anal swabs from 13 064 bats collected between 2016 and 2021 at 703 locations across China for sarbecoviruses, covering almost all known southern hotspots, and found 146 new bat sarbecoviruses. Phylogenetic analyses of all available sarbecoviruses show that there are three different lineages-L1 as SARS-CoV-related CoVs (SARSr-CoVs), L2 as SARS-CoV-2-related CoVs (SC2r-CoVs) and novel L-R (recombinants of L1 and L2)-present in Rhinolophus pusillus bats, in the mainland of China. Among the 146 sequences, only four are L-Rs. Importantly, none belong in the L2 lineage, indicating that circulation of SC2r-CoVs in China might be very limited. All remaining 142 sequences belong in the L1 lineage, of which YN2020B-G shares the highest overall sequence identity with SARS-CoV (95.8%). The observation suggests endemic circulations of SARSr-CoVs, but not SC2r-CoVs, in bats in China. Geographic analysis of the collection sites in this study, together with all published reports, indicates that SC2r-CoVs may be mainly present in bats of Southeast Asia, including the southern border of Yunnan province, but absent in all other regions within China. In contrast, SARSr-CoVs appear to have broader geographic distribution, with the highest genetic diversity and sequence identity to human sarbecoviruses along the southwest border of China. Our data provide the rationale for further extensive surveys in broader geographical regions within, and beyond, Southeast Asia in order to find the most recent ancestors of human sarbecoviruses.

Automatic Segmentation for Favourable Delineation of Ten Wrist Bones on Wrist Radiographs Using Convolutional Neural Network.

Purpose: This study aimed to develop and validate an automatic segmentation algorithm for the boundary delineation of ten wrist bones, consisting of eight carpal and two distal forearm bones, using a convolutional neural network (CNN). Methods: We performed a retrospective study using adult wrist radiographs. We labeled the ground truth masking of wrist bones, and propose that the Fine Mask R-CNN consisted of wrist regions of interest (ROI) using a Single-Shot Multibox Detector (SSD) and segmentation via Mask R-CNN, plus the extended mask head. The primary outcome was an improvement in the prediction of delineation via the network combined with ground truth masking, and this was compared between two networks through five-fold validations. Results: In total, 702 images were labeled for the segmentation of ten wrist bones. The overall performance (mean (SD] of Dice coefficient) of the auto-segmentation of the ten wrist bones improved from 0.93 (0.01) using Mask R-CNN to 0.95 (0.01) using Fine Mask R-CNN (p < 0.001). The values of each wrist bone were higher when using the Fine Mask R-CNN than when using the alternative (all p < 0.001). The value derived for the distal radius was the highest, and that for the trapezoid was the lowest in both networks. Conclusion: Our proposed Fine Mask R-CNN model achieved good performance in the automatic segmentation of ten overlapping wrist bones derived from adult wrist radiographs.

The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2.

Bat coronavirus (CoV) RaTG13 shares the highest genome sequence identity with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among all known coronaviruses, and also uses human angiotensin converting enzyme 2 (hACE2) for virus entry. Thus, SARS-CoV-2 is thought to have originated from bat. However, whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive. Here, we found that Rhinolophus affinis bat ACE2 (RaACE2) is an entry receptor for both SARS-CoV-2 and RaTG13, although the binding of RaACE2 to the receptor-binding domain (RBD) of SARS-CoV-2 is markedly weaker than that of hACE2. We further evaluated the receptor activities of ACE2s from additional 16 diverse animal species for RaTG13, SARS-CoV, and SARS-CoV-2 in terms of S protein binding, membrane fusion, and pseudovirus entry. We found that the RaTG13 spike (S) protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2, and seven out of sixteen different ACE2s function as entry receptors for all three viruses, indicating that all three viruses might have broad host rages. Of note, RaTG13 S pseudovirions can use mouse, but not pangolin ACE2, for virus entry, whereas SARS-CoV-2 S pseudovirions can use pangolin, but not mouse, ACE2 enter cells efficiently. Mutagenesis analysis revealed that residues 484 and 498 in RaTG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2s. Finally, two polymorphous Rhinolophous sinicus bat ACE2s showed different susceptibilities to virus entry by RaTG13 and SARS-CoV-2 S pseudovirions, suggesting possible coevolution. Our results offer better understanding of the mechanism of coronavirus entry, host range, and virus-host coevolution.

Decoding the RNA viromes in rodent lungs provides new insight into the origin and evolutionary patterns of rodent-borne pathogens in Mainland Southeast Asia.

BACKGROUND: As the largest group of mammalian species, which are also widely distributed all over the world, rodents are the natural reservoirs for many diverse zoonotic viruses. A comprehensive understanding of the core virome of diverse rodents should therefore assist in efforts to reduce the risk of future emergence or re-emergence of rodent-borne zoonotic pathogens. RESULTS: This study aimed to describe the viral range that could be detected in the lungs of rodents from Mainland Southeast Asia. Lung samples were collected from 3284 rodents and insectivores of the orders Rodentia, Scandentia, and Eulipotyphla in eighteen provinces of Thailand, Lao PDR, and Cambodia throughout 2006-2018. Meta-transcriptomic analysis was used to outline the unique spectral characteristics of the mammalian viruses within these lungs and the ecological and genetic imprints of the novel viruses. Many mammalian- or arthropod-related viruses from distinct evolutionary lineages were reported for the first time in these species, and viruses related to known pathogens were characterized for their genomic and evolutionary characteristics, host species, and locations. CONCLUSIONS: These results expand our understanding of the core viromes of rodents and insectivores from Mainland Southeast Asia and suggest that a high diversity of viruses remains to be found in rodent species of this area. These findings, combined with our previous virome data from China, increase our knowledge of the viral community in wildlife and arthropod vectors in emerging disease hotspots of East and Southeast Asia. Video abstract.

Corrigendum: Identification of Diverse Bat Alphacoronaviruses and Betacoronaviruses in China Provides New Insights Into the Evolution and Origin of Coronavirus-Related Diseases.

[This corrects the article DOI: 10.3389/fmicb.2019.01900.].

Identification of Diverse Bat Alphacoronaviruses and Betacoronaviruses in China Provides New Insights Into the Evolution and Origin of Coronavirus-Related Diseases.

Outbreaks of severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome in 2012 and fatal swine acute diarrhea syndrome in 2017 caused serious infectious diseases in humans and in livestock, resulting in serious public health threats and huge economic losses. All such coronaviruses (CoVs) were confirmed to originate from bats. To continuously monitor the epidemic-related CoVs in bats, virome analysis was used to classify CoVs from 831 bats of 15 species in Yunnan, Guangxi, and Sichuan Provinces between August 2016 and May 2017. We identified 11 CoV strains from 22 individual samples of four bat species. Identification of four alpha-CoVs from Scotophilus kuhlii in Guangxi, which was closely related to a previously reported bat CoV and porcine epidemic diarrhea virus (PEDV), revealed a bat-swine lineage under the genus Alphacoronavirus. A recombinant CoV showed that the PEDV probably originated from the CoV of S. kuhlii. Another alpha-CoV, α-YN2018, from Rhinolophus affinis in Yunnan, suggested that this alpha-CoV lineage had multiple host origins, and α-YN2018 had recombined with CoVs of other bat species over time. We identified five SARS-related CoVs (SARSr-CoVs) in Rhinolophus bats from Sichuan and Yunnan and confirmed that angiotensin-converting enzyme 2 usable SARSr-CoVs were continuously circulating in Rhinolophus spp. in Yunnan. The other beta-CoV, strain ß-GX2018, found in Cynopterus sphinx of Guangxi, represented an independently evolved lineage different from known CoVs of Rousettus and Eonycteris bats. The identification of diverse CoVs here provides new genetic data for understanding the distribution and source of pathogenic CoVs in China.

Discovery of Diverse Rodent and Bat Pestiviruses With Distinct Genomic and Phylogenetic Characteristics in Several Chinese Provinces.

Bats and rodents are widely distributed worldwide and can be native or intermediate reservoirs of many important zoonotic viruses. Pestiviruses are a group of virus species of the genus Pestivirus under the family Flaviviridae that can infect a wide variety of artiodactylous hosts, including swine and ruminants. Two classic types of pestiviruses, bovine viral diarrhea virus and classical swine fever virus, are important causative agents of mild-to-severe disease in bovine and swine hosts, respectively, and cause tremendous economic losses in these industries. Recent reports revealed that bats and rodents could also act as natural hosts of pestiviruses and an atypical porcine pestivirus, which cause disease in piglets, showed a close genetic relationship with a specific bat pestivirus, RaPestV-1. This study aimed to describe the detection and characterization of novel pestiviruses from bats and rodents in different locations by analyzing the available bat and rodent virome data from throughout China. Two bat pestivirus species and four rodent pestivirus species that are distinct from other known viruses were identified and sequenced. These viruses were identified from two bat species and four rodent species in different Chinese provinces. There were two distinct lineages present in these viruses, that differ from artiodactylous pestivirus. These findings expand our understanding of the genetic diversity of pestiviruses in bats and rodents and suggest the presence of a diverse set of pestiviruses in non-artiodactylous hosts. This study may provide new insight for the prevention of future viral disease outbreaks originating from bats and rodents.

Simultaneous spectrophotometric determination of trace copper, nickel, and cobalt ions in water samples using solid phase extraction coupled with partial least squares approaches.

A simultaneous spectrophotometric determination method for trace heavy metal ions based on solid-phase extraction coupled with partial least squares approaches was developed. In the proposed method, trace metal ions in aqueous samples were adsorbed by cation exchange fibers and desorbed by acidic solution from the fibers. After the ion preconcentration process, the enriched solution was detected by ultraviolet and visible spectrophotometer (UV-Vis). Then, the concentration of heavy metal ions were quantified by analyzing ultraviolet and visible spectrum with the help of partial least squares (PLS) approaches. Under the optimal conditions of operation time, flow rate and detection parameters, the overlapped absorption peaks of mixed ions were obtained. The experimental data showed that the concentration, which can be calculated through chemometrics method, of each metal ion increased significantly. The heavy metal ions can be enriched more than 80-fold. The limits of detection (LOD) for the target analytes of copper ions (Cu2+), cobalt ions (Co2+) and nickel ions (Ni2+) mixture was 0.10µgL-1, 0.15µgL-1 and 0.13µgL-1, respectively. The relative standard deviations (RSD) were less than 5%. The performance of the solid-phase extraction can enrich the ions efficiently and the combined method of spectrophotometric detection and PLS can evaluate the ions concentration accurately. The work proposed here is an interesting and promising attempt for the trace ions determination in water samples and will have much more applied field.