The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-2
. This outbreak has been tentatively associated with a seafood market in Wuhan, ...China, where the sale of wild animals may be the source of zoonotic infection
. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel ...variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS‐CoV‐2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell‐specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco‐2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22,995 and 28,866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS‐CoV‐2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS‐CoV‐2 viruses, as well as a model for investigating SARS‐CoV‐2 recombination.
Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health
. Bats have been recognized as one of the most important reservoirs for emerging ...viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)
. Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.
Invasion and subsequent metastasis are major characteristics of malignant human renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial pyruvate carrier (MPC), a key factor ...that controls pyruvate transportation in mitochondria, is frequently dysregulated in tumor cells and loss of MPC predicts poor prognosis in various types of cancer. However, the clinical relevance and functional significance of MPC in RCC remain to be elucidated. In this study, we investigated the expression of MPC1 and MPC2 in specimens from RCC patients and observed downregulation of MPC1, but not MPC2, in RCC tissues compared with adjacent non-cancerous tissue. Moreover, RCC patients with higher MPC1 expression exhibited longer overall survival rate than those with lower MPC1. Functionally, MPC1 suppressed the invasion of RCC cells in vitro and reduced the growth of RCC cells in vivo, possibly through inhibition of MMP7 and MMP9. Further studies revealed that loss of MPC1 was induced by hypoxia in RCC cells, and notably, MPC1 expression, was negatively correlated with HIF1α expression in RCC cells and patient samples. Taken together, our results identify anti-tumor function of MPC1 in RCC and revealed MPC1 as a novel prognostic biomarker to predict better patient survival.
Mitochondrial pyruvate carrier1 (MPC1) is a key factor that controls pyruvate transportation in mitochondria. Renal cell carcinoma (RCC) patients with higher MPC1 expression in tumors exhibit longer overall survival rate than those with lower MPC1. This study shows that MPC1 is a novel prognostic biomarker to predict patient.
As a key supporting technology in the fields of life sciences and medicine, high-throughput sequencing has developed rapidly and become increasingly mature. The workflow of this technology can be ...divided into nucleic acid extraction, library construction, sequencing, and data analysis. Among these, library construction is a pivotal step that bridges the previous and subsequent stages. The effectiveness of library construction is contingent on the quality of upstream samples and also impacts the data analysis following sequence data output. The selection and implementation of library construction quality control techniques are crucial for enhancing the reliability of results and reducing errors in sequencing data. This review provides an in-depth discussion of library construction quality control techniques, summarizing and evaluating their principles, advantages and disadvantages, and applicability. It also discusses the selection of relevant technologies in practical application scenarios. The aim is to offer theoretical foundations and references for researchers, disease prevention and control personnel, and others when choosing library quality control techniques, thereby promoting the quality and efficiency of high-throughput sequencing work.
In prostate cancer (PCa), the functional synergy between androgen receptor (AR) and nuclear factor-κ B (NF-κB) escalates the resistance to therapeutic regimens and promotes aggressive tumor growth. ...Although the underlying mechanisms are less clear, gene regulatory abilities of coactivators can bridge the transcription functions of AR and NF-κB. The present study shows that MYST1 (MOZ, YBF2 and SAS2, and TIP60 protein 1) costimulates AR and NF-κB functions in PCa cells. We demonstrate that activation of NF-κB promotes deacetylation of MYST1 by sirtuin 1. Further, the mutually exclusive interactions of MYST1 with sirtuin 1 vs AR regulate the acetylation of lysine 16 on histone H4. Notably, in AR-lacking PC3 cells and in AR-depleted LNCaP cells, diminution of MYST1 activates the cleavage of poly(ADP-ribose) polymerase and caspase 3 that leads to apoptosis. In contrast, in AR-transformed PC3 cells (PC3-AR), depletion of MYST1 induces cyclin-dependent kinase (CDK) N1A/p21, which results in G2M arrest. Concomitantly, the levels of phospho-retinoblastoma, E2F1, CDK4, and CDK6 are reduced. Finally, the expression of tumor protein D52 (TPD52) was unequivocally affected in PC3, PC3-AR, and LNCaP cells. Taken together, the results of this study reveal that the functional interactions of MYST1 with AR and NF-κB are critical for PCa progression.
We performed Ebola virus disease diagnosis and viral load estimation for Ebola cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January-March 2015) and analyzed antibody and ...cytokine levels and the viral genome sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with an overall case fatality rate of 46.8%. Fatal cases exhibited significantly higher levels of viral loads, cytokines, and chemokines at late stages of infection versus early stage compared with survivors. The viruses converged in a new clade within sublineage 3.2.4, which had a significantly lower case fatality rate.
Over the course of two waves of infection, H7N9 avian influenza A virus has caused 436 human infections and claimed 170 lives in China as of July 2014. To investigate the prevalence and genetic ...diversity of H7N9, we surveyed avian influenza viruses in poultry in Jiangsu province within the outbreak epicenter. We found frequent occurrence of H7N9/H9N2 coinfection in chickens. Molecular clock phylogenetic analysis confirms coinfection by H7N9/H9N2 viruses and also reveals that the identity of the H7N9 outbreak lineage is confounded by ongoing reassortment between outbreak viruses and diverse H9N2 viruses in domestic birds. Experimental inoculation of a coinfected sample in cell culture yielded two reassortant H7N9 strains with polymerase segments from the original H9N2 strain. Ongoing reassortment between the H7N9 outbreak lineage and diverse H9N2 viruses may generate new strains with the potential to infect humans, highlighting the need for continued viral surveillance in poultry and humans.
We found frequent occurrence of H7N9/H9N2 coinfection in chickens. The H7N9 outbreak lineage is confounded by ongoing reassortment between H7N9 and H9N2 viruses. The importance of H9N2 viruses as the source of novel avian influenza virus infections in humans requires continuous attention.
To investigate the effects of clearing the Governor Vessel and refreshing the mind needling in neural development and remediation of children with cerebral palsy. Methods： A total of 200 cases of ...children with cerebral palsy were randomly assigned to the treatment group （100 patients） and the control group （100 patients）. The treatment group was given the combined therapy of acupuncture and rehabilitation training, and the chosen acupoints were 13 points of the Governor Vessel, Shenshu （BL 23）, Taixi （KI 3）, Yanglingquan （GB 34）, Zusanli （ST 36） and Sanyinjiao （SP 6）, and points of refreshing the mind were also selected, which included puncturing Shenting （GV 24） toward Qianding （GV 21）, puncturing Qianding （GV 21） toward Baihui （GV 20）, puncturing Baihui （GV 20） toward Naohu （GV 17） and Sishencong （Ex-HN 1）. The control group was only treated with rehabilitation training. A contrastive analysis of the therapeutic effect between acupuncture combined with rehabilitation training and rehabilitation training alone was made after a treatment course of 3 months. The Gross Motor Function Measure （GMFM） and Beijing Gesell Developmental Scale were adopted to assess the neural development and rehabilitation outcomes of the two groups. In addition, skull CT/MRI was adopted to evaluate the plerosis of injured cerebral nerve after treatment. Results： The total effective rate in treatment group was 87% （87/100）, significantly higher than the 55% （55/100） in the control group. The children＇s development quotient （DQ） tested by Gesell Developmental Scale and scores tested by GMFM in the treatment group were obviously higher than those in the control group （P〈0.01）. The improving and curing rates presented by skull CT/MRI in the treatment group were higher than those in the control group （P〈0.01）. Conclusions： Clearing the Governor Vessel and refreshing the mind needling could accelerate the recovery of injured brain nerve and the reconstruction of brain function. The acupuncture therapy could ameliorate both the motor development and cognitive development. On the other hand, the forward curative effect of acupuncture combined with rehabilitation training was significantly better than the rehabilitation training alone.
The Neoproterozoic Doushantuo Formation, South China, preserves a unique assemblage of what are probably the earliest metazoan fossils (sponges, cnidarians, and bilaterians) in the world that could ...contribute to a better understanding of early faunal evolution on Earth. The formation spans an interval of dramatic biological, chemical, and climatic change. In Weng'an mine in southwest China, extensive paleontological investigations show embryonic, larval, and adult animal fossils occur in the upper ore bed of the Doushantuo phosphorite, but no animal forms have been found in the lower ore bed. Taphonomy and experiments on fossilization suggest that no fauna lived on or in the lower ore bed as it was deposited. Rare-earth element (REE) data for the Doushantuo phosphorites in Weng'an document the paleoenvironmental condition under which the phosphorites were deposited. The shale-normalized REE patterns of the upper phosphorite bed (UPB) are characterized by “old” (Vendian–Early Cambrian) phosphorite patterns. The REE patterns of the lower phosphorite bed (LPB) are significantly different with less negative Ce anomalies and less LREE and HREE depletion. The REE characteristics suggest that the Doushantuo phosphorites record seawater condition at the time of sediment deposition and are not affected by subsequent diagenesis. The REE compositions of the Doushantuo phosphorites show that the marine depositional environment changed from anoxic in the lower ore bed to oxic in the upper ore bed. The uniquely diverse and abundant Doushantuo eukaryote fossil accumulations at Weng'an thus may be related to a change from anoxic to oxic bottom-water conditions.
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