A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS ...coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.
At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to ...public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.
Tuberculosis (TB) is a severe infectious disease that seriously endangers human health. The immune defence mechanism of the body against TB is still unclear. The purpose of this study was to find the ...key molecules involved in the immune defence response during TB infection, and provide reference for the treatment of TB and further understanding of the immune defence mechanism of the body. Data from GSE83456 were downloaded from GEO data sets for analysis, and a total of 192 differentially expressed genes were screened out. Most of these genes are enriched in the interferon signalling pathway and are defence response–related. We also found that STAT1 plays an important role in the immune defence of TB infection and it is one of the key genes related to interferon signalling pathway. STAT1‐related molecules including hsa‐miR‐448, hsa‐miR‐223‐3p, SAMD8_hsa_circRNA 994 and TWF1_hsa_circRNA 9897 were therefore screened out. Furthermore, expression levels of hsa‐miR‐448 and hsa‐miR‐223‐3p were then verified by qRT‐PCR. Results showed that both hsa‐miR‐448 and hsa‐miR‐223‐3p were down‐regulated in plasma from patients with pulmonary TB. Taken together, our data indicate that an mRNA‐miRNA‐circRNA interaction chain may play an important role in the infection of MTB, and STAT1 and related molecules including hsa‐miR‐223‐3p, has‐miR‐448, SAMD8_hsa_circRNA994 and TWF1_hsa_circRNA9897 were identified as potential biomarkers in the development of active TB.
•ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 strongly inhibited type I interferon (IFN-β) activation and NF-κB pathway.•ORF6 and ORF8, but not nucleocapsid proteins, were capable of inhibiting ...ISRE-driven transcription activated by IFN-β.•ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibited interferon-stimulated genes (ISGs) such as ISG54 and ISG56.•ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 played critical roles in innate immune suppression during viral infection.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus causing the pandemic of severe pneumonia (Coronavirus Disease 2019, COVID-19). SARS-CoV-2 is highly pathogenic in human, having posed immeasurable public health challenges to the world. Innate immune response is critical for the host defense against viral infection and the dysregulation of the host innate immune responses probably aggravates SARS-CoV-2 infection, contributing to the high morbidity and lethality of COVID-19. It has been reported that some coronavirus proteins play an important role in modulating innate immunity of the host, but few studies have been conducted on SARS-CoV-2. In this study, we screened the viral proteins of SARS-CoV-2 and found that the viral ORF6, ORF8 and nucleocapsid proteins were potential inhibitors of type I interferon signaling pathway, a key component for antiviral response of host innate immune. All the three proteins showed strong inhibition on type I interferon (IFN-β) and NF-κB-responsive promoter, further examination revealed that these proteins were able to inhibit the interferon-stimulated response element (ISRE) after infection with Sendai virus, while only ORF6 and ORF8 proteins were able to inhibit the ISRE after treatment with interferon beta. These findings would be helpful for the further study of the detailed signaling pathway and unveil the key molecular player that may be targeted.
Energy efficient buildings require materials with a low thermal conductivity and a high fire resistance. Traditional organic insulation materials are limited by their poor fire resistance and ...inorganic insulation materials are either brittle or display a high thermal conductivity. Herein we report a mechanically resilient organic/inorganic composite aerogel with a thermal conductivity significantly lower than expanded polystyrene and excellent fire resistance. Co‐polymerization and nanoscale phase separation of the phenol‐formaldehyde‐resin (PFR) and silica generate a binary network with domain sizes below 20 nm. The PFR/SiO2 aerogel can resist a high‐temperature flame without disintegration and prevents the temperature on the non‐exposed side from increasing above the temperature critical for the collapse of reinforced concrete structures.
Fire not starter: Taking advantage of a co‐polymerization strategy an organic–inorganic binary network hybrid aerogel with a nanoscale homogeneity can be prepared. The phenol‐formaldehyde‐resin/SiO2 aerogel is mechanically resilient and has a thermal conductivity significantly lower than expanded polystyrene and excellent fire resistance.
The electrochemical nitrogen reduction reaction (NRR) offers a sustainable solution towards ammonia production but suffers poor reaction performance owing to preferential catalyst–H formation and the ...consequential hydrogen evolution reaction (HER). Now, the Pt/Au electrocatalyst d‐band structure is electronically modified using zeolitic imidazole framework (ZIF) to achieve a Faradaic efficiency (FE) of >44 % with high ammonia yield rate of >161 μg mgcat−1 h−1 under ambient conditions. The strategy lowers electrocatalyst d‐band position to weaken H adsorption and concurrently creates electron‐deficient sites to kinetically drive NRR by promoting catalyst–N2 interaction. The ZIF coating on the electrocatalyst doubles as a hydrophobic layer to suppress HER, further improving FE by >44‐fold compared to without ZIF (ca. 1 %). The Pt/Au‐NZIF interaction is key to enable strong N2 adsorption over H atom.
A kinetically driven ambient nitrogen reduction reaction has a Faradaic efficiency of over 44 % and an ammonia yield rate of over 161 μg mgcat−1 h−1. It employs a zeolitic imidazole framework to induce electron‐deficient sites on the catalyst and a lower d‐band to weaken catalyst–H interactions whilst promoting the catalyst–N2 interaction.
Understanding ecological niches of major tick species and prevalent tick-borne pathogens is crucial for efficient surveillance and control of tick-borne diseases. Here we provide an up-to-date review ...on the spatial distributions of ticks and tick-borne pathogens in China. We map at the county level 124 tick species, 103 tick-borne agents, and human cases infected with 29 species (subspecies) of tick-borne pathogens that were reported in China during 1950-2018. Haemaphysalis longicornis is found to harbor the highest variety of tick-borne agents, followed by Ixodes persulcatus, Dermacentor nutalli and Rhipicephalus microplus. Using a machine learning algorithm, we assess ecoclimatic and socioenvironmental drivers for the distributions of 19 predominant vector ticks and two tick-borne pathogens associated with the highest disease burden. The model-predicted suitable habitats for the 19 tick species are 14‒476% larger in size than the geographic areas where these species were detected, indicating severe under-detection. Tick species harboring pathogens of imminent threats to public health should be prioritized for more active field surveillance.
Alternative splicing is a tightly regulated biological process by which the number of gene products for any given gene can be greatly expanded. Genomic variants in splicing regulatory sequences can ...disrupt splicing and cause disease. Recent developments in sequencing technologies and computational biology have allowed researchers to investigate alternative splicing at an unprecedented scale and resolution. Population-scale transcriptome studies have revealed many naturally occurring genetic variants that modulate alternative splicing and consequently influence phenotypic variability and disease susceptibility in human populations. Innovations in experimental and computational tools such as massively parallel reporter assays and deep learning have enabled the rapid screening of genomic variants for their causal impacts on splicing. In this review, we describe technological advances that have greatly increased the speed and scale at which discoveries are made about the genetic variation of alternative splicing. We summarize major findings from population transcriptomic studies of alternative splicing and discuss the implications of these findings for human genetics and medicine.
Photothermal materials are crucial for diverse heating applications, but it remains challenging to achieve high energy conversion efficiency due to the difficulty to concurrently improve light ...absorbance and suppress heat loss. Herein, a zeolitic imidazolate framework‐isolated graphene (G@ZIF) nanohybrid is demonstrated that utilizes ultrathin, heat‐insulating ZIF layers, and G@ZIF interfacial nanocavity to synergistically intensify light absorbance and heat localization. Under artificial sunlight illumination (≈1 kW m−2), the G@ZIF film attains a maximum temperature of 120 °C in an open environment with a 98% solar‐to‐thermal conversion efficiency. Importantly, the porous ZIF layer allows small molecules/media to enter and access the embedded hot graphene surface for targeted heat transfer in practical applications. As a proof‐of‐concept, the G@ZIF‐based steam generator realizes 96% energy conversion from light to vapor with near‐perfect desalination and water purification efficiencies (>99.9%). This design is generic and can be extended to other photothermal systems for advanced solar‐thermal applications, including catalysis, water treatments, sterilization, and mechanical actuation.
MOF‐isolated graphene (G@ZIF) nanohybrids demonstrate strong solar light absorbance and a 98% solar‐to‐thermal conversion efficiency, owing to its ultrathin, heat‐insulating ZIF layers, and G@ZIF interfacial nanocavity to synergistically intensify light absorbance and minimize heat loss. The maximum surface temperature reaches 120 °C under simulated one‐sun illumination, enabling efficient interfacial water evaporation for desalination.
SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia pandemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to ...humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2. As a result, we predicted that SARS-CoV-2 tends to utilize ACE2s of various mammals, except murines, and some birds, such as pigeon. This prediction may help to screen the intermediate hosts of SARS-CoV-2.
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