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Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1 – 4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5 – 7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV. Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to ‘drink drugs’ for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood–brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras -activated cancers. Drug delivery in brain tumours is still a significant clinical concern. In this study, the authors develop a biomimetic lipoprotein nanoparticle for the efficient delivery of ATF5 siRNA in Ras -activated brain cancer cells, where the nanoparticle is internalized by macropinocytosis in a Ras -dependent manner.

Background The adaptive evolution of plateau indigenous animals is a current research focus. However, phenotypic adaptation is complex and may involve the interactions between multiple genes or pathways, many of which remain unclear. As a kind of livestock with important economic value, cashmere goat has a high ability of plateau adaptation, which provides us with good materials for studying the molecular regulation mechanism of animal plateau adaptation. Results In this study, 32 Jiangnan (J) and 32 Tibetan (T) cashmere goats were sequenced at an average of 10. Phylogenetic, population structure, and linkage disequilibrium analyses showed that natural selection or domestication has resulted in obvious differences in genome structure between the two breeds. Subsequently, 553 J vs. T and 608 T vs. J potential selected genes (PSGs) were screened. These PSGs showed potential relationships with various phenotypes, including myocardial development and activity ( LOC106502520 , ATP2A2 , LOC102181869 , LOC106502520 , MYL2 , ISL1 , and LOC102181869 genes), pigmentation ( MITF and KITLG genes), hair follicles/hair growth ( YAP1 , POGLUT1 , AAK1 , HES1 , WNT1 , PRKAA1 , TNKS , WNT5A , VAX2 , RSPO4 , CSNK1G1, PHLPP2 , CHRM2 , PDGFRB , PRKAA1 , MAP2K1 , IRS1 , LPAR1 , PTEN , PRLR , IBSP , CCNE2 , CHAD , ITGB7 , TEK , JAK2 , and FGF21 genes), and carcinogenesis ( UBE2R2 , PIGU , DIABLO , NOL4L , STK3 , MAP4 , ADGRG1 , CDC25A , DSG3 , LEPR , PRKAA1 , IKBKB , and ABCG2 genes). Phenotypic analysis showed that Tibetan cashmere goats has finer cashmere than Jiangnan cashmere goats, which may allow cashmere goats to better adapt to the cold environment in the Tibetan plateau. Meanwhile, KRTs and KAPs expression in Jiangnan cashmere goat skin was significantly lower than in Tibetan cashmere goat. Conclusions The mutations in these PSGs maybe closely related to the plateau adaptation ability of cashmere goats. In addition, the expression differences of KRTs and KAPs may directly determine phenotypic differences in cashmere fineness between the two breeds. In conclusion, this study provide a reference for further studying plateau adaptive mechanism in animals and goat breeding.

The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection. We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

FAGV is a kind of heavy equipment in the storage environment. Its path needs to be simple and smooth and should be able to avoid sudden obstacles in the process of driving. According to the environmental characteristics of intelligent storage and the task requirements of FAGV, this paper proposed a hybrid dynamic path planning algorithm for FAGV based on improved A* and improved DWA. The improved A* algorithm can plan the global optimal path more suitable for FAGV. The improved evaluation function of DWA can ensure that the local path of FAGV is closer to the global path. DWA combines the rolling window method for local path planning to avoid sudden unknown static and dynamic obstacles. In addition, this paper verifies the effectiveness of the algorithm through simulation. The simulation results show that the algorithm can avoid obstacles dynamically without being far away from the global optimal path.

The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.

This study was conducted to examine the effects of Lactobacillus plantarum (LP) and sucrose (S) on clostridial community dynamics and correlation between clostridia and other bacteria in alfalfa silage during ensiling. Fresh alfalfa was directly ensiled without (CK) or with additives (LP, S, LP + S) for 7, 14, 28 and 56 days. Clostridial and bacterial communities were evaluated by next-generation sequencing. Severe clostridial fermentation occurred in CK, as evidenced by the high contents of butyric acid, ammonia nitrogen, and clostridia counts, whereas all additives, particularly LP + S, decreased silage pH and restrained clostridial fermentation. Clostridium perfringens and Clostridium butyricum might act as the main initiators of clostridial fermentation, with Clostridium tyrobutyricum functioning as the promoters of fermentation until the end of ensiling. Clostridium tyrobutyricum (33.5 to 98.0%) dominated the clostridial community in CK from 14 to 56 days, whereas it was below 17.7% in LP + S. Clostridium was negatively correlated with the genus Lactobacillus , but positively correlated with the genera Enterococcus, Lactococcus and Leuconostoc . Insufficient acidification promoted the vigorous growth of C. tyrobutyricum of silage in later stages, which was mainly responsible for the clostridial fermentation of alfalfa silage.

Spore killers in fungi are selfish genetic elements that distort Mendelian segregation in their favor. It remains unclear how many species harbor them and how diverse their mechanisms are. Here, we discover two spore killers from a natural isolate of the fission yeast Schizosaccharomyces pombe. Both killers belong to the previously uncharacterized wtf gene family with 25 members in the reference genome. These two killers act in strain-background-independent and genome-location-independent manners to perturb the maturation of spores not inheriting them. Spores carrying one killer are protected from its killing effect but not that of the other killer. The killing and protecting activities can be uncoupled by mutation. The numbers and sequences of wtf genes vary considerably between S. pombe isolates, indicating rapid divergence. We propose that wtf genes contribute to the extensive intraspecific reproductive isolation in S. pombe, and represent ideal models for understanding how segregation-distorting elements act and evolve. During evolution, new species emerge when individuals from different populations of similar organisms no longer breed with each other, or when the offspring produced if they do breed are sterile. This process is known as “reproductive isolation” and, for over 100 years, evolutionary biologists have tried to better understand how this process happens. Animals, plants and fungi produce sex cells – known as gametes – when they are preparing to reproduce. These cells are made when cells containing two copies of every gene in the organism divide to produce new cells that each only have one copy of each gene. Therefore, a particular gene copy usually has a 50% chance of being carried by an individual gamete. There are genes that selfishly increase their chances of being transmitted to the next generation by destroying the gametes that do not carry them. These “gamete killer” genes reduce the fertility of the organism and lead to reproductive isolation. Fission yeast is a fungus that is widely used in research. There are different strains of fission yeast that are reproductively isolated from each other, but it is not known whether gamete killers are responsible for this isolation. To address this question, Hu et al. investigated the causes of reproductive isolation in fission yeast. The experiments identified two gamete killers, referred to as cw9 and cw27. Both genes belong to the wtf gene family. Each gene is believed to encode two different proteins, one that acts as a poison and one that acts as an antidote. The poison is capable of killing all gametes, but the antidote protects the cells that contain the gamete killer gene. Further experiments show that the antidote produced by one of the gamete killer genes cannot protect cells against the poison produced by the other gene. A separate study by Nuckolls et al. found that another member of the wtf family also acts as a gamete killer in fission yeast. Together, these findings shed new light on the causes of reproductive isolation, and will contribute to deeper understanding of speciation and evolution in general.

The electrocatalytic reduction of nitrate toward ammonia under mild conditions addresses many challenges of the Haber-Bosch reaction, providing a sustainable method for ammonia synthesis, yet it is limited by sluggish reduction kinetics and multiple competing reactions. Here, the titanium hydride electrocatalyst is synthesized by electrochemical hydrogenation reconstruction of titanium fiber paper, which achieves a large ammonia yield rate of 83.64 mg h −1 cm −2 and a high Faradaic efficiency of 99.11% with an ampere-level current density of 1.05 A cm −2 at −0.7 V versus the reversible hydrogen electrode. Electrochemical evaluation and kinetic studies indicate that the lattice hydrogen transfer from titanium hydride promotes the electrocatalytic performance of nitrate reduction reaction and the reversible equilibrium reaction between lattice hydrogen and activate hydrogen not only improves the electrocatalytic activity of nitrate reduction reaction but also demonstrates notable catalytic stability. These finding offers a universal design principle for metal hydrides as catalysts for effectively electrochemical ammonia production, highlighting their potential for sustainable ammonia synthesis. The electrocatalytic reduction of nitrate to ammonia offers a sustainable alternative to the Haber-Bosch process. Here, the authors report a lattice hydrogen transfer mechanism that enhances electrocatalytic activity by enabling reversible equilibrium reactions between lattice and active hydrogen.

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.