Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge ...disease burden worldwide every year. It has been more than 60 years since RSV was discovered, and the palivizumab monoclonal antibody, the only approved specific treatment, is limited to use for passive immunoprophylaxis in high-risk infants; no other intervention has been approved to date. However, in the past decade, substantial progress has been made in characterizing the structure and function of RSV components, their interactions with host surface molecules, and the host innate and adaptive immune response to infection. In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. A large number of promising monoclonal antibodies and inhibitors have been screened, and new vaccine candidates have been designed for clinical evaluation. In this review, we first briefly introduce the structural composition, host cell surface receptors and life cycle of RSV virions. Then, we discuss the latest findings related to the pathogenesis of RSV. We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. Finally, we look forward to the prospects and challenges of future RSV research and clinical intervention.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we ...obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.
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•The complex structure of RaTG13 RBD with hACE2 was determined•Binding of RaTG13 RBD to 24 additional ACE2 orthologs was evaluated•Residue 501 plays a key role in determining the potential host range of RaTG13•SARS-CoV-2 induces strong cross-protective antibodies to RaTG13 RBD
Structural and molecular analysis of the receptor binding domain of RaTG13, a coronavirus phylogenetically closely related to SARS-CoV-2, bound to the human receptor ACE2 as well as ACE2 orthologs in 24 other species provides a framework to understand its host range as well as the basis of antibody cross-reactivity between the two viruses.
Infectious diseases cause great economic loss and individual and even social anguish. Existing detection methods lack sensitivity and specificity, have a poor turnaround time, and are dependent on ...expensive equipment. In recent years, the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system has been widely used in the detection of pathogens that cause infectious diseases owing to its high specificity, sensitivity, and speed, and good accessibility. In this review, we discuss the discovery and development of the CRISPR-Cas system, summarize related analysis and interpretation methods, and discuss the existing applications of CRISPR-based detection of infectious pathogens using Cas proteins. We conclude the challenges and prospects of the CRISPR-Cas system in the detection of pathogens.
Objective
Respiratory syncytial virus (RSV) and respiratory adenovirus (ADV) are two common pathogens that cause acute respiratory tract infections in children. We aimed to develop a rapid method for ...detecting both pathogens simultaneously.
Methods
The recombinase polymerase isothermal amplification (RPA) method was combined with the CRISPR/Cas detection system. The assay’s specificity and sensitivity were explored by designing RPA primers and CRISPR RNAs (crRNAs) through multi-sequence comparisons, optimizing the reaction conditions, and using a fluorescent reading device. The consistency of the test results of 160 clinical pharyngeal swab samples was studied using quantitative polymerase chain reaction (qPCR) results as a comparative control.
Results
RSV and ADV could be detected at levels as low as 104 copies/mL and 103 copies/mL, respectively, within 50 minutes with no cross-reactivity with other similar pathogens. For the clinical samples, compared with the qPCR method, the sensitivities for RSV and ADV were 98.1% and 91.4%, respectively, and the detection specificities were both 100%. The Kappa values were greater than 0.95, suggesting a high degree of consistency.
Conclusion
This method for detecting RSV and ADV is rapid, sensitive, and specific. It can accurately detect mixed infections in a timely manner, making it suitable for use in areas with scarce healthcare resources.
Abstract Background Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and ...sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy. Methods Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL). Results Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM. Conclusions This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.
Wing-in-ground craft often encounter waves when flying over the sea surface, and the ground effect is more complicated than that of flat ground. Therefore, the aerodynamic characteristics of the NACA ...4412 airfoil in proximity to wavy ground for a wide range of angles of attack is studied by solving the Reynolds Averaged Navier–Stokes equations. The validation of the numerical method is carried out by comparing it with the experimental data. The results show that the aerodynamic coefficients will fluctuate periodically when the airfoil moves over wavy ground at a small ride height. Except for the angle of attack of 0°, the fluctuation trend of aerodynamic coefficients at other angles of attack is the same. The analysis of aerodynamic fluctuation amplitude found that the medium angle of attack should be selected as the design cruise angle of attack for wing-in-ground craft. The time-averaged aerodynamic coefficients in the case of wavy ground are almost the same as those of flat ground. Hence, wavy ground mainly causes a fluctuation in aerodynamic coefficients. Considering the difference between aerodynamic coefficients at the angle of attack of 0° and at other angles of attack, the flow field structure at an angle of attack of 0° and 4° is analyzed. The results reveal the aerodynamic characteristics of the airfoil moving over wavy ground, which gives a deeper understanding of the ground effect in the conditions of wavy surface/ground. This has a certain guiding significance for the design of wing-in-ground craft.
Understanding the phenotypic and functional diversity of cerebral cortical GABAergic neurons requires a comprehensive analysis of key transcriptional signatures and neuronal subtype identity. ...However, the diversity and conservation of GABAergic neurons across multiple mammals remain unclear. Here, we collected the single-nucleus RNA sequencing (snRNA-seq) datasets of cerebral cortex from human, macaque, mouse, and pig to identify the conserved neuronal cell types across species. After systematic analysis of the heterogeneity of GABAergic neurons, we defined four major conserved GABAergic neuron subclasses (Inc SST, Inc LAMP5, Inc PVALB, and Inc VIP) across species. We characterized the species-enriched subclasses of GABAergic neurons from four mammals, such as Inc Meis2 in mouse. Then, we depicted the genetic regulatory network (GRNs) of GABAergic neuron subclasses, which showed the conserved and species-specific GRNs for GABAergic neuron cell types. Finally, we investigated the GABAergic neuron subclass-specific expression modules of Alzheimer's disease (AD)-related genes in GABAergic neuron cell types. Overall, our study reveals the conserved and divergent GABAergic neuron subclasses and GRNs across multiple species and unravels the gene expression modules of AD-risk genes in GABAergic neuron subclasses, facilitating the GABAergic neurons research and clinical treatment.
This study focuses on the characteristics of low Reynolds number flow around airfoil of high-altitude unmanned aerial vehicles（HAUAVs） cruising at low speed.Numerical simulation on the flows around ...several representative airfoils is carried out to investigate the low Reynolds number flow.The water tunnel model tests further validate the accuracy and effectiveness of the numerical method.Then the effects of the relative thickness of airfoil on aerodynamic performance are explored, using the above numerical method, by simulating flows around airfoils of different relative thicknesses（12%, 14%, 16%, 18%）, as well as different locations of the maximum relative thickness（x/c = 22%, 26%, 30%, 34%）, at a low Reynolds number of 5 × 10^5.Results show that performance of airfoils at low Reynolds number is mainly affected by the laminar separation bubble.On the premise of good stall characteristics, the value of maximum relative thickness should be as small as possible, and the location of the maximum relative thickness ought to be closer to the trailing edge to obtain fine airfoil performance.The numerical method is feasible for the simulation of low Reynolds number flow.The study can help to provide a basis for the design of low Reynolds number airfoil.
The temperature of the solar cells on the upper surface of a solar unmanned aerial vehicle (UAV) wing is much higher than the atmospheric temperature during flight. The temperature difference will ...induce buoyancy-driven Görtler vortices that may influence the aerodynamic characteristics of the wing. In the present study, a hybrid RANS-LES-based approach was used to simulate the flow above a heated flat plate under different flow velocities (from 0.34 m/s to 0.63 m/s) and temperature differences (from 0 K to 60 K), and the influence of Görtler vortices on the flow was analyzed. The existence of buoyancy-driven Görtler vortices would induce velocity normal to the plate, and a negative velocity normal to the plate at the peak position would enhance the momentum exchange within the boundary layer, accelerate the transition, and increase the friction drag coefficient. The drag coefficient with a 60 K temperature difference is almost three times that with a 0 K temperature difference. With an increase in temperature difference or decrease in flow velocity, the intensity of Görtler vortices would increase. A couple of different buoyancy parameters were studied, and a combined parameter based on both the Reynolds number and Grashoff number was proposed as the index parameter of heated plate flow. The flow above a heated flat plate can be divided into three regions by the buoyancy parameter. When the buoyancy parameter is between 100 and 200, the Görtler vortices are stable, and the flow exhibits significant three-dimensional characteristics.
Flame-retardant, thermal insulation, mechanically robust, and comprehensive protection against extreme environmental threats aerogels are highly desirable for protective equipment. Herein, inspired ...by the core (organic)-shell (inorganic) structure of lobster antenna, fire-retardant and mechanically robust aramid fibers@silica nanocomposite aerogels with core-shell structures are fabricated via the sol-gel-film transformation and chemical vapor deposition process. The thickness of silica coating can be well-defined and controlled by the CVD time. Aramid fibers@silica nanocomposite aerogels show high heat resistance (530 °C), low thermal conductivity of 0.030 W·m
·K
, high tensile strength of 7.5 MPa and good flexibility. More importantly, aramid fibers@silica aerogels have high flame retardancy with limiting oxygen index 36.5. In addition, this material fabricated by the simple preparation process is believed to have potential application value in the field of aerospace or high-temperature thermal protection.
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