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Human metapneumovirus (HMPV) is a common pathogen that can cause acute respiratory tract infections and is prevalent worldwide. There is yet no effective vaccine or specific treatment for HMPV. Early, rapid, and accurate detection is essential to treat the disease and control the spread of infection. In this study, we created the One-tube assay by combining Reverse Transcription-Recombinase Polymerase Amplification (RT-RPA) with the CRISPR/Cas12a system. By targeting the nucleoprotein (N) gene of HMPV to design specific primers and CRISPR RNAs (crRNAs), combining RT-RPA and CRISPR/Cas12a, established the One-tube assay. Meanwhile, the reaction conditions of the One-tube assay were optimized to achieve rapid and visual detection of HMPV. This assay could detect HMPV at 1 copy/µL in 30â¯min, without cross-reactivity with nine other respiratory pathogens. We validated the detection performance using clinical specimens and showed that the coincidence rate was 98.53â¯%ï¼compared to the quantitative reverse-transcription polymerase chain reaction. The One-tube assay reduced the detection time and simplified the manual operation, while maintaining the detection performance and providing a new platform for HMPV detection.
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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.
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Encefalitis , Humanos , Pronóstico , Niño , Encefalitis/diagnóstico , Encefalitis/microbiología , Encefalitis/virología , Encefalitis/tratamiento farmacológico , Preescolar , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/tratamiento farmacológico , Masculino , Femenino , Metagenómica/métodos , Lactante , Secuenciación de Nucleótidos de Alto Rendimiento , ARN/genéticaRESUMEN
Importance: Treatments are needed to slow progression of or reduce incidence of myopia. Objective: To evaluate the efficacy and safety of daily 650-nm low-level red light (LLRL) for myopia treatment. Design, Setting, and Participants: Single-masked, randomized clinical trial at 1 site in China. Baseline measurements were completed from August to September 2021. Participants were children aged 6 to 12 years with spherical equivalent error (SER) of -6 diopters (D) to 3 D. Data were analyzed from March to July 2023. Interventions: Irradiation daily with 650-nm LLRL for 3 minutes twice daily 4 or more hours apart or no intervention. Main Outcomes and Measures: Primary outcomes were changes in cycloplegia SER and axial length (AL) at 6- and 12-month follow-up visits. Safety was assessed on masked fundus photograph evaluations. Results: A total of 336 children were randomly allocated into the LLRL group or control group in a 1:1 ratio. The control group contained 86 female patients (51.2%), and the treatment group contained 90 female patients (53.6%). The mean (SD) age, SER, and AL were 9.0 (1.9) years, -1.3 (1.5) D, and 23.8 (1.0) mm for all patients. A total of 161 (95.8%) in the LLRL group and 159 (94.6%) in the control group returned for the 6-month follow-up. A total of 157 (93.5%) in the LLRL group and 152 (90.5%) in the control group returned for the 12-month follow-up. Mean (SD) changes in SER were 0.15 (0.16) D and -0.26 (0.21) D for the LLRL group and the control group, respectively (difference, -0.41 D; 95% CI, -0.48 to -0.34 D; P < .001), at 6 months and 0.24 (0.27) D and -0.65 (0.33) D for the LLRL group and the control group, respectively (difference, -0.89 D; 95% CI, -0.95 to -0.83 D; P < .001), at 12 months. Mean (SD) changes in AL were -0.06 (0.08) mm and 0.13 (0.12) mm for the LLRL group and control group, respectively (difference, 0.19 mm; 95% CI, 0.16 to 0.22 mm; P < .001), at 6 months and -0.11 (0.10) mm and 0.26 (0.16) mm for the LLRL group and control group, respectively (difference, 0.37 mm; 95% CI, 0.34 to 0.40 mm; P < .001). Masked fundus photograph review did not identify retinal changes in either group. Conclusions and relevance: These findings suggest daily use of 650-nm LLRL for 1 year can slow progression of SER and AL without safety concerns identified. Confirmation of these findings at independent sites seems warranted, as well as determining whether these effects can be sustained with or without continued treatment and whether LLRL has any effect on pathological myopia. Trial Registration: ChiCTR2200058963.
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Longitud Axial del Ojo , Miopía , Refracción Ocular , Agudeza Visual , Humanos , Femenino , Masculino , Niño , Longitud Axial del Ojo/diagnóstico por imagen , Miopía/fisiopatología , Miopía/terapia , Refracción Ocular/fisiología , Método Simple Ciego , Agudeza Visual/fisiología , Terapia por Luz de Baja Intensidad/métodos , Resultado del Tratamiento , Estudios de Seguimiento , Luz RojaRESUMEN
Taraxacum kok-saghyz (TKS) latex is a natural latex produced from its root, and its extraction optimization process is mainly studied in the present paper. The composition of fresh roots of TKS was quantitatively analyzed, and the results showed that the moisture content of the fresh root was approximately 70 %, and the rubber content averaged to 6 % (dry weight ratio). An optimal process route for extracting the TKS latex was finally determined, making the extraction efficiency reach about 80 %, and a new latex extraction process was established and optimized and named "the process of Buffer Extraction TKS Latex (BETL)". Hevea latex, extracted TKS latex and TKS latex collected directly from the broken roots were compared for study. The results showed that, like Hevea latex, the appearance of TKS latex was milky white; and after centrifugation, both showed four layers from top to bottom: rubber particles, Frey-Wyssling particles, C-serum and lutoids. The results of the composition analysis showed that the concentration of TKS latex ranged from 54.54 % to 68.25 %, which is close to that of concentrated Hevea latex; the moisture content of TKS latex was between 31.75 % and 45.46 %. The protein content of TKS latex was 13.51 mg/mL, which was lower than that of Hevea latex at the same rubber hydrocarbon concentration. The molecular structures and properties of Hevea latex, the extracted TKS latex, and the collected TKS latex were characterized by FTIR, 13C NMR, GPC, TG, SEM and LPSA, and the results showed that the main components and structure of the three latexes were similar, which are all cis-1,4-polyisoprene, and include the proteins and lipids. The distributions molecular weights of the three latexes all showed a bimodal distribution, but the molecular weight of the latex collected from TKS was lower, which indicates the larger molecules were difficult to flow outside the root automatically. The Hevea latex and TKS latex rubber particles were both core-shell structure and the size distribution were bimodal, which was consistent with the GPC analysis results.
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Introduction. Respiratory tract infection, which is associated with high morbidity and mortality, occurs frequently in children. At present, the main diagnostic method is culture. However, the low pathogen detection rate of the culture approach prevents timely and accurate diagnosis. Fortunately, next-generation sequencing (NGS) can compensate for the deficiency of culture, and its application in clinical diagnostics has become increasingly available.Gap Statement. Targeted NGS (tNGS) is a platform that can select and enrich specific regions before data enter the NGS pipeline. However, the performance of tNGS in the detection of respiratory pathogens and antimicrobial resistance genes (ARGs) in infections in children is unclear.Aim and methodology. In this study, we estimated the performance of tNGS in the detection of respiratory pathogens and ARGs in 47 bronchoalveolar lavage fluid (BALF) specimens from children using conventional culture and antimicrobial susceptibility testing (AST) as the gold standard.Results. RPIP (Respiratory Pathogen ID/AMR enrichment) sequencing generated almost 500â000 reads for each specimen. In the detection of pathogens, RPIP sequencing showed targeted superiority in detecting difficult-to-culture bacteria, including Mycoplasma pneumoniae. Compared with the results of culture, the sensitivity and specificity of RPIP were 84.4â% (confidence interval 70.5-93.5â%) and 97.7â% (95.9â-98.8%), respectively. Moreover, RPIP results showed that a single infection was detected in 10 of the 47 BALF specimens, and multiple infections were detected in 34, with the largest number of bacterial/viral coinfections. Nevertheless, there were also three specimens where no pathogen was detected. Furthermore, we analysed the drug resistance genes of specimens containing Streptococcus pneumoniae, which was detected in 25 out of 47 specimens in the study. A total of 58 ARGs associated with tetracycline, macrolide-lincosamide-streptogramin, beta-lactams, sulfonamide and aminoglycosides were identified by RPIP in 19 of 25 patients. Using the results of AST as a standard, the coincidence rates of erythromycin, tetracycline, penicillin and sulfonamides were 89.5, 79.0, 36.8 and 42.1â%, respectively.Conclusion. These results demonstrated the superiority of RPIP in pathogen detection, particularly for multiple and difficult-to-culture pathogens, as well as in predicting resistance to erythromycin and tetracycline, which has significance for the accurate diagnosis of pathogenic infection and in the guidance of clinical treatment.
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Antibacterianos , Antiinfecciosos , Humanos , Niño , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Sulfanilamida , Tetraciclina , EritromicinaRESUMEN
PURPOSE: To evaluate whether the six-month repeated irradiation of 650 nm low-level red light (LLRL) decreases the risk of myopia onset in children. METHODS: This was a single-masked, randomized controlled trial. A total of 112 children (aged 6-12 years) were enrolled and randomized to the treatment group or control group in a 1:1 ratio. The cycloplegic spherical equivalent error (SER) of children at baseline was -0.5 diopter (D) to 3D. Children in the treatment group were irradiated with the 650 nm LLRL for 6 min daily. No intervention was given to the control. The primary outcomes are myopia incidence, change in cycloplegic SER, and change in axial length (AL). RESULTS: For the treatment group and control group, the six-month myopia incidence rates were 1.8% (95% confidence interval, CI: 0.2-4.9%) and 12.5% (95% CI: 5.5-21.9%), respectively. The difference was significant (p = 0.028). The median changes in AL for the treatment group and control group were -0.02 (interquartile range, IQR: -0.12 to 0.06) mm, and 0.09 (IQR: 0-0.18) mm, respectively. The difference was significant (p < 0.001). The median changes in cycloplegic SER for the treatment group and control group were 0 (IQR: 0-0.25) D, and -0.125 (IQR: -0.375 to 0) D, respectively. The difference was significant (p < 0.001). There was no adverse event. CONCLUSION: The repeated irradiation of 650 nm LLRL may have a strong effect for myopia prevention in children, without risk of adverse events. TRIAL REGISTRATION: this trial is retrospectively registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ), the registration number is ChiCTR2200058963.
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Midriáticos , Miopía , Humanos , Niño , Miopía/epidemiología , Refracción Ocular , Luz , Incidencia , Progresión de la EnfermedadRESUMEN
Osteoarthritis (OA) is a common degenerative joint disease with a gradually increasing morbidity in the aging and obese population. Emerging evidence has implicated pyroptosis in the etiology of OA and it may be recognized as a therapeutic target in OA. We have previously reported regarding another disease that peroxisome proliferator-activated receptor gamma (PPAR-γ) activation exerts an anti-inflammatory effect by suppressing the nucleotide-binding and oligomerization domain-like receptor containing protein (NLRP) 3 inflammasome. However, the relationship between PPAR-γ and NLRP3-mediated pyroptosis in OA cartilage and its underlying mechanisms is fully unclear. In this study, we found that the level of NLRP3-mediated pyroptosis in severe lateral femoral condyle cartilage wear in the knee of an OA patient was significantly higher than that in the mild lateral femoral condyle cartilage wear areas. Moreover, in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced primary chondrocytes and knee OA rat models, we demonstrated that activation of PPAR-γ by pioglitazone (Piog) attenuated LPS/ATP-induced chondrocyte pyroptosis and arthritis. These effects were partially counteracted by either blocking the nuclear factor erythroid-2-related factor (Nrf2)/NLRP3 or PGC1-α/Δψ m signaling pathway. Simultaneous depression of these two signaling pathways can completely abrogate the protective effects of Piog on OA and chondrocytes. Taken together, Piog protects OA cartilage against pyroptosis-induced damage by simultaneously activating both the Nrf2/NLRP3 and PGC-1α/Δψ m pathways, which enhances antioxidative and anti-inflammatory responses as well as mitochondrial biogenesis. Therefore, Piog may be a promising agent for human OA cartilage damage in future clinical treatments.
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Serological assays are indispensable tools in public health. Presently deployed serological assays, however, largely overlook research progress made in the last two decades that jeopardizes the conceptual foundation of these assays, i.e., antibody (Ab) specificity. Challenges to traditional understanding of Ab specificity include Ab polyspecificity and most recently nonreproducible Ab-probe interactions (NRIs). Here, using SARS-CoV-2 and four common livestock viruses as a test bed, we developed a new serological platform that integrates recent understanding about Ab specificity. We first demonstrate that the response rate (RR) from a large-sized serum pool (â¼100) is not affected by NRIs or by nonspecific Ab-probe interactions (NSIs), so RR can be incorporated into the diagnostic probe selection process. We subsequently used multiple probes (configured as a "protein peptide hybrid microarray", PPHM) to generate a digital microarray index (DMI) and finally demonstrated that DMI-based analysis yields an extremely robust probabilistic trend that enables accurate diagnosis of viral infection that overcomes multiple negative impacts exerted by NSI/NRI. Thus, our study with SARS-CoV-2 confirms that the PPHM-RR-DMI platform enables very rapid development of serological assays that outperform traditional assays (for both sensitivity and specificity) and supports that the platform is extendable to other viruses.
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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.
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Enfermedad de Alzheimer , Neuronas GABAérgicas , Animales , Humanos , Ratones , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Corteza Cerebral/metabolismo , Neuronas GABAérgicas/metabolismo , Redes Reguladoras de Genes , Porcinos , Factores de Transcripción/metabolismo , MacacaRESUMEN
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.
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Sistemas CRISPR-Cas , Enfermedades Transmisibles , Humanos , Edición Génica/métodosRESUMEN
INTRODUCTION: To evaluate the 6-month efficacy and safety of 650 nm low-level red light (LLRL) for myopia control in children. METHODS: This was a single-center, single-masked randomized controlled trial. A total of 224 children aged 6-12 years with spherical equivalent error (SER) of - 6 diopter (D) to - 0.5 D were enrolled, and were randomized to LLRL group or control group. Children in the LLRL group underwent treatment twice daily, each lasting for 3 min, there was an interval of at least 4 h between treatments. Children in both groups were allowed to wear single-vision spectacles; no additional intervention was given to the control. The primary outcomes included change in cycloplegic SER and change in axial length (AL) during 6 months. RESULTS: The median 6-month changes in AL of the LLRL and control groups were - 0.06 mm (interquartile range, IQR - 0.15, 0) and 0.14 mm (IQR 0.07, 0.22), respectively. The difference between groups was significant (Z = 10.021, p < 0.001). The median 6-month changes in SER were 0.125 D (IQR 0, 0.375) and - 0.25 D (IQR - 0.5, 0) for the LLRL and control groups, respectively. The difference between groups was significant (Z = 8.827, p < 0.001). Compared with the control, the proportion of children with hyperopic shift in the LLRL group was higher (51.65% vs. 3.41%, p < 0.001), and the proportion of children with shortened AL in the LLRL group was higher (63.74% vs. 2.27%, p < 0.001). No adverse event was observed. CONCLUSION: 650 nm LLRL significantly slowed down the myopia progression in children aged 6-12 years, and there was no observable side effect in the short term.
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BACKGROUND: The purpose of this study was to evaluate different pretreatment, extraction, amplification, and library generation methods for metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and to develop an efficient procedure for the simultaneous detection of DNA and RNA pathogens. METHODS: We generated thirteen mock CSF samples with four representative pathogens of encephalitis. Each sample was subjected to ten different methods by varying sample pretreatment/nucleic acid extraction (microbial DNA, total DNA, total NA, total RNA, Whole Transcriptome Amplification (WTA)) and library generation (Illumina or NEB). Negative extraction controls (NECs) were used for each method variation. RESULTS: We found that the quality of mNGS sequencing reads was higher from the NEB kit for library generation. Microbial DNA and total RNA increased microbial deposition by depleting the host DNA. Methods total NA and total RNA can detect gram-positive, gram-negative, RNA and DNA pathogens. We applied mNGS, including total NA and NEB library generation, to CSF samples from five patients diagnosed with infectious encephalitis and correctly determined all pathogens identified in clinical etiological tests. CONCLUSIONS: Our findings suggested that total nucleic acid extraction combined with NEB library generation is the most effective mNGS procedure in CSF pathogen detection. The optimization of positive criteria and databases can improve the specificity and sensitivity of mNGS diagnosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015425 (29/03/2018), https://www.chictr.org.cn/edit.aspx?pid=26292&htm=4 .
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Metagenómica , ARN , ADN , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Metagenómica/métodos , Sensibilidad y EspecificidadRESUMEN
Immune checkpoint therapy (ICT) with a monoclonal antibody (MAb) against programmed cell death protein 1 (PD-1) is a powerful clinical treatment for tumors. Cemiplimab is a human IgG4 antibody approved in 2018 and is the first MAb proven to be effective for locally advanced basal cell carcinoma. Here, we report the crystal structure of cemiplimab bound to PD-1 and the effects of PD-1 N-glycosylation on the interactions with cemiplimab. The structure of the cemiplimab/PD-1 complex shows that cemiplimab mainly binds to PD-1 with its heavy chain, whereas the light chain serves as the predominant region to compete with the binding of PD-L1 to PD-1. The interaction network of cemiplimab to PD-1 resembles that of camrelizumab (another PD-1-binding MAb), and the N58 glycan on the BC loop of PD-1 may be involved in the interaction with cemiplimab. The binding affinity of cemiplimab with PD-1 was substantially decreased with N58-glycan-deficient PD-1, whereas the PD-1/PD-L1 blocking efficiency of cemiplimab was attenuated upon binding to the N58-glycosylation-deficient PD-1. These results indicate that both the binding and blocking efficacy of cemiplimab require the N58 glycosylation of PD-1. Taken together, these findings expand our understanding of the significance of PD-1 glycosylation in the interaction with cemiplimab.
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Antígeno B7-H1 , Receptor de Muerte Celular Programada 1 , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales Humanizados , Antígeno B7-H1/metabolismo , Glicosilación , Humanos , Receptor de Muerte Celular Programada 1/metabolismoRESUMEN
Zero waste multistage utilization of biomass from Ginkgo biloba branches (GBBs) was achieved through extraction of bioactive components, analysis of antioxidant and antibacterial activities, preparation and composition of pyrolyzate, adsorption and reuse of modified biochar. The results showed that GBBs had abundant bioactive components for potential application in the industry of food, chemical raw materials and biomedicine. Especially, the bioactive compounds in acetone extract (10 mg/mL) of GBBs identified by DPPH and ABTS had free radical scavenging abilities of 92.28% and 98.18%, respectively, which are equivalent to Vitamin C used as an antioxidant in food additives. Fourier Transform Infrared and X-Ray Diffraction analysis showed that carboxymethyl cellulose (CMC) and magnetic Fe3O4 were successfully incorporated into raw biochar (RB) to form CMC-Fe3O4-RB nanomaterial. Scanning electron microscopy and X-Ray Diffraction spectroscopy displayed Fe, C, and O existed on the surface of CMC-Fe3O4-RB. Compared with RB, CMC-Fe3O4-RB had a larger specific surface area, pore volume and pore size. Meanwhile, nanomagnetic CMC-Fe3O4-RB solved the problem of agglomeration in traditional magnetized biochar production, and improved the adsorption capacity of Pb2+, which was 29.90% higher than that of RB by ICP-OES. Further, the Pb2+ (10 mg/L) adsorption capacity of CMC-Fe3O4-RB reached the highest level in 2 h at the dosage of 0.01 g/L, and remained stable at 52.987 mg/g after five cycles of adsorption and desorption. This research aided in the creation of a strategy for GBBs zero waste multistage usage and a circular economic model for GBBs industry development, which can be promoted and applied to the fields of food industry and environment improvement.
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Ginkgo biloba , Contaminantes Químicos del Agua , Adsorción , Carboximetilcelulosa de Sodio , Carbón Orgánico , Extractos Vegetales , Contaminantes Químicos del Agua/análisisRESUMEN
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-1·K-1, 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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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.
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Antivirales/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Virus Sincitial Respiratorio Humano/patogenicidad , Genoma Viral , Humanos , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/inmunología , Vacunas Virales/uso terapéuticoRESUMEN
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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Enzima Convertidora de Angiotensina 2/metabolismo , Sitios de Unión/fisiología , COVID-19/metabolismo , Quirópteros/virología , SARS-CoV-2/patogenicidad , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , COVID-19/inmunología , Quirópteros/inmunología , Quirópteros/metabolismo , Especificidad del Huésped/inmunología , Humanos , Filogenia , Unión Proteica/fisiología , Receptores Virales/metabolismo , SARS-CoV-2/inmunología , Alineación de SecuenciaRESUMEN
OBJECTIVE: This research was carried out to investigate the effects of corn particle size on the apparent total tract digestibility (ATTD) of energy and nutrients fed to pigs at four different growth stages and therefore to provide basis for better application of corn in pig feeds. METHODS: Eighteen weanling piglets, 18 growing barrows, 24 gestating sows and 24 lactating sows were used in this study. Within each stage, pigs were allotted to 1 of 3 or 4 corn-soybean meal diets which were formulated with different corn particle size in a completely randomized design with 6 replicate pigs per diet. Each stage lasted for 19 days, including 7 days for cages adaptation, 7 days for adaptation to diets and followed by 5 days for total collection of feces and urine. RESULTS: For nursery and growing stages, the results showed that digestible energy content and ATTD of gross energy (GE), dry matter (DM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) was increased (p<0.05) as the corn particle size reduced. Meanwhile, the metabolizable energy content and ATTD of crude protein (CP) tended to increase. For gestating sows, no differences were found in the ATTD of nutrients among dietary treatments. As for lactating sows, there were linear and quadratic increases (p<0.05) in the ATTD of DM, GE, NDF as the corn being finer milled. Quadratic response in ATTD of ADF and CP (p<0.05) were observed as sows fed with four different diets. CONCLUSION: Reducing corn particle size can increase digestibility of nutrients fed to young pigs and lactating sows. No effects were observed in present experiment when gestating sows were fed with different particle sized corn.
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The objectives of this study were (a) to investigate the effect of body weight (BW) on available energy in fibre-rich diets containing two NDF levels; and (b) to evaluate the effect of fibre type and NDF level on AA digestibility. In Exp. 1, barrows (24 at 33.4 ± 1.1 kg; 24 at 86.8 ± 3.3 kg) were randomly allotted to 4 diets containing a high protein basal (HPB), a low protein basal (LPB), 70% HPB + 30% wheat bran (WB) (HPB-WB) and 70% LPB + 30% sunflower meal (SFM) (LPB-SFM). In Exp. 2, barrows (24 at 33.5 ± 1.8 kg; 24 at 87.0 ± 3.8 kg) were randomly allotted to 4 diets containing no SFM with 12% NDF (SFM0LF), no SFM with 16% NDF (SFM0HF), 24% SFM with 12% NDF (SFM24LF) and 24% SFM with 16% NDF (SFM24HF). In Exp. 3, twelve barrows (35.5 ± 3.4 kg) fitted with T-cannulas were allotted to two 6 × 4 Youden square design with 6 diets (4 same diets as in Exp. 2 and 2 nitrogen-free diets). The concentration of DE, ME and ATTD of GE, CP, NDF and ADF in diets was greater (p < .01) when fed to 90 kg pigs compared with 30 kg pigs. The ME in ingredients was not affected by BW. The ATTD of NDF was negatively correlated with the CF (r = -.98; p < .01), ADF (r = -.99; p < .01) and ADL content (r = -.96; p < .01). The ME of diets was negatively correlated with the ATTD of CF (r = -.98; p < .01). The addition of SFM increased the standardized ileal digestibility (SID) of Met (p < .05). In conclusion, diets rich in fibre had different nutritional values at different pig weight stages. The AA digestibility depends mainly on chemical composition of diets.
Asunto(s)
Alimentación Animal/análisis , Dieta/veterinaria , Fibras de la Dieta/farmacología , Helianthus , Porcinos/crecimiento & desarrollo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Peso Corporal , Fibras de la Dieta/administración & dosificación , Digestión , Metabolismo Energético , Masculino , Nutrientes , Valor Nutritivo , SemillasRESUMEN
AIM: To explore whether the same corneal curvature parameters and anterior chamber depth measured by Pentacam and VX120 have a good consistency and can replace each other. METHODS: This study enrolled 140 eyes of 70 patients ranging in age from 19 to 53y. All eyes underwent a comprehensive ophthalmologic examination including an anterior segment analysis with the VX120 system (Visionix-Luneau Technologies, Chartres, France) and Pentacam (Oculus Optikgerate GmbH) respectively. The comparison on corneal curvature parameters was done between Pentacam and VX120 using clustered signed rank test; the interclass correlation coefficients (ICC) with 95% confidence intervals (CI) was calculated for each parameter between Pentacam and VX120; the Bland-Altman plot of each parameter was supplemented. RESULTS: The anterior corneal curvature measured by VX120 was Ks: 44.00±1.78 D, KsAt: 89.45±22.18, Kf: 42.84±1.58 D, KfAt: 93.91±79.34; which measured by Pentacam was Ks: 43.80±1.82 D, KsAt: 91.17±21.40, Kf: 42.61±1.64 D, KfAt: 91.16±78.69. There was statistical difference between Pentacam and VX120 for anterior corneal curvature parameter (P<0.001). The posterior corneal curvature measured by VX120 was Ks: -6.42±1.23 D, KsAt: 91.00±23.45, Kf: -5.85±1.24 D, KfAt: 95.93±79.11; which measured by Pentacam was Ks: -6.44±0.32 D, KsAt: 92.24±11.75, Kf: -6.01±1.05 D, KfAt: 74.43±80.64. There was statistical difference between Pentacam and VX120 for posterior corneal curvature parameters (P<0.001). Anterior chamber depth (ACD) measured by Pentacam and VX120 was statistically different. Pentacam and VX120 achieved high consistency only on corneal anterior surface, including Ks and Kf. The ICCs were 0.96 (95%CI: 0.95, 0.97) and 0.95 (95%CI: 0.94, 0.97) respectively. For other corneal surface curvature parameters, all ICCs of between Pentacam and VX120 were below 0.87. Bland-Altman plots indicated of low consistency of corneal surface curvature parameters measured by Pentacam and VX120. CONCLUSION: The corneal curvature parameters and anterior chamber depth measured by Pentacam and VX120 were statistically different. Data measured by Pentacam and VX120 is not suggested to replace each other, mixing data measured by Pentacam and VX120 together is not suggested either.