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Influenza is an acute viral respiratory disease that can also cause gastroenteritis-like symptoms, such as abdominal pain, nausea, vomiting, and diarrhea. Immune dysfunction of adipose tissue is involved in the occurrence and prognosis of influenza viral pneumonia. In this study, we analyzed intestinal and adipose immune responses in mice infected with influenza virus and found that the impairment of intestinal and adipose immunity to influenza virus infection could be reversed by treatment with puerarin, a medicinal compound isolated from Pueraria lobata (called "gegen" in Chinese). We found that the lungs, small intestines (duodenum, ileum, jejunum) and large intestines (colon and rectum) of infected mice showed obvious inflammatory lesions, with significantly increased levels of virus, inflammatory cytokines (interleukin [IL]-6, IL-17, and tumor necrosis factor-α), Toll-like receptors 3, 4, and 9, and integrin αvß3 and α4, and a decreased level of secreted IgA compared to the normal control group (NC) (P < 0.05-0.001). Influenza virus infected mesenteric lymph nodes and adipose tissue, and adipokines (leptin, visfatin, "chemerin", and adiponectin) of lung and mesenteric adipose tissue were dysregulated. Puerarin treatment reversed the impairment of the intestinal and adipose immune responses in mice infected with influenza virus. Our findings suggest that influenza virus can infect adipose tissue and lead to intestinal adipose immune dysfunction in normal-weight mice and that the impairment of the intestinal and adipose immune response to influenza virus infection can be reversed by puerarin treatment.
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Tejido Adiposo/inmunología , Inmunidad/efectos de los fármacos , Intestinos/inmunología , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/inmunología , Vasodilatadores/farmacología , Animales , Citocinas/metabolismo , Femenino , Humanos , Inmunoglobulina A Secretora , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/inmunología , Intestinos/patología , Intestinos/virología , Isoflavonas , Pulmón/patología , Pulmón/virología , Masculino , Ratones , Ratones Endogámicos BALB C , Nicotinamida Fosforribosiltransferasa , Neumonía , Pueraria/química , ARN Viral , Carga ViralRESUMEN
Understanding the effects of climate change on primate ranging patterns is crucial for conservation planning. Rhinopithecus roxellana is an endangered primate species distributed in mountainous forests at the elevation of 1500-3500 m a.s.l. in China. Our study site, the Shennongjia National Nature Reserve, represents the eastern-most distribution of this species. This area has experienced significant habitat loss and fragmentation because of human population growth, increased farming and logging, and climate change. To estimate how changes in temperature and rainfall will affect the presumed future distribution of this species, we examined eco-geographic factors including bioclimate, habitat (vegetation type, landcover, etc.), topography, and human impact (human population, gross domestic product, etc.), and provide suggestions for management and conservation. We used a maximum entropy approach to predict the location and distribution of habitats suitable for R. roxellana in the present, 2020, 2050, and 2080 based on 33 environmental parameters, three general circulation models, three emissions scenarios, and two dispersal hypotheses. According to the ensemble modeling, we found range reductions of almost 30% by 2020, 70% by 2050, and over 80% by 2080. Although no obvious differences were found in distribution change based on full and zero dispersal assumptions, our results revealed range reductions in response to elevational, latitudinal, and longitudinal gradients, with the monkeys forced to migrate to higher elevations over time. Bioclimte factors, such as temperature, precipitation, evapo-transpiration, and aridity condition, were dominant contributors to range shifting. As habitat loss due to human influence and climate change is likely to be even more severe in the future, we considered three conservation hot-spots in the Shennongjia area and recommended: (i) securing existing reserves and establishing new reserves, (ii) re-designing management systems to include the Shenongjia reserve and the surrounding reserves and highlighting ecosystem protection at higher elevations, and (iii) using finer-scale research to guide the conservation planning and education in order to enhance protection and awareness in the local community. National and provincial conservation policies should integrate projections of climate change in making effective conservation strategies.
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Distribución Animal , Cambio Climático , Colobinae/fisiología , Conservación de los Recursos Naturales , Altitud , Animales , China , Ecosistema , Especies en Peligro de Extinción , Geografía , Actividades HumanasRESUMEN
Epilepsy is a chronic neurological disorder that causes a major threat to public health and the burden of disease worldwide. High-performance diagnostic tools for epilepsy need to be developed to improve diagnostic accuracy and efficiency while still missing. Herein, we utilized nanoparticle-enhanced laser desorption/ionization mass spectrometry (NELDI MS) to acquire plasma metabolic fingerprints (PMFs) from epileptic and healthy individuals for timely and accurate screening of epilepsy. The NELDI MS enabled high detection speed (â¼30 s per sample), high throughput (up to 384 samples per run), and favorable reproducibility (coefficients of variation <15 %), acquiring high-performed PMFs. We next constructed an epilepsy diagnostic model by machine learning of PMFs, achieving desirable diagnostic capability with the area under the curve (AUC) value of 0.941 for the validation set. Furthermore, four metabolites were identified as a diagnostic biomarker panel for epilepsy, with an AUC value of 0.812-0.860. Our approach provides a high-performed and high-throughput platform for epileptic diagnostics, promoting the development of metabolic diagnostic tools in precision medicine.
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Epilepsia , Aprendizaje Automático , Humanos , Epilepsia/diagnóstico , Epilepsia/sangre , Biomarcadores/sangre , Masculino , Femenino , Adulto , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
[This corrects the article DOI: 10.1021/acsomega.2c06533.].
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The wooden sluice site of the Nanyue Kingdom in Guangzhou, China, is covered with white magnesium sulfate salt whiskers continuously growing from the surface. In this paper, polarizing microscopy, scanning electron microscopy, infrared thermography, Fourier transform infrared spectrometry, and surface tension analysis were utilized to comprehensively analyze the micromorphology of whiskers grown on the surfaces of porous materials collected at the site of Nanyue Kingdom, as well as the change laws of magnesium sulfate solution droplets on the porous hydrophilic matrix, and the migration and crystallization of magnesium sulfate solution in the capillary tube. The diameters of magnesium sulfate salt whiskers grown on the surfaces of porous samples range from 30 to 110 µm. For the first time, it is clear to see that the whisker's structure is hollow and nodular. There are solid crystalline salts in hollow tubes, and some of them are aqueous. The top sections of whiskers are approximately circular and are composed of particles with a size of about 0.4-4.0 µm. Their growth conditions are mainly characterized by the high humidity environment where the porous material is located or locally located, the formation of an annular whisker base, and the pressure difference generated during the formation progress of water-bearing crystals in the capillary of the whisker. The research results expound on the circumstances and mechanism of magnesium sulfate solution-induced whisker development on the surface of porous materials, providing a reference for the study of the whisker growth mechanism.
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Emissions from wildfires worsen air quality and can adversely impact human health. This study utilized the fire inventory from NCAR (FINN) as wildfire emissions, and performed air quality modeling of April-October 2012, 2013, and 2014 using the U.S. Environmental Protection Agency CMAQ model under two cases: with and without wildfire emissions. This study then assessed the health impacts and economic values attributable to PM2.5 from fires. Results indicated that wildfires could lead annually to 4000 cases of premature mortality in the U.S., corresponding to $36 billion losses. Regions with high concentrations of fire-induced PM2.5 were in the west (e.g., Idaho, Montana, and northern California) and Southeast (e.g., Alabama, Georgia). Metropolitan areas located near fire sources, exhibited large health burdens, such as Los Angeles (119 premature deaths, corresponding to $1.07 billion), Atlanta (76, $0.69 billion), and Houston (65, $0.58 billion). Regions in the downwind of western fires, although experiencing relatively low values of fire-induced PM2.5, showed notable health burdens due to their large population, such as metropolitan areas of New York (86, $0.78 billion), Chicago (60, $0.54 billion), and Pittsburgh (32, $0.29 billion). Results suggest that impacts from wildfires are substantial, and to mitigate these impacts, better forest management and more resilient infrastructure would be needed.
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Contaminantes Atmosféricos , Contaminación del Aire , Incendios , Incendios Forestales , Humanos , Mortalidad Prematura , Contaminación del Aire/análisis , Material Particulado , Contaminantes Atmosféricos/análisisRESUMEN
Geraniin is a polyphenolic compound first isolated from Geranium thunbergii. The major protease (Mpro), namely 3 C-like protease (3CLpro), of coronaviruses is considered an attractive drug target as it is essential for the processing and maturation of viral polyproteins. Thus, our primary goal is to explore the efficiency of geraniin on 3CLpro of SARS-CoV-2 using the computational biology strategy. In this work, we studied the anti-coronavirus effect of geraniin in vitro and its potential inhibitory mode against the 3CLpro of SARS-CoV-2. We found that geraniin inhibited HCoV-OC43 coronavirus-infected cells during the attachment and penetration phases. Molecular docking and dynamics simulations exhibited that geraniin had a strong binding affinity and high stable binding to 3CLpro of SARS-CoV-2. Geraniin showed a strong inhibitory activity on coronavirus and may be a potential inhibitor of SARS-CoV-2 3CLpro.
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Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Humanos , Proteasas 3C de Coronavirus , Simulación del Acoplamiento Molecular , Cisteína EndopeptidasasRESUMEN
COVID-19 pandemic poses a severe threat to public health. However, so far, there are no effective drugs for COVID-19. Transcriptomic changes and key genes related to Th2 cells in COVID-19 have not been reported. These genes play an important role in host interactions with SARS-COV-2 and may be used as promising target. We analyzed five COVID-19-associated GEO datasets (GSE157103, GSE152641, GSE171110, GSE152418, and GSE179627) using the xCell algorithm and weighted gene co-expression network analysis (WGCNA). Results showed that 5 closely correlated modular genes to COVID-19 and Th2 cell enrichment levels, including purple, blue, pink, tan and turquoise, were intersected with differentially expressed genes (DEGs) and 648 shared genes were obtained. GO and KEGG pathway enrichment analyses revealed that they were enriched in cell proliferation, differentiation, and immune responses after virus infection. The most significantly enriched pathway involved the regulation of viral life cycle. Three key genes, namely CCNB1, BUB1, and UBE2C, may clarify the pathogenesis of COVID-19 associated with Th2 cells. 11 drug candidates were identified that could down-regulate three key genes using the cMAP database and demonstrated strong drugs binding energies aganist the three keygenes using molecular docking methods. BUB1, CCNB1 and UBE2C were identified key genes for COVID-19 and could be promising therapeutic targets.
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COVID-19 , Humanos , COVID-19/genética , Simulación del Acoplamiento Molecular , Pandemias , SARS-CoV-2/genética , Linfocitos T Colaboradores-InductoresRESUMEN
BACKGROUND: Influenza often leads to acute lung injury (ALI). Few therapeutics options such as vaccines and other antiviral drugs are available. Paeoniflorin is a monoterpene glucoside isolated from the roots of Paeonia lactiflora Pall. that has showed good anti-inflammatory and anti-fibrotic effects. However, it is not known whether paeoniflorin has an effect on influenza virus-induced ALI. PURPOSE: To investigative the protective effect and potential mechanism of paeoniflorin on ALI induced by influenza A virus (IAV). STUDY DESIGN AND METHODS: The anti-influenza activity of paeoniflorin in vitro was investigated. Influenza virus A/FM/1/47 was intranasally infected in mice to induce ALI, and paeoniflorin (50 and 100 mg/kg) was given orally to mice during 5 days, beginning 2 h after infection. On day 6 post-infection, body and lung weights, histology and survival were observed, and the lungs were examined for viral load, cytokine and cellular pathway protein expression. RESULTS: Results showed that paeoniflorin (50 and 100 mg/kg) reduced IAV-induced ALI. It reduces pulmonary oedema and improves histopathological changes in the lung, and also diminishes the accumulation of inflammatory cells in the lung. It was shown that paeoniflorin (50 and 100 mg/kg) alleviated IAV-induced ALI, as evidenced by improved survival in infected mice (40% and 50%, respectively), reduced viral titer in lung tissue, improved histological changes, and reduced lung inflammation. Paeoniflorin also improves pulmonary fibrosis by reducing the levels of pulmonary fibrotic markers (collagen type IV, alpha-smooth muscle actin, hyaluronic acid, laminin, and procollagen type III) and downregulating the expression levels of type I collagen (Col I) and type III collagen (Col III) in the lung tissues. Additionally, paeoniflorin inhibits the expression of αvß3, TGF-ß1, Smad2, NF-κB, and p38MAPK in the lung tissues. CONCLUSION: The results showed that paeoniflorin (50 and 100 mg/kg) protected against IAV-induced ALI, and the underlying mechanism may be related to the reduction of pro-inflammatory cytokine production and lung collagen deposition through down-regulation of activation of αvß3/TGF-ß1 pathway in lung tissue.
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Lesión Pulmonar Aguda , Virus de la Influenza A , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Glucósidos/farmacología , Pulmón , Ratones , Monoterpenos/farmacologíaRESUMEN
The recent emergence of the novel coronavirus (SARS-CoV-2) has resulted in a devastating pandemic with global concern. However, to date, there are no regimens to prevent and treat SARS-CoV-2 virus. There is an urgent need to identify novel leads with anti-viral properties that impede viral pathogenesis in the host system. Esculentoside A (EsA), a saponin isolated from the root of Phytolacca esculenta, is known to exhibit diverse pharmacological properties, especially anti-inflammatory activity. To our knowledge, SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) to enter host cells. This is mediated through the proteins of SARS-CoV-2, especially the spike glycoprotein receptor binding domain. Thus, our primary goal is to prevent virus replication and binding to the host, which allows us to explore the efficiency of EsA on key surface drug target proteins using the computational biology paradigm approach. Here, the anti-coronavirus activity of EsA in vitro and its potential mode of inhibitory action on the S-protein of SARS-CoV-2 were investigated. We found that EsA inhibited the HCoV-OC43 coronavirus during the attachment and penetration stage. Molecular docking results showed that EsA had a strong binding affinity with the spike glycoprotein from SARS-CoV-2. The results of the molecular dynamics simulation revealed that EsA had higher stable binding with the spike protein. These results demonstrated that Esculentoside A can act as a spike protein blocker to inhibit SARS-CoV-2. Considering the poor bioavailability and low toxicity of EsA, it is suitable as novel lead for the inhibitor against binding interactions of SARS-CoV-2 of S-protein and ACE2.
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Enzima Convertidora de Angiotensina 2 , Antivirales , Tratamiento Farmacológico de COVID-19 , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Ácido Oleanólico/análogos & derivados , SARS-CoV-2 , Saponinas , Glicoproteína de la Espiga del Coronavirus , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , Antivirales/química , Antivirales/farmacología , Línea Celular Tumoral , Coronavirus Humano OC43/química , Coronavirus Humano OC43/metabolismo , Humanos , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , SARS-CoV-2/química , SARS-CoV-2/fisiología , Saponinas/química , Saponinas/farmacología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismoRESUMEN
PREMISE OF THE STUDY: Microsatellite markers were developed for Smilax rotundifolia (Smilacaceae), an understory vine widely distributed in eastern North America, to investigate genetic diversity and structure. Cross-amplification was tested in three congeneric species: S. china, S. riparia, and S. walteri. METHODS AND RESULTS: A total of 6153 simple sequence repeat primer pairs were detected from the de novo-assembled transcriptome data (88,3962 contigs) of S. rotundifolia. Thirty-three polymorphic microsatellite loci were selected for further analysis among 96 individuals representing four natural populations of the species. The number of alleles ranged from two to 15, and 87.9% of the developed primer pairs could be cross-amplified in at least one of three congeneric Smilax species. CONCLUSIONS: The simple sequence repeat markers developed in this study will facilitate further studies on genetic diversity and phylogeographic patterns of S. rotundifolia and provide additional potential microsatellite resources for other Smilax species.
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Tricyrtis (Liliaceae) is an endemic genus in East Asia. Many of the species in the genus are in Endangered condition due to habitat loss and extensive horticultural usage in recent decades. In present study, we reported the first Tricyrtis chloroplast (cp) genome, Tricyrtis macropoda, based on Illumina pair-end sequencing data. The complete chloroplast genome size is 155,778 bp. In total, 131 genes were identified, including 85 protein-coding genes, 8 rRNA genes, and 38 tRNA genes. Fifteen genes are containing introns (clpP and ycf3 contained two introns) and 14 genes had two copies. The overall GC content of this genome was 37.4%. A further phylogenomic analysis of Liliales, including 62 taxa, was conducted for the placement of genus Tricyrtis. The complete plastome of T. marcropoda will provide a valuable resource for further genetic conservation, phylogenomic, and evolution studies in the genus and family.