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Little is known about the blood-feeding physiology of arbovirus vector Aedes aegypti although this type of mosquito is known to transmit infectious diseases dengue, Zika, yellow fever, and chikungunya. Blood feeding in the female A. aegypti mosquito is essential for egg maturation and for transmission of disease agents between human subjects. Here, we identify the A. aegypti sulfakinin receptor gene SKR from the A. aegypti genome and show that SKR is expressed at different developmental stages and in varied anatomical localizations in the adult mosquito (at three days after eclosion), with particularly high expression in the CNS. Knockingdown sulfakinin and sulfakinin receptor gene expression in the female A. aegypti results in increased blood meal intake, but microinjection in the thorax of the sulfakinin peptide 1 and 2 both inhibits dose dependently blood meal intake (and delays the time course of blood intake), which is reversible with receptor antagonist. Sulfakinin receptor expressed ectopically in mammalian cells CHO-K1 responds to sulfakinin stimulation with persistent calcium spikes, blockable with receptor antagonist. These data together suggest that activation of the Gq protein-coupled (i.e., calcium-mobilizing) sulfakinin receptor inhibits blood meal intake in female A. aegypti mosquitoes and could serve as a strategic node for the future control of A. aegypti mosquito reproduction/population and disease transmission.
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Aedes , Receptores Acoplados a Proteínas G , Animais , Aedes/metabolismo , Aedes/genética , Feminino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Células CHO , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Cricetulus , Comportamento Alimentar/fisiologia , Mosquitos VetoresRESUMO
Dendrobium loddigesii is a precious traditional Chinese medicine with high medicinal and ornamental value. However, the characterization of its mitochondrial genome is still pending. Here, we assembled the complete mitochondrial genome of D. loddigesii and discovered that its genome possessed a complex multi-chromosome structure. The mitogenome of D. loddigesii consisted of 17 circular subgenomes, ranging in size from 16,323 bp to 56,781 bp. The total length of the mitogenome was 513,356 bp, with a GC content of 43.41%. The mitogenome contained 70 genes, comprising 36 protein-coding genes (PCGs), 31 tRNA genes, and 3 rRNA genes. Furthermore, we detected 403 repeat sequences as well as identified 482 RNA-editing sites and 8154 codons across all PCGs. Following the sequence similarity analysis, 27 fragments exhibiting homology to both the mitogenome and chloroplast genome were discovered, accounting for 9.86% mitogenome of D. loddigesii. Synteny analysis revealed numerous sequence rearrangements in D. loddigesii and the mitogenomes of related species. Phylogenetic analysis strongly supported that D. loddigesii and D. Amplum formed a single clade with 100% bootstrap support. The outcomes will significantly augment the orchid mitochondrial genome database, offering profound insights into Dendrobium's intricate mitochondrial genome architecture.
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Dendrobium , Espécies em Perigo de Extinção , Genoma Mitocondrial , Filogenia , Dendrobium/genética , Dendrobium/classificação , Genoma Mitocondrial/genética , China , RNA de Transferência/genética , Sequenciamento Completo do Genoma , Composição de Bases , Cromossomos de Plantas/genética , Genoma de Planta , Genoma de CloroplastosRESUMO
Drought, especially terminal drought, severely limits wheat growth and yield. Understanding the complex mechanisms behind the drought response in wheat is essential for developing drought-resistant varieties. This study aimed to dissect the genetic architecture and high-yielding wheat ideotypes under terminal drought. An automated high-throughput phenotyping platform was used to examine 28 392 image-based digital traits (i-traits) under different drought conditions during the flowering stage of a natural wheat population. Of the i-traits examined, 17 073 were identified as drought-related. A genome-wide association study (GWAS) identified 5320 drought-related significant single-nucleotide polymorphisms (SNPs) and 27 SNP clusters. A notable hotspot region controlling wheat drought tolerance was discovered, in which TaPP2C6 was shown to be an important negative regulator of the drought response. The tapp2c6 knockout lines exhibited enhanced drought resistance without a yield penalty. A haplotype analysis revealed a favored allele of TaPP2C6 that was significantly correlated with drought resistance, affirming its potential value in wheat breeding programs. We developed an advanced prediction model for wheat yield and drought resistance using 24 i-traits analyzed by machine learning. In summary, this study provides comprehensive insights into the high-yielding ideotype and an approach for the rapid breeding of drought-resistant wheat.
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Secas , Estudo de Associação Genômica Ampla , Fenótipo , Polimorfismo de Nucleotídeo Único , Triticum , Triticum/genética , Triticum/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Haplótipos/genética , Característica Quantitativa Herdável , Adaptação Fisiológica/genética , Resistência à SecaRESUMO
AIMS: Investigating the impact of stemness-related circadian rhythm disruption (SCRD) on hepatocellular carcinoma (HCC) prognosis and its potential as a predictor for immunotherapy response. BACKGROUND: Circadian disruption has been linked to tumor progression through its effect on the stemness of cancer cells. OBJECTIVE: Develop a novel signature for SCRD to accurately predict clinical outcomes and immune therapy response in patients with HCC. METHODS: The stemness degree of patients with HCC was assessed based on the stemness index (mRNAsi). The co-expression circadian genes significantly correlated with mRNAsi were identified and defined as stemness- and circadian-related genes (SCRGs). The SCRD scores of samples and cells were calculated based on the SCRGs. Differentially expressed genes with a prognostic value between distinct SCRD groups were identified in bulk and single-cell datasets to develop an SCRD signature. RESULTS: A higher SCRD score indicates a worse patient survival rate. Analysis of the tumor microenvironment revealed a significant correlation between SCRD and infiltrating immune cells. Heterogeneous expression patterns, functional states, genomic variants, and cell-cell interactions between two SCRD populations were revealed by transcriptomic, genomic, and interaction analyses. The robust SCRD signature for predicting immunotherapy response and prognosis in patients with HCC was developed and validated in multiple independent cohorts. CONCLUSIONS: In summary, distinct tumor immune microenvironment patterns were confirmed under SCRD in bulk and single-cell transcriptomic, and SCRD signature associated with clinical outcomes and immunotherapy response was developed and validated in HCC.
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Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.
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Injúria Renal Aguda , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Microbioma Gastrointestinal/efeitos dos fármacos , Limosilactobacillus reuteri/fisiologia , Limosilactobacillus reuteri/metabolismo , Animais , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Camundongos , Lipopolissacarídeos/metabolismo , Masculino , Rim/microbiologia , Rim/metabolismo , Fezes/microbiologia , Modelos Animais de Doenças , Creatinina/sangue , Camundongos Endogâmicos C57BL , Apoptose/efeitos dos fármacosRESUMO
Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC50 values of 0.26 ± 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the α-helix content and increasing the ß-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor.
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Apigenina , Inibidores Enzimáticos , Lipase , Pâncreas , Espectrometria de Fluorescência , Animais , Apigenina/química , Apigenina/farmacologia , Dicroísmo Circular , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Lipase/antagonistas & inibidores , Lipase/metabolismo , Lipase/química , Pâncreas/enzimologiaRESUMO
Wedelolactone (WEL) is a small molecule compound isolated from Eclipta prostrate L., which has been reported to possess various biological activities such as anti-hepatotoxicity, anti-hypertension, anti-tumour, anti-phospholipase A2 and detoxification activity against snake venom. In the present study, we investigated the interaction of WEL with human serum albumin (HSA) using simultaneous fluorescence, UV-visible spectroscopy, 3D fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), molecular docking technique and molecular dynamics simulation. We found that the interaction between HSA and WEL can exhibit a static fluorescence burst mechanism, and the binding process is essentially spontaneous, with the main forces manifested as hydrogen bonding, van der Waals force and electrostatic interactions. Competitive binding and molecular docking studies showed that WEL preferentially bound to HSA in substructural region IIA (site I); molecular dynamics simulations showed that HSA interacted with WEL to form a stable complex, which also induced conformational changes in HSA. The study of the interaction between WEL and HSA can provide a reference for a more in-depth study of the pharmacodynamic mechanism of WEL and its further development and utilisation.
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Cumarínicos , Simulação de Dinâmica Molecular , Albumina Sérica Humana , Humanos , Albumina Sérica Humana/química , Simulação de Acoplamento Molecular , Sítios de Ligação , Ligação Proteica , Dicroísmo Circular , Espectrometria de Fluorescência , TermodinâmicaRESUMO
Liposomes as drug carriers for the delivery of therapeutic agents have triggered extensive research but it remains a grand challenge to develop a novel technology for enabling rapid and mass fabrication of monodisperse liposomes. In this work, we constructed a novel ultrasonic microfluidic technology, namely ultrasonic microreactor (USMR) with two different conjunction structure (co-flow and impinge flow, corresponding to USMR-CF and USMR-IF, respectively), to prepare uniform liposomes by antisolvent precipitation method. In this process, the monodisperse liposomes with tunable droplet sizes (DS) in 60-100 nm and a polydispersity index (PDI) less than 0.1 can easily be achieved by tuning the total flow rate, flow rate ratio, ultrasonic power, and lipid concentration within the two USMRs. Impressively, the USMR-IF is superior for reducing the PDI and tuning DS of the liposomes over the USMR-CF. More importantly, the ultrasonic can effectively reduce DS and PDI at the low TFR and support the IF-micromixer in reducing the PDI even at a high TFR. These remarkable performances are mainly due to the rapid active mixing, fouling-free property and high operation stability for USMR-IF. In addition, diverse lipid formulations can also be uniformly assembled into small liposomes with narrow distribution, such as the prepared HSPC-based liposome with DS of 59.6 nm and PDI of 0.08. The liposomes show a high stability and the yield can reach a high throughput with 108 g/h by using the USMR-IF at an initial lipid concentration of 60 mM. The results in the present work highlight a novel ultrasonic microfluidic technology in the preparation of liposomes and may pave an avenue for the rapid, fouling-free, and high throughput fabrication of different and monodisperse nanomedicines with controllable sizes and narrow distribution.
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Lipossomos , Ultrassom , Lipossomos/química , Portadores de Fármacos/química , Microfluídica , Lipídeos/química , Tamanho da PartículaRESUMO
BACKGROUND: Despite EIF5A upregulation related to tumor progression in LUAD (lung adenocarcinoma), the underlying mechanisms remain elusive. In addition, there are few comprehensive analyses of EIF5A in LUAD. METHODS: We investigated the EIF5A expression level in LUAD patients using data from the TCGA and GEO databases. We employed qRT-PCR and western blot to verify EIF5A expression in cell lines, while immunohistochemistry was utilized for clinical sample analysis. We analyzed EIF5A expression in tumor-infiltrating immune cells using the TISCH database and assessed its association with immune infiltration in LUAD using the "ESTIMATE" R package. Bioinformatics approaches were developed to discover the EIF5A-related genes and explore EIF5A potential mechanisms in LUAD. Proliferation ability was verified through CCK-8, clone formation, and EdU assays, while flow cytometry assessed apoptosis and cell cycle. Western blot was used to detect the expression of pathway-related proteins. RESULTS: EIF5A was significantly upregulated in LUAD. Moreover, we constructed a MAZ-hsa-miR-424-3p-EIF5A transcriptional network. We explored the potential mechanism of EIF5A in LUAD and further investigated the cAMP signaling pathway and the cell cycle. Finally, we proved that EIF5A silencing induced G1/S Cell Cycle arrest, promoted apoptosis, and inhibited proliferation via the cAMP/PKA/CREB signaling pathway. CONCLUSION: EIF5A serves as a prognostic biomarker with a negative correlation to immune infiltrates in LUAD. It regulated the cell cycle in LUAD by inhibiting the cAMP/PKA/CREB signaling pathway.
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Adenocarcinoma de Pulmão , Fator de Iniciação de Tradução Eucariótico 5A , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fator de Iniciação de Tradução Eucariótico 5A/metabolismo , Biomarcadores Tumorais/metabolismo , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/imunologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Pontos de Checagem do Ciclo Celular , Apoptose , Proliferação de Células , Transdução de Sinais , Linhagem Celular TumoralRESUMO
Lead (Pb) is a heavy metal that can have harmful effects on the environment, which has severe cytotoxicity in many animal tissues. N-acetylcysteine (NAC) has antioxidant activity, reducing lead-induced oxidative stress and apoptosis, but its role in chicken cells is unknown. The current study explored the antagonistic effect of NAC on lead-induced apoptosis and oxidative stress in chicken embryo fibroblast (CEF). In this study, CEF was used as a model to measure the cytotoxic effects of lead nitrate at different concentrations, demonstrating a dose-dependent effect on CEF activity. Employing inverted microscopy, the investigation of morphological alterations in CEF cells was conducted. Fluorescence staining methodology enabled the assessment of reactive oxygen species (ROS) levels within CEF cells. Moreover, an enzyme-linked immunosorbent assay was utilized to detect the presence of oxidative damage indicators encompassing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activity, malondialdehyde (MDA) content, and total antioxidant capacity (T-AOC) within CEF cells. Furthermore, the determination of the apoptosis rate of CEF cells was accomplished through the utilization of the Hoechst 33258 staining method in combination with the Annexin V-FITC dual staining method. By using RT-qPCR for detection, lead treatment increased expression of pro-apoptotic genes, caspase-3, and caspase-9, and reduced expression of anti-apoptotic genes, Bcl-2, and BI-1. Reduced antioxidant capacity was shown by increased ROS and MDA levels in CEF cells after lead treatment. The results showed that NAC inhibited the expression of caspase-3 and caspase-9 in lead-treated CEF cells, while NAC had a certain inhibitory effect on the relative expression of Bcl-2 and BI-1 mRNA in lead-induced CEF cells. NAC significantly reduced lead-induced oxidative damage and apoptosis. Overall, our results demonstrate a novel protective effect of NAC against lead-induced injury in chicken cells, providing a theoretical basis for future investigations of drugs that are effective in preventing lead poisoning in animals.
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IMPORTANCE: Marek's disease virus (MDV) is a highly infectious and oncogenic virus that can induce severe T cell lymphomas in chickens. MDV encodes more than 100 genes, most of which have unknown functions. This work indicated that the LORF9 gene is necessary for MDV early cytolytic replication in B lymphocytes. In addition, we have found that the LORF9 deletion mutant has a comparative immunological protective effect with CVI988/Rispens vaccine strain against very virulent MDV challenge. This is a significant discovery that LORF9 can be exploited as a possible target for the development of an MDV gene deletion vaccine.
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Herpesvirus Galináceo 2 , Vacinas contra Doença de Marek , Doença de Marek , Doenças das Aves Domésticas , Animais , Linfócitos B , Galinhas , Deleção de Genes , Herpesvirus Galináceo 2/genética , Doença de Marek/prevenção & controle , Doença de Marek/genética , Vacinas contra Doença de Marek/genética , Replicação ViralRESUMO
Introduction: The masked palm civet (Paguma larvata) serves as a reservoir in transmitting pathogens, such as Toxoplasma gondii, to humans. However, the pathogenesis of T. gondii infection in masked palm civets has not been explored. We studied the molecular changes in the brain tissue of masked palm civets chronically infected with T. gondii ME49. Methods: The differentially expressed proteins in the brain tissue were investigated using iTRAQ and bioinformatics. Results: A total of 268 differential proteins were identified, of which 111 were upregulated and 157 were downregulated. KEGG analysis identified pathways including PI3K-Akt signaling pathway, proteoglycans in cancer, carbon metabolism, T-cell receptor signaling pathway. Combing transcriptomic and proteomics data, we identified 24 genes that were differentially expressed on both mRNA and protein levels. The top four upregulated proteins were REEP3, REEP4, TEP1, and EEPD1, which was confirmed by western blot and immunohistochemistry. KEGG analysis of these 24 genes identified signaling cascades that were associated with small cell lung cancer, breast cancer, Toll-like receptor signaling pathway, Wnt signaling pathways among others. To understand the mechanism of the observed alteration, we conducted immune infiltration analysis using TIMER databases which identified immune cells that are associated with the upregulation of these proteins. Protein network analysis identified 44 proteins that were in close relation to all four proteins. These proteins were significantly enriched in immunoregulation and cancer pathways including PI3K-Akt signaling pathway, Notch signaling pathway, chemokine signaling pathway, cell cycle, breast cancer, and prostate cancer. Bioinformatics utilizing two cancer databases (TCGA and GEPIA) revealed that the four genes were upregulated in many cancer types including glioblastoma (GBM). In addition, higher expression of REEP3 and EEPD1 was associated with better prognosis, while higher expression of REEP4 and TEP1 was associated with poor prognosis in GBM patients. Discussion: We identified the differentially expressed genes in the brain of T. gondii infected masked palm civets. These genes were associated with various cellular signaling pathways including those that are immune- and cancer-related.
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Neoplasias da Mama , Toxoplasma , Masculino , Animais , Humanos , Viverridae/metabolismo , Multiômica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Encéfalo/metabolismo , Biologia Computacional , Neoplasias da Mama/metabolismo , Proteínas de Membrana Transportadoras/metabolismoRESUMO
Black carbon (BC) has a significant impact on air quality, climate change, and human health. Studies on BC from vessel exhaust have been focused on in recent years. To realize the contribution of BC from vessels to ambient air quality, 28 months of BC variation were observed from February 2019 to May 2022, including 3 fishing moratoriums and 2 normal periods. The results showed that the average daily concentration of BC in the fishing moratorium was significantly lower than that in the normal period. The difference proportion of the BC concentration between 370 and 880 nm was calculated over the whole period. As a result, the mean difference value in the fishing moratorium from February to May was 0.06 ± 0.07, and the normal period was -0.02 ± 0.05. The aethalometer model indicated that BC was greatly affected by fossil fuel combustion in the normal period. The effect of vessel emissions on regional BC concentrations was considerable. In addition, 16 PAHs and 21 elements in PM emitted from 24 vessels of different types were sampled and analyzed in Dianshan Lake and the Taipu River. EC accounted for the highest proportion (23.64%) in the sample of small trawlers compared to the emissions from cargo ships with large tonnages. The component profiles of vessel exhaust showed that Zn, As, phenanthrene (Phe), anthracene (Ant), fluoranthene (Fla), and pyrene (Pyr) were the dominant species, although some of these species were mainly recognized as characteristic factors of coal combustion. To improve the accuracy of identifying the vessel source, the diagnostic ratios of Ant/(Ant + Phe), BaA/(BaA + Chr), Phe/Ant, and BaA/Chr were provided, and they exhibited the obvious characteristics of fuel combustion.
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In order to illustrate pollution characterization, source apportionment, and risk assessment of VOCs in Beijing, Baoding, and Shanghai, field observations of CO, NO, NO2, O3, and volatile organic compounds (VOCs) were conducted in 2019. Concentrations of VOCs were the highest in Beijing (105.4 ± 52.1 ppb), followed by Baoding (97.1 ± 47.5 ppb) and Shanghai (91.1 ± 41.3 ppb). Concentrations of VOCs were the highest in winter (120.3 ± 61.5 ppb) among the three seasons tested, followed by summer (98.1 + 50.8 ppb) and autumn (75.5 + 33.4 ppb). Alkenes were the most reactive VOC species in all cities, accounting for 56.0%, 53.7%, and 39.4% of ozone formation potential in Beijing, Baoding, and Shanghai, respectively. Alkenes and aromatics were the reactive species, particularly ethene, propene, 1,3,5-trimethylbenzene, and m/p-xylene. Vehicular exhaust was the principal source in all three cities, accounting for 27.0%, 30.4%, and 23.3% of VOCs in Beijing, Baoding, and Shanghai, respectively. Industrial manufacturing was the second largest source in Baoding (23.6%) and Shanghai (21.3%), and solvent utilization was the second largest source in Beijing (25.1%). The empirical kinetic modeling approach showed that O3 formation was limited by both VOCs and nitric oxides at Fangshan (the suburban site) and by VOCs at Xuhui (the urban site). Acrolein was the only substance with an average hazard quotient greater than 1, indicating significant non-carcinogenic risk. In Beijing, 1,2-dibromoethane had an R-value of 1.1 × 10-4 and posed a definite carcinogenic risk.
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Particulate matter 2.5 (PM2.5) is a prevalent risk factor in many diseases, but its molecular mechanism remains ambiguous and may be diverse. RNA m6A is an important epigenetic modification that regulates gene expression at the post-transcriptional level. Some previous animal exposure studies found that PM2.5 exposure up-regulated m6A RNA methylation in the lung, but there is no research on m6A RNA methylation in humans from PM2.5 exposure now. Here, in the present experiment, we performed a panel study of 65 students at the Chinese research academy of environmental sciences (CRAES) with 3 rounds of follow-up visits from August 2021 to January 2022. We examined m6A RNA modification profiles of peripheral blood mononuclear cells (PBMCs) from subjects after low and high concentrations of ambient PM2.5 exposure. We applied a linear mixed-effect (LME) model to investigate the association between PM2.5 exposure and global m6A RNA methylation and PTGS2 level in peripheral blood. We found that increased levels of global m6A RNA methylation and PTGS2 level were associated with higher PM2.5 exposure. Among the methylated mRNAs, PTGS2 was hyper-methylated after high concentrations of PM2.5 exposure, which coincided with the increased expression of PTGS2 mRNA. In the present study, we determined that PM2.5 exposure promoted RNA m6A modification, and PTGS2 in peripheral blood could serve as a novel regulatory factor of inflammation induced by PM2.5 exposure. Furthermore, RNA m6A modification may contribute to the altered expression of PTGS2 induced by PM2.5 exposure. Our finding provided a new perspective for the prevention and treatment of PM2.5 exposure-induced adverse health effects.
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Poluentes Atmosféricos , Leucócitos Mononucleares , Animais , Humanos , Ciclo-Oxigenase 2/genética , Material Particulado/toxicidade , Material Particulado/análise , Metilação , RNA , Exposição Ambiental , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análiseRESUMO
Previous studies have proved that exposure to extreme temperature in specific windows of pregnancy could cause some complications, such as pregnancy induced hypertension (PIH) and gestational diabetes mellitus (GDM), but differences in the effect of extreme temperature on the 2 complications are rarely studied. We carried a retrospective study on the impact of temperature on GDM/PIH in different trimesters based on data from a maternal and child health center in Beijing, China. Ambient temperatures (°C) were obtained from the China Meteorological Administration from January 1st, 2013 to May 15th, 2018. We use distributed lag non-linear models (DLNMs) combined with logistic regression to calculate the lag exposure-response relationships between the temperature and GDM/PIH from 1st to 24th/20th weeks of pregnancy. In both first and second trimesters, the risk of GDM was increased in summer with high temperatures; in second trimester, the risk of GDM increased in winter with low temperatures. In first half of pregnancy, risk of PIH was decreased in winter with low temperatures. These findings can provide the guideline for preventing the GDM and PIH induced by extreme temperature during pregnancy.
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Diabetes Gestacional , Hipertensão Induzida pela Gravidez , Gravidez , Feminino , Criança , Humanos , Diabetes Gestacional/epidemiologia , Temperatura , Estudos Retrospectivos , Hipertensão Induzida pela Gravidez/epidemiologia , Trimestres da GravidezRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Qingjin Huatan Decoction (QJHTT) consists of 11 herbal medicines: Scutellaria baicalensis Georgi, Gardenia jasminoides J.Ellis, Platycodon grandiflorus (Jacq.) A.DC., Ophiopogon japonicus (Thunb.) Ker Gawl., Morus alba L., Fritillaria thunbergii Miq., Anemarrhena asphodeloides Bunge, Trichosanthes kirilowii Maxim., Citrus reticulata Blanco, Poria cocos (Schw.) Wolf, and Glycyrrhiza uralensis Fisch. As a traditional compound Chinese medicinal formula, QJHTT has been used for more than 400 years in China. Historically, it was used to treat respiratory diseases and had shown beneficial clinical results for diseases related to lung inflammation. AIM OF THE STUDY: To investigate the therapeutic effect of QJHTT on influenza A virus (IAV) pneumonia in mice and explore its possible mechanism of action. MATERIALS AND METHODS: The components in QJHTT were analyzed by UPLC-Q-TOF-MS and some antiviral active components reported in the literature were determined and quantified by HPLC. The protective effects of QJHTT were investigated using lethal and sublethal doses (2 LD50 or 0.8 LD50 viral suspension, separately) of H1N1-infected mice. Mortality and lung lesions in H1N1-infected mice were used to evaluate the efficacy of QJHTT. The potential mechanism of QJHTT in the treatment of viral pneumonia was determined at the gene level by RNA sequencing and validated by qRT-PCR. Following this, the changes in protein levels of JAK2/STAT3 were analyzed since it is a key downstream target of the chemokine signaling pathways. Preliminary elucidation of the mechanism of QJHTT to protect mice against IAV pneumonia through this pathway was conducted. RESULTS: In this study, 12 antiviral active constituents including baicalin, geniposide, and mangiferin were identified from QJHTT. In vivo treatment of QJHTT reduced the virus titers of lung tissue significantly and improved the survival rate, lung index, and pulmonary histopathological changes; additionally, a reduction in the serum levels of TNF-α, IL-1ß, IL-6, and IFN-γ inflammatory factors in H1N1-infected mice was observed. RNA-seq analysis and qRT-PCR showed that QJHTT primarily reversed the activities CCL2, CCL7, CCR1, and other chemokines and their reception-related genes, suggesting that QJHTT may produce disease-resistant pneumonia by inhibiting the downstream JAK2/STAT3 pathway. Western blot analysis confirmed that QJHTT effectively reduced the protein levels of JAK2, STAT3, and related phosphorylated products in the lung tissue of H1N1-infected mice. CONCLUSIONS: Our results indicated that QJHTT alleviated IAV pneumonia in mice by regulating related chemokines and their receptor-related genes in lung tissue, thereby inhibiting JAK2/STAT3 pathway. This could pave way for the design of novel therapeutic strategies to treat viral pneumonia.
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Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Infecções por Orthomyxoviridae , Pneumonia Viral , Animais , Camundongos , Pneumonia Viral/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Quimiocinas , Transdução de SinaisRESUMO
The African swine fever virus (ASFV) causes high mortality in domestic pigs. ASFV encodes an important protein target for subunit vaccine development, CD2v, but its most effective immunological regions are not known. Herein, we generated a monoclonal antibody (mAb) named IF3 by immunizing mice against the intracellular region of the CD2v protein (CD2v-IR). 1F3 specifically recognized CD2v, which is expressed transiently in transfected Sf9 cells and also in inactivated ASFV-infected porcine alveolar macrophage (PAM) cells. The epitope recognized by 1F3 is 264EPSPREP270, which is highly conserved in ASFV genotypes. Immunization of mice with this epitope elicited an increased IgG response, including IgG1 and IgG2a subtypes, and also increased CD8+ T cells and cytokine expression. Overall, these results indicate that this epitope induces both humoral and cellular immune responses that may be used for ASFV-related subunit vaccine design and development.
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In clinical neuroscience, epileptic seizures have been associated with the sudden emergence of coupled activity across the brain. The resulting functional networks-in which edges indicate strong enough coupling between brain regions-are consistent with the notion of percolation, which is a phenomenon in complex networks corresponding to the sudden emergence of a giant connected component. Traditionally, work has concentrated on noise-free percolation with a monotonic process of network growth, but real-world networks are more complex. We develop a class of random graph hidden Markov models (RG-HMMs) for characterizing percolation regimes in noisy, dynamically evolving networks in the presence of edge birth and edge death. This class is used to understand the type of phase transitions undergone in a seizure, and in particular, distinguishing between different percolation regimes in epileptic seizures. We develop a hypothesis testing framework for inferring putative percolation mechanisms. As a necessary precursor, we present an EM algorithm for estimating parameters from a sequence of noisy networks only observed at a longitudinal subsampling of time points. Our results suggest that different types of percolation can occur in human seizures. The type inferred may suggest tailored treatment strategies and provide new insights into the fundamental science of epilepsy.
Assuntos
Epilepsia , Convulsões , Humanos , Encéfalo , Transição de Fase , AlgoritmosRESUMO
Ultrasonically-induced nanoemulsions have been widely investigated for the development of functional food, cosmetics, and pharmaceuticals due to ideal droplet sizes (DS), low polydispersity index (PDI), and superior physical stability. However, a series of frequently-used ultrasonic set-ups mainly suffered from a low ultrasonic energy efficiency caused by the large acoustic impedance and energy consumption, subordinately confronted with a low throughput, complicated fabrication with complex structure and weak ultrasonic cavitation. Herein, we employed a typical ultrasonic microreactor (USMR) that ensured the high-efficient energy input and generated intense cavitation behavior for efficient breakage of droplets and continuous production of unified oil-in-water (O/W) nanoemulsions in a single cycle and without any pre-emulsification treatment. The emulsification was optimized by tuning the formula indexes, technological parameters, and numerical analysis using Response Surface Methodology (RSM), followed by a comparison with the emulsification by a traditional ultrasonic probe. The USMR exhibited superior emulsification efficiency and easy scale-up with remarkable uniformity by series mode. In addition, concurrent and uniform nanoemulsions with high throughput could also be achieved by a larger USMR with high ultrasonic power. Based on RSM analysis, uniform DS and PDI of 96.4â¯nm and 0.195 were observed under the optimal conditions, respectively, well consistent with the predicted values. Impressively, the optimal nanoemulsions have a uniform spherical morphology and exhibited superior stability, which held well in 45â¯days at 4â and 25â. The results in the present work may provide a typical paradigm for the preparation of functional nanomaterials based on the novel and efficient emulsification tools.