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Considering both electrokinetic remediation and phytoremediation have limitations, an electrokinetic phytoremediation (EP) system was constructed to obtain efficient and environmentally friendly remediation results. This study indicates that the electric field can promote the absorption of Cd by ryegrass with little impact on soil physicochemical properties under the condition of rotary switching electrodes, and the accumulation of Cd in the aboveground and underground parts of ryegrass increased by 145.2% and 93.7%, respectively. The DC electric field combined with ryegrass under rotary switching electrode mode proved to be the optimal condition for the remediation of Cd contaminated soil with a remediation efficiency of 66.7%. Moreover, the rotary switching of the electrodes alleviated the suppression of the growth of ryegrass by the DC electric field. During the EP remediation process, the electric field promoted the transformation of the residue state of Cd to the other forms, which accelerated the desorption rate of Cd from the soil and facilitated the migration of Cd into plants. In conclusion, EP is a green and efficient remediation technology for heavy metal contaminated soil with good application prospects.
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Biodegradação Ambiental , Cádmio , Eletrodos , Lolium , Poluentes do Solo , Poluentes do Solo/metabolismo , Cádmio/metabolismo , Cádmio/química , Lolium/metabolismo , Recuperação e Remediação Ambiental/métodos , Solo/químicaRESUMO
Human cytomegalovirus (HCMV), a widely prevalent human beta-herpesvirus, establishes lifelong persistence in the host following primary infection. In healthy individuals, the virus is effectively controlled by HCMV-specific T cells and typically exhibits asymptomatic. The T cell immune response plays a pivotal role in combating HCMV infection, while HCMV employs various strategies to counteract it within the host. Previously, we reported that UL23, a tegument protein of HCMV, facilitates viral immune evasion from interferon-gamma (IFN-γ) responses, and it is well known that IFN-γ is mainly derived from T cells. However, the involvement of UL23 in viral immune evasion from T cell-mediated immunity remains unclear. Herein, we present compelling evidence that UL23 significantly enhances viral resistance against T cell-mediated cytotoxicity during HCMV infection from the co-culture assays of HCMV-infected cells with T cells. We found that IFN-γ plays a major role in regulating T cell cytotoxicity mediated by UL23. More interestingly, we demonstrated that UL23 not only regulates the IFN-γ downstream responses but also modulates the IFN-γ secretion by regulating T cell activities. Further experiments indicate that UL23 upregulates the expression and signaling of programmed death ligand 1 (PD-L1), which is responsible for inhibiting multiple aspects of T cell activities, including activation, apoptosis, and IFN-γ secretion, as determined through RNA-seq analysis and inhibitor-blocking experiments, ultimately facilitating viral replication and spread. Our findings highlight the potential role of UL23 as an alternative antagonist in suppressing T cell cytotoxicity and unveil a novel strategy for HCMV to evade T cell immunity. IMPORTANCE: T cell immunity is pivotal in controlling primary human cytomegalovirus (HCMV) infection, restricting periodic reactivation, and preventing HCMV-associated diseases. Despite inducing a robust T cell immune response, HCMV has developed sophisticated immune evasion mechanisms that specifically target T cell responses. Although numerous studies have been conducted on HCMV-specific T cells, the primary focus has been on the impact of HCMV on T cell recognition via major histocompatibility complex molecules. Our studies show for the first time that HCMV exploits the programmed death ligand 1 (PD-L1) inhibitory signaling pathway to evade T cell immunity by modulating the activities of T cells and thereby blocking the secretion of IFN-γ, which is directly mediated by HCMV-encoded tegument protein UL23. While PD-L1 has been extensively studied in the context of tumors and viruses, its involvement in HCMV infection and viral immune evasion is rarely reported. We observed an upregulation of PD-L1 in normal cells during HCMV infection and provided strong evidence supporting its critical role in UL23-induced inhibition of T cell-mediated cytotoxicity. The novel strategy employed by HCMV to manipulate the inhibitory signaling pathway of T cell immune activation for viral evasion through its encoded protein offers valuable insights for the understanding of HCMV-mediated T cell immunomodulation and developing innovative antiviral treatment strategies.
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Antígeno B7-H1 , Infecções por Citomegalovirus , Citomegalovirus , Evasão da Resposta Imune , Interferon gama , Transdução de Sinais , Humanos , Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Linfócitos T/imunologia , Linfócitos T/virologia , Proteínas Virais/metabolismo , Proteínas Virais/imunologia , Proteínas Virais/genéticaRESUMO
BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. CASE PRESENTATION: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. CONCLUSIONS: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.
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Síndrome POEMS , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/patologia , Masculino , Pessoa de Meia-Idade , Lenalidomida/uso terapêutico , Talidomida/uso terapêutico , Talidomida/análogos & derivados , Fator A de Crescimento do Endotélio Vascular , Dexametasona/uso terapêutico , Resultado do Tratamento , Proteínas do Mieloma/análiseRESUMO
Infertility is a condition characterized by a low fertility rate, which significantly affects the physical and mental health of women of reproductive age. Typically, the treatment duration is prolonged, and the therapeutic outcomes are often unsatisfactory. Professor Cheng-yao He, a renowned expert in traditional Chinese medicine, commonly uses the herb Cnidii Fructus (SCZ) for the treatment of infertility. However, the exact mechanism remains unclear, and there is limited research available on this topic. The active ingredients of SCZ were obtained from the traditional chinese medicine system pharmacology (TCMSP) database and screened for pharmacokinetics (PK), involving absorption, distribution, metabolism, and excretion (ADME). Target prediction was performed by SwissTargetPrediction database, and infertility-related disease targets were searched in GeneCards, TTD, DrugBank, and OMIM database. The protein-protein interaction (PPI) network was constructed using the STRING database (Version 11.5) and analyzed by Cytoscape software (Version 3.9.1). Additionally, the target genes were subjected to biological enrichment analysis in the Metascape database, including gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and the "Disease-Ingredient-pathway-target" network was constructed using Cytoscape software. With the assistance of AutoDockVina, Ligplot, and PyMOL software, a validation of Molecular docking results and a visualization of the results were performed. This study identified 11 retained active ingredients of SCZ, 447 drug targets, 233 of which were related to infertility, and 5393 disease targets. GO enrichment analysis mainly involved 221 biological processes such as cellular response to chemical stress and gland development. KEGG enrichment analysis mainly involved 68 pathways such as thyroid hormone signaling pathway, estrogen signaling pathway, FOXO signaling pathway, and PI3K/Akt signaling pathway. Molecular docking showed that the core active ingredients of SCZ, including Ammidin, Diosmetin, Xanthoxylin N, and Prangenidin, had strong binding abilities with core targets such as MDM2, MTOR, CCND1, EGFR, and AKT1. This study preliminarily demonstrated that SCZ may act on the PI3K/Akt signaling pathway, exerting its therapeutic effects on infertility by improving energy metabolism disorders and endometrial receptivity, inducing primordial follicle activation, regulating oocyte proliferation, differentiation, and apoptosis, and promoting the release of dominant follicles.
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BACKGROUND: The aim of this study was to evaluate the efficacy and safety of recombinant human endostatin in combination with vinorelbineâ +â cisplatin (NPE) for the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) of NPE for advanced NSCLC in PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched using a computerized search of the database from the time of creation to May 2023. Two investigators independently extracted literature information and assessed the quality of the included literature. Meta-analysis was performed using RevMan 5.4.0 software. RESULTS: A total of 24 RCTs with 2114 patients with advanced NSCLC were finally included. The results of meta-analysis showed that the total effective rate in the group received NPE regimen was significantly higher than those in the group without NPE regimen (RRâ =â 1.70, 95% CI: 1.48-1.95, Pâ <â .00001). Meanwhile, the clinical benefit rate in the group received NPE regimen was also significantly higher than those in the group without NPE regimen (RRâ =â 1.22, 95% CI: 1.15-1.29, Pâ <â .00001). However, there was no significant difference in the incidence of adverse event rate between the 2 groups (RRâ =â 0.98, 95% CI: 0.76-1.27, Pâ =â .88). CONCLUSIONS: Compared with NP (vinorelbineâ +â cisplatin) regimens for patients with advanced NSCLC, NPE regimens improve the total effective rate and clinical benefit rate of treatment, but there can be no significant difference in adverse effects. Prospective randomized trials are needed to further validate the safety and efficacy of this treatment modality.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Cisplatino , Endostatinas , Neoplasias Pulmonares , Proteínas Recombinantes , Vinorelbina , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Endostatinas/administração & dosagem , Endostatinas/uso terapêutico , Endostatinas/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Vinorelbina/administração & dosagem , Vinorelbina/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Drug discovery often begins with a new target. Protein-protein interactions (PPIs) are crucial to multitudinous cellular processes and offer a promising avenue for drug-target discovery. PPIs are characterized by multi-level complexity: at the protein level, interaction networks can be used to identify potential targets, whereas at the residue level, the details of the interactions of individual PPIs can be used to examine a target's druggability. Much great progress has been made in target discovery through multi-level PPI-related computational approaches, but these resources have not been fully discussed. Here, we systematically survey bioinformatics tools for identifying and assessing potential drug targets, examining their characteristics, limitations and applications. This work will aid the integration of the broader protein-to-network context with the analysis of detailed binding mechanisms to support the discovery of drug targets.
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Biologia Computacional , Descoberta de Drogas , Descoberta de Drogas/métodos , Biologia Computacional/métodos , Humanos , Proteínas/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapeamento de Interação de Proteínas/métodos , Ligação ProteicaRESUMO
Background/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-ß-induced epithelial-mesenchymal transition (EMT) in HCC. Methods: Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-ß-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot. Results: In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells. Conclusion: PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.
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INTRODUCTION: Over decades, the source-function relationships of bioactive polysaccharides have been progressively investigated, however, it is still unclear how a defined structure may conduce to the bioactivities of polysaccharides. OBJECTIVES: To explore the structure-function relationship of fungus polysaccharides, we employed a dextran sulfate sodium (DSS)-induced colitis mouse model to compare the anti-inflammatory activity of two fungus polysaccharides from Dictyophora indusiata (DIP) and Tremella fuciformis (TFP), which exhibit distinct glycosidic linkages. METHODS: The structures of DIP and TFP were characterized through molecular weight detection, molecular morphology analysis, methylation analysis, and NMR analysis. Subsequently, we employed a DSS-induced colitis model to assess the anti-inflammatory efficacy of DIP and TFP. The colitis symptoms, histological morphology, intestinal inflammatory cytokines, and the composition and function of gut microbiota before and after polysaccharides treatment in colitis mice were also investigated. RESULTS: DIP, l,3-ß-D-glucan with 1,4-ß and 1,6-ß-D-Glcp as branched chains, exhibited superior therapeutic effect than that of TFP consisted of a linear 1,3-α-D-mannose backbone with D-xylose and L-fucose in the side chains. Both DIP and TFP relieved DSS-induced colitis in a gut microbiota-dependent manner. Furthermore, metagenomics showed that DIP and TFP could partially reverse the bacterial function in colitis mice. Glycoside Hydrolase 1 (GH1) and GH3 were identified as being involved in hydrolyzing the glucose linkages in DIP, while GH92 and GH29 were predicted to be active in cleaving the α-1,3-linked mannose linkages and the glycosidic bonds of L-fucose residues in TFP. CONCLUSION: Our findings highlight the pivotal role of glycosidic linkages in anti-inflammatory activities of fungus polysaccharides and would promote the design and discovery of polysaccharides with designated activity to be used as functional foods and/or therapeutics.
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Objectives: The Albumin-Bilirubin (ALBI) score has been widely used to assess the prognosis in patients with cirrhosis and hepatocellular carcinoma. This study aimed to analyze the relationship between ALBI score and all-cause mortality in patients with hepatitis B virus (HBV) infection in general. Methods: Patients aged ≥ 18 years with previous or current HBV infection from the National Health and Nutrition Examination Survey (NHANES) in the United States between 1999 and 2018 were enrolled in this retrospective cohort study. Weight univariate and multivariate Cox regression models were used to assess the relationship between ALBI score and all-cause mortality. The area under the receiver operating characteristic curve (AUC) was utilized to assess the predictive effect of ALBI score for all-cause mortality. Results: A total of 3,666 patients were included, of whom 925 (23.53 %) patients died. Compared with ALBI score ≤ -2.6, HBV-infected patients with ALBI score > -2.6 [hazard ratio (HR) = 1.75; 95 % confidence interval (CI): 1.43-2.14] were corrected with a higher all-cause mortality risk after adjusting for confounders. Stratified analyses showed that higher ALBI score was related to a higher risk of all-cause mortality in different patients with HBV infection (All P < 0.05). Furthermore, the ALBI score had good predictive ability for 1-year (AUC = 0.816, 95 %CI: 0.754-0.878), 3-year (AUC = 0.808, 95 %CI: 0.775-0.841), 5-year (AUC = 0.809, 95 %CI: 0.783-0.835), and 10-year (AUC = 0.806, 95 %CI: 0.784-0.827) all-cause mortality. Conclusion: Higher ALBI score was related to a higher risk of all-cause mortality in patients with HBV infection, and the ALBI score showed a good predictive effect for short- and long-term all-cause mortality.
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The gut microbiota plays a central role in maintaining human health and has been linked to many gastrointestinal diseases such as ulcerative colitis (UC). Agaricus bisporus is a famous edible mushroom, and Agaricus bisporus polysaccharides (ABPs) and the two purified fractions (ABP-1 and ABP-2) were demonstrated to exhibit immunomodulatory activity in our previous study. Herein, we further found that ABPs, ABP-1, and ABP-2 possessed therapeutic effects against dextran sodium sulfate (DSS)-induced colitis in mice. ABPs, ABP-1, and ABP-2 could relieve body weight loss, colon atrophy, and histological injury, increase tight junction proteins, restore gut-barrier function, and inhibit inflammation. ABP-2 with a lower molecular weight (1.76 × 104 Da) showed a superior therapeutic effect than ABP-1 with a higher molecular weight (8.86 × 106 Da). Furthermore, the effects of ABP-1 and ABP-2 were microbiota-dependent, which worked by inducing Norank_f__Muribaculaceae and Akkermansia and inhibiting Escherichia-Shigella and Proteus. In addition, untargeted fecal metabolomic analysis revealed distinct modulation patterns of ABP-1 and ABP-2. ABP-1 mainly enriched steroid hormone biosynthesis, while ABP-2 significantly enriched bile secretion and tryptophan metabolism. In summary, ABPs, especially low-molecular-weight fraction, represent novel prebiotics for treatment of inflammatory gastrointestinal diseases.
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Agaricus , Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Polissacarídeos/farmacologia , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , ColoRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high case mortality rates, which is caused by Dabie bandavirus (DBV), a novel pathogen also termed as SFTS virus (SFTSV). Currently, no specific therapeutic drugs or vaccines are available for SFTS. Myxovirus resistance protein A (MxA) has been shown to inhibit multiple viral pathogens; however, the role of MxA in DBV infection is unknown. Here, we demonstrated that DBV stimulates MxA expression which, in turn, restricts DBV infection. Mechanistic target analysis revealed that MxA specifically interacts with the viral nucleocapsid protein (NP) in a manner independent of RNA. Minigenome reporter assay showed that in agreement with its targeting of NP, MxA inhibits DBV ribonucleoprotein (RNP) activity. In detail, MxA interacts with the NP N-terminal and disrupts the interaction of NP with the viral RNA-dependent RNA polymerase (RdRp) but not NP multimerization, the critical activities of NP for RNP formation and function. Furthermore, MxA N-terminal domain was identified as the functional domain inhibiting DBV infection, and, consistently, then was shown to interact with NP and obstruct the NP-RdRp interaction. Additionally, threonine 103 within the N-terminal domain is important for MxA inhibition to DBV, and its mutation (T103A) attenuates MxA binding to NP and obstruction of the NP-RdRp interaction. This study uncovers MxA inhibition of DBV with a series of functional and mechanistical analyses, providing insights into the virus-host interactions and probably helping inform the development of antiviral agents in the future.IMPORTANCEDBV/SFTSV is an emerging high-pathogenic virus. Since its first identification in China in 2009, cases of DBV infection have been reported in many other countries, posing a significant threat to public health. Uncovering the mechanisms of DBV-host interactions is necessary to understand the viral pathogenesis and host response and may advance the development of antiviral therapeutics. Here, we found that host factor MxA whose expression is induced by DBV restricts the virus infection. Mechanistically, MxA specifically interacts with the viral NP and blocks the NP-RdRp interaction, inhibiting the viral RNP activity. Further studies identified the key domain and amino acid residue required for MxA inhibition to DBV. Consistently, they were then shown to be important for MxA targeting of NP and obstruction of the NP-RdRp association. These findings unravel the restrictive role of MxA in DBV infection and the underlying mechanism, expanding our knowledge of the virus-host interactions.
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Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Proteínas do Nucleocapsídeo , Ribonucleoproteínas/metabolismo , RNA Polimerase Dependente de RNA , Febre Grave com Síndrome de Trombocitopenia/metabolismo , Febre Grave com Síndrome de Trombocitopenia/virologia , Phlebovirus/fisiologia , Interações Hospedeiro-PatógenoRESUMO
Meteorological conditions play a key role in the occurrence and evolution of atmospheric complex pollution. Considering the different pollution formation mechanisms of PM2.5 and O3, statistical calculation and in-depth learning methods were used to construct the PM2.5 and O3 meteorological condition indexes based on long-term pollution meteorological observation data. A research method was developed to study the meteorological characteristics and impact contribution of atmospheric complex pollution by using the meteorological condition index, and quantitative analysis of the distribution and variation of pollution excluding the influence of regional meteorological differences was also conducted. The results showed that in the summer of 2021, the pollution meteorological conditions in the key regions in central and eastern China were generally worse in the north and better in the south(index:"2+26" cities>the border area of Jiangsu, Anhui, Shandong, and Henan>the Yangtze River Delta) and the worst in June and the best in July. The "double high" pollution began to appear when the PM2.5 meteorological condition index>30 and O3 meteorological condition index>100; meanwhile, the unfavorable meteorological conditions for O3 also promoted the increase in PM2.5 concentration, resulting in the frequency of "double high" increases with the increase in O3 meteorological condition index. Compared with that during the same period last year, ρ(PM2.5) of each region decreased by 3.9 µg·m-3, 3.3 µg·m-3, and 1.4 µg·m-3 due to the contribution of the improvement in the pollution meteorological conditions, which is nearly 58.5% on average of the total decrease in PM2.5 concentration. However, the change in O3 pollution meteorological conditions was better in the north and worse in the south, and the overall deterioration in the Yangtze River Delta Region led to approximately 2.8 µg·m-3 growth for the O3 concentration. The PM2.5 and O3 concentrations after excluding the impact of meteorological differences showed different distribution characteristics from the air quality monitoring, in which the high concentrations of PM2.5 were distributed along the Bohai Sea, the inter-provincial border, and the south of the region, whereas the high concentrations of O3 were concentrated along the Taihang Mountains, around Mount Tai, and in parts of the Yangtze River Delta. The daily concentration variations in a single city during a specific pollution control period could be used as a basis for evaluating the effectiveness of local supervision and control, which will provide a reference for the dynamic supervision and daily scheduling of local control management.
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Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 pathogen requiring urgent research and development efforts. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in multiple cellular biological processes potentially associated with the physiological actions of the viral glycoproteins. Then, we elucidated the role of a representative cellular protein, HAX1. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is required for functional glycoprotein-mediated progeny virion packaging. Consistently, the inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections in cellular and animal models. Together, the findings provide a systematic CCHFV Gn/Gc-cell protein-protein interaction map, but also unravel a HAX1/mitochondrion-associated host antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches.
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Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia , Animais , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Vírus da Febre Hemorrágica da Crimeia-Congo/metabolismo , Febre Hemorrágica da Crimeia/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismoRESUMO
In order to effectively treat respiratory diseases, a non-invasive positive pressure ventilator system is designed, the overall structure design of the system is proposed, and the hardware construction is completed. The breathing state of the patient is identified by the threshold triggering method of the flow rate of change, and the calculation of the flow rate of change is realized by the least squares method. At the same time, the breathing parameters are calculated in real time according to the flow-time and pressure-time characteristic curves. In addition, CMV, CPAP, BiPAP and PSV ventilation modes are also implemented. Finally, the parameter measurement accuracy and ventilation mode setting tests are carried out. The results show that the calculation of key breathing parameters provided by the system meets the relevant standards, and supports the stable output of 4 ventilation modes at the same time, provides breathing treatment for patients, and meets the basic functional requirements of the ventilator.
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Respiração , Ventiladores Mecânicos , HumanosRESUMO
Th17 cells triggered inflammation is a critical element in cerebral ischemic injury, and the gut microbiota intricately impacts T lymphocytes. Nevertheless, it remains unclear whether the gut microbiota involves in cardiac arrest/cardiopulmonary resuscitation (CA/CPR) induced-brain injury through Th17 cells. The present study investigated the interaction between gut microbiota and Th17 cells in a rat model. We observed that CA/CPR induced the alterations of the gut microbial community structure, and elevated the level of IL-17 in the serum, and a slight infiltration of Th17 cells into the brain. The Th17 cells were increased significantly in the peripheral blood, 28.33 ± 6.18% of these Th17 cells were derived from the Peyer's patches of small intestine. Furthermore, fecal microbiota transplantation (FMT) from rats with CA/CPR induced Th17 cell response, promoting hippocampal cell apoptosis and declining learning ability and memory in recipient rats. Taken together, CA/CPR-induced alterations of the gut microbial community structure stimulated Th17 cell response which aggravated brain injury.
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BACKGROUND: Recently, a group of hepatologists proposed to rename non-alcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) with modified diagnostic criteria. It is important to note, however, that there are some differences between the diagnostic criteria used for NAFLD and MAFLD. Since the research on MAFLD is just beginning, however, evidence on its incidence and prevalence in the general population and in speciï¬c subpopulations remains limited. AIM: To assess epidemiology of fatty liver in new definition and compare MAFLD with NAFLD. Exploring risk factors of MAFLD individuals. METHODS: This was a retrospective, cross-sectional study. A total of 85242 adults were selected from the Chinese health management database in 2017-2022. The data of general information, laboratory indicators, lifestyle management and psychological status were obtained. MAFLD was diagnosed as ultrasound diagnosis of fatty liver and at least one between these three conditions: Overweight/obesity, type 2 diabetes mellitus (T2DM) or metabolic dysregulation. Metabolic factors were not considered in NAFLD diagnosis standard. The clinical characteristics of MAFLD and NAFLD were analysed using descriptive statistics. Continuous variables normally distributed were expressed as means ± SD. Categorical variables were expressed as frequencies and proportions. Binary logistic regression was used to determine risk factors of the MAFLD. RESULTS: The prevalence of MAFLD and NAFLD was 40.5% and 31.0%, respectively. The MAFLD or NAFLD population is more likely to be older (M: 47.19 ± 10.82 vs 43.43 ± 11.96; N: 47.72 ± 11.17 vs 43.71 ± 11.66), male (M: 77.21% vs 44.43%; N: 67.90% vs 53.12%) and high body mass index (M: 26.79 ± 2.69 vs 22.44 ± 2.48; N: 26.29 ± 2.84 vs 23.29 ± 3.12) than the non-MAFLD or non-MAFLD population. In multivariate analysis, general information (e.g., ≥ 2 metabolic abnormalities OR = 3.38, (95%CI: 2.99-3.81), P < 0.001; diastolic blood pressure OR = 1.01, (95%CI: 1.00-1.01), P = 0.002), laboratory results [e.g.,total bilirubin (TBIL) OR = 0.98, (95%CI: 0.98-0.99), P < 0.001; serum uric acid(SUA) OR = 1.01, (95%CI: 1.01-1.01), P < 0.001], and lifestyle factors [e.g., drink beverage OR = 0.32, (95%CI: 0.17-0.63), P = 0.001] were influence factors for MAFLD. Our study results offer new insight into potential risk factors associated with fatty liver disease, including SUA, TBIL and creatinine, all of which are related to chronic renal disease (CKD). CONCLUSION: MAFLD is more prevalent than NAFLD, with two-fifths of individuals meeting the diagnosis criteria. MAFLD and NAFLD populations have different clinical characteristics. CKD may be related with MAFLD.
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BACKGROUND: Uterine intravenous leiomyomatosis is defined as leiomyoma tissue invading the vein outside the leiomyoma. Reports of extension to the right pulmonary artery are relatively rare. CASE SUMMARY: We describe a 31-year-old woman with a benign leiomyoma that extended into the right ventricular lumen, causing mechanical obstruction and corresponding clinical symptoms. Tumors located in the pulmonary artery can cause pulmonary artery obstruction. After diagnosis, surgical treatment should be performed as soon as possible. CONCLUSION: In this case, the uterine leiomyoma extended to the right pulmonary system, which is clinically rare.
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BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, traditional teaching methods were disrupted and online teaching became a new topic in education reform and informatization. In this context, it is important to investigate the necessity and effectiveness of online teaching methods for medical students. This study explored stomatology education in China to evaluate the development and challenges facing the field using massive open online courses (MOOCs) for oral medicine education during the pandemic. AIM: To investigate the current situation and challenges facing stomatology education in China, and to assess the necessity and effectiveness of online teaching methods among medical students. METHODS: Online courses were developed and offered on personal computers and mobile terminals. Behavioral analysis and formative assessments were conducted to evaluate the learning status of students. RESULTS: The results showed that most learners had already completed MOOCs and achieved better results. Course behavior analysis and student surveys indicated that students enjoyed the learning experience. However, the development of oral MOOCs during the COVID-19 pandemic faced significant challenges. CONCLUSION: This study provides insights into the potential of using MOOCs to support online professional learning and future teaching innovation, but emphasizes the need for careful design and positive feedback to ensure their success.
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Endophytic fungi can promote host plant growth, enhance antioxidant defense enzyme activity, and induce the biosynthesis and accumulation of secondarymetabolites. Therefore, using endophytic fungi to improve the quality and yield of medicinal plants or important crops is an effective means of regulation. Colletotrichum sp. AP12 has been reported to produce andrographolide compounds (ADCs). This study aimed to investigate the effects of AP12 and its elicitors on the growth, defense enzyme activity, accumulation, and transcription levels of key genes in Andrographis paniculata (Burm. f.) Nees (A. paniculata). Using fermentation method to prepare AP12 into the inactivated fermentation solution (IFS), fermentation solution (FS), inactivated mycelium solution (IMS), and mycelium solution (MS), and the results showed that all four fungal elicitor components (ECs) could promote A. paniculata growth, enhance antioxidant defense enzymes, and increase ADC content and yield, especially the IMS group that had the highest leaf area, whole plant dry weight, superoxide dismutase (SOD), catalase (CAT) enzyme activities, total lactone contents, and yields, which were 2.37-, 1.60-, 2.20-, 3.27-, 1.59-, and 2.65-fold of the control, respectively. The 14-deoxyandrographolide (NAD) in the host irrigated with MS was 3.35-fold that of the control. In addition, AP12-infected A. paniculata sterile seedlings could significantly increase ADC content and expression levels of key enzyme genes, especially on day 12, when the total lactone content of the host reached 88.881± 5.793 mg/g DW, while on day 6, CPS gene expression level reached 10.79-fold that of the control, in turn promoting the biosynthesis and accumulation of andrographolide. In conclusion, the endophytic fungus AP12 is beneficial to the growth and secondary metabolism of A. paniculata, which is helpful for the cultivation and application of the biological bacterial fertilizer in A. paniculata, providing a theoretical and research basis for the use of endophytic fungi as a microbial resource to improve the quality and yield of medicinal plants.
RESUMO
Multiple myeloma (MM) is a neoplasm of aberrant plasma cells and ranks second among hematologic malignancies. Despite a substantial improvement in clinical outcomes with advances in therapeutic modalities over the past two decades, MM remains incurable, necessitating the development of new and potent therapies. Herein, we engineered a daratumumab-polymersome-DM1 conjugate (DPDC) based highly potent and CD38-selective immuno-nano-DM1 toxin for depleting MM cells in vivo. DPDC with controllable daratumumab density and disulfide-linked DM1 is of small size (51-56 nm), with high stability and reduction-triggered DM1 release. D6.2PDC potently inhibited the proliferation of CD38-overexpressed LP-1 and MM.1S MM cells with IC50 values of 2.7 and 1.2 ng DM1 equiv. per mL, about 4-fold stronger than non-targeted PDC. Moreover, D6.2PDC effectively and safely depleted LP-1-Luc MM cells in an orthotopic mouse model at a low DM1 dosage of 0.2 mg kg-1, thus alleviating osteolytic bone lesion and extending the median survival by 2.8-3.5-fold compared to all controls. This CD38-selective DPDC provides a safe and potent treatment strategy for MM.