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1.
J Virol ; 98(2): e0137723, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38197629

RESUMO

Gut microbiota-derived metabolites are important for the replication and pathogenesis of many viruses. However, the roles of bacterial metabolites in swine enteric coronavirus (SECoV) infection remain poorly understood. Recent studies show that SECoVs infection in vivo significantly alters the composition of short-chain fatty acids (SCFAs)-producing gut microbiota. This prompted us to investigate whether and how SCFAs impact SECoV infection. Employing alphacoronavirus transmissible gastroenteritis virus (TGEV), a major cause of diarrhea in piglets, as a model, we found that SCFAs, particularly butyrate, enhanced TGEV infection both in porcine intestinal epithelial cells and swine testicular (ST) cells at the late stage of viral infection. This effect depended on the inhibited productions of virus-induced type I interferon (IFN) and downstream antiviral IFN-stimulated genes (ISGs) by butyrate. Mechanistically, butyrate suppressed the expression of retinoic acid-inducible gene I (RIG-I), a key viral RNA sensor, and downstream mitochondrial antiviral-signaling (MAVS) aggregation, thereby impairing type I IFN responses and increasing TGEV replication. Using pharmacological and genetic approaches, we showed that butyrate inhibited RIG-I-induced type I IFN signaling by suppressing class I histone deacetylase (HDAC). In summary, we identified a novel mechanism where butyrate enhances TGEV infection by suppressing RIG-I-mediated type I IFN responses. Our findings highlight that gut microbiota-derived metabolites like butyrate can be exploited by SECoV to dampen innate antiviral immunity and establish infection in the intestine.IMPORTANCESwine enteric coronaviruses (SECoVs) infection in vivo alters the composition of short-chain fatty acids (SCFAs)-producing gut microbiota, but whether microbiota-derived SCFAs impact coronavirus gastrointestinal infection is largely unknown. Here, we demonstrated that SCFAs, particularly butyrate, substantially increased alphacoronavirus TGEV infection at the late stage of infection, without affecting viral attachment or internalization. Furthermore, enhancement of TGEV by butyrate depended on impeding virus-induced type I interferon (IFN) responses. Mechanistically, butyrate suppressed the cytoplasmic viral RNA sensor RIG-I expression and downstream type I IFN signaling activation by inhibiting class I HDAC, thereby promoting TGEV infection. Our work reveals novel functions of gut microbiota-derived SCFAs in enhancing enteric coronavirus infection by impairing RIG-I-dependent type I IFN responses. This implies that bacterial metabolites could be therapeutic targets against SECoV infection by modulating antiviral immunity in the intestine.


Assuntos
Butiratos , Infecções por Coronavirus , Coronavirus , Microbioma Gastrointestinal , Interferon Tipo I , Doenças dos Suínos , Vírus da Gastroenterite Transmissível , Animais , Butiratos/metabolismo , Coronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Interferon Tipo I/imunologia , RNA Viral , Suínos , Vírus da Gastroenterite Transmissível/fisiologia , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia
2.
Cytokine ; 181: 156680, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38885591

RESUMO

BACKGROUND: In recent years, relevant studies have reported that inflammatory cytokines are related to the occurrence of cancer. However, the correlation with lung cancer is not clear. This study used the Mendelian random grouping method to investigate the correlation between inflammatory factors and lung cancer in different populations. METHODS: We obtained the single nucleotide polymorphisms (SNPs) of inflammatory cytokines through the open database and the SNPs of lung cancer (European and East Asian) through the IEU OpenGWAS project. Inverse variance-weighted (IVW) MR analyses were used to determine the causalities of exposures and outcomes. Supplementary analyses were also performed using weighted median and MR-Egger regressions. Afterward, sensitivity analyses were performed to test the robustness. Search the ChEMBL database for target drugs and indications for CTACK, IL-2, and IL-13. RESULTS: By IVW method, we found that CTACK, IL-2, and IL-13 were associated with an increased risk of lung cancer in the European population (CTACK, OR = 1.098, 95 % CI 1.001-1.204, P = 0.047; IL-2, OR = 1.112, 95 % CI 1.009-1.225, P = 0.032; IL-13, OR = 1.068, 95 % CI 1.007-1.132, P = 0.029), while only IL-13 was associated with an increased risk of lung cancer in the East Asian population (IL-13, OR = 1.110, 95 % CI 1.010-1.220, P = 0.030). The weighted median and MR-Egger regression methods were in the same direction as the IVW effect sizes. Furthermore, no evidence of multidirectionality was detected using the MR-Egger intercept as a sensitivity analysis. Currently, there are no approved or phase III studied indications for CTACK, IL-2, and IL-13 targets in lung cancer. CONCLUSION: The study outcomes supported that the inflammatory cytokines CTACK, IL-2, and IL-13 increase the risk of lung cancer. There is a lack of indications for drugs in these three targets. We explored the causal relationship between inflammatory cytokines and lung cancer, providing a basis for future cancer prediction models and targets for anti-tumor therapy.


Assuntos
Quimiocina CCL27 , Interleucina-13 , Interleucina-2 , Neoplasias Pulmonares , Humanos , Predisposição Genética para Doença , Interleucina-13/genética , Interleucina-2/genética , Neoplasias Pulmonares/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , População Branca/genética , População do Leste Asiático/genética , Quimiocina CCL27/genética
3.
Langmuir ; 40(12): 6317-6329, 2024 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-38483835

RESUMO

Lead contamination poses significant and lasting health risks, particularly in children. This study explores the efficacy of dried mycelium membranes, distinct from live fungal biomass, for the remediation of lead (Pb(II)) in water. Dried mycelium offers unique advantages, including environmental resilience, ease of handling, biodegradability, and mechanical reliability. The study explores Pb(II) removal mechanisms through sorption and mineralization by dried mycelium hyphae in aqueous solutions. The sorption isotherm studies reveal a high Pb(II) removal efficiency, exceeding 95% for concentrations below 1000 ppm and ∼63% above 1500 ppm, primarily driven by electrostatic interactions. The measured infrared peak shifts and the pseudo-second-order kinetics for sorption suggests a correlation between sorption capacity and the density of interacting functional groups. The study also explores novel surface functionalization of the mycelium network with phosphate to enhance Pb(II) removal, which enables remediation efficiencies >95% for concentrations above 1500 ppm. Scanning electron microscopy images show a pH-dependent formation of Pb-based crystals uniformly deposited throughout the entire mycelium network. Continuous cross-flow filtration tests employing a dried mycelium membrane demonstrate its efficacy as a microporous membrane for Pb(II) removal, reaching remediation efficiency of 85-90% at the highest Pb(II) concentrations. These findings suggest that dried mycelium membranes can be a viable alternative to synthetic membranes in heavy metal remediation, with potential environmental and water treatment applications.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Criança , Humanos , Chumbo , Reprodutibilidade dos Testes , Adsorção , Micélio , Cinética , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio
4.
J Virol ; 96(16): e0077522, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35916510

RESUMO

Emerging severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, especially the Omicron variant, have impaired the efficacy of existing vaccines and most therapeutic antibodies, highlighting the need for additional antibody-based tools that can efficiently neutralize emerging SARS-CoV-2 variants. The use of a "single" agent to simultaneously target multiple distinct epitopes on the spike is desirable in overcoming the neutralizing escape of SARS-CoV-2 variants. Herein, we generated a human-derived IgG-like bispecific antibody (bsAb), Bi-Nab35B5-47D10, which successfully retained parental specificity and simultaneously bound to the two distinct epitopes on receptor-binding domain (RBD) and S2. Bi-Nab35B5-47D10 showed improved spike binding breadth among wild-type (WT) SARS-CoV-2, variants of concern (VOCs), and variants being monitored (VBMs) compared with its parental monoclonal antibodies (MAbs). Furthermore, pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs, including Alpha (B.1.1.7), Beta (B.1.351), and Kappa (B.1.617.1), as well as VOCs, including Delta (B.1.617.2), Omicron BA.1, and Omicron BA.2. Crucially, Bi-Nab35B5-47D10 substantially improved neutralizing activity against Omicron BA.1 (IC50 = 0.15 nM) and Omicron BA.2 (IC50 = 0.67 nM) compared with its parental MAbs. Therefore, Bi-Nab35B5-47D10 represents a potential effective countermeasure against SARS-CoV-2 Omicron and other variants of concern. IMPORTANCE The new, highly contagious SARS-CoV-2 Omicron variant caused substantial breakthrough infections and has become the dominant strain in countries across the world. Omicron variants usually bear high mutations in the spike protein and exhibit considerable escape of most potent neutralization monoclonal antibodies and reduced efficacy of current COVID-19 vaccines. The development of neutralizing antibodies with potent efficacy against the Omicron variant is still an urgent priority. Here, we generated a bsAb, Bi-Nab35B5-47D10, which simultaneously targets SARS-CoV-2 RBD and S2 and improves the neutralizing potency and breadth against SARS-CoV-2 WT and the tested variants compared with their parental antibodies. Notably, Bi-Nab35B5-47D10 has more potent neutralizing activity against the VOC Omicron pseudotyped virus. Therefore, Bi-Nab35B5-47D10 is a feasible and potentially effective strategy by which to treat and prevent COVID-19.


Assuntos
Anticorpos Biespecíficos , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Anticorpos Biespecíficos/metabolismo , Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Epitopos , Humanos , Testes de Neutralização , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Tratamento Farmacológico da COVID-19
5.
J Virol ; 96(2): e0176821, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-34730400

RESUMO

Classical swine fever (CSF) is an economically important disease of pigs caused by classical swine fever virus (CSFV). The live attenuated vaccine C-strain (also called HCLV strain) against CSF was produced by multiple passages of a highly virulent strain in rabbits. However, the molecular determinants for its attenuation and protection remain unclear. In this study, we identified a unique glycosylation at position 986 (986NYT988) on the E2 glycoprotein Domain IV of C-strain but not (986NYA988) the highly virulent CSFV Shimen strain. We evaluated the infectivity, virulence, and protective efficacy of the C-strain-based mutant rHCLV-T988A lacking the glycosylation and Shimen strain mutant rShimen-A988T acquiring an additional glycosylation at position 986. rShimen-A988T showed a significantly decreased viral replication ability in SK6 cells, while rHCLV-T988A exhibited a growth kinetics indistinguishable from that of C-strain. Removal of the C-strain glycosylation site does not affect viral replication in rabbits and the attenuated phenotype in pigs. However, rShimen-A988T was attenuated and protected the pigs from a lethal challenge at 14 days postinoculation. In contrast, the rHCLV-T988A-inoculated pigs showed transient fever, a few clinical signs, and pathological changes in the spleens upon challenge with the Shimen strain. Mechanistic investigations revealed that the unique glycosylation at position 986 influences viral spreading, alters the formation of E2 homodimers, and leads to increased production of neutralizing antibodies. Collectively, our data for the first time demonstrate that the unique glycosylation at position 986 on the E2 glycoprotein is responsible for viral attenuation and protection. IMPORTANCE Viral glycoproteins involve in infectivity, virulence, and host immune responses. Deglycosylation on the Erns, E1, or E2 glycoprotein of highly virulent classical swine fever virus (CSFV) attenuated viral virulence in pigs, indicating that the glycosylation contributes to the pathogenicity of the highly virulent strain. However, the effects of the glycosylation on the C-strain E2 glycoprotein on viral infectivity in cells, viral attenuation, and protection in pigs have not been elucidated. This study demonstrates the unique glycosylation at position 986 on the C-strain E2 glycoprotein. C-strain mutant removing the glycosylation at the site provides only partial protection against CSFV challenge. Remarkably, the addition of the glycan to E2 of the highly virulent Shimen strain attenuates the viral virulence and confers complete protection against the lethal challenge in pigs. Our findings provide a new insight into the contribution of the glycosylation to the virus attenuation and protection.


Assuntos
Vírus da Febre Suína Clássica/imunologia , Vírus da Febre Suína Clássica/patogenicidade , Peste Suína Clássica/prevenção & controle , Proteínas do Envelope Viral/metabolismo , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Peste Suína Clássica/virologia , Vírus da Febre Suína Clássica/genética , Vírus da Febre Suína Clássica/metabolismo , Glicosilação , Imunização/veterinária , Mutação , Multimerização Proteica , Coelhos , Suínos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/metabolismo , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Vacinas Virais/metabolismo , Virulência , Replicação Viral
6.
Crit Rev Food Sci Nutr ; : 1-22, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36785889

RESUMO

The safety and integrity of the global food system is in a constant state of flux with persistent chemical and microbial risks. While chemical risks are being managed systematically, microbial risks pose extra challenges. Antimicrobial resistant microorganism and persistence of related antibiotic resistance genes (ARGs) in the food chain adds an extra dimension to the management of microbial risks. Because the food chain microbiome is a key interface in the global health system, these microbes can affect health in many ways. In this review, we systematically summarize the distribution of ARGs in foods, describe the potential transmission pathway and transfer mechanism of ARGs from farm to fork, and discuss potential food safety problems and challenges. Modulating antimicrobial resistomes in the food chain facilitates a sustainable global food production system.

7.
Plant Cell Rep ; 42(2): 409-420, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36576553

RESUMO

KEY MESSAGE: Novel function and mechanism of a PNP molecule VaEG45 from adzuki bean involved in plant immunity. Plant natriuretic peptides (PNPs) can affect a broad spectrum of physiological responses in plants acting as peptidic signaling molecules. However, PNPs may play additional roles in plant immunity. Our previous transcriptome data of adzuki bean (Vigna angularis) in response to Uromyces vignae infection revealed association of PNP-encoding gene VaEG45 with U. vignae resistance. To determine the function of VaEG45 in disease resistance, we cloned the 589 bp nucleotide sequence of VaEG45 containing 2 introns, encoding a putative 13.68 kDa protein that is 131 amino acids in length. We analyzed expression in different resistant cultivars of V. angularis and found significant induction of VaEG45 expression after U. vignae infection. Transient expression of VaEG45 improved tobacco resistance against Botrytis cinerea. We next analyzed the mechanism by which VaEG45 protects plants from fungal infection by determination of the biological activity of the prokaryotic expressed VaEG45. The results showed that the fusion protein VaEG45 can significantly inhibit urediospores germination of U. vignae, mycelial growth, and the infection of tobacco by B. cinerea. Further analysis revealed that VaEG45 exhibits ß-1, 3-glucanase activity. These findings uncover the function of a novel PNP molecule VaEG45 and provide new evidence about the mechanism of PNPs in plant immunity.


Assuntos
Vigna , Vigna/genética , Sequência de Bases , Transcriptoma , Germinação , Peptídeos Natriuréticos
8.
Sensors (Basel) ; 23(12)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37420596

RESUMO

Optical fiber sensors are newly established gas pipeline leakage monitoring technologies with advantages, including high detection sensitivity to weak leaks and suitability for harsh environments. This work presents a systematic numerical study on the multi-physics propagation and coupling process of the leakage-included stress wave to the fiber under test (FUT) through the soil layer. The results indicate that the transmitted pressure amplitude (hence the axial stress acted on FUT) and the frequency response of the transient strain signal strongly depends on the types of soil. Furthermore, it is found that soil with a higher viscous resistance is more favorable to the propagation of spherical stress waves, allowing FUT to be installed at a longer distance from the pipeline, given the sensor detection limit. By setting the detection limit of the distributed acoustic sensor to 1 nε, the feasible range between FUT and the pipeline for clay, loamy soil and silty sand is numerically determined. The gas-leakage-included temperature variation by the Joule-Thomson effect is also analyzed. Results provide a quantitative criterion on the installation condition of distributed fiber sensors buried in soil for the great-demanding gas pipeline leakage monitoring applications.


Assuntos
Fibras Ópticas , Solo , Física , Argila , Acústica
9.
J Therm Biol ; 114: 103567, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37209632

RESUMO

In this study, we explored the association between physiological and perceptual heat strain while wearing stab-resistant body armor (SRBA). Human trials were performed on ten participants in warm and hot environments. Physiological responses (core temperature, skin temperature, and heart rate), and perceptual responses (thermal sensation vote, thermal comfort vote, restriction of perceived exertion (RPE), wetness of skin, and wetness of clothing) were recorded throughout the trials, and subsequently, the physiological strain index (PSI), and perceptual strain index (PeSI) were calculated. The results indicated that the PeSI showed a significant moderate association with the PSI, and was capable of predicting PSI for low (PSI = 3) and high (PSI = 7) levels of physiological strain with the areas under the curves of 0.80 and 0.64, respectively. Moreover, Bland-Altman analysis indicated that the majority of the PSI ranged within the 95% confidence interval, and the mean difference between PSI and PeSI was 0.14 ± 2.02 with the lower 95% limit and upper 95% limit being -3.82 to 4.10, respectively. Therefore, the subjective responses could be used as an indicator for predicting physiological strain while wearing SRBA. This study could provide fundamental knowledge for the usage of SRBA, and the development of physiological heat strain assessment.


Assuntos
Temperatura Corporal , Temperatura Alta , Humanos , Temperatura Corporal/fisiologia , Temperatura Cutânea , Frequência Cardíaca/fisiologia , Sensação Térmica/fisiologia , Regulação da Temperatura Corporal , Roupa de Proteção
10.
Scand J Gastroenterol ; 57(2): 131-142, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34738858

RESUMO

BACKGROUND AND OBJECTIVES: The association between abdominal obesity and reflux esophagitis (RE) has been extensively evaluated, but the current findings are mixed and more convincing epidemiological evidence urgently needs to be established. To thoroughly explore this relationship, we summarized the latest studies, performed an updated meta-analysis, and examined the dose-response relationship. METHODS: We performed a systematic search of PubMed, Web of Science, and Embase up to 28 March 2021, using prespecified terms to identify studies investigating the association between abdominal obesity and RE. Odds ratios (ORs) with 95% confidence intervals (CIs), mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs were taken as effect-size estimates. RESULTS: Forty-two observational studies, including 11 cohort studies, were meta-analyzed. Overall, a statistically significant association was observed between abdominal obesity and RE, by both the pooled OR (adjusted OR = 1.51, 95% CI: 1.37-1.66, p < .001) and the pooled SMD (SMD = 0.36, 95% CI: 0.30-0.42, p < .001). Moreover, this significant relationship persisted with subgroup stratification. In subgroup analyses, we found that study design, abdominal obesity measurement, adjustment for covariates and sex were possible sources of between-study heterogeneity. For the dose-response analyses, the risk of RE increased with the degree of abdominal obesity, and the increasing trend accelerated when waist circumference (WC) reached 87.0 cm. CONCLUSION: This meta-analysis indicated a significant association between abdominal obesity and RE, and the risk of RE increased with abdominal obesity especially when the WC was over 87.0 cm.


Assuntos
Esofagite Péptica , Obesidade Abdominal , Índice de Massa Corporal , Esofagite Péptica/epidemiologia , Esofagite Péptica/etiologia , Humanos , Obesidade Abdominal/complicações , Fatores de Risco , Circunferência da Cintura/fisiologia
11.
Cell Mol Biol (Noisy-le-grand) ; 68(5): 177-185, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36029514

RESUMO

Venous thrombosis is a semi-solid formation of blood components that coalesce in the venous system, and the pathological process of its formation is called venous thrombosis. The deep veins of the lower extremities are a common site of prevalence, and the clinical diagnosis of lower extremity deep vein thrombosis can occur independently or as a complication of other diseases. There is a clear link between inflammation and coagulation/anticoagulation, with inflammatory mechanisms upregulating pro-inflammatory factors, downregulating natural anticoagulant substances, and inhibiting fibrinolytic activity; systemic inflammation is a strong pro-thrombotic stimulus; and in vivo, natural anticoagulant substances not only prevent thrombosis, but also deter inflammatory processes. The interconnection between inflammation and coagulation plays an important role in venous thrombosis. In this study, we analyzed the relationship between inflammatory markers CRP and Fg, FVIII:C and FIX:C by measuring plasma CRP concentration, Fg level, FVIII:C and FIX:C levels in patients with DVT diagnosed by ultrasound, and explored the role and mechanism of inflammatory response and coagulation factor abnormalities and the interaction between them in the development of DVT. In this paper, human blood DNA was extracted by phenol-chloroform-isoamyl alcohol extraction, and CRP 1059G/C gene polymorphism was detected by polymerase chain reaction-restriction enzyme segment length polymorphism (PCR-RFLP) nucleotide typing technique, and the genotypes of each subject were distinguished according to the bands seen by gel electrophoresis, and the frequency of each genotype was counted. Plasma CRP concentrations were measured by immunoturbidimetric assay, FVIII:C and FIX:C levels were measured by phase I assay, and plasma Fg levels were measured by coagulation assay in 59 cases (38 males and 21 females, aged 21-82 years, mean 49.67±11.12 years) and 26 controls (17 males and 9 females, aged 32-67 years, mean 50.13±8.96 years). The above indexes were compared between the two groups, and the correlation between CRP and FVIII:C, FIX:C and Fg was analyzed. Polymerase chain reaction-restriction enzyme segment length polymorphism nucleotide typing technique was used to detect the relationship between CRP 1059G/C gene polymorphism and DVT, to further search for risk factors of venous thrombosis, thus providing new ideas for the future prevention and treatment of this disease in clinical practice.


Assuntos
Embolia Pulmonar , Trombose , Trombose Venosa , Anticoagulantes , Biomarcadores , Células Sanguíneas , Diagnóstico Precoce , Feminino , Humanos , Inflamação , Masculino , Nucleotídeos , Fatores de Risco
12.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36430829

RESUMO

The localization of lipoprotein (Lol) system is responsible for the transport of lipoproteins in the outer membrane (OM) of Vibrio parahaemolyticus. LolB catalyzes the last step in the Lol system, where lipoproteins are inserted into the OM. If the function of LolB is impeded, growth of V. parahaemolyticus is inhibited, due to lack of an intact OM barrier for protection against the external environment. Additionally, it becomes progressively harder to generate antimicrobial resistance (AMR). In this study, LolB was employed as the receptor for a high-throughput virtual screening from a natural compounds database. Compounds with higher glide score were selected for an inhibition assay against V. parahaemolyticus. It was found that procyanidin, stevioside, troxerutin and rutin had both exciting binding affinity with LolB in the micromolar range and preferable antibacterial activity in a concentration-dependent manner. The inhibition rates of 100 ppm were 87.89%, 86.2%, 91.39% and 83.71%, respectively. The bacteriostatic mechanisms of the four active compounds were explored further via fluorescence spectroscopy and molecular docking, illustrating that each molecule formed a stable complex with LolB via hydrogen bonds and pi-pi stacking interactions. Additionally, the critical sites for interaction with V. parahaemolyticus LolB, Tyr108 and Gln68, were also illustrated. This paper demonstrates the inhibition of LolB, thus, leading to antibacterial activity, and identifies LolB as a promising drug target for the first time. These compounds could be the basis for potential antibacterial agents against V. parahaemolyticus.


Assuntos
Proteínas de Escherichia coli , Proteínas Periplásmicas de Ligação , Vibrio parahaemolyticus , Proteínas de Escherichia coli/metabolismo , Proteínas Periplásmicas de Ligação/metabolismo , Proteínas da Membrana Bacteriana Externa/química , Vibrio parahaemolyticus/metabolismo , Escherichia coli/metabolismo , Simulação de Acoplamento Molecular , Chaperonas Moleculares/metabolismo , Lipoproteínas/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo
13.
J Virol ; 94(17)2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32581110

RESUMO

The classical swine fever virus (CSFV) live attenuated vaccine C-strain is adaptive to rabbits and attenuated in pigs, in contrast with the highly virulent CSFV Shimen strain. Previously, we demonstrated that P108 and T109 on the E2 glycoprotein (E2P108-T109) in domain I (E2DomainI) rather than R132, S133, and D191 in domain II (E2DomainII) determine C-strain's adaptation to rabbits (ATR) (Y. Li, L. Xie, L. Zhang, X. Wang, C. Li, et al., Virology 519:197-206, 2018). However, it remains elusive whether these critical amino acids affect the ATR of the Shimen strain and virulence in pigs. In this study, three chimeric viruses harboring E2P108-T109, E2DomainI, or E2DomainII of C-strain based on the non-rabbit-adaptive Shimen mutant vSM-HCLVErns carrying the Erns glycoprotein of C-strain were generated and evaluated. We found that E2P108-T109 or E2DomainI but not E2DomainII of C-strain renders vSM-HCLVErns adaptive to rabbits, suggesting that E2P108-T109 in combination with the Erns glycoprotein (E2P108-T109-Erns) confers ATR on the Shimen strain, creating new rabbit-adaptive CSFVs. Mechanistically, E2P108-T109-Erns of C-strain mediates viral entry during infection in rabbit spleen lymphocytes, which are target cells of C-strain. Notably, pig experiments showed that E2P108-T109-Erns of C-strain does not affect virulence compared with the Shimen strain. Conversely, the substitution of E2DomainII and Erns of C-strain attenuates the Shimen strain in pigs, indicating that the molecular basis of the CSFV ATR and that of virulence in pigs do not overlap. Our findings provide new insights into the mechanism of adaptation of CSFV to rabbits and the molecular basis of CSFV adaptation and attenuation.IMPORTANCE Historically, live attenuated vaccines produced by blind passage usually undergo adaptation in cell cultures or nonsusceptible hosts and attenuation in natural hosts, with a classical example being the classical swine fever virus (CSFV) lapinized vaccine C-strain, which was developed by hundreds of passages in rabbits. However, the mechanism of viral adaptation to nonsusceptible hosts and the molecular basis for viral adaptation and attenuation remain largely unknown. In this study, we demonstrated that P108 and T109 on the E2 glycoprotein together with the Erns glycoprotein of the rabbit-adaptive C-strain confer adaptation to rabbits on the highly virulent CSFV Shimen strain by affecting viral entry during infection but do not attenuate the Shimen strain in pigs. Our results provide vital information on the different molecular bases of CSFV adaptation to rabbits and attenuation in pigs.


Assuntos
Adaptação Fisiológica/fisiologia , Vírus da Febre Suína Clássica/fisiologia , Peste Suína Clássica/imunologia , Glicoproteínas/química , Proteínas do Envelope Viral/química , Animais , Linhagem Celular , Quimera , Peste Suína Clássica/prevenção & controle , Peste Suína Clássica/virologia , Modelos Animais de Doenças , Genoma Viral , Glicoproteínas/genética , Coelhos , Receptor EphB2 , Baço/virologia , Suínos , Vacinas Atenuadas , Proteínas do Envelope Viral/genética , Vacinas Virais/imunologia , Viremia , Virulência , Internalização do Vírus , Replicação Viral
14.
Theor Appl Genet ; 133(8): 2387-2399, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32472264

RESUMO

KEY MESSAGE: SG3, an R2R3 MYB protein coding gene that tightly linked to a major QTLGS3, negatively regulates grain length while dependent on the status ofGS3in rice. It is often very difficult to isolate a minor QTL that is closely linked to a major QTL in rice. In this study, we focused on the isolation of a minor grain length QTL, small grain 3 (SG3), which is closely linked to the major QTL grain size 3 (GS3). The genetic effect of SG3 on grain length was dependent on GS3 status. Its genetic effect was larger in the presence of nonfunctional sg3 than functional SG3. A large number of near-isogenic F2 plants in which GS3 was fixed with nonfunctional alleles were developed to clone SG3. A gene encoding an R2R3 MYB domain transcriptional regulator was identified as the candidate gene for SG3. SG3 overexpression and knockdown plants showed shortened and elongated grains, respectively, which demonstrated that SG3 acts as a negative regulator of grain length. SG3 was preferentially expressed in panicles after flowering, and SG3 acted as a transcription activator. Comparative sequencing analysis identified a 12-bp insertion in the third exon of NYZ that led to a frameshift and resulted in a premature stop codon. The insertion/deletion was associated with grain length in the presence of functional GS3 in the indica subspecies. SG3 and GS3 were frequently in coupling phase in indica rice, making them good targets for the breeding of cultivars with short or long grains. The isolation of the SG3 MYB gene provides new gene resource and contributes to the regulatory network of grain length in rice.


Assuntos
Mapeamento Cromossômico/métodos , Grão Comestível/genética , Genes de Plantas , Oryza/genética , Melhoramento Vegetal/métodos , Sementes/genética , Fatores de Transcrição/genética , Alelos , Sistemas CRISPR-Cas , Núcleo Celular/metabolismo , Códon sem Sentido , Éxons , Regulação da Expressão Gênica de Plantas/genética , Técnicas de Inativação de Genes , Mutação INDEL , Oryza/crescimento & desenvolvimento , Filogenia , Plantas Geneticamente Modificadas , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sementes/crescimento & desenvolvimento , Fatores de Transcrição/metabolismo
15.
J Therm Biol ; 86: 102451, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31789239

RESUMO

The aim of this study was to investigate the physiological and perceptual responses of the human body wearing stab-resistant body armor (SRBA) in a hot and humid environment. The responses of five healthy male volunteers wearing SRBA were compared with those under a Control condition (wearing T-shirt) in a hot and humid environment (38 °C and relative humidity of 60%). The participants walked on a treadmill at a speed of 6 km/h for 60 min and this was followed by 60 min of recovery. The physiological responses (core temperature, skin temperature, heart rate, oxygen consumption) and perceptual parameters (thermal sensation, thermal comfort, rate of perceived exertion (RPE), and restriction to movement) were recorded throughout the tests. The results showed that the use of SRBA resulted in higher values of core temperature, mean skin temperature, heart rate, and oxygen consumption during exercise, and a significant difference (p < 0.05) between the SRBA and Control trials in terms of oxygen consumption was observed. The subjects wearing SRBA exhibited higher RPE and restriction to movement during exercise when compared with those in the Control condition, and a significant difference (p < 0.05) between the two trials in terms of restriction to movement was observed. Moreover, no significant differences (p > 0.05) in terms of thermal sensation and thermal comfort were observed between the SRBA and Control trials. It was concluded that the use of SRBA imposed high thermoregulatory and cardiovascular strain, reduced perceived exertion, and restricted movement during exercise in the hot and humid environment, whereas its effect on thermal sensation and thermal comfort was negligible when compared with those in the Control condition.


Assuntos
Regulação da Temperatura Corporal , Frequência Cardíaca , Consumo de Oxigênio , Roupa de Proteção , Temperatura Cutânea , Adulto , Temperatura Alta , Humanos , Umidade , Masculino , Movimento/fisiologia , Esforço Físico/fisiologia , Sensação Térmica , Adulto Jovem
16.
J Exp Bot ; 67(6): 1759-68, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26798026

RESUMO

Heterotrimeric Heme Activator Protein (HAP) family genes are involved in the regulation of flowering in plants. It is not clear how many HAP genes regulate heading date in rice. In this study, we identified 35 HAP genes, including seven newly identified genes, and performed gene duplication and candidate gene-based association analyses. Analyses showed that segmental duplication and tandem duplication are the main mechanisms of HAP gene duplication. Expression profiling and functional identification indicated that duplication probably diversifies the functions of HAP genes. A nucleotide diversity analysis revealed that 13 HAP genes underwent selection. A candidate gene-based association analysis detected four HAP genes related to heading date. An investigation of transgenic plants or mutants of 23 HAP genes confirmed that overexpression of at least four genes delayed heading date under long-day conditions, including the previously cloned Ghd8/OsHAP3H. Our results indicate that the large number of HAP genes in rice was mainly produced by gene duplication, and a few HAP genes function to regulate heading date. Selection of HAP genes is probably caused by their diverse functions rather than regulation of heading.


Assuntos
Flores/crescimento & desenvolvimento , Flores/genética , Duplicação Gênica , Genes de Plantas , Estudos de Associação Genética , Família Multigênica , Oryza/genética , Evolução Biológica , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Variação Genética , Nucleotídeos/genética , Fenótipo , Fotoperíodo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Transformação Genética
17.
Molecules ; 21(12)2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27916965

RESUMO

Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days) from fresh-cut CWC were investigated using LC-MS and analyzed by pattern recognition methods (principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structures-discriminant analysis (OPLS-DA)). The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p-coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC.


Assuntos
Eleocharis/metabolismo , Estiolamento/fisiologia , Metaboloma/fisiologia , Metabolômica
18.
Zhonghua Yi Xue Za Zhi ; 94(22): 1696-700, 2014 Jun 10.
Artigo em Zh | MEDLINE | ID: mdl-25151897

RESUMO

OBJECTIVE: To explore the effects of estrogen (E2) on angiotensin converting enzyme-angiotensin II-angiotensin type 1 receptor (ACE-Ang II-AT1) axis in hypoxic pulmonary hypertension rats. METHODS: A total of 60 healthy female Sprague-Dawdley (SD) rats were divided randomly into 6 groups (n = 10 each) of sham operation, pure ovariectomy (OVX), pure hypoxia,OVX+hypoxia,OVX+E2 and OVX+hypoxia+E2. Abdominal cavity was opened for sham operation group and bilateral ovaries were left intact without any other procedure. The pure OVX group underwent oophorectomy. The pure hypoxia group were placed into a low-oxygen environment (24 hour, 8 weeks). The OVX+hypoxia group were placed into a low-oxygen environment after bilateral oophorectomy. The OVX+E2 group received a subcutaneous injection of E2 (20 µg×kg(-1)×d(-1)) after bilateral oophorectomy. The OVX+hypoxia+E2 group had an injection of E2 and was placed into a low-oxygen environment after bilateral oophorectomy. The rats were feed continuously for 8 weeks to establish hypoxic pulmonary hypertension model. The mean pulmonary artery pressure (mPAP) was measured after bloodletting. Then right ventricle hypertrophy index (RVHI) and hematoxylin-eosin pulmonary artery remodeling (HPSR) were observed. And electron microscope was employed to observe pulmonary arteriolar ultrastructure. The methods of radio-immunity assay, ultraviolet spectroscopy, Western blot and reverse transcription PCR were used to measure the levels of CE,Ang II and AT1 in sera, lung and pulmonary artery. RESULTS: The vascular walls of pure hypoxia and OVX+hypoxia groups became thickened and lumen narrowed.mPAP and RVHI were (32.4 ± 2.2) mmHg (1 mmHg = 0.133 kPa),0.331 ± 0.032 and (37.9 ± 1.6) mmHg,0.433 ± 0.033. Both were significantly higher than those of Sham operation group ((12.6 ± 1.8) mmHg,0.233 ± 0.029) (both P < 0.05); the above parameters of OVX+Hypoxia+E2 group changed little. And mPAP ((26.1 ± 1.4) mmHg) was significantly higher than that in sham operation group (P < 0.05) while the difference in RVHI between OVX+ Hypoxia+ E2 (0.267 ± 0.040) and sham operation groups had no statistical significance (P > 0.05). Compared with Sham operation group, the expression levels of ACE,Ang II and AT1 in pure OVX, pure hypoxia and OVX+ hypoxia groups rose markedly (all P < 0.05).However, the OVX+E2 and OVX+ hypoxia+E2 groups had no obvious change (all P > 0.05). CONCLUSION: The intervention effect of E2 for hypoxic pulmonary hypertension may be partly mediated by the down-regulated expressions of ACE and AT1 in lung tissue resulting in the reduced activity of ACE-AngII-AT1 axis.


Assuntos
Angiotensina II/metabolismo , Estrogênios/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/complicações , Peptidil Dipeptidase A/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Animais , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Pulmão , Ovariectomia , Oxigênio , Artéria Pulmonar , Ratos , Ratos Sprague-Dawley
19.
Heliyon ; 10(8): e29113, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628747

RESUMO

With the increasing lethality of modern weapons, the development of body armor has become increasingly important. The main objective of current research is to make protective gear lighter and increase material ballistic performance. Here, a model ballistic-resistant composite material was produced consisting of a polyurea coating on Kevlar plain weave fabric. The effects of coating location and thickness on the ballistic performance of this aramid fabric was examined using yarn pull-out test, ballistic impact test, and numerical simulation. The results demonstrated that the polyurea coating significantly increased the friction between yarns. The maximum yarn pull-out force of the polyurea-coated fiber composite was 40-fold greater than that of the uncoated fiber. Moreover, the application of the coating on the front side outperformed the rear side in terms of ballistic performance. In particular, the front-side 0.2 mm coating was observed to result in the most considerable ballistic limit improvement, increasing the ballistic limit of a single layer of Kevlar fabric from 90.8 to 143.45 m/s. A high precision mesoscale simulation model was developed to analyze the impact of the polyurea coating on the deformation and damage of the Kevlar fabric. These results will contribute to developing new bullet-proof composite materials for the safety protection of personnel.

20.
Medicine (Baltimore) ; 103(9): e37338, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428887

RESUMO

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese prescription, originally derived from Yi Lin Gai Cuo during the Qing Dynasty. This study aimed to evaluate the efficacy and safety of BYHWD in the prevention of taxane-induced peripheral neuropathy (TIPN) in patients with breast cancer. METHODS: This single-center, statistician-blinded, parallel-group, simple randomized, no-treatment controlled study was conducted at the China-Japan Friendship Hospital in Beijing. Sixty breast cancer patients scheduled to receive nab-paclitaxel-based chemotherapy were randomly assigned to either the BYHWD group (N = 30) or the control group (N = 30) using simple randomization procedures. The data analysts were unaware of the treatment allocation. The primary efficacy endpoints were the incidence and severity of TIPN in the 2 groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Patients' Neurotoxicity Questionnaire (PNQ). The secondary efficacy endpoint was the score of Functional Assessment of Cancer Therapy-Breast for both groups. The primary safety endpoints were routine blood test results and liver and renal functions. Both groups were subjected to 4 chemotherapy cycles. Efficacy and safety analyses were conducted on an intention-to-treat basis. RESULTS: The incidence of TIPN in the BYHWD group was 50.0%, which was lower than the 80.0% incidence in the control group (ß = -1.881 [95%CI -3.274, -.488]; P = .008, adjusted). The probability of TIPN in the BYHWD group was 15.2% of that in the control group, representing a significant reduction in incidence (odds ratio = .152, [95%CI .038, 0.614]; P = .008, adjusted). The CTCAE and PNQ grades of the BYHWD group were 1.527 and 1.495 points lower than those of the control group at the same cycle, respectively (CTCAE: ß = -1.527 [95%CI -2.522, -.533]; P = .003, adjusted; PNQ: ß = -1.495 [95%CI -2.501, -.489]; P = .004, adjusted, respectively). After treatment, the Functional Assessment of Cancer Therapy-Breast scores in the BYHWD group were significantly better than those in the control group (P = .003), especially in the physiological, functional, and additional concerns domains. CONCLUSION: Buyang Huanwu decoction (BYHWD) can effectively prevent TIPN and improve the quality of life in patients with breast cancer.


Assuntos
Neoplasias da Mama , Hidrocarbonetos Aromáticos com Pontes , Medicamentos de Ervas Chinesas , Síndromes Neurotóxicas , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Medicina Tradicional Chinesa , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/induzido quimicamente , Qualidade de Vida , Estudos Prospectivos , Medicamentos de Ervas Chinesas/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Taxoides/efeitos adversos
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