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1.
Appl Microbiol Biotechnol ; 108(1): 350, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809284

RESUMO

The African swine fever virus (ASFV) has the ability to infect pigs and cause a highly contagious acute fever that can result in a mortality rate as high as 100%. Due to the viral epidemic, the pig industry worldwide has suffered significant financial setbacks. The absence of a proven vaccine for ASFV necessitates the development of a sensitive and reliable serological diagnostic method, enabling laboratories to effectively and expeditiously detect ASFV infection. In this study, four strains of monoclonal antibodies (mAbs) against p72, namely, 5A1, 4C4, 8A9, and 5E10, were generated through recombinant expression of p72, the main capsid protein of ASFV, and immunized mice with it. Epitope localization was performed by truncated overlapping polypeptides. The results indicate that 5A1 and 4C4 recognized the amino acid 20-39 aa, 8A9 and 5E10 are recognized at 263-282 aa, which is consistent with the reported 265-280 aa epitopes. Conserved analysis revealed 20-39 aa is a high conservation of the epitopes in the ASFV genotypes. Moreover, a blocking ELISA assay for detection ASFV antibody based on 4C4 monoclonal antibody was developed and assessed. The receiver-operating characteristic (ROC) was performed to identify the best threshold value using 87 negative and 67 positive samples. The established test exhibited an area under the curve (AUC) of 0.9997, with a 95% confidence interval ranging from 99.87 to 100%. Furthermore, the test achieved a diagnostic sensitivity of 100% (with a 95% confidence interval of 95.72 to 100%) and a specificity of 98.51% (with a 95% confidence interval of 92.02 to 99.92%) when the threshold was set at 41.97%. The inter- and intra-batch coefficient of variation were below 10%, demonstrating the exceptional repeatability of the method. This method can detect the positive standard serum at a dilution as high as 1:512. Subsequently, an exceptional blocking ELISA assay was established with high diagnostic sensitivity and specificity, providing a novel tool for detecting ASFV antibodies. KEY POINTS: • Four strains of ASFV monoclonal antibodies against p72 were prepared and their epitopes were identified. • Blocking ELISA method was established based on monoclonal antibody 4C4 with an identified conservative epitope. • The established blocking ELISA method has a good effect on the detection of ASFV antibody.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Anticorpos Monoclonais , Anticorpos Antivirais , Proteínas do Capsídeo , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos , Animais , Anticorpos Monoclonais/imunologia , Vírus da Febre Suína Africana/imunologia , Vírus da Febre Suína Africana/genética , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Suínos , Febre Suína Africana/diagnóstico , Febre Suína Africana/imunologia , Febre Suína Africana/virologia , Camundongos , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/genética , Camundongos Endogâmicos BALB C , Sensibilidade e Especificidade , Epitopos/imunologia
2.
J Am Chem Soc ; 145(49): 26678-26687, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38051561

RESUMO

Nitrate electroreduction (NO3RR) holds promise as an energy-efficient strategy for the removal of toxic nitrate to restore the natural nitrogen cycle and mitigate the adverse impacts caused by overfertilization from suboptimal agricultural practices. However, existing catalysts suffer from limited electrocatalytic activity, poor selectivity, inadequate durability, and low scalability. To address this quadrilemma, in this study, we developed a cost-effective layered double hydroxide (LDH) electrocatalyst with a lamellar structure that presents trimetallic CuCoAl active sites on the nanomaterial surface. This codoping design enabled electrochemical upcycling of nitrate into ammonia exclusively and efficiently with an onset potential at 0 V vs RHE, where the electrocatalytic process is less energy intensive and has a lower carbon footprint than conventional practices. The synergistic interaction among Cu, Co, and Al further afforded a 99.5% Faradic efficiency (FE) and a yield rate of 0.22 mol h-1 g-1 for nitrate-to-ammonia electroreduction, surpassing the performance of state-of-the-art nonprecious metal NO3RR electrocatalysts over an extended operation period. To gain insights into the origin of the catalytic performance observed on LDH, control materials were employed to elucidate the roles of Cu and Co. Cu was found to improve the NO3RR onset potential despite displaying limited FE for ammonia synthesis, while Co was discovered to suppress the formation of nitrite byproduct though requiring large overpotential. Simulated wastewater containing phosphate and sulfate, which are typically present in industrial effluents, was used to further investigate the effect of electrolytes on NO3RR. Intriguingly, the use of phosphate buffer resulted in a superior yield rate and FE for ammonia production while simultaneously inhibiting nitrite byproduct formation compared with the sulfate case. These experimental findings were supported by density functional theory (DFT) calculations, which explored the adsorption strength of nitrate adducts adjacent to coadsorbed electrolytes on the LDH surface. Additionally, the relative free energies of NO3RR species were also computed to examine the proton-coupled electron transfer (PCET) mechanism on CuCoAl LDH, shedding light on the potential-dependent step (PDS) and the exclusive selectivity for nitrate-to-ammonia conversion. The CuCoAl LDH developed here offers scalability by eliminating the need for precious metals, rendering this earth-abundant catalyst particularly appealing for sustainable nitrate electrovalorization technology.

3.
Int J Cancer ; 152(1): 79-89, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36062503

RESUMO

Immune checkpoint inhibitors (ICIs), which represent the new standard of care for advanced nonsmall cell lung cancer (NCSLC), are not effective in many patients. Biomarkers are needed to guide treatment. Sequencing data of an ICI-treated cohort were analyzed to identify genomic signatures predicting ICI efficacy, followed by validation using multiple independent cohorts. Their predictive mechanism was explored by evaluating the tumor immune microenvironment and tumor mutational burden (TMB). In the discovery cohort, patients carrying FGFR4 alterations (FGFR4altered ) had a better objective response rate (ORR) (50.0% vs 19.4%; P = .057) and improved median progression-free survival (mPFS) (13.17 vs 3.17 months; HR 0.37; 95% CI 0.14-1; P = .04) than wild-type patients (FGFR4wt ). In the publicly available validation cohorts, FGFR4 alterations correlated with higher ORR (100% vs 31%; P = .028), longer median overall survival (mOS) (not reached [NR] vs 11 months; HR 0.28, 95% CI 0.09-0.89, P = .02), and mPFS (NR vs 6.07 months; HR 0.05, 95% CI 0-3.94, P = .039). FGFR4 alterations were confirmed as an independent predictor of superior PFS (P = .014) and OS (P = .005). FGFR4altered patients also exhibited a significantly improved disease control rate (100% vs 60%, P = .045) and prolonged mPFS (9.70 vs 3.16 months; P = .095) compared to FGFR4wt patients in our Shanghai Pulmonary Hospital cohort. FGFR4 alterations associated with a higher TMB levels, more CD8+ T cells in the tumor stroma, and a higher M1/M2 ratio for tumor-associated macrophages in the tumor center and stroma. Thus, FGFR4 alterations may serve as a potential independent predictor of ICI efficacy in NSCLC.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfócitos T CD8-Positivos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Mutação , China , Biomarcadores Tumorais/genética , Microambiente Tumoral , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética
4.
Langmuir ; 39(24): 8404-8413, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37283301

RESUMO

In this work, the strategy of immobilizing enzymes in bimetallic-organic frameworks was adopted to overcome the disadvantages of free laccases. The surface amino-silanizing of bimetallic CoCu-MOF-H hydrothermally synthesized was performed by (3-Aminopropyl)triethoxysilane (APTES). Then, glutaraldehyde was used as the cross-linking agent, laccase was covalently grafted onto CoCu-MOF-H-APTES to prepare Lac-CoCu-MOF-H-APTE. In addition, CoCu-MOF-OH also was synthesized by alkali etching of CoCu-MOF-H, and Lac-CoCu-MOF-OH-APTES composites were obtained by a similar strategy. The result showed that the relative enzyme activity of Lac-CoCu-MOF-OH-APTES exhibited 264.02% (1.8 times than that of Lac-CoCu-MOF-H-APTES) after six cycles of stability tests, while the free enzyme was almost inactivated. Moreover, the Congo red (CR) removal rate of Lac-CoCu-MOF-OH-APTES exceeded 95% within 1 h and exceeded 89.18% after six cycles at pH 3.5 and 50 °C. This work has the potential to provide a broader application prospect for CR degradation by laccase in the future.


Assuntos
Enzimas Imobilizadas , Lacase , Lacase/metabolismo , Enzimas Imobilizadas/metabolismo , Vermelho Congo , Álcalis
5.
COPD ; 20(1): 327-337, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37870866

RESUMO

In COPD patients, exacerbation has a detrimental influence on the quality of life, disease progression and socioeconomic burden. This study aimed to develop and validate models to predict exacerbation, frequent exacerbations and severe exacerbations in COPD patients. We conducted an observational prospective multicenter study. Clinical data of all outpatients with stable COPD were collected from Beijing Chaoyang Hospital and Beijing Renhe Hospital between January 2018 and December 2019. Patients were followed up for 1 year. The data from Chaoyang Hospital was used for modeling dataset, and that of Renhe Hospital was used for external validation dataset. The final dataset included 456 patients, with 326 patients as the model group and 130 patients as the validation group. Using LABA + ICS, frequent exacerbations in the past year and CAT score were independent risk factors for exacerbation in the next year (OR = 2.307, 2.722 and 1.147), and FVC %pred as a protective factor (OR = 0.975). Combined with chronic heart failure, frequent exacerbations in the past year, blood EOS counts and CAT score were independent risk factors for frequent exacerbations in the next year (OR = 4.818, 2.602, 1.015 and 1.342). Using LABA + ICS, combined with chronic heart failure, frequent exacerbations in the past year and CAT score were independent risk factors for severe exacerbations in the next year (OR = 1.950, 3.135, 2.980 and 1.133). Based on these prognostic models, nomograms were generated. The prediction models were simple and useful tools for predicting the risk of exacerbation, frequent exacerbations and severe exacerbations of COPD patients in North China.


Assuntos
Insuficiência Cardíaca , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Progressão da Doença , Sistema de Registros
6.
Cancer Immunol Immunother ; 71(1): 219-228, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34097116

RESUMO

OBJECTIVES: Immune checkpoint inhibitors (ICI) monotherapy was standard of care in second-line treatment of patients with advance non-small cell lung cancer (NSCLC). This study aims to investigate the efficacy of ICI plus chemotherapy in patients with previously treated advanced NSCLC. PATIENTS AND METHODS: An investigator-initiated trial (IIT) aiming to evaluate the efficacy and safety of ICI in combination with chemotherapy as second line and beyond for patients with advanced NSCLC was undergone at Shanghai Pulmonary Hospital (ChiCTR1900026203). Patients who received ICI monotherapy as second or later line setting during the same period were also collected as a comparator. RESULTS: From April 2018 to June 2019, 31 patients were included into this IIT study, simultaneously 51 patients treated with ICI monotherapy were selected as a comparator. ICI plus chemotherapy showed a significantly higher ORR (35.5% vs. 15.7%, p=0.039), prolonged PFS (median: 5.6 vs. 2.5 months, p = 0.013) and OS (median: NE vs. 12.6 months, p = 0.038) compared with ICI alone. In the subgroup of negative PD-L1 expression (9 patients in combination group and 12 patients in monotherapy group), ICI plus chemotherapy also had a favorable ORR (44.4% vs. 8.3%, p = 0.119), longer PFS (median: 6.5 vs 3.0 months, p < 0.05) and OS (median: NE vs. 8.2 months, p = 0.117). Meanwhile, the addition of chemotherapy did not increase immune-related adverse events. CONCLUSIONS: ICI plus chemotherapy showed superior ORR, PFS and OS than ICI alone patients with previous treated advanced NSCLC. These findings warrant further investigation.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
7.
J Antimicrob Chemother ; 76(7): 1712-1723, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-33948657

RESUMO

OBJECTIVES: Vancomycin-intermediate Staphylococcus aureus (VISA) is increasingly being reported. Previous studies have shown that vraC and vraP may be involved in vancomycin resistance, although the molecular mechanism remains elusive. METHODS: The vraC (SAV0577), vraP (SAV0578) and vraCP mutants were constructed in Mu50 by allelic replacement. Some common VISA phenotypes were assessed in mutants, such as, susceptibility to the cell wall-associated antibiotics, cell wall thickness, autolysis activity and growth rate. RT-qPCR was performed to reveal the differential genes associated with these phenotypes. The binding abilities of VraC and VraCP to the promoters of target genes were determined by electrophoretic mobility shift assay (EMSA). RESULTS: VraP forms a stable complex with VraC to preserve their own stability. The vraC, vraP and vraCP mutants exhibited increased susceptibility to the cell wall-associated antibiotics and thinner cell walls compared with the WT strain. Consistent with these phenotypes, RT-qPCR revealed downregulated transcription of glyS, sgtB, ddl and alr2, which are involved in cell wall biosynthesis. Moreover, the transcription of cell wall hydrolysis genes, including sceD, lytM and isaA, was significantly downregulated, supporting the finding that mutants exhibited reduced autolysis rates. EMSA confirmed that both VraC and VraCP can directly bind to the sceD, lytM and isaA promoter regions containing the consensus sequence (5'-TTGTAAN2AN3TGTAA-3'), which is crucial for the binding of VraCP with target genes. GFP-reporter assays further revealed VraC and VraCP can enhance promoter activity of sceD to positively regulate its expression. CONCLUSIONS: vraCP plays a significant role in cell wall metabolism and antibiotic resistance in Mu50.


Assuntos
Staphylococcus aureus , Vancomicina , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Parede Celular , Testes de Sensibilidade Microbiana , Staphylococcus aureus/genética , Vancomicina/farmacologia , Staphylococcus aureus Resistente à Vancomicina
8.
Pharmacol Res ; 163: 105187, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916255

RESUMO

Traditional Chinese Medicine (TCM) is a medical science and cultural heritage empirically applied and reserved by Chinese people for thousands of years. With comprehensive prosperity of China and rapid elaboration of technology, healthcare status of Chinese people has become one of the most crucial concerns of the country. Nearly 30 policies and measures regarding TCM development have been issued since the 18th National Congress of the Communist Party of People's Republic of China in 2012. This review introduced a detailed evolutionary course of TCM in China with an emphasis on understanding the roadmap of TCM related policies and measures in China.


Assuntos
Política de Saúde , Medicina Tradicional Chinesa , China , História do Século XX , História do Século XXI , Medicina Tradicional Chinesa/história
9.
Inorg Chem ; 60(10): 6900-6910, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33621073

RESUMO

Precise regulation of proton-coupled electron-transfer (PCET) rates holds the key to simultaneously optimizing the turnover frequency and product selectivity of redox reactions that are central to the realization of renewable energy schemes in a sustainable future. In this work, a self-assembled monolayer (SAM) of a Ru complex electrografted onto a glassy carbon (GC) electrode was prepared as a heterogeneous electrocatalytic interface to facilitate the hydrogen peroxide (H2O2) oxidation half-cell reaction of a direct hydrogen peroxide/hydrogen peroxide fuel cell. A functional lipid membrane embedded with catalytic amounts of proton carriers was appended on top of the Ru SAM to construct a hybrid bilayer membrane (HBM) platform that can modulate the thermodynamics and kinetics of proton- and electron-transfer steps independently. The performances of the as-prepared Ru SAMs and HBMs toward H2O2 oxidation were investigated using electrochemical means, kinetic isotope effect (KIE) studies, and Tafel analyses. Proton carriers featuring borate, phosphate, and nitrile headgroups were found to dictate the transmembrane proton removal rate, thereby controlling the H2O2 oxidation activity. The first significance of this work was the expansion of HBM platforms to GC substrates to overcome the limited redox potential window on gold thiol systems, thereby enabling electrochemical investigations of anodic reactions at the SAM-lipid interface. The second highlight of this work was demonstrating for the first time that deprotonation kinetics can be taken advantage of to enhance the electrocatalytic oxidation performance of a metal complex anchored at the SAM-lipid interface of a HBM platform. When the knowledge gaps regarding how PCET steps govern redox pathways are closed, the advances achieved using our unique bioinorganic platform are envisioned to accelerate the understanding and optimization of electrocatalytic processes involving proton- and electron- transfer steps that are fundamental to the development of high-performance energy devices.

10.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1039-1046, 2020 Mar.
Artigo em Zh | MEDLINE | ID: mdl-32237443

RESUMO

Percolation extraction is a conventional extraction method used in the processing of traditional Chinese medicines. After medicinal material powder is placed in a percolation tank, the extraction solvent is continuously added, and percolation extract is collected simultaneously. The percolation equipment is simple. The percolation operation is easy. It is applicable to a wide range of medicinal materials. Components that are unstable under thermal conditions can be effectively extracted. However, there are also disadvantages, such as high solvent consumption, long extraction time, and high energy consumption in subsequent concentration processes. This article mainly reviews the research progress on the common equipment types, affecting factors, parameter optimization methods, and process monitoring. According to analysis on literatures, solvent composition, impregnation time, percolation speed, and solvent consumption are considered as the important factors of percolation processes. At present, near-infrared spectroscopy is widely used in the monitoring of percolation process, and partial least square is a commonly used quantitative modeling method. According to the concept of "Quality by Design", in-depth investigation of the percolation process mechanism and development of process control methods are future development trends. Therefore, process modeling, process optimization and process monitoring shall be improved. The mechanism models and the empirical models of column chromatography can be used as references to construct the percolation process models. The effect of the quality changes of medicinal materials shall be taken into account when optimizing the percolation process parameters. More simple and easy methods shall be developed to monitor the percolation process status and key properties of percolation extracts.


Assuntos
Química Farmacêutica , Medicamentos de Ervas Chinesas/química , Análise dos Mínimos Quadrados , Medicina Tradicional Chinesa , Pós , Espectroscopia de Luz Próxima ao Infravermelho
11.
Int J Med Microbiol ; 309(1): 39-53, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30392856

RESUMO

Staphylococcus aureus can produce numerous surface proteins involved in the adhesion and internalization of host cells, immune evasion, and inflammation initiation. Among these surface proteins, the microbial surface components recognizing adhesive matrix molecules contain many crucial cell wall-anchored virulence factors. The Sar-family regulatory protein Rot has been reported to regulate many important extracellular virulence factors at the transcriptional level, including Spa and clumping factor B. SpoVG, a global regulator in S. aureus, is known to control the expression of numerous genes. Here, we demonstrate that SpoVG can positively regulate the transcription of rot by directly binding to its promoter. SpoVG can also positively regulate the transcription of spa and clfB through direct-binding to their promoters and in a Rot-mediated manner. Furthermore, SpoVG can positively modulate the human fibrinogen-binding ability of S. aureus. In addition, phosphorylation of SpoVG by the serine/threonine kinase, Stk1, can positively regulate its binding to the promoters of rot, spa, and clfB. The human cell infection assay showed that the adhesion and internalization abilities were reduced in the spoVG mutant strain in comparison to those in the wild-type strain. Collectively, our data reveal a SpoVG-Rot regulatory cascade and novel molecular mechanisms in the virulence control in S. aureus.


Assuntos
Adesinas Bacterianas/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Repressoras/metabolismo , Staphylococcus aureus/genética , Adesinas Bacterianas/genética , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Células HEK293 , Humanos , Mutação , Fosforilação , Regiões Promotoras Genéticas , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/genética , Infecções Estafilocócicas/microbiologia , Células THP-1 , Transcrição Gênica , Virulência/genética , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
12.
Adv Exp Med Biol ; 1155: 1049-1056, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468466

RESUMO

This study investigated the effects of taurine on bowel inflammation resulting from heat stress in broilers, with the intent of providing insight into potential improvement of the condition of broilers. A total of 300 healthy 1 day AA broilers were selected, fed normally until day 7, and allocated randomly to 5 treatment groups, namely, the control group(C), the heat stress group(HS), the low Tau (LTau) group, the middle Tau (MTau) group and the high Tau (HTau) group, which represent low, medium and high concentrations of taurine respectively. In the study, various concentrations of taurine were added to the drinking water. The Heat Stress model was produced by maintaining Broilers in a room at 34 °C.Heat stress persisted for 6 h, 12 h, 7 days, and 14 days. The results showed that the expression levels of TNF-α, IFN-γ, and IL-1ß of the HTau group were significantly lower than that of the HS group at all time points examined (6 h, 12 h, 7 days, and 14 days) (P < 0.05). Compared with the HS group subjected to 6 h, 12 h and 14 days of heat stress, the MTau group exhibited significantly lower degrees of TNF-α and IL-1ß expression. Moreover, the expression of IFN-γ was higher in the HS group after 6 h, 12 h and 7 days of heat stress than that of the MTau group subjected to similar times of heat stress (P < 0.05).There were no significant difference among the groups at other periods of heat stress (P > 0.05).


Assuntos
Resposta ao Choque Térmico , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Taurina/farmacologia , Animais , Galinhas , Citocinas/metabolismo , Temperatura Alta , Distribuição Aleatória
13.
Pak J Pharm Sci ; 30(3(Special)): 1125-1127, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28671094

RESUMO

To construct the pIRES2-MLAA34-HSP70 recombinant vector and express the MLAA34-HSP70 recombinant proteins in Escherichia coli (E. coli). The MLAA34 and the HSP70 genes were extracted from U937 cells by RT-PCR, and then we amplified the fusion gene MLAA34-HSP70 by SOE-PCR and inserted it into the pIRES2-EGFP vector to construct the pIRES2-MLAA34-HSP70 recombinant vector. We amplified the fusion gene MLAA34-HSP70 successfully and identified the correctness of pIRES2-MLAA34-HSP70 recombinant vector by PCR and restriction endonuclease. Moreover, the MLAA34-HSP70 recombinant proteins expressed in E. coli were consistent with the expected molecular weight. We constructed the pIRES2-MLAA34-HSP70 recombinant vector successfully and the MLAA34-HSP70 recombinant proteins were successfully expressed by the induction of IPTG.


Assuntos
Antígenos de Neoplasias/genética , Proteínas Reguladoras de Apoptose/genética , Expressão Gênica/genética , Linhagem Celular Tumoral , Escherichia coli/metabolismo , Vetores Genéticos , Proteínas de Fluorescência Verde/genética , Proteínas de Choque Térmico HSP70/genética , Humanos , Isopropiltiogalactosídeo/farmacologia , Plasmídeos , Reação em Cadeia da Polimerase , Proteínas Recombinantes de Fusão
15.
Front Psychol ; 15: 1265047, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323156

RESUMO

Introduction: Due to the limitations of traditional didactic teaching, inquiry-based teaching has attracted increasing attention and has become an important content of curriculum teaching reform in college education. Nevertheless, it is vital to investigate students' subjective acceptance of inquiry-based instruction and its influencing factors before inquiry-based teaching methods are widely implemented. Methods: In light of this, taking into account the psychological factors of students, an acceptance model of inquiry-based teaching pedagogy was established based on the extended technology acceptance model (TAM). Three additional variables, namely self-efficacy, implementation quality, and risk perception, were incorporated into the TAM. Firstly, subjective evaluation data of the influencing factors of inquiry teaching acceptance were obtained through a network questionnaire survey from university students in Guangdong, China, using snowball sampling and convenient sampling. A total of 485 valid questionnaires were retrieved, with an effective response rate of 88.2%. Then, internal consistency and reliability, convergent validity and discriminant validity of the model and its hypothesis were tested with reliability and validity tests. Finally, path analysis was used to examine key determinants of students' acceptance of inquiry teaching and moderators. Results: Results indicated that the constructed model can explain the acceptability of inquiry teaching for college students by 88.6%; Attitude has a positive significant impact on behavioral intention; Perceived ease of use indirectly affects behavioral intention through perceived usefulness, while perceived usefulness indirectly affects behavioral intention through attitude; self-efficacy not only directly affects behavioral intention but also indirectly affects behavioral intention through implementation quality; implementation quality indirectly affects behavioral intention through perceived usefulness and attitude; students' risk perception of inquiry-based teaching has no negative impact on behavioral intention. Conclusion: Overall, this study has implications for policymakers, teachers or learners in terms of the implementation and promotion of inquiry-based teaching in college classroom.

16.
Phytomedicine ; 132: 155826, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38897045

RESUMO

BACKGROUND: Perillyl alcohol (POH) is a aroma monoterpene commonly obtained from various plants' essential oil. Recently, increasing researches have demonstrated that POH may be useful, not only as flavor compound, but also as bioactive molecule because of a variety of biological activities. PURPOSE: The aim of this review is to summarize the production, pharmacological activities and molecular mechanism, active derivatives, toxicity and parmacokinetics, and industrial application of POH. METHODS: A systematic search of published articles up to January 2024 in Web of Science, China Knowledge Network, and PubMed databases is conducted using the following keywords: POH, POH derivatives, biological or pharmacological, production or synthesis, pharmacokinetics, toxicity and application. RESULTS: Biotechnological production is considered to be a potential alternative approach to generate POH. POH provides diverse pharmacological benefits, including anticancer, antimicrobial, insecticidal, antioxidant, anti-inflammatory, hypotensive, vasorelaxant, antinociceptive, antiasthmatic, hepatoprotective effects, etc. The underlying mechanisms of action include modulation of NF-κB, JNK/c-Jun, Notch, Akt/mTOR, PI3K/Akt/eNOS, STAT3, Nrf2 and ERS response pathways, mitigation of mitochondrial dysfunction and membrane integrity damage, and inhibition of ROS accumulation, pro-inflammatory cytokines release and NLRP3 activation. What's more, the proteins or genes influenced by POH against diseases refer to Bax, Bcl-2, cyclin D1, CDK, p21, p53, HIF-1α, AP-1, caspase-3, M6P/IGF2R, PARP, VEGF, etc. Some clinical studies report that intranasal delivery of POH is a safe and effective treatment for cancer, but further clinical investigations are needed to confirm other health benefits of POH in human healthy. Depending on these health-promoting properties together with desirable flavor and safety, POH can be employed as dietary supplement, preservative and flavor additive in food and cosmetic fields, as building block in synthesis fields, as anticancer drug in medicinal fields, and as pesticides and herbicides in agricultural fields. CONCLUSION: This review systematically summarizes the recent advances in POH and highlights its therapeutic effects and potential mechanisms as well as the clinical settings, which is helpful to develop POH into functional food and new candidate drug for prevention and management of diseases. Future studies are needed to conduct more biological activity studies of POH and its derivatives, and check their clinical efficacy and potential side effects.


Assuntos
Monoterpenos , Monoterpenos/farmacologia , Monoterpenos/química , Humanos , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química
17.
Int J Biol Macromol ; 267(Pt 2): 131487, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599430

RESUMO

Oral absorption of ginsenoside Rb1 (Rb1) is often hindered by the gastrointestinal tract. Carboxymethyl chitosan deoxycholic acid loaded with ginsenoside Rb1 nanoparticles (CMDA@Rb1-NPs), were prepared as a delivery system using a self-assembly technique with amphipathic deoxycholic acid grafted carboxymethyl chitosan as the carrier, which improved the stability and embedding rate of Rb1. In addition, the CMDA@Rb1-NPs was encapsulated with sodium alginate by ion crosslinking method with additional layer (CMDAlg@Rb1-NPs). Scanning electron microscopy showed that the nanoparticles were spherical, evenly distributed, smooth and without obvious adhesion. By evaluating drug loading, entrapment efficiency, the encapsulation efficiency of Rb1 increased from 60.07 % to 72.14 % after grafting deoxycholic acid improvement and optimization. In vitro release results showed that the cumulative release of Rb1 by CMDAlg-NPs showed a pH dependent effect, which was <10 % in simulated gastric juice with pH 1.2, completely released with pH 7.4 for about 48 h. In addition, Rb1 and CMDAlg@Rb1-NPs had inhibitory effects on A549 cells, and the inhibitory effect of CMDAlg@Rb1-NPs was better. Therefore, all results indicated that CMDA/Alg@Rb1 nanoparticles might be a novel drug delivery system to improve the stability and embedding rate of Rb1, and has the potential to be applied in oral pharmaceutical preparations.


Assuntos
Quitosana , Portadores de Fármacos , Liberação Controlada de Fármacos , Ginsenosídeos , Nanopartículas , Quitosana/química , Quitosana/análogos & derivados , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Ginsenosídeos/farmacocinética , Concentração de Íons de Hidrogênio , Nanopartículas/química , Humanos , Portadores de Fármacos/química , Linhagem Celular Tumoral , Tamanho da Partícula
18.
Int J Biol Macromol ; 254(Pt 3): 127724, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37898252

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

19.
J Colloid Interface Sci ; 657: 334-343, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38043235

RESUMO

Reconstruction universally occurs over non-layered transition metal sulfides (TMSs) during oxygen evolution reaction (OER), leading to the formation of active species metal (oxy)hydroxide and thus significantly influences the OER performance. However, the reconstruction process and underlying mechanism quantitatively remain largely unexplored. Herein, we proposed an electrochemical reaction mechanism, namely sulfide oxidation reaction (SOR), to elucidate the reconstruction process of pyrite-type TMSs. Based on this mechanism, we evaluated the reconstruction capability of NiS2 doped with transition metals V, Cr, Mn, Fe, Co, Cu, Mo, Ru, Rh, and Ir within different doped systems. Two key descriptors were thus proposed to describe the reconstruction abilities of TMSs: USOR (the theoretical electric potential of SOR) and ΔU (the difference between the theoretical electric potential of SOR and OER), representing the initiation electric potential of reconstruction and the intrinsic reconstruction abilities of TMSs, respectively. Our finding shows that a lower USOR readily initiate reconstruction at a lower potential and a larger ΔU indicating a poorer reconstruction ability of the catalyst during OER. Furthermore, Fe-doped CoS2 was used to validate the rationality of our proposed descriptors, being consistent with the experiment findings. Our work provides a new perspective on understanding the reconstruction mechanism and quantifying the reconstruction of TMSs.

20.
Front Pharmacol ; 15: 1423075, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045047

RESUMO

Background: Atypical antipsychotics (AAPs)-induced sexual dysfunction (SD) is a frequent issue in clinical practice, often underestimated by clinicians and not extensively researched. The current study aimed to quantify the strength of association between the use of different AAPs and SD using real-world data from the FDA Adverse Event Reporting System (FAERS), as well as investigate the receptor mechanisms that are involved. Methods: Data from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were queried through OpenVigil 2.1. Disproportionality analysis was estimated using the reporting odds ratio (ROR) and information component (IC) methods, and linear regression was used to investigate the relationship between ROR and receptor occupancy which was estimated using in vitro receptor binding profiles. Results: Our analysis yielded 4839 reports that co-mentioned AAP and SD events, and the findings revealed statistical associations between 12 AAPs and SD. The highest signal value was identified for iloperidone reporting retrograde ejaculation with iloperidone (ROR = 832.09, ROR025 = 552.77; IC = 9.58, IC025 = 6.36), followed by compulsive sexual behavior with aripiprazole (ROR = 533.02, ROR025 = 435.90; IC = 7.30, IC025 = 5.97), and psychosexual disorder for aripiprazole (ROR = 145.80, ROR025 = 109.57; IC025 = 6.47, IC025 = 4.86). Different characteristics of the SD side effects in each AAPs were discovered after further data mining. Regression analysis revealed potential effects for receptor occupancy of D2, D3, and 5-HT1A receptors on ROR. However, no significant correlation persisted following sensitivity analyses. Conclusion: This is the first study to investigate the AAP-SD associations by using FAERS. In this study, we report for the first time a significant association between aripiprazole and SD based on real-world data. The study suggests that different AAPs have varying levels of association with SD, and the D2, D3, and 5-HT1A receptor occupancy may contribute to potential mechanisms. The findings of this study warrant further validation of more studies and clinical causality assessment.

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