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1.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35074916

RESUMO

Pogona vitticeps has female heterogamety (ZZ/ZW), but the master sex-determining gene is unknown, as it is for all reptiles. We show that nr5a1 (Nuclear Receptor Subfamily 5 Group A Member 1), a gene that is essential in mammalian sex determination, has alleles on the Z and W chromosomes (Z-nr5a1 and W-nr5a1), which are both expressed and can recombine. Three transcript isoforms of Z-nr5a1 were detected in gonads of adult ZZ males, two of which encode a functional protein. However, ZW females produced 16 isoforms, most of which contained premature stop codons. The array of transcripts produced by the W-borne allele (W-nr5a1) is likely to produce truncated polypeptides that contain a structurally normal DNA-binding domain and could act as a competitive inhibitor to the full-length intact protein. We hypothesize that an altered configuration of the W chromosome affects the conformation of the primary transcript generating inhibitory W-borne isoforms that suppress testis determination. Under this hypothesis, the genetic sex determination (GSD) system of P. vitticeps is a W-borne dominant female-determining gene that may be controlled epigenetically.


Assuntos
Alelos , Cromossomos/genética , Splicing de RNA , Processos de Determinação Sexual , Fator Esteroidogênico 1/genética , Sequência de Aminoácidos , Animais , Cromossomos/química , Feminino , Dosagem de Genes , Lagartos , Masculino , Modelos Moleculares , Conformação Molecular , Conformação Proteica , Répteis , Cromossomos Sexuais , Fatores Sexuais , Fator Esteroidogênico 1/química , Relação Estrutura-Atividade
2.
Ann Pharmacother ; 58(4): 349-359, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37488978

RESUMO

BACKGROUND: Different clinical trials for recurrent or metastatic nasopharyngeal carcinoma have studied different combinations of immuno-oncology in first-line treatment, but the optimal choice has not been determined. OBJECTIVE: To systematically examine and compare the efficacy and safety of different immune checkpoint inhibitors (ICIs) combined with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. METHODS: Several electronic databases were systematically searched up to February 2023. Articles meeting the inclusion criteria were included. RESULTS: Three RCTs were eligible in the study. Compared with placebo plus gemcitabine-cisplatin (GP), toripalimab plus GP (HR = 0.59, 95% CI: 0.37-0.95) was significantly associated with a better OS. Tislelizumab plus GP generated best progression-free survival (PFS) benefit (HR = 0.50, 95% CI: 0.37-0.67), greatest improvement in 1-year PFS rate (RR = 3.00, 95% CI: 1.84-5.22), and objective response rate (ORR) (RR = 1.26, 95% CI: 1.04-1.53) over the placebo plus GP. Furthermore, tislelizumab plus GP appeared to be safer than toripalimab plus GP and camrelizumab plus GP in terms of adverse events (AEs)-grade ≥3, treatment-related AEs (TRAEs)-grade ≥3, serious AEs (SAEs), treatment-related SAEs (TRSAEs), and AEs leading to discontinuation of treatment. CONCLUSION AND RELEVANCE: In recurrent or metastatic nasopharyngeal carcinoma, programmed death 1 (PD-1) inhibitors plus GP as first-line treatment have better survival outcomes than placebo plus GP with comparable toxicity. Toripalimab plus GP shows the best OS benefit over placebo plus GP, while tislelizumab plus GP generates the best PFS, 1-year PFS rate, ORR, and safety. Tislelizumab plus GP could be the best choice among the ICIs combined with chemotherapy regimens as first-line treatment in recurrent or metastatic nasopharyngeal carcinoma.


Assuntos
Neoplasias Pulmonares , Neoplasias Nasofaríngeas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/etiologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/patologia , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Int Ophthalmol ; 43(7): 2477-2486, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36869982

RESUMO

PURPOSE: To perform a systematic evaluation of the efficacy and safety of loteprednol etabonate (LE) 0.5% versus fluorometholone (FML) 0.1% for treating patients after corneal refractive surgery with the aim of providing an evidence-based rationale for clinical drug selection. METHODS: Electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, WanFang, and CNKI) were searched (from inception to December 2021) for comparative clinical studies that evaluated LE versus FML treatment for post-corneal refractive surgery patients. Meta-analysis was performed using the RevMan 5.3 software. The pooled risk ratio (RR) and weighted mean difference (WMD) with corresponding 95% confidence interval (CI) were calculated. RESULTS: Nine studies with a total sample size of 2677 eyes were included in this analysis. FML 0.1% and LE 0.5% produced a similar incidence of corneal haze within 6 months after surgery (P = 0.13 at 1 month, P = 0.66 at 3 months, and P = 0.12 at 6 months). There was no statistically significant difference between the two groups in terms of the mean logMAR postoperative uncorrected distance visual acuity (WMD: - 0.00; 95% CI: - 0.01 to 0.00; P = 0.29) and spherical equivalent (WMD: 0.01; 95% CI: - 0.01 to 0.03; P = 0.35). LE 0.5% appears to have a higher tendency to reduce the incidence of ocular hypertension compared FML 0.1%, but there was no statistical significance (RR: 0.63; 95% CI: 0.27 to 1.50; P = 0.30). CONCLUSION: This meta-analysis demonstrated that LE 0.5% and FML 0.1% had comparable efficacy in preventing corneal haze and corticosteroid-induced ocular hypertension, with no difference in visual acuity in patients after corneal refractive surgery.


Assuntos
Opacidade da Córnea , Hipertensão Ocular , Procedimentos Cirúrgicos Refrativos , Humanos , Etabonato de Loteprednol/efeitos adversos , Fluormetolona/uso terapêutico , Córnea/cirurgia , Procedimentos Cirúrgicos Refrativos/efeitos adversos
4.
J Environ Sci (China) ; 127: 273-283, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36522059

RESUMO

The occurrence of antibiotic resistance genes (ARGs) in various environments has drawn worldwide attention due to their potential risks. Previous studies have reported that a variety of substances can enhance the occurrence and dissemination of ARGs. However, few studies have compared the response of ARGs under the stress of different organic matters in biological wastewater treatment systems. In this study, seven organic pollutants were added into wastewater treatment bioreactors to investigate their impacts on the ARG occurrence in activated sludge. Based on high-throughput sequencing, it was found that the microbial communities and ARG patterns were significantly changed in the activated sludge exposed to these organic pollutants. Compared with the non-antibiotic refractory organic matters, antibiotics not only increased the abundance of ARGs but also significantly changed the ARG compositions. The increase of Gram-negative bacteria (e.g., Archangium, Prosthecobacter and Dokdonella) carrying ARGs could be the main cause of ARG proliferation. In addition, significant co-occurrence relationships between ARGs and mobile genetic elements were also observed in the sludge samples, which may also affect the ARG diversity and abundance during the organic matter treatment in the bioreactors. Overall, these findings provide new information for better understanding the ARG occurrence and dissemination caused by organic pollutants in wastewater treatment systems.


Assuntos
Poluentes Ambientais , Esgotos , Esgotos/microbiologia , Antibacterianos/farmacologia , Genes Bacterianos , Resistência Microbiana a Medicamentos/genética
5.
Cell Biol Toxicol ; 38(2): 259-272, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33797657

RESUMO

Stanniocalcin-2 (STC2) has been proved to regulate a variety of signaling pathways including cell growth, metastasis, and therapeutic resistance. However, the role of STC2 in the regulation of nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, we investigated the regulatory function of STC2 on epithelial-mesenchymal transition (EMT) and glycolysis traits in NPC and revealed the underlying molecular mechanisms. We found that STC2 was highly expressed in primary nasopharyngeal carcinoma tissues and lymph node metastatic tissues. Silencing of STC2 inhibited cell proliferation, invasion, and glycolysis. Further analyses for the clinical samples demonstrated that STC2 expression was associated with the poor clinical progression. Moreover, we demonstrated the interaction of ITGB2 with STC2 and its involvement in STC2-mediated ITGB2/FAK/SOX6 axis. Collectively, our results provide new insights into understanding the regulatory mechanism of STC2 and suggest that the STC2/ITGB2/FAK/SOX6 signaling axis may be a potential therapeutic target for NPC.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias Nasofaríngeas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glicólise , Glicoproteínas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Fatores de Transcrição SOXD/metabolismo , Transdução de Sinais
6.
Phys Chem Chem Phys ; 24(35): 21388-21395, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36047321

RESUMO

Two dimensional α-Te holds great promise in optoelectronic devices because of its high mobility and excellent environmental stability. In this study, the electronic structures and interfacial contact characteristics of the Ti2NF2/α-Te van der Waals heterostructure are investigated by means of first-principles calculations. It is found that p-type Schottky contacts with a Schottky barrier (SB) of 0.21 eV are formed at the Ti2NF2/α-Te interface. By applying external electric fields or controlling the interlayer coupling between the Ti2NF2 and α-Te monolayers, the SB height can be effectively tuned, and all the n-type Schottky, p-type Schottky, n-type ohmic and p-type ohmic contacts can be achieved. Such an extremely high tunability is further found to be closely associated with the charge transfer at the interface, as well as the interface dipole and the potential step. Our results provide an avenue for the design of future α-Te-based electronic devices with high performance.

7.
Environ Geochem Health ; 44(8): 2669-2684, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34398366

RESUMO

Winter-wheat-summer-maize rotations are important cropping patterns in China, and the quality of the food produced from these systems can affect human health. However, the effects of heavy metal pollution on both crops remain unclear. We analyzed soil-wheat and soil-maize samples from eastern China for their Cd, Cu, Zn, Cr, Ni, and Pb contents. The concentrations of these metals in the soils analyzed were found to be lower than those recommended by the national guidelines, but the Cd, Cr, Cu, and Ni concentrations were higher than the natural soil background values in China. Quality indices showed that subpollution was predominant in wheat/maize (95.00%/81.25%) samples. Positive matrix factorization model data revealed that the contributions from natural sources, agricultural activities, and traffic to the heavy metal pollution levels were 30.40-43.07%, 34.67-26.63%, and 34.92-30.27%, respectively, in the wheat-maize rotations. Although the health hazard quotient values for wheat were higher than those for maize, there were no health risks for children or adults.


Assuntos
Metais Pesados , Poluentes do Solo , Adulto , Cádmio , Criança , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Medição de Risco , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Triticum , Zea mays
8.
Cancer Sci ; 112(6): 2260-2271, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33837611

RESUMO

The lncRNA LINC01123 has been reported to act as an oncogene in many human cancers. Nevertheless, the function and underlying mechanism of LINC01123 in osteosarcoma (OS) remain unclear. This study aimed to explore the roles and mechanisms of LINC01123 in OS progression. In this study, the expression of LINC01123 was significantly upregulated in OS cell lines than in a human osteoblast cell line. Furthermore, in vitro and in vivo experiments confirmed that knockdown of LINC01123 suppressed cell progression. Mechanistically, LINC01123 acted as a competing endogenous RNA by sponging miR-516b-5p, thus, increasing Gli1 expression by directly targeting its 3'UTR. Taken together, LINC01123 enhances OS proliferation and metastasis via the miR-516b-5p/Gli1 axis. Therefore, LINC01123 may be a potential therapeutic target for OS treatment.


Assuntos
Neoplasias Ósseas/patologia , Proteínas Hedgehog/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/patologia , RNA Longo não Codificante/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , MicroRNAs/genética , Metástase Neoplásica , Osteossarcoma/genética , Osteossarcoma/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Proteína GLI1 em Dedos de Zinco/genética
9.
BMC Cancer ; 21(1): 1218, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774019

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC. METHODS: The expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP). RESULTS: miR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3'untranslated region (3'UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What's more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. CONCLUSIONS: These findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/genética , Expressão Gênica , Chaperonas de Histonas/genética , Neoplasias Pulmonares/genética , MicroRNAs/fisiologia , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/genética , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Feminino , Genes Reporter , Genes Supressores de Tumor/fisiologia , Chaperonas de Histonas/antagonistas & inibidores , Chaperonas de Histonas/metabolismo , Humanos , Fator 4 Semelhante a Kruppel/genética , Fator 4 Semelhante a Kruppel/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Metiltransferases/genética , Metiltransferases/metabolismo , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
10.
Langmuir ; 37(24): 7611-7616, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34115514

RESUMO

Semiconductor nanocrystals are normally dispersed in the solvent for property studies as well as practical applications. However, rare attention has been paid to their orientation status in the colloidal solution. Herein, with the help of linear dichroism (LD) spectroscopy, we demonstrate that isotropic NCs of high symmetry (i.e., quantum dots, QDs) and anisotropic NCs (e.g., quantum rods, QRs and nanoplates, NPLs) but under diluted concentration are randomly dispersed without any preferential orientation. Meanwhile, anisotropic NCs under a high concentration can behave with some net orientation along a certain direction. For example, CdSe quantum rods (QRs) and nanoplatelets (NPLs) both show an obviously preferred orientation along the vertical direction in solution when their solution absorbances increase to certain values. An in-depth analysis of QRs' LD spectrum shows that the first excitonic transition of QRs is strongly quantumly confined while its higher-energy excitonic transitions are weakly quantumly confined. In contrast, the NPLs' LD spectrum indicates that their excitonic transitions are isotropic in the spatial space. This work provides a new viewpoint of the real status of anisotropic semiconductor NCs in solution.

11.
Phys Chem Chem Phys ; 23(17): 10545-10550, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33900337

RESUMO

Topological insulation is widely predicted in two-dimensional (2D) materials realized by epitaxial growth or van der Waals (vdW) exfoliation. Such 2D topological insulators (TI's) host many interesting physical properties such as the quantum spin Hall effect and superconductivity. Here, we extend the search of 2D TI's into the exfoliatable non-vdW 2D crystals. We find that three-dimensional Dirac semimetals A3Bi (A = Na, K, Rb) (P3[combining macron]c1) can be exfoliated into 2D materials with exfoliation energies of 0.479-0.990 J m-2. Our careful examination of the topological invariants of exfoliated A3Bi monolayers/multilayers by using two well-established approaches reveals that bilayer and tetralayer Na3Bi are 2D TI's. It is found that the band gap of 2D TI's can be significantly increased by external strain. We further find that the predicted 2D TI's possess interesting hidden Rashba-like spin textures. Our results suggest a new arena to search for two-dimensional topological insulators and spintronic materials.

12.
Nature ; 523(7558): 79-82, 2015 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-26135451

RESUMO

Sex determination in animals is amazingly plastic. Vertebrates display contrasting strategies ranging from complete genetic control of sex (genotypic sex determination) to environmentally determined sex (for example, temperature-dependent sex determination). Phylogenetic analyses suggest frequent evolutionary transitions between genotypic and temperature-dependent sex determination in environmentally sensitive lineages, including reptiles. These transitions are thought to involve a genotypic system becoming sensitive to temperature, with sex determined by gene-environment interactions. Most mechanistic models of transitions invoke a role for sex reversal. Sex reversal has not yet been demonstrated in nature for any amniote, although it occurs in fish and rarely in amphibians. Here we make the first report of reptile sex reversal in the wild, in the Australian bearded dragon (Pogona vitticeps), and use sex-reversed animals to experimentally induce a rapid transition from genotypic to temperature-dependent sex determination. Controlled mating of normal males to sex-reversed females produces viable and fertile offspring whose phenotypic sex is determined solely by temperature (temperature-dependent sex determination). The W sex chromosome is eliminated from this lineage in the first generation. The instantaneous creation of a lineage of ZZ temperature-sensitive animals reveals a novel, climate-induced pathway for the rapid transition between genetic and temperature-dependent sex determination, and adds to concern about adaptation to rapid global climate change.


Assuntos
Adaptação Fisiológica , Processos de Determinação Sexual/fisiologia , Temperatura , Animais , Austrália , Feminino , Masculino , Dados de Sequência Molecular , Répteis , Cromossomos Sexuais/genética , Processos de Determinação Sexual/genética , Razão de Masculinidade
13.
Int J Mol Sci ; 22(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34681789

RESUMO

Plant thaumatin-like proteins (TLPs) play pleiotropic roles in defending against biotic and abiotic stresses. However, the functions of TLPs in broccoli, which is one of the major vegetables among the B. oleracea varieties, remain largely unknown. In the present study, bolTLP1 was identified in broccoli, and displayed remarkably inducible expression patterns by abiotic stress. The ectopic overexpression of bolTLP1 conferred increased tolerance to high salt and drought conditions in Arabidopsis. Similarly, bolTLP1-overexpressing broccoli transgenic lines significantly improved tolerance to salt and drought stresses. These results demonstrated that bolTLP1 positively regulates drought and salt tolerance. Transcriptome data displayed that bolTLP1 may function by regulating phytohormone (ABA, ethylene and auxin)-mediated signaling pathways, hydrolase and oxidoreductase activity, sulfur compound synthesis, and the differential expression of histone variants. Further studies confirmed that RESPONSE TO DESICCATION 2 (RD2), RESPONSIVE TO DEHYDRATION 22 (RD22), VASCULAR PLANT ONE-ZINC FINGER 2 (VOZ2), SM-LIKE 1B (LSM1B) and MALATE DEHYDROGENASE (MDH) physically interacted with bolTLP1, which implied that bolTLP1 could directly interact with these proteins to confer abiotic stress tolerance in broccoli. These findings provide new insights into the function and regulation of bolTLP1, and suggest potential applications for bolTLP1 in breeding broccoli and other crops with increased tolerance to salt and drought stresses.


Assuntos
Brassica/genética , Proteínas de Plantas/fisiologia , Tolerância ao Sal/genética , Estresse Fisiológico/genética , Brassica/classificação , Secas , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Homologia de Sequência
14.
Pharm Biol ; 59(1): 880-883, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34214011

RESUMO

CONTEXT: Baicalein and simvastatin possess similar pharmacological activities and indications. The risk of their co-administration was unclear. OBJECTIVE: The interaction between baicalein and simvastatin was investigated to provide reference and guidance for the clinical application of the combination of these two drugs. MATERIALS AND METHODS: The pharmacokinetics of simvastatin was investigated in Sprague-Dawley rats (n = 6). The rats were pre-treated with 20 mg/kg baicalein for 10 days and then administrated with 40 mg/kg simvastatin. The single administration of simvastatin was set as the control group. The rat liver microsomes were employed to assess the metabolic stability and the effect of baicalein on the activity of CYP3A4. RESULTS: Baicalein significantly increased the AUC(0-t) (2018.58 ± 483.11 vs. 653.05 ± 160.10 µg/L × h) and Cmax (173.69 ± 35.49 vs. 85.63 ± 13.28 µg/L) of simvastatin. The t1/2 of simvastatin was prolonged by baicalein in vivo and in vitro. The metabolic stability of simvastatin was also improved by the co-administration of baicalein. Baicalein showed an inhibitory effect on the activity of CYP3A4 with the IC50 value of 12.03 µM, which is responsible for the metabolism of simvastatin. DISCUSSION AND CONCLUSION: The co-administration of baicalein and simvastatin may induce drug-drug interaction through inhibiting CYP3A4. The dose of baicalein and simvastatin should be adjusted when they are co-administrated.


Assuntos
Inibidores do Citocromo P-450 CYP3A/farmacologia , Citocromo P-450 CYP3A/efeitos dos fármacos , Flavanonas/farmacologia , Sinvastatina/farmacocinética , Animais , Área Sob a Curva , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Interações Medicamentosas , Flavanonas/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Concentração Inibidora 50 , Masculino , Microssomos Hepáticos/metabolismo , Ratos , Ratos Sprague-Dawley
15.
Microb Pathog ; 149: 104577, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33122048

RESUMO

Aeromous veronii is a severe pathogen that can infect aquatic organisms and mammals also causes irreparable damage to fish aquaculture. Analysis of the results of epidemiological investigations have revealed that its tolerance to drugs and the virulence of A. veronii have increased in recent years. Most of the researches on A. veronii focuse on the strain isolation, identification, and drug susceptibility. However, we do not know so much about the molecular mechanism of the pathogenesis on A. veronii. Here we identified and obtained the highly expressed TH0426 Nucleoside Diphosphate Kinases (NDK) of A. veronii. We first constructed a mutant strain (△-ndk) by generating an in-frame deletion of the ndk gene, to investigate the functional role in A. veronii TH0426. The ability in the adhesion and invasion of EPC cells and biofilm formation significantly reduced of the △-ndk strain. The motility test showed that the ndk gene affected on the swimming ability, while did not affect the swarming motility. Compared with the wild-type strain TH0426, the pathogenicity of △-ndk strain to zebrafish reduced severely. Besides, the ndk gene has affected the apoptosis rate of A. veronii TH0426. These results would help to demonstrate the function of ndk further and realize the pathogenesis on A. veronii.


Assuntos
Aeromonas veronii , Núcleosídeo-Difosfato Quinase , Animais , Aquicultura , Núcleosídeo-Difosfato Quinase/genética , Virulência , Peixe-Zebra
16.
Biometals ; 33(4-5): 241-254, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32935165

RESUMO

Cadmium (Cd) is a widespread toxic occupational and environmental pollutant, and its effect on lipid metabolism dysregulation has been observed. In this study, we utilized two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) technologies to explore changes in the blood plasma proteins of mice exposed to Cd. From the 2-DE, 8 protein spots were screened in response to Cd exposure, and the identities of these proteins were revealed by MALDI-TOF MS. Western blotting was applied to analyze the expression of the apolipoproteins in both plasma and liver, which were consistent with Cd-induced dyslipidemia of their composed lipid. Moreover, the Cd-induced apolipoprotein ApoE upregulation was due to inhibition of autopahgic flux in the Cd exposed mice. It was further observed from the mouse liver that Cd reduced the expression of the lipid uptake receptor low-density lipoprotein receptor (LDLR), which might be responsible for the coordinated elevation in blood triglycerides and abnormal apolipoproteins. This study may provide a new insight into the mechanism of Cd-induced dyslipidemia and the risk of cardiovascular diseases.


Assuntos
Apolipoproteínas E/sangue , Cádmio/farmacologia , Triglicerídeos/sangue , Animais , Cádmio/administração & dosagem , Exposição Dietética , Masculino , Camundongos , Camundongos Endogâmicos ICR
17.
J Chem Phys ; 152(9): 091102, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33480710

RESUMO

Understanding the defect chemistry of lead-halide perovskites and its effects on the hot-carrier lifetime is of significance for both fundamental understanding and applications as solar cell light absorbing materials. In this study, the mechanistic details of hot carrier decay in hybrid perovskites are investigated using a newly developed non-adiabatic molecular dynamics method. In this approach, the nuclear trajectory is based on Born-Oppenheimer ground state molecular dynamics, which is then followed by the evolution of carrier wave function including the detailed balance and decoherence effects. We found the longer decay time for hot electrons due to the incorporation of interstitial iodine in the hybrid lead-halide perovskites (MAPbI3), while the hot hole decay time is not affected significantly by the interstitial iodine. The underlying mechanism for such modulation of hot carrier dynamics is attributed to the changes of carrier density of states and the electron-phonon coupling strength. Hence, iodine interstitial is the necessary condition to create long-lived hot electrons in perovskites, which is further demonstrated by the comparative analysis with the pure MAPbI3.

18.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1202-1208, 2020 Mar.
Artigo em Zh | MEDLINE | ID: mdl-32237466

RESUMO

With the continuous improvement of modern medical technology, medical practice has become more and more procedural. The medical process is often dominated by doctors, while the value orientation of patients is often ignored, lacking effective communication between doctors and patients. In response to this phenomenon, Charon R proposed the concept of narrative medicine, which has been recognized by all walks of life. In recent years, the value of medical humanism has attracted more attention, and the research on narrative medicine at home and abroad is increasing gradually. But at present, most of the research on narrative medicine is in terms of theory, lacking clinical research. How to make narrative medicine applied in the real world is the focus of current research. Following the concept of narrative medicine, and taking the study on doctor-patient parallel medical record to evaluate the real clinical efficacy of traditional Chinese medicine(TCM) and Western medicine(WM) in the treatment of digestive diseases as an example, this study is to explore the design contents and key points of the clinical trial scheme of doctor-patient co-construction of TCM and WM under narrative medicine, and discuss the activity form and clinical efficacy evaluation method under narrative medicine. Clinical trial design includes four aspects: medicine, ethics, statistics and trial management. This study explored the design of the doctor-patient co-construction clinical trial scheme under narrative medicine from both theoretical and practical aspects, providing reference for the design and research of future doctor-patient co-construction scheme, and expecting to establish a better efficacy evaluation method of TCM and WM.


Assuntos
Ensaios Clínicos como Assunto , Medicina Narrativa , Projetos de Pesquisa , Humanos , Prontuários Médicos , Medicina Tradicional Chinesa , Participação do Paciente
19.
Zhongguo Zhong Yao Za Zhi ; 45(2): 436-443, 2020 Jan.
Artigo em Zh | MEDLINE | ID: mdl-32237329

RESUMO

To analyze the efficacy and safety of Shensong Yangxin Capsules in treatment of bradycardia combined with premature beat. Databases, such as CNKI, VIP, WanFang, SinoMed, PubMed, Cochrane Library, ClinicalTrials were retrieved by computers for relevant randomized controlled trials of Shensong Yangxin Capsules in treatment of bradycardia combined with premature beat. Two researchers independently screened out the literatures, extracted data according to the inclusion criteria, and applied the Risk of Bias assessment tool in assessing the methodological quality. The Cochrane systematic evaluation software RevMan 5.3 was used for data analysis. Totally 9 randomized controlled trials including 706 subjects were included. The intervention measure was the single administration with Shensong Yangxin Capsules, and the control measure was the blank control. The results showed that Shensong Yangxin Capsules had an obvious effect on average heart rate(MD=6.59, 95%CI[3.87, 9.31], I~2=90%), premature beat efficacy(RR=1.72, 95%CI[1.53, 1.93], I~2=0%), heart rate efficacy(RR=1.74, 95%CI[1.40, 2.17], I~2=47%), and objective efficacy(RR=1.50, 95%CI[1.31, 1.70], I~2=31%). Eight studies reported safety events, with no significant adverse reaction. In conclusion, the single administration with Shensong Yangxin Capsules may have a certain effect in improving heart rate, controlling premature beats and alleviating clinical symptoms in patients with bradycardia combined with premature beat, with no obvious adverse reaction. Shensong Yangxin Capsules can be used in clinic. This potential conclusion needs to be confirmed in future trials using rigorous methodology.


Assuntos
Bradicardia/tratamento farmacológico , Complexos Cardíacos Prematuros/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Cápsulas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Small ; 15(47): e1903233, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31609534

RESUMO

Van der Waals (vdW)-integrated heterojunctions have been widely investigated in optoelectronics due to their superior photoelectric conversion capability. In this work, 0D bismuth quantum dots (Bi QDs)-decorated 1D tellurium nanotubes (Te NTs) vdW heterojunctions (Te@Bi vdWHs) are constructed by a facile bottom-up assembly process. Transient absorption spectroscopy suggests that Te@Bi vdWH is a promising candidate for new-generation optoelectronic devices with fast response properties. The subsequent experiments and density functional theory calculations demonstrate the vdW interaction between Te NTs and Bi QDs, as well as the enhanced optoelectronic characteristics owing to the plasma effects at the interface between Te NTs and Bi QDs. Moreover, Te@Bi vdWHs-based photodetectors show significantly improved photoresponse behavior in the ultraviolet region compared to pristine Te NTs or Bi QDs-based photodetectors. The proposed integration of vdWHs is expected to pave the way for constructing new nanoscale heterodevices.

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