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1.
Proc Natl Acad Sci U S A ; 119(48): e2214313119, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36417436

RESUMO

Nucleosome acetyltransferase of H4 (NuA4), one of two major histone acetyltransferase complexes in Saccharomyces cerevisiae specifically acetylates histone H2A and H4, resulting in increased transcriptional activity. Here we present a 3.8-4.0 Å resolution structure of the NuA4 complex from cryoelectron microscopy and associated biochemical studies. The determined structure comprises six subunits and appropriately 5,000 amino acids, with a backbone formed by subunits Eaf1 and Eaf2 spanning from an Actin-Arp4 module to a platform subunit Tra1. Seven subunits are missing from the cryo-EM map. The locations of missing components, Yaf9, and three subunits of the Piccolo module Esa1, Yng2, and Eaf6 were determined. Biochemical studies showed that the Piccolo module and the complete NuA4 exhibit comparable histone acetyltransferase activities, but the Piccolo module binds to nucleosomes, whereas the complete NuA4 does not. The interaction lifetime of NuA4 and nucleosome is evidently short, possibly because of subunits of the NuA4 complex that diminish the affinity of the Piccolo module for the nucleosome, enabling rapid movement from nucleosome to nucleosome.


Assuntos
Nucleossomos , Proteínas de Saccharomyces cerevisiae , Nucleossomos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Histona Acetiltransferases/metabolismo , Microscopia Crioeletrônica , Saccharomyces cerevisiae/metabolismo , Histonas/metabolismo
2.
Nano Lett ; 24(22): 6805-6812, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38787360

RESUMO

Near-field enhanced mid-infrared light-matter interactions via metallic plasmonic antennae (PA) have attracted much attention but are inevitably limited by the detuning between their narrow band and the broad applied spectral range. Here, we develop a new low-temperature incubation synthetic method to acquire uniform Ag microparticles (MPs) with numerous hotspots. Their plasmonic band is remarkably extended by the plasmonic coupling of numerous hotspots and covers the entire mid-infrared range (400-4000 cm-1). Hence, the almost complete molecular fingerprint of 4-mercaptobenzonitrile was successfully probed for the first time via resonant surface-enhanced infrared absorption (rSEIRA), and the rSEIRA spectra of different essential amino acids were further detected and exhibit a high spectral identification degree assisted by machine learning. This work changes the inertia perception of "narrow band and large size but small hotspot area" of mid-infrared metallic PA and paves the way for the ultrasensitive mid-infrared optical sensing.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38695863

RESUMO

Human breast milk contains lactic acid bacteria (LAB), which have an important influence on the composition of the intestinal microbia of infants. In this study, one strain of an α-hemolytic species of the genus Streptococcus, IMAU99199T, isolated from the breast milk of a healthy nursing mother in Hohhot city PR China, was studied to characterise its taxonomic status using phenotypic and molecular taxonomic methods. The results indicated that it represented a member of the mitis-suis clade, pneumoniae subclade of the genus Streptococcus. It is a Gram-stain-positive, catalase-negative and oxidase-negative bacterium, and the cells are globular, paired or arranged in short chains. The results of a phylogenetic analysis of its 16S rRNA gene and two housekeeping genes (gyrB and rpoB) placed it in the genus Streptococcus. A phylogenetic tree based on 135 single-copy genes sequences indicated that IMAU99199T formed a closely related branch well separated from 'Streptococcus humanilactis' IMAU99125, 'Streptococcus bouchesdurhonensis' Marseille Q6994, Streptococcus mitis NCTC 12261T, 'Streptococcus vulneris' DM3B3, Streptococcus toyakuensis TP1632T, Streptococcus pseudopneumoniae ATCC BAA-960T and Streptococcus pneumoniae NCTC 7465T. IMAU99199T and 'S. humanilactis' IMAU99125 had the highest average nucleotide identity (93.7 %) and digital DNA-DNA hybridisation (55.3 %) values, which were below the accepted thresholds for novel species. The DNA G+C content of the draft genome of IMAU99199T was 39.8 %. The main cellular fatty acids components of IMAU99199T were C16 : 0 and C16 : 1ω7. It grew at a temperature range of 25-45 °C (the optimum growth temperature was 37 °C) and a pH range of 5.0-8.0 (the optimum growth pH was 7.0). These data indicate that strain IMAU99199T represents a novel species in the genus Streptococcus, for which the name Streptococcus hohhotensis sp. nov. is proposed. The type strain is IMAU99199T (=GDMCC 1.1874T=KCTC 21155T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Leite Humano , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Streptococcus , RNA Ribossômico 16S/genética , Humanos , Feminino , China , DNA Bacteriano/genética , Leite Humano/microbiologia , Streptococcus/genética , Streptococcus/isolamento & purificação , Streptococcus/classificação , Ácidos Graxos/análise , Hibridização de Ácido Nucleico , Genes Bacterianos
4.
J Appl Microbiol ; 135(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39152088

RESUMO

AIMS: Carbon source is a necessary nutrient for bacterial strain growth. In industrial production, the cost of using different carbon sources varies greatly. Moreover, the complex environment in space may cause metabolic a series of changes in the strain, and this method has been successfully applied in some basic research. To date, space mutagenesis is still limited number of studies, particularly in carbon metabolism of probiotics. METHODS AND RESULTS: HG-R7970-41 was isolated from bacterium suspension (Probio-M9) after space flight, which can produce capsular polysaccharide after space mutagenesis. Phenotype Microarray (PM) was used to evaluated the metabolism of HG-R7970-41 in 190 single carbon sources. RNA sequencing and total protein identification of two strains revealed their different carbon metabolism mechanisms. PM results demonstrated the metabolism of 10 carbon sources were different between Probio-M9 and HG-R7970-41. Transcriptomic and proteomic analyses revealed that this change in carbon metabolism of HG-R7970-41 mainly related to changes in phosphorylation and the glycolysis pathway. Based on the metabolic mechanism of different carbon sources and related gene cluster analysis, we found that the final metabolic activities of HG-R7970-41 and Probio-M9 were mainly regulated by PTS-specific membrane embedded permease, carbohydrate kinase and two rate-limiting enzymes (phosphofructokinase and pyruvate kinase) in the glycolysis pathway. The expanded culture test also confirmed that HG-R7970-41 had different metabolic characteristics from original strain. CONCLUSIONS: These results suggested that space environment could change carbon metabolism of Probio-M9. The new isolate (HG-R7970-41) showed a different carbon metabolism pattern from the original strain mainly by the regulation of two rate-limiting enzymes.


Assuntos
Carbono , Lacticaseibacillus rhamnosus , Carbono/metabolismo , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/metabolismo , Lacticaseibacillus rhamnosus/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Mutação , Mutagênese , Proteômica , Probióticos/metabolismo , Transcriptoma
5.
J Nanobiotechnology ; 22(1): 267, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764014

RESUMO

Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPSL.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPSL.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPSL. p-delivered OVA compared to OVA alone. Notably, NAPSL.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPSL.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPSL.p-based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPSL.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.


Assuntos
Adjuvantes Imunológicos , Melanoma Experimental , Camundongos Endogâmicos C57BL , Ovalbumina , Probióticos , Animais , Ovalbumina/imunologia , Ovalbumina/química , Camundongos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Probióticos/farmacologia , Melanoma Experimental/imunologia , Feminino , Células Dendríticas/imunologia , Receptor 4 Toll-Like/metabolismo , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/química , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Humanos , Nanopartículas/química , Linfócitos T CD4-Positivos/imunologia
6.
Proc Natl Acad Sci U S A ; 118(15)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33833056

RESUMO

Embryonic stem cells (ESCs) and induced pluripotent stem cells have the potential to differentiate to all cell types of an adult individual and are useful for studying development and for translational research. However, extrapolation of mouse and human ESC knowledge to deriving stable ESC lines of domestic ungulates and large livestock species has been challenging. In contrast to ESCs that are usually established from the blastocyst, mouse expanded potential stem cells (EPSCs) are derived from four-cell and eight-cell embryos. We have recently used the EPSC approach and established stem cells from porcine and human preimplantation embryos. EPSCs are molecularly similar across species and have broader developmental potential to generate embryonic and extraembryonic cell lineages. We further explore the EPSC technology for mammalian species refractory to the standard ESC approaches and report here the successful establishment of bovine EPSCs (bEPSCs) from preimplantation embryos of both wild-type and somatic cell nuclear transfer. bEPSCs express high levels of pluripotency genes, propagate robustly in feeder-free culture, and are genetically stable in long-term culture. bEPSCs have enriched transcriptomic features of early preimplantation embryos and differentiate in vitro to cells of the three somatic germ layers and, in chimeras, contribute to both the embryonic (fetal) and extraembryonic cell lineages. Importantly, precise gene editing is efficiently achieved in bEPSCs, and genetically modified bEPSCs can be used as donors in somatic cell nuclear transfer. bEPSCs therefore hold the potential to substantially advance biotechnology and agriculture.


Assuntos
Bovinos/genética , Células-Tronco Embrionárias/citologia , Técnicas de Transferência Nuclear/veterinária , Cultura Primária de Células/métodos , Animais , Blastocisto/citologia , Linhagem da Célula , Células Cultivadas , Células-Tronco Embrionárias/metabolismo , Cultura Primária de Células/veterinária , Transcriptoma
7.
Biol Reprod ; 108(6): 887-901, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-37040346

RESUMO

The mule is the interspecific hybrid of horse and donkey and has hybrid vigor in muscular endurance, disease resistance, and longevity over its parents. Here, we examined adult fibroblasts of mule (MAFs) compared with the cells from their parents (donkey adult fibroblasts and horse adult fibroblasts) (each species has repeated three independent individuals) in proliferation, apoptosis, and glycolysis and found significant differences. We subsequently derived mule, donkey, and horse doxycycline (Dox)-independent induced pluripotent stem cells (miPSCs, diPSCs, and hiPSCs) from three independent individuals of each species and found that the reprogramming efficiency of MAFs was significantly higher than that of cells of donkey and horse. miPSCs, diPSCs, and hiPSCs all expressed the high levels of crucial endogenous pluripotency genes such as POU class 5 homeobox 1 (POU5F1, OCT4), SRY-box 2 (SOX2), and Nanog homeobox (NANOG) and propagated robustly in single-cell passaging. miPSCs exhibited faster proliferation and higher pluripotency and differentiation than diPSCs and hiPSCs, which were reflected in co-cultures and separate-cultures, teratoma formation, and chimera contribution. The establishment of miPSCs provides a unique research material for the investigation of "heterosis" and perhaps is more significant to study hybrid gamete formation.


Assuntos
Células-Tronco Pluripotentes Induzidas , Cavalos , Animais , Reprogramação Celular , Equidae , Células Cultivadas , Diferenciação Celular/genética , Fibroblastos , Fator 3 de Transcrição de Octâmero/genética
8.
Horm Metab Res ; 55(12): 876-884, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37820700

RESUMO

Circular RNAs (circRNAs) participate in the progression of human cancers and have been broadly elucidated. Here, we aimed to elucidate the roles and functional mechanisms of hsa_circ_0080608 (circ_0080608) in lung cancer. Quantitative real-time PCR (qPCR) was performed to assess the mRNA expression levels of circ_0080608, miR-661, and adrenoceptor alpha 1A (ADRA1A). Western blotting was performed to measure ADRA1A protein levels. CCK-8, colony formation, and Transwell assays were performed to determine the effect of circ_0080608 on cell proliferation and migration. Animal models were used to assess how circ_0080608 influences tumor progression in vivo. The binding relationships of miR-661's with circ_0080608 and ADRA1A was confirmed using dual-luciferase reporter and RIP assays. Circ_0080608 exhibited relatively low expression in lung cancer samples and cells. Lung cancer cells overexpressing circ_0080608 exhibited reduced migratory and proliferative abilities. Additionally, circ_0080608 binds to miR-661 and operates as a competing endogenous RNA (ceRNA) and shares a miR-661 binding site with the 3' UTR of ADRA1A. Furthermore, circ_0080608 inversely regulates miR-661 expression, consequently restraining the aggressive behavior of lung cancer cells. Lung cancer cells overexpressing ADRA1A also exhibit repressed migratory and proliferative abilities. However, reintroduction of miR-661 led to a decline in ADRA1A expression, thereby attenuating the functional effects of ADRA1A. Circ_0080608 impedes lung cancer progression by regulating the miR-661/ADRA1A pathway. Our findings provide new insights into the progression of lung cancer.


Assuntos
Neoplasias Pulmonares , MicroRNAs , RNA Circular , Receptores Adrenérgicos alfa 1 , Animais , Humanos , Regiões 3' não Traduzidas , Bioensaio , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Receptores Adrenérgicos alfa 1/metabolismo , RNA Circular/metabolismo
9.
Environ Sci Technol ; 57(30): 11173-11184, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37462533

RESUMO

Brown carbon (BrC) is one of the most mysterious aerosol components responsible for global warming and air pollution. Iron (Fe)-induced catalytic oxidation of ubiquitous phenolic compounds has been considered as a potential pathway for BrC formation in the dark. However, the reaction mechanism and product composition are still poorly understood. Herein, 13 phenolic precursors were employed to react with Fe under environmentally relevant conditions. Using Fourier transform ion cyclotron resonance mass spectrometry, a total of 764 unique molecular formulas were identified, and over 85% of them can be found in atmospheric aerosols. In particular, products derived from precursors with catechol-, guaiacol-, and syringol-like-based structures can be distinguished by their optical and molecular characteristics, indicating the structure-dependent formation of BrC from phenolic precursors. Multiple pieces of evidence indicate that under acidic conditions, the contribution of either autoxidation or oxygen-induced free radical oxidation to BrC formation is extremely limited. Ligand-to-Fe charge transfer and subsequent phenoxy radical coupling reactions were the main mechanism for the formation of polymerization products with high molecular diversity, and the efficiency of BrC generation was linearly correlated with the ionization potential of phenolic precursors. The present study uncovered how chemically diverse BrC products were formed by the Fe-phenolic compound reactions at the molecular level and also provide a new paradigm for the study of the atmospheric aerosol formation mechanism.


Assuntos
Poluentes Atmosféricos , Compostos de Ferro , Carbono , Aerossóis/análise , Compostos de Ferro/análise , Ferro , Guaiacol/análise , Poluentes Atmosféricos/análise
10.
Environ Sci Technol ; 57(49): 20595-20604, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38007712

RESUMO

Microbial reduction plays a crucial role in Hg redox and the global cycle. Although intracellular Hg(II) reduction mediated by MerA protein is well documented, it is still unclear whether or how bacteria reduce Hg(II) extracellularly without its internalization. Herein, for the first time, we discovered the extracellular reduction of Hg(II) by a widely distributed aerobic marine bacterium Alteromonas sp. KD01 through a superoxide-dependent mechanism. The generation of superoxide by Alteromonas sp. KD01 was determined using 3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide and methyl cypridina luciferin analogue as probes via UV-vis and chemiluminescence detection, respectively. The results demonstrated that Hg(II) reduction was inhibited by superoxide scavengers (superoxide dismutase (SOD) and Cu(NO3)2) or inhibitors of reduced nicotinamide adenine dinucleotide (NADH) oxidoreductases. In contrast, the addition of NADH significantly improved superoxide generation and, in turn, Hg(II) reduction. Direct evidence of superoxide-mediated Hg(II) reduction was provided by the addition of superoxide using KO2 in deionized water and seawater. Moreover, we observed that even superoxide at an environmental concentration of 9.6 ± 0.5 nM from Alteromonas sp. KD01 (5.4 × 106 cells mL-1) was capable of significantly reducing Hg(II). Our findings provide a greater understanding of Hg(II) reduction by superoxide from heterotrophic bacteria and eukaryotic phytoplankton in diverse aerobic environments, including surface water, sediment, and soil.


Assuntos
Alteromonas , Mercúrio , Superóxidos/metabolismo , Alteromonas/metabolismo , NAD/metabolismo , Bactérias/metabolismo , Água
11.
Phys Chem Chem Phys ; 25(38): 25899-25924, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37746773

RESUMO

Semiconductor photocatalysis has become an increasing area of interest for use in water treatment methods. This review systematically presents the recent developments of emerging semiconductor photocatalysis system and their application in the removal of water pollutants. A brief overview of the semiconductor photocatalysis mechanism involved with the generation of reactive oxygen species (ROS) is provided first. Then a detailed explanation of the development of TiO2-based, g-C3N4-based, and bismuth-based semiconductor materials and their applications in the degradation of water pollutants are highlighted with recent illustrative examples. Furthermore, the future prospects of semiconductor photocatalysis for water treatment are critically analyzed.

12.
Pharmacoepidemiol Drug Saf ; 32(4): 416-425, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36305574

RESUMO

PURPOSE: We explored the adverse drug reaction signals of drug-induced neutropenia (DIN) and drug-induced agranulocytosis (DIA) in hospitalized patients and evaluated the novelty of these correlations. METHOD: A two-step method was established to identify the relationship between drugs and DIN or DIA using 5-year electronic medical records (EMRs) obtained from 242 000 patients at Qilu Hospital of Shandong University. First, the drugs suspected to induce DIN or DIA were selected. The associations between suspected drugs and DIN or DIA were evaluated by a retrospective cohort study using unconditional logistic regression analysis and multiple linear regression model. RESULTS: Twelve suspected drugs (vancomycin, meropenem, voriconazole, acyclovir, ganciclovir, fluconazole, oseltamivir, linezolid, compound borax solution, palonosetron, polyene phosphatidylcholine, and sulfamethoxazole) were associated with DIN, and six suspected drugs (vancomycin, voriconazole, acyclovir, ganciclovir, fluconazole, and oseltamivir) were associated with DIA. The multivariate linear regression model revealed that nine drugs (vancomycin, meropenem, voriconazole, ganciclovir, fluconazole, oseltamivir, compound borax solution, palonosetron, and polyene phosphatidylcholine) and four drugs (vancomycin, voriconazole, ganciclovir, and fluconazole) were found to be associated with DIN and DIA, respectively. While logistic regression analysis revealed that palonosetron and ganciclovir were associated with DIN and DIA, respectively. CONCLUSION: Palonosetron and ganciclovir were found to be correlated with drug-induced granulocytopenia. The results of this study provide an early warning of drug safety signals for drug-induced granulocytopenia, facilitating a quick and appropriate response for clinicians.


Assuntos
Agranulocitose , Neutropenia , Trombocitopenia , Idoso , Humanos , Agranulocitose/induzido quimicamente , Agranulocitose/epidemiologia , Agranulocitose/diagnóstico , Registros Eletrônicos de Saúde , Neutropenia/induzido quimicamente , Neutropenia/diagnóstico , Neutropenia/epidemiologia , Trombocitopenia/induzido quimicamente , Vancomicina/efeitos adversos , Meropeném/efeitos adversos , Voriconazol/efeitos adversos , Aciclovir/efeitos adversos , Ganciclovir/efeitos adversos , Palonossetrom/efeitos adversos
13.
Artigo em Inglês | MEDLINE | ID: mdl-37971440

RESUMO

Objective: To assess the effectiveness and benefits of retrospective outcome special attention nursing in providing continuous care for patients with heart failure during a vulnerable period. Methods: 96 patients with heart failure discharged from the hospital between January 2021 and January 2022 were included in the study. Patients discharged from January 2021 to June 2021 (48 cases) formed the single group, while those from July 2021 to January 2022 (48 cases) constituted the combined group. The single group received standard continuous nursing, while the combined group underwent retrospective outcome special attention nursing intervention in addition to standard care. Following the interventions, cardiac function-related indicators, negative emotions, self-management ability, health behavior, quality of life, and readmission rates were compared between the two groups. Results: Following the intervention, the combined group exhibited significant improvements, including enhanced 6-minute walk test (6MWT) results (P < .05) and lower scores on the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) (P < .05), indicating reduced anxiety and depression levels. The combined group also demonstrated superior self-management abilities, with higher scores in health behavior dimensions (nutrition, exercise, health responsibility, stress coping) and a higher overall self-management score (P < .05). However, the combined group had lower quality of life scores (P < .05). Notably, the combined group's readmission rate was significantly lower at 14.58% (7/48), compared to 33.33% (16/48) in the single group (P < .05). Conclusion: Retrospective outcome special attention nursing improves cardiac function, emotional regulation, self-management, health behaviors, quality of life, and reduces readmission rates in heart failure patients during vulnerable periods.

14.
Prev Chronic Dis ; 20: E61, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37441752

RESUMO

INTRODUCTION: Adults with severe obesity are at increased risk for poor metabolic health and may need more intensive clinical and community supports. The prevalence of severe obesity is underestimated from self-reported weight and height data. We examined severe obesity prevalence among US adults by sociodemographic characteristics and by state after adjusting for self-report bias. METHODS: Using a validated bias-correction method, we adjusted self-reported body mass index (BMI) data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS) by using measured data from the National Health and Nutrition Examination Survey. We compared bias-corrected prevalence of severe obesity (BMI ≥40) with self-reported estimates by sociodemographic characteristics and state. RESULTS: Self-reported BRFSS data significantly underestimated the prevalence of severe obesity compared with bias-corrected estimates. In 2020, 8.8% of adults had severe obesity based on the bias-corrected estimates, whereas 5.3% of adults had severe obesity based on self-reported data. Women had a significantly higher prevalence of bias-corrected severe obesity (11.1%) than men (6.5%). State-level prevalence of bias-corrected severe obesity ranged from 5.5% (Massachusetts) to 13.2% (West Virginia). Based on bias-corrected estimates, 16 states had a prevalence of severe obesity greater than 10%, a level not seen in the self-reported estimates. CONCLUSION: Self-reported BRFSS data underestimated the overall prevalence of severe obesity by 40% (5.3% vs 8.8%). Accurate state-level estimates of severe obesity can help public health and health care decision makers prioritize and plan to implement effective prevention and treatment strategies for people who are at high risk for poor metabolic health.


Assuntos
Obesidade Mórbida , Masculino , Humanos , Adulto , Feminino , Estados Unidos/epidemiologia , Obesidade Mórbida/epidemiologia , Índice de Massa Corporal , Autorrelato , Prevalência , Inquéritos Nutricionais , Obesidade/epidemiologia
15.
Pestic Biochem Physiol ; 192: 105390, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37105629

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD, a Fe(II)/α-ketoglutarate dependent oxygenases), is a popular herbicide target. In this work, two pharmacophore models based on common molecular characteristics (HipHop) and receptor-ligand complex (CBP) were generated for virtual screening for HPPD inhibitors. About 1,000,000 molecules containing diketone structure from PubChem were filtered by Lipinski's rules to build a 3D database. Then the database was screened through combining HipHop model, CBP model, ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction and molecular docking. Subsequently, based on the specific binding mode and affinity of HPPD inhibitors, 4 molecules with high -CDOCKER energy, good aqueous solubility and human safety predicative properties values were screened. From the screening results and combined with previous work, three novel HPPD inhibitors were designed and synthesized through fragment splicing and bioisosterism strategies. Compound IV-a exhibited similar inhibition of Arabidopsis thaliana HPPD (AtHPPD) and herbicidal activity as mesotrione. Crop selectivity showed that compound IV-a had better crop safety than mesotrione. Comparing the molecular properties, ADMET and molecular docking studies indicated that compounds IV-a exhibited better properties than mesotrione, which could be further modified as novel HPPD inhibitor herbicides.


Assuntos
Arabidopsis , Herbicidas , Humanos , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Cicloexanonas/farmacologia , Herbicidas/farmacologia , Herbicidas/química , Estrutura Molecular , Inibidores Enzimáticos/farmacologia
16.
Pestic Biochem Physiol ; 196: 105588, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37945239

RESUMO

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is the last common enzyme in the biosynthetic pathway in the synthesis of heme and chlorophyll. The high-frequency use of PPO inhibitor herbicides has led to the gradual exposure of pesticide damage and resistance problems. In order to solve this kind of problem, there is an urgent need to develop new PPO inhibitor herbicides. In this paper, 16 phenylpyrazole derivatives were designed by the principle of active substructure splicing through the electron isosterism of five-membered heterocycles. Greenhouse herbicidal activity experiments and in vitro PPO activity experiments showed that the inhibitory effect of compound 9 on weed growth was comparable to that of pyraflufen-ethyl. Crop safety experiments and cumulative concentration experiments in crops showed that when the spraying concentration was 300 g ai/ha, wheat, corn, rice and other cereal crops were more tolerant to compound 9, among which wheat showed high tolerance, which was comparable to the crop safety of pyraflufen-ethyl. Herbicidal spectrum experiments showed that compound 9 had inhibitory activity against most weeds. Molecular docking results showed that compound 9 formed one hydrogen bond interaction with amino acid residue ARG-98 and two π-π stacking interactions with amino acid residue PHE-392, indicating that compound 9 had better herbicidal activity than pyraflufen-ethyl. It shows that compound 9 is expected to be a lead compound of phenylpyrazole PPO inhibitor herbicide and used as a herbicide in wheat field.


Assuntos
Herbicidas , Herbicidas/química , Protoporfirinogênio Oxidase , Simulação de Acoplamento Molecular , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Aminoácidos , Relação Estrutura-Atividade
17.
Molecules ; 28(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36615581

RESUMO

In this study, Co-doped TiO2 was synthesized using waste tobacco stem silk (TSS) as a template via a one-pot impregnation method. These samples were characterized using various physicochemical techniques such as N2 adsorption/desorption analysis, diffuse reflectance UV-visible spectroscopy, X-ray diffraction, field-emission scanning electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, photoluminescence spectroscopy, and electron paramagnetic resonance spectroscopy. The synthesized material was used for the photodegradation of tetracycline hydrochloride (TCH) under visible light (420-800 nm). No strong photodegradation activity was observed for mesoporous TiO2 synthesized using waste TSS as a template, mesoporous Co-doped TiO2, or TiO2. In contrast, Co-doped mesoporous TiO2 synthesized using waste TSS as a template exhibited significant photocatalytic degradation, with 86% removal of TCH. Moreover, owing to the unique chemical structure of Ti-O-Co, the energy gap of TiO2 decreased. The edge of the absorption band was redshifted, such that the photoexcitation energy for generating electron-hole pairs decreased. The electron-hole separation efficiency improved, rendering the microstructured biotemplated TiO2 a much more efficient catalyst for the visible-light degradation of TCH.


Assuntos
Nicotiana , Tetraciclina , Luz , Antibacterianos/química , Titânio/química , Catálise
18.
J Sci Food Agric ; 103(11): 5547-5559, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37052266

RESUMO

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) herbicides control broadleaf and gramineous weeds with better crop safety for corn, sorghum and wheat. Multiple screening models in silico have been established to obtain novel lead compounds as HPPD inhibition herbicides. RESULTS: Topomer comparative molecular field analysis (CoMFA) combined with topomer search technology and Bayesian, genetic approximation functions (GFA) and multiple linear regression (MLR) models generated by calculating different descriptors were constructed for the quinazolindione derivatives of HPPD inhibitors. The coefficient of determination (r2 ) of topomer CoMFA, MLR and GFA were 0.975, 0.970 and 0.968, respectively; all the models established displayed excellent accuracy and high predictive capacity. Five compounds with potential HPPD inhibition were obtained via screening fragment library combined with the validation of the above models and molecular docking studies. After molecular dynamics (MD) validation and absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction, the compound 2-(2-amino-4-(4H-1,2,4-triazol-4-yl) benzoyl)-3-hydroxycyclohex-2-en-1-one not only exhibited stable interactions with the protein but also high solubility and low toxicity, and has potential as a novel HPPD inhibition herbicide. CONCLUSION: In this study, five compounds were obtained through multiple quantitative structure-activity relationship screening. Molecular docking and MD experiments showed that the constructed approach had good screening ability for HPPD inhibitors. This work provided molecular structural information for developing novel, highly efficient and low-toxicity HPPD inhibitors. © 2023 Society of Chemical Industry.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase , Herbicidas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Teorema de Bayes , Herbicidas/farmacologia , Herbicidas/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Estrutura Molecular
19.
J Cell Mol Med ; 26(18): 4792-4804, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35971640

RESUMO

Many progresses have recently been achieved in animal somatic cell nuclear transfer (SCNT). However, embryos derived from SCNT rarely result in live births. Single-cell RNA sequencing (scRNA-seq) can be used to investigate the development details of SCNT embryos. Here, bovine fibroblasts and three factors bovine iPSCs (3F biPSCs) were used as donors for bovine nuclear transfer, and the single blastomere transcriptome was analysed by scRNA-seq. Compared to in vitro fertilization (IVF) embryos, SCNT embryos exhibited many defects. Abnormally expressed genes were found at each stage of embryos, which enriched in metabolism, and epigenetic modification. The DEGs of the adjacent stage in SCNT embryos did not follow the temporal expression pattern similar to that of IVF embryos. Particularly, SCNT 8-cell stage embryos showed failures in some gene activation, including ZSCAN4, and defects in protein association networks which cored as POLR2K, GRO1, and ANKRD1. Some important signalling pathways also showed incomplete activation at SCNT zygote to morula stage. Interestingly, 3F biPSCNT embryos exhibited more dysregulated genes than SCNT embryos at zygote and 2-cell stage, including genes in KDM family. Pseudotime analysis of 3F biPSCNT embryos showed the different developmental fate from SCNT and IVF embryos. These findings suggested partial reprogrammed 3F biPS cells as donors for bovine nuclear transfer hindered the reprogramming of nuclear transfer embryos. Our studies revealed the abnormal gene expression and pathway activation of SCNT embryos, which could increase our understanding of the development of SCNT embryos and give hints to improve the efficiency of nuclear transfer.


Assuntos
Clonagem de Organismos , Técnicas de Transferência Nuclear , Animais , Bovinos , Reprogramação Celular/genética , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/genética , Fertilização in vitro , Análise de Sequência de RNA , Transcriptoma
20.
Biochem Biophys Res Commun ; 606: 23-28, 2022 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35338855

RESUMO

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerging infectious disease currently spreading across the world. The spike (S) protein plays a key role in the receptor recognition and cell membrane fusion, making it an important target for developing vaccines, therapeutic antibodies and diagnosis. In this study, we constructed a baculovirus surface display system that efficiently presents both SARS-CoV and SARS-CoV-2 S proteins (including ectodomain, S1 subunit and receptor-binding-domain, RBD) on the surface of recombinant baculoviruses, utilizing transmembrane anchors from gp64 (signal peptide) and vesicular stomatitis virus (VSV). These recombinant baculoviruses were capable of transducing engineered HEK 293T cells overexpressing ACE2 receptors with significantly higher transduction efficiencies, indicating that S proteins displayed on baculovirus surface have antigenicity and can recognize and bind ACE2 receptors. Additionally, the transduction of SARS-CoV-2 S proteins can be inhibited by an antibody against the SARS-CoV-2 RBD. These results demonstrate that this baculovirus surface display system is a promising tool for developing antibodies, vaccines and recombinant protein production.


Assuntos
COVID-19 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Enzima de Conversão de Angiotensina 2/genética , Baculoviridae/genética , Baculoviridae/metabolismo , Humanos , Ligação Proteica , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química
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