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1.
Micromachines (Basel) ; 15(8)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39203608

RESUMO

The thermal-controlled fracture method has been increasingly focused upon in the high-quality cutting of advanced ceramic materials due to its excellent characteristics. The successful application of this method in cutting ceramics mainly depends on the volumetric heating effect. However, most ceramics are treated using the surface heating mode. For the surface heating mode, the processing quality, including fracture trajectory and fracture quality, is far lower than the industrial application standards. This work was conducted to reveal the mechanism of this processing quality. Experiments involving cutting ceramics in single-surface heating mode indicate that the fracture trajectories of the upper and lower surfaces display a significant inconsistency, and the fracture quality is worse than that using the dual-surface heating mode. A cutting model was established to calculate the thermal stress distribution and to simulate the crack-propagation behaviors. The simulation results show good agreement with the experiment and provide the stress distribution, and are used to understand the reason for the processing quality problem. The mechanism of the trajectory deviation and uneven distribution of the fracture quality is revealed based on the simulation and calculation results. This study helps provide a deep understanding of the processing problems arising from this method and thus helps to innovate high-quality processing methods in this field.

2.
Bioorg Chem ; 149: 107477, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38820938

RESUMO

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis targeting chimeras (PROTACs) emerge as a promising approach to overcome the limitations of FLT3 inhibitors, while the development of orally bioavailable FLT3-PROTACs faces great challenges. Here, we report the rational design and evaluation of a series of Gilteritinib-based FLT3-PROTACs. Among them, B3-2 exhibited the strongest antiproliferative activity against FLT3-ITD mutant AML cells, and significantly induced FLT3-ITD protein degradation. Mechanistic investigations demonstrated that B3-2 induced FLT3-ITD degradation in a ubiquitin-proteasome-dependent manner. More importantly, B3-2 exhibited an oral bioavailability of 5.65%, and oral administration of B3-2 showed good antitumor activity in MV-4-11 xenograft models. Furthermore, B3-2 showed strong antiproliferative activity against FLT3 resistant mutations, highlighting its potential in overcoming drug resistance.


Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia Mieloide Aguda , Inibidores de Proteínas Quinases , Pirazinas , Tirosina Quinase 3 Semelhante a fms , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Pirazinas/química , Pirazinas/farmacologia , Pirazinas/síntese química , Proliferação de Células/efeitos dos fármacos , Animais , Relação Estrutura-Atividade , Estrutura Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Camundongos , Descoberta de Drogas , Tiofenos/química , Tiofenos/farmacologia , Tiofenos/síntese química , Proteólise/efeitos dos fármacos , Compostos de Anilina/química , Compostos de Anilina/farmacologia , Compostos de Anilina/síntese química , Linhagem Celular Tumoral , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismo
3.
J Mater Chem B ; 12(24): 5861-5868, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38775046

RESUMO

The development of a simple, rapid, and sensitive technology for the simultaneous detection of mycotoxins is of great significance in ensuring the safety of foods and drugs. Herein, a fluorescence aptasensor with high sensitivity and reproducibility for the simultaneous detection of aflatoxin B1 (AFB1) and ochratoxin A (OTA) was developed. In this sensing system, AFB1 and OTA aptamers were co-immobilized on the surface of magnetic beads (MBs) to form a Y-shaped structure through the principle of complementary base pairing, and were used as recognition probes to specifically capture the target. Activators regenerated by electron transfer for atom transfer radical polymerization (ARGET ATRP) was used as a signal amplification strategy to improve the sensitivity. The initiator modified at the end of an antibody initiates the ARGET ATRP reaction. Different fluorescence signals were designed to achieve the simultaneous detection of OTA and AFB1 with limits of 426.18 and 79.55 fg mL-1 for AFB1 and OTA, respectively. In addition, experiments were conducted on three types of samples, and the recoveries of the two mycotoxins ranged from 87.30% to 109.50%, with relative standard deviations ranging from 0.50% to 4.92% under reproducible conditions. The results suggest that the developed aptasensor is sufficient to meet the different regulatory requirements of the two mycotoxins in food and drug safety and shows great potential.


Assuntos
Aflatoxina B1 , Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Ocratoxinas , Aflatoxina B1/análise , Ocratoxinas/análise , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , DNA/química , Polimerização , Limite de Detecção , Transporte de Elétrons
4.
BMC Vet Res ; 20(1): 180, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715028

RESUMO

BACKGROUND: Infectious bovine rhinotracheitis (IBR), caused by Bovine alphaherpesvirus-1 (BoAHV-1), is an acute, highly contagious disease primarily characterized by respiratory tract lesions in infected cattle. Due to its severe pathological damage and extensive transmission, it results in significant economic losses in the cattle industry. Accurate detection of BoAHV-1 is of paramount importance. In this study, we developed a real-time fluorescent quantitative PCR detection method for detecting BoAHV-1 infections. Utilizing this method, we tested clinical samples and successfully identified and isolated a strain of BoAHV-1.1 from positive samples. Subsequently, we conducted a genetic evolution analysis on the isolate strain's gC, TK, gG, gD, and gE genes. RESULTS: The study developed a real-time quantitative PCR detection method using SYBR Green II, achieving a detection limit of 7.8 × 101 DNA copies/µL. Specificity and repeatability analyses demonstrated no cross-reactivity with other related pathogens, highlighting excellent repeatability. Using this method, 15 out of 86 clinical nasal swab samples from cattle were found to be positive (17.44%), which was higher than the results obtained from conventional PCR detection (13.95%, 12/86). The homology analysis and phylogenetic tree analysis of the gC, TK, gG, gD, and gE genes of the isolated strain indicate that the JL5 strain shares high homology with the BoAHV-1.1 reference strains. Amino acid sequence analysis revealed that gC, gE, and gG each had two amino acid mutations, while the TK gene had one synonymous mutation and one H to Y mutation, with no amino acid mutations observed in the gD gene. Phylogenetic tree analysis indicated that the JL5 strain belongs to the BoAHV-1.1 genotype and is closely related to American strains such as C33, C14, and C28. CONCLUSIONS: The established real-time fluorescent quantitative PCR detection method exhibits good repeatability, specificity, and sensitivity. Furthermore, genetic evolution analysis of the isolated BoAHV-1 JL-5 strain indicates that it belongs to the BoAHV-1.1 subtype. These findings provide a foundation and data for the detection, prevention, and control Infectious Bovine Rhinotracheitis.


Assuntos
Alphaherpesvirinae , Rinotraqueíte Infecciosa Bovina , Reação em Cadeia da Polimerase em Tempo Real , Rinotraqueíte Infecciosa Bovina/virologia , Animais , Bovinos , Alphaherpesvirinae/classificação , Alphaherpesvirinae/genética , Alphaherpesvirinae/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Sensibilidade e Especificidade , Manejo de Espécimes/veterinária , Filogenia
5.
J Med Chem ; 67(9): 7197-7223, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38655686

RESUMO

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader A20 with excellent pharmacokinetic properties was discovered through reasonable design. A20 selectively inhibited the proliferation of FLT3-ITD mutant acute myeloid leukemia (AML) cells and potently induced FLT3-ITD degradation through the ubiquitin-proteasome system. Notably, oral administration of A20 resulted in complete tumor regression on subcutaneous AML xenograft models. Furthermore, on systemic AML xenograft models, A20 could completely eliminate the CD45+CD33+ human leukemic cells in murine and significantly prolonged the survival time of mice. Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.


Assuntos
Antineoplásicos , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Inibidores de Proteínas Quinases , Tirosina Quinase 3 Semelhante a fms , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Humanos , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Administração Oral , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Proteólise/efeitos dos fármacos , Descoberta de Drogas , Ensaios Antitumorais Modelo de Xenoenxerto , Disponibilidade Biológica , Relação Estrutura-Atividade
6.
Enzyme Microb Technol ; 178: 110446, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38626535

RESUMO

Formaldehyde (FALD) has gained prominence as an essential C1 building block in the synthesis of valuable chemicals. However, there are still challenges in converting FALD into commodities. Recently, cell-free biocatalysis has emerged as a popular approach for producing such commodities. Acetoin, also known as 3-hydroxy-2-butanone, has been widely used in food, cosmetic, agricultural and the chemical industry. It is valuable to develop a process to produce acetoin from FALD. In this study, a cell-free multi-enzyme catalytic system for the production of acetoin using FALD as the substrate was designed and constructed. It included three scales: FALD utilization pathway, glycolysis pathway and acetoin synthesis pathway. After the optimization of the reaction system, 20.17 mM acetoin was produced from 122 mM FALD, with a yield of 0.165 mol/mol, reaching 99.0% of the theoretical yield. The pathway provides a new approach for high-yield acetoin production from FALD, which consolidates the foundation for the production of high value-added chemicals using cheap one-carbon compounds.


Assuntos
Acetoína , Biocatálise , Formaldeído , Acetoína/metabolismo , Formaldeído/metabolismo , Sistema Livre de Células
7.
Nano Lett ; 24(10): 3282-3289, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38421230

RESUMO

X-ray radiation information storage, characterized by its ability to detect radiation with delayed readings, shows great promise in enabling reliable and readily accessible X-ray imaging and dosimetry in situations where conventional detectors may not be feasible. However, the lack of specific strategies to enhance the memory capability dramatically hampers its further development. Here, we present an effective anion substitution strategy to enhance the storage capability of NaLuF4:Tb3+ nanocrystals attributed to the increased concentration of trapping centers under X-ray irradiation. The stored radiation information can be read out as optical brightness via thermal, 980 nm laser, or mechanical stimulation, avoiding real-time measurement under ionizing radiation. Moreover, the radiation information can be maintained for more than 13 days, and the imaging resolution reaches 14.3 lp mm-1. These results demonstrate that anion substitution methods can effectively achieve high storage capability and broaden the application scope of X-ray information storage.

8.
Plant Dis ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173266

RESUMO

Cucumis melo L. is an important fruit with widespread consumption and commercial value. However, an undescribed disease affecting Hami melon (Cucumis melo L. var. Luhoutian) plants has consistently emerged in the Qihe region of Dezhou, Shandong Province of China since 2021. The disease can occur in both seedling and mature stages of Hami melon plants, and in severely diseased areas, the incidence rate was seen as 40 to 80%. During the seedling stage, the initial symptom is the appearance of water-soaked spots on the leaves. As the disease progresses, the leaves develop necrotic spots, and severely affected plants may exhibit stem rot and decay. In the mature stage, the disease primarily affects the leaves, causing necrotic spots and chlorosis. Under conditions of high humidity, black mold can be observed in the affected areas. Small pieces of symptomatic leaves from six different infected plants were collected and surface-sterilized with 5% NaClO for 3 min and 75% alcohol for 30 s for pathogen isolation (Wang et al., 2020). After rinsing with sterile water and blotted on sterile filter paper, the tissues were established on potato dextrose agar (PDA) media and incubated at 28℃ for 3-4 days. Pure isolates showed up at PDA were obtained through single-spore isolation. Colonies of all 16 isolates obtained by single-spore isolation had similar morphological characteristics on the PDA medium, the mycelium of the isolate appears dense and yellowish-brown on the PDA medium, and also secretes a brownish-red pigment on PDA. Under the opticalmicroscope, the perithecia from PDA media are subglobose spherical in shape, 80-100 µm in diameter, brownish by reflected light, wholly and densely hairy. Terminal hairs are very dense, greyish by reflected light, olive brown to reddish brown by transmitted light, thick-walled, arcuate, circinate, or spirally coiled at the apex. The ascospores within the perithecia are elliptical or droplet-shaped, initially colorless hyaline but later becoming subhyaline slightly gray, with dimensions of 7-9 µm × 4-5 µm. The morphological characteristics of the isolates were consistent with the description of Arcopilus aureus (Wang et.al. 2016). The internal transcribed spacer (ITS) region and ß-tubulin genes of three randomly selected isolates were PCR amplified and sequenced using primers ITS4/ITS5 and Bt2a/Bt2b. The sequences of ITS and ß-tubulin genes were submitted to NCBI with GenBank Accession No. OR539527 and OR640972, respectively. Based on morphological features and phylogenetic analysis, we concluded that the isolates belonged to A. aureus. Pathogenicity tests were conducted by placing agar plugs-containing fungal mycelia and agar blocks (control) on leaves of Hami melon seedlings (n=12) grown at 28°C with 60% humidity in a greenhouse, the assay was repeated three times. Symptoms appeared on the pathogen-inoculated leaves seven days after inoculation, whereas the control treatment remained symptomless. The pathogens were reisolated from diseased leaves and identified as A. aureus based on morphological, and molecular phylogenetic analysis, while Koch'sostulate was used to confirm its life mode. To the best of our knowledge, this is the first report of leaf spot caused by A. aureus on Cucumis melo L. in China.

9.
Clinics (Sao Paulo) ; 78: 100297, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37924679

RESUMO

OBJECTIVES: This study explored the association between insomnia and the clinical outcome of large vessel occlusion Acute Ischemic Stroke (AIS) and attempted to explore its potential mechanisms from the perspectives of inflammation and oxidative stress. METHODS: AIS patients who underwent endovascular treatment for large vessel occlusion at Binzhou Central Hospital from 2018 to 2022 (n = 508) were included. Patients were divided into an insomnia group and a non-insomnia group. Insomnia was judged by self-reported Athens Insomnia Scale score. Regression analysis was used to compare the differences in the 24-hour and 7-day National Institutes of Health Stroke Scale (NIHSS) score, Early Neurological Deterioration (END), early adverse event incidence, 90-day prognosis and mortality, and serum biomarkers levels. RESULTS: The incidence of insomnia in the study population was 39.6% (n = 144, insomnia group; n = 364, non-insomnia group). Compared with the non-insomnia group, a worse prognosis outcome (63% vs. 49%, adjusted rate ratio: 1.8, 95% Confidence Interval: 1.2-3.7; p = 0.016), higher 24-h and 7-day NIHSS score (17 [9-36] vs. 13 [5-20]; p = 0.024, and 11 [4‒24) vs. 8 [2‒14]; p = 0.031, respectively), higher END (24% vs. 15%, p = 0.022), and higher incidence of adverse events were observed in the insomnia group (79% vs. 59%, p = 0.010). The 90-day mortality was higher in the insomnia group than that in the non-insomnia group (22% vs. 17%), however, such a difference was not statistically significant. CONCLUSION: Insomnia is closely related to the clinical outcome of AIS with large vessel occlusion, and inflammation and oxidative stress mechanisms may be involved.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Distúrbios do Início e da Manutenção do Sono , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia Encefálica/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Resultado do Tratamento , Trombectomia/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Inflamação , Estudos Retrospectivos
10.
Mikrochim Acta ; 190(11): 432, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37806989

RESUMO

An ochratoxin A (OTA) electrochemical biosensor based on a cascade signal amplification strategy with Ag nanoparticles (AgNPs) and ring opening polymerization (ROP) was constructed. The large specific surface area of AgNPs was used to increase the loading of OTA aptamer on the electrode surface, enhancing the ability to capture OTA as a way to achieve the first signal amplification. The OTA antibody modified with polyethylenimine specifically recognizes the OTA, forming an aptamer-OTA-antibody sandwich structure. The amino group on polyethylenimine initiates the ROP reaction with α-amino acid-n-carboxylic anhydride-ferrocene (NCA-Fc) as the monomer. A large number of electrochemical signal units of ferrocene are introduced into the sensing system for a second signal amplification. By amplifying the signal twice, the sensitivity of the sensor is improved. Under the optimal conditions, the detection range of the sensor is 1 pg·mL-1 ~ 1 µg·mL-1, while the detection limit is as low as 117 fg·mL-1. Moreover, the sensor has the advantages of high sensitivity, good stability and selectivity. Standard addition recovery experiment proved that the sensing system can be successfully used for the detection of OTA in four actual samples with recoveries in the range 90.0 to 113% with RSDs of 0.6 to 5.2%, providing a new idea for the pollution assessment of mycotoxins.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Metalocenos/química , Nanopartículas Metálicas/química , Polietilenoimina , Polimerização , Técnicas Eletroquímicas , Prata
11.
Front Microbiol ; 14: 1205297, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37588885

RESUMO

Mink circovirus disease caused by Mink Circovirus (MiCV) is a serious infectious disease of mink that has become prevalent in recent years in China, severely affecting the reproductive performance of mink and causing significant economic losses to farms. To date, there have been few studies on MiCV, its pathogenic mechanism is not clear, and there is no effective vaccine or drug to prevent and control the disease. Therefore, it is necessary to establish a rapid and reliable molecular diagnostic method, which would aid future studies of this novel virus. In our study, we developed a sensitive and specific TaqMan-based quantitative real-time PCR assay targeting the MiCV Cap gene. The assay showed no cross-reaction with other tested animal viruses. The assay is highly sensitive, with a detection limit of as low as 10 plasmid DNA copies and 2.38 × 10-2 pg of viral DNA. The intra and inter--assay coefficients of variation were both low. The positive detection rate of MiCV in clinical samples from minks, foxes, and raccoon dogs were 58.8% (133/226), 50.7% (72/142), and 42.2% (54/128), respectively, giving a total positive detection rate of 52.2% (259/496). Higher contamination levels were observed in samples from the environment in direct or indirect contact with animals, with a total positive detection rate of 75.1% (220/293). These epidemiological results showed that minks, foxes, and raccoon dogs had high infection rates of MiCV. This was also the first study to detect MiCV on the ground and equipment of fur-bearing animal farms. Our assay is highly sensitive and specific for the diagnosis and quantification of MiCV, and should provide a reliable real-time tool for epidemiological and pathogenetic study of MiCV infection.

12.
Bioorg Chem ; 138: 106645, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37327602

RESUMO

FLT3-ITD mutant has been extensively studied as a drug discovery target for acute myeloid leukemia. Based on our previous discovered FLT3 inhibitor (2), a series of urea group based indolone derivatives were designed, synthesized, and biological evaluated as novel FLT3 inhibitors for the treatment of FLT3-ITD positive AML. Among them, compound LC-3 exhibited potent inhibitory effects against FLT3 (IC50 = 8.4 nM) and significantly inhibited the proliferation of FLT3-ITD positive AML cells MV-4-11 (IC50 = 5.3 nM). In the cellular context, LC-3 strongly inhibited FLT3-mediated signaling pathways and induced cellular apoptosis by arresting cell cycle in G1 phase. In the in vivo studies, LC-3 significantly suppressed the tumor growth on MV-4-11 xenograft models (10 mg/kg/day, TGI = 92.16%) without exhibiting obvious toxicity. These results suggested that compound LC-3 might be a potential drug candidate for FLT3-ITD positive AML.


Assuntos
Leucemia Mieloide Aguda , Inibidores de Proteínas Quinases , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Apoptose , Transdução de Sinais , Descoberta de Drogas , Leucemia Mieloide Aguda/patologia , Tirosina Quinase 3 Semelhante a fms/metabolismo , Linhagem Celular Tumoral , Mutação , Proliferação de Células
13.
Front Pediatr ; 11: 1090919, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228431

RESUMO

Objective: To investigate the effectiveness of hip continuous passive motion (hCPM) on hip development at skeletal maturity and gross motor function for spastic cerebral palsy children with hip dysplasia. Methods: Prospective case-control research of hCPM with goal-directed training versus merely goal-directed training. On the basis of goal-directed training, the hCPM group used the hip joint CPM instrument (the external fixator was connected to the power device to make the hip joint carry out continuous passive movement) for 40-60 min, twice a day, and five times a week, and received continuous training for 8 weeks simultaneously. The control group received only goal-directed training for 8 weeks. Functional outcomes pertaining to the affected hip joints were assessed via gross motor function measure (GMFM), migration percentage (MP), acetabular index (AI), and Harris hip functional score (HHS) at the time of enrollment and the end of the intervention. Results: The case-control research included 65 participants (mean age = 46.20 months, SD = 17.09 months; Gross Motor Function Grading System level: III = 41, IV = 24) who were randomly selected to either the hCPM (n = 45) or the control group (n = 20). No differences were found in baseline (acquisition phase) GMFM, MP, AI, or HHS (t = -1.720, P = 0.090; t* = 1.836, P* = 0.071; t# = -1.517, P# = 0.139; t* = -1.310, P* = 0.195; t# = -1.084, P# = 0.097; t = -1.041, P = 0.301). At the 8-week follow-up, GMFM, MP, AI, and HHS significantly improved over baseline in the hCPM group (hCPM group: t = 18.59, 20.172*, 40.291#, 16.820*, 32.900#, 28.081; P < 0.001). Between-group differences at 8-week follow-up times points favored the hCPM group for GMFM (t = -2.637, P = 0.011), MP (t* = 2.615, P* = 0.014; t# = 3.000, P# = 0.006), AI (t* = 2.055, P* = 0.044; t# = 2.223, P# = 0.030), HHS (t = -4.685, P < 0.001) (*: left side; #: right side). Conclusion: Spastic cerebral palsy children with hip dysplasia achieved meaningful functional improvement after 8 weeks of goal-directed training with hCPM therapy.

14.
Food Chem Toxicol ; 177: 113854, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37230458

RESUMO

Xanthine oxidase (XO), a key enzyme in purine catabolism, catalyzes the oxidation of xanthine to uric acid in the body, but overproduction of uric acid may lead to hyperuricemia. This study aims to investigate in vitro XO inhibitory and in vivo anti-hyperuricemic properties of sodium kaempferol-3'-sulfonate (KS). The kinetic analysis indicates that KS is a reversible competitive inhibitor and has significant inhibitory effects on XO activity with an IC50 value of 0.338 µM. Fluorescence spectra suggested that KS could cause fluorescence quenching and conformational changes of XO due to the formation of a KS-XO complex. Molecular docking studies demonstrated that KS interacted with several amino acid residues of XO by the π-π stacking, hydrogen bonds, and hydrophobic interactions. The inhibitory mechanism of KS on XO activity might be the insertion of KS into the active site of XO to prevent the entrance of the substrate xanthine and induce conformational changes of XO. The results carried out in hyperuricemic mice showed that KS reduced serum XO activity, serum uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) levels, as well as alleviating renal histopathological injury. These findings suggest that KS may be a new potent XO inhibitor against hyperuricemia-related diseases.


Assuntos
Hiperuricemia , Ácido Úrico , Camundongos , Animais , Xantina Oxidase , Simulação de Acoplamento Molecular , Hiperuricemia/tratamento farmacológico , Quempferóis/farmacologia , Cinética , Inibidores Enzimáticos/química , Xantinas
15.
Appl Microbiol Biotechnol ; 107(12): 3911-3924, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37178309

RESUMO

Acetoin, an important and high-value added bio-based platform chemical, has been widely applied in fields of foods, cosmetics, chemical synthesis, and agriculture. Lactate is a significant intermediate short-chain carboxylate in the anaerobic breakdown of carbohydrates that comprise ~ 18% and ~ 70% in municipal wastewaters and some food processing wastewaters, respectively. In this work, a series of engineered Escherichia coli strains were constructed for efficient production of acetoin from cheaper and abundant lactate through heterogenous co-expression of fusion protein (α-acetolactate synthetase and α-acetolactate decarboxylase), lactate dehydrogenase and NADH oxidase, and blocking acetate synthesis pathways. After optimization of whole-cell bioconversion conditions, the engineered strain BL-11 produced 251.97 mM (22.20 g/L) acetoin with a yield of 0.434 mol/mol in shake flasks. Moreover, a titer of 648.97mM (57.18 g/L) acetoin was obtained in 30 h with a yield of 0.484 mol/mol lactic acid in a 1-L bioreactor. To the best of our knowledge, this is the first report on the production of acetoin from renewable lactate through whole-cell bioconversion with both high titer and yield, which demonstrates the economy and efficiency of acetoin production from lactate. Key Points • The lactate dehydrogenases from different organisms were expressed, purified, and assayed. • It is the first time that acetoin was produced from lactate by whole-cell biocatalysis. • The highest titer of 57.18 g/L acetoin was obtained with high theoretical yield in a 1-L bioreactor.


Assuntos
Acetoína , Ácido Láctico , Acetoína/metabolismo , Ácido Láctico/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Águas Residuárias , Reatores Biológicos , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo
16.
BMC Pediatr ; 23(1): 174, 2023 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-37060094

RESUMO

BACKGROUND: Several previous studies have identified a potential role that the gut microbiome can play in autism spectrum disorder (ASD) in children, but little is known about how variations in the virome may be involved in ASD. We aimed to understand the changes in the gut DNA virome of children with ASD. METHODS: A case-control study was presented, in which 13 two-children families were observed while considering the age, mode of birth, history of antibiotic use, and vaccination history to minimize the influence of confounding factors. DNA viral metagenomic sequencing was successfully performed on stool samples from 11 children with ASD and 12 healthy non-ASD children. The basic composition and gene function of the participants' fecal DNA virome were detected and analyzed. Finally, the abundance and diversity of the DNA virome of children with ASD and their healthy siblings were compared. RESULTS: The gut DNA virome in children aged 3-11 years was found to be dominated by the Siphoviridae family of Caudovirales. The proteins encoded by the DNA genes mainly carry out the functions of genetic information transmission and metabolism. Compared the gut DNA virome of ASD and healthy non-ASD children, their abundance of Caudovirales and Petitvirales both showed a significant negative correlation (r = -0.902, P < 0.01), there was no statistically significant difference in the relative abundance of viruses at the order and family levels, and a difference in the relative abundance at the genus level for Skunavirus (Ζ = -2.157, P = 0.031). Viral α diversity was reduced in children with ASD, but α diversity and ß diversity did not differ statistically between groups. CONCLUSIONS: This study indicates that elevated Skunavirus abundance and decreased α diversity in the gut DNA virulence group of children with ASD, but no statistically significant difference in the change in alpha and beta diversity. This provides preliminary cumulative information on virological aspects of the relationship between the microbiome and ASD, and should benefit future multi-omics and large sample studies on the gut microbes in children with ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Transtorno do Espectro Autista/genética , Estudos de Casos e Controles , Viroma , DNA
17.
Bioresour Technol ; 378: 129010, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37011842

RESUMO

A combined chemical-bacterial process was developed to convert vegetable straw waste to high value antifungal iturins. Straws from three widely cultivated vegetable (cucumber, tomato and pepper) were evaluated as feedstocks for iturin production. Microwave assisted hydrolysis with very dilute acid (0.2% w/w H2SO4) achieved efficient reducing sugar recovery. The high glucose concentration in non-detoxified hydrolysate from pepper straw facilitated the optimal growth of Bacillus amyloliquefaciens strain Cas02 and stimulated the production of iturin. The fermentation parameters were optimised to enhance the iturin production efficiency. The obtained fermentation extract was further purified using macroporous adsorption resin, resulting in an iturin-rich extract that exhibited strong antifungal activity against Alternaria alternata with an IC50 of 176.44 µg/mL. Each iturin homologue was identified using NMR. Overall, 1.58 g iturin-rich extract containing 164.06 mg/g iturins was obtained from 100 g pepper straw, illustrating the great potential of valorising pepper straw via this process.


Assuntos
Antifúngicos , Bacillus amyloliquefaciens , Antifúngicos/farmacologia , Antifúngicos/química , Verduras/metabolismo , Bacillus amyloliquefaciens/metabolismo , Fermentação , Extratos Vegetais , Peptídeos Cíclicos/química , Peptídeos Cíclicos/metabolismo
18.
Mol Plant ; 16(5): 882-902, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37029489

RESUMO

In rice, the Ca2+/calmodulin-dependent protein kinase OsDMI3 is an important positive regulator of abscisic acid (ABA) signaling. In ABA signaling, H2O2 is required for ABA-induced activation of OsDMI3, which in turn increase H2O2 production. However, how OsDMI3 regulates H2O2 production in ABA signaling remains unknown. Here we show that OsRbohB is the main NADPH oxidase involved in ABA-induced H2O2 production and ABA-mediated physiological responses. OsDMI3 directly interacts with and phosphorylates OsRbohB at Ser-191, which is OsDMI3-mediated site-specific phosphorylation in ABA signaling. Further analyses revealed that OsDMI3-mediated OsRbohB Ser-191 phosphorylation positively regulates the activity of NADPH oxidase and the production of H2O2 in ABA signaling, thereby enhancing the sensitivity of seed germination and root growth to ABA and plant tolerance to water stress and oxidative stress. Moreover, we discovered that the OsDMI3-mediated OsRbohB phosphorylation and H2O2 production is dependent on the sucrose non-fermenting 1-related protein kinases SAPK8/9/10, which phosphorylate OsRbohB at Ser-140 in ABA signaling. Taken together, these results not only reveal an important regulatory mechanism that directly activates Rboh for ABA-induced H2O2 production but also uncover the importance of this regulatory mechanism in ABA signaling.


Assuntos
Oryza , Proteínas Quinases , Proteínas Quinases/metabolismo , Fosforilação , Peróxido de Hidrogênio/metabolismo , Oryza/metabolismo , Ácido Abscísico/metabolismo , NADPH Oxidases/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-36901317

RESUMO

In order to study the vertical distribution characteristics of phytoplankton in the Danjiangkou Reservoir, the water source of the Middle Route Project of the South-North Water Diversion, seven sampling sites were set up in the Reservoir for quarterly sampling from 2017 to 2019, and water environment surveys were conducted simultaneously. The results showed that 157 species (including varieties) were identified, belonging to 9 phyla and 88 genera. In terms of species richness, Chlorophyta had the largest number of species, accounting for 39.49% of the total species. The Bacillariophyta and Cyanobacteria accounted for 28.03% and 13.38% of the total species, respectively. From the whole Danjiangkou Reservoir, the total phytoplankton abundance varied from 0.09 × 102 to 20.01 × 106 cells/L. In the vertical distribution, phytoplankton were mainly observed in the surface-thermospheric layer (I-II layer) and the bottom layer, while the Shannon-Wiener index showed a trend of gradually decreasing from the I-V layer. The Surfer model analysis showed that there was no significant stratification in the Q site's water temperature (WT) and dissolved oxygen (DO) levels in the water diversion area during the dynamic water diversion process. A canonical correspondence analysis (CCA) showed that DO, WT, pH, electrical conductivity (Cond), chemical oxygen demand (CODMn), total phosphorus (TP), ammonia nitrogen (NH4+-N), and total nitrogen (TN) had significant effects on the vertical distribution of phytoplankton (p < 0.05). A partial Mantel analysis showed that the vertical distribution of the phytoplankton community was related to WT, and the phytoplankton community structure at the other sites, except for Heijizui (H) and Langhekou (L), was affected by DO. This study has positive significance for exploring the vertical distribution characteristics of a phytoplankton community in a deep-water dynamic water diversion reservoir.


Assuntos
Fitoplâncton , Água , Temperatura , Oxigênio , Nitrogênio/análise
20.
Molecules ; 28(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36838875

RESUMO

3-Hydroxypropionic acid (3-HP) is a platform chemical with a wide range of existing and potential applications, including the production of poly(3-hydroxypropionate) (P-3HP), a biodegradable plastic. The microbial synthesis of 3-HP has attracted significant attention in recent years due to its green and sustainable properties. In this paper, we provide an overview of the microbial synthesis of 3-HP from four major aspects, including the main 3-HP biosynthesis pathways and chassis strains used for the construction of microbial cell factories, the major carbon sources used for 3-HP production, and fermentation processes. Recent advances in the biosynthesis of 3-HP and related metabolic engineering strategies are also summarized. Finally, this article provides insights into the future direction of 3-HP biosynthesis.


Assuntos
Vias Biossintéticas , Redes e Vias Metabólicas , Ácido Láctico , Fermentação , Engenharia Metabólica
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