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1.
Int Wound J ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34558192

RESUMO

Mechanical force plays a pivotal role in the pathogenesis of hypertrophic scar (HTS). Dermal fibroblasts and myofibroblasts are the key cells involved in HTS. Myofibroblasts in HTS possess different biochemical and biophysical characteristics by which myofibroblasts are often distinguished from fibroblasts. The role of mechanotransducers outside the nucleus in the pathogenesis of HTS has been reported in many studies. However, the role of Nesprin-2 in HTS is not clear. Hence, we aim to construct a cell model of HTS and explore the role of Nesprin-2 in this process. Myofibroblasts and fibroblasts were isolated from HTS and healthy skin tissues of the same patient. Fibroblasts were exposed to cyclic stretch with 10% magnitude and a frequency of 0.1 Hz for 3 days, 5 days, and 7 days, respectively. After the cell model was confirmed, fibroblasts transfected with siRNA targeting human Nesprin-2 were exposed to cyclic stretch. The mechanical behaviour and biochemical reaction of the dermal fibroblasts were analysed. The stretched fibroblasts at day 5 showed the same mechanotransductive and biochemical features as unstretched myofibroblasts. Mechanical strain could induce the myofibroblasts differentiation and a cell model of HTS was established successfully at day 5. The expressions of lamin A/C, alpha-smooth muscle actin, transforming growth factor beta 1, and collagen type I in fibroblasts were reduced by the silencing of Nesprin-2. Mechanical strain could induce the myofibroblasts differentiation and silencing of Nesprin-2 could block the mechanical stimulation of terminal myofibroblasts differentiation. Nesprin-2 might be a potential target to treat the HTS.

2.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4175-4186, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467730

RESUMO

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1ß(IL-1ß), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.


Assuntos
Neuralgia , Receptores de N-Metil-D-Aspartato , Animais , Sensibilização do Sistema Nervoso Central , Neuralgia/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo
3.
Stem Cell Rev Rep ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510359

RESUMO

Scar is a common way of healing after tissue injury. The poor scar healing will not only cause dysfunction of tissues and organs but also affect the appearance of the patients' body surface, which causes the pressure of life and spirit to the patients. However, the formation of scar tissue is an extremely complex process and its mechanism is not fully understood. At present, there is no treatment method to eliminate scars completely. Fibroblasts are the most abundant cells in the dermis, which have the ability to synthesize and remodel extracellular matrix (ECM). Myofibroblasts actively participate in the wound healing process and influence the outcome. Therefore, both of them play important roles in wound healing and scar formation. Adipose tissue-derived stem cells (ADSCs) are pluripotent stem cells that can act on target cells by paracrine. Adipose tissue stem cell-derived exosomes (ADSC-Exos) are important secretory substances of ADSCs. They are nanomembrane vesicles that can transport a variety of cellular components and fuse with target cells. In this review, we will discuss the effects of ADSCs and ADSC-Exos on the behavior of fibroblasts and myofibroblasts during wound healing and scarring stage in combination with recent studies.

4.
Anal Bioanal Chem ; 413(26): 6649-6660, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34495385

RESUMO

A rapid in situ analytical method was developed for the detection of generated carcinogenic aromatic amines from banned azo dyes utilizing a photocatalytic reduction-based liquid microjunction surface sampling (LMJSS)-mass spectrometry (MS) system. We utilized photocatalytic reduction under UV irradiation with TiO2 as catalyst to have rapid and mild reduction of azo dyes. The reaction conditions were optimized to have complete photocatalytic reduction within 2-5 min in pure methanol at room temperature. TiO2 was immobilized in the inner wall of the capillaries in the LMJSS system to achieve in situ sampling-online rapid reduction-MS detection for aromatic amines originating from azo dyes in packaging surface. The yields of in-tube photocatalytic reduction were near 100% by delivering the azo dye extracts through the capillary at 1 µL/min under UV irradiation. With this design, in situ analysis was completed within 2 min via direct MS detection and 7 min via liquid chromatography (LC)-MS detection. The detection limits for five aromatic amines originating from four different azo dyes were in the range of 1-17 mg/kg with relative standard deviations (RSDs) < 8.5%. In the application of the new method, four carcinogenic aromatic amines were detected and identified in three commercial packaging materials, and the quantitation results were comparable with those obtained by the conventional chemical reduction-LC-MS method (relative recovery, 81-121%). Moreover, due to the spatial resolution of the present method with a flow probe, MS imaging was achieved demonstrating clear azo dye patterns of a lab-made sample.

5.
Blood Adv ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34448835

RESUMO

Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, 70 allo-HSCT patients with ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. We used these 2 cohorts to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors, lactate dehydrogenase level, albumin level, white blood cell count and disease status, were retained in the multivariable logistic regression model, and a simplified grading scale, termed the LAWS score, was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, p>0.05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic of 0.859, 95% CI 0.776-0.945) and the external validation cohort (C-statistic of 0.795, 95% CI 0.645-0.945). The LAWS score is the first scoring system capable of predicting the 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk-stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.

6.
J Int Med Res ; 49(8): 3000605211035107, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34340582

RESUMO

Endoscopic retrograde cholangiopancreatography is widely used in the diagnosis and treatment of pancreatobiliary diseases; however, successful biliary cannulation is a prerequisite for this operation. We herein present a new method in a patient in whom cannulation was difficult. A 56-year-old man was admitted to the hospital with choledocholithiasis. Endoscopic retrograde cholangiopancreatography was performed, and duodenoscopy revealed that the patient's duodenal papilla was located at the initial part of the horizontal segment of the duodenum. Because of the ectopic location of the duodenal papilla, the guidewire could not be inserted into the biliary and pancreatic duct. Therefore, we performed a new method to resolve the problem of difficult cannulation. A polypectomy snare was used to excise the mucosa covering the surface of the intramural segment of the common bile duct, and a dual knife was used to form a fistula. A guidewire was then inserted through the stoma into the bile duct. After the procedure, the bile duct was successfully cannulated and the stones were removed. No complications occurred. This new method may be an alternative treatment to precutting for difficult biliary cannulation in patients with a protruded papilla of Vater.


Assuntos
Cateterismo , Esfinterotomia Endoscópica , Colangiopancreatografia Retrógrada Endoscópica , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/cirurgia , Resultado do Tratamento
7.
BMC Public Health ; 21(1): 1338, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34229643

RESUMO

OBJECTIVE: Adverse events following immunization is an important factor influencing public trust in vaccination. Publicizing its incidence timely can increase public trust. The aim of this study is to describe the incidence and characteristics of adverse events following immunization in Jiangsu province of China from 2015 to 2018. METHODS: All information of adverse events following immunization (AEFIs) was gained from Jiangsu Province Vaccination Integrated Service Management Information System. The reported AEFI trend was analyzed using Chi-square test. RESULTS: A total of 77,980 AEFI cases were reported through the AEFI system; Among which, 77,731 were classified as non-serious AEFI cases and 249 were serious AEFI cases. The male to female ratio was 1.31:1, cases less than 7 years old accounted for 97.7%. The total estimated AEFI rate was 62.70/100,000 doses. By severity, 60.75/100,000, 4.46/100,000 and 0.11/100,000 AEFI cases were common vaccine reaction, rare vaccine reaction, and serious rare vaccine reaction, respectively. The top two serious AEFI were thrombocytopenic purpura and febrile. The incidence rates showed the increasing trend and the linear trend of the increasing incidence rates passed the significant test at 0.05 levels. CONCLUSION: The sensitivity of AEFI monitoring in Jiangsu Province is increasing and higher than the national average and most countries. The majority of AEFI cases were common adverse reactions, while the serious vaccine reactions caused by vaccines were extremely low. To elevate the sensitivity of AEFI surveillance may reduce the incidence of developing serious AEFI cases.


Assuntos
Imunização , Vacinas , Sistemas de Notificação de Reações Adversas a Medicamentos , Criança , China/epidemiologia , Feminino , Humanos , Lactente , Sistemas de Informação , Masculino , Vacinação , Vacinas/efeitos adversos
8.
J Mol Model ; 27(8): 228, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34291349

RESUMO

The O(3P)-initiated conversion mechanism and dynamics of CH3CHCO were researched in atmosphere by executing density functional theory (DFT) computations. Optimizations of all the species and single-point energy computations were implemented at the B3LYP/6-311++G(d,p) and CCSD(T)/cc-pVTZ level, respectively. The explicit oxidation mechanism was introduced and discussed. The results state clearly that the O(3P) association was more energetically beneficial than the abstraction of H. The rate coefficients over the probable temperature range of 200-3000 K were forecasted by implementing Rice-Ramsperger-Kassel-Marcus (RRKM) theory. Specifically, the total rate coefficient of O(3P) association reactions is 1.19 × 10-11 cm3 molecule-1 s-1 at 298 K, which is consistent with the experimental results (1.16 × 10-11 cm3 molecule-1 s-1). The rate coefficients for the O(3P) with CH2CO, CH3CHCO, and (CH3)2CCO suggest that rate coefficient of ketene derivatives increase with the increase of methylation degree. Graphical abstract.

9.
Br J Clin Pharmacol ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240463

RESUMO

AIMS: The bivalent oral poliovirus vaccine (bOPV; Sabin types 1 and 3) replaced the trivalent OPV (Sabin types 1, 2 and 3) globally in April 2016. A routine schedule of 1 dose of inactivated poliovirus vaccine and 3 subsequent doses of bOPV was implemented in Jiangsu simultaneously. The schedule was changed to 2 inactivated poliovirus vaccines + 2 bOPV on 1 September 2019. Although OPV type 2 has been removed, challenges persist because of adverse events following immunization (AEFIs) with bOPV. Therefore, we analysed and evaluated the safety profile of bOPV administered in children based on passive postmarketing AEFI surveillance. METHODS: We collected all bOPV-related AEFI reports in Jiangsu from the Chinese National AEFI Information System (CNAEFIS) between May 2016 and April 2020. We obtained the administered doses of bOPV from the Jiangsu Provincial Electronic Immunization Registries System. A descriptive analysis was performed. RESULTS: In total, 2084 bOPV-related AEFIs were retrieved from the CNAEFIS. The overall reporting rate was 24.16 per 100 000 doses. Most AEFIs were nonserious. The most frequently reported symptoms were fever, rash and gastrointestinal disorders. Only 1.34% of AEFIs were serious, which thrombocytopenic purpura accounted for the largest category. Seventeen serious adverse events, including 2 vaccine-associated paralytic poliomyelitis (VAPP) cases, were considered to be related to bOPV vaccination. The rate of VAPP was 0.2 per million doses. CONCLUSION: AEFI analysis showed that bOPV was well tolerated. The events most frequently reported were nonserious. However, bOPV can still cause VAPP. Attention should be given to risks related to bOPV.

10.
J Hazard Mater ; 420: 126638, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34280716

RESUMO

The contamination of heavy metals in urban soil and dust is closely related to anthropogenic emissions, while to what extent the metal contamination varies among different functional areas in industrial cities remains unclear. In this study, the contamination and health risk of seven heavy metals in the soil and dust were assessed at different functional areas of Panzhihua City, Southwest China, and their sources were identified by the spatial divisions and Pb isotopes. The results showed that the contamination of V and Cr in the vanadium/steel plant (VsA) and the contamination of Cd, Pb and Zn in the iron-ore smelting (IsA) were significantly higher relative to other functional areas. The sources of the contaminated heavy metals in the soil and dust were mainly from smelting and manufacturing vanadium/steel products, coal combustion and traffic. Vanadium and Cr were the major metals primarily contributing to the noncarcinogenic and carcinogenic risks, despite the low contamination level of Cr. The results indicate that the VsA is the priority control area in the Panzhihua City, and besides V, more attention should be paid in the future to monitor Cr risk in the soil and dust because of its high contribution to the health risk.

11.
Hum Vaccin Immunother ; 17(10): 3729-3734, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34096830

RESUMO

Background: The purpose of this paper was to analyze the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc)in1-29 years old living in the most populous eastern province of China,22 years after introduction of hepatitis B vaccine (HepB) vaccination of infants and provide provincial baseline data for developping a better prevention and control plan for hepatitis B virus (HBV)in Jiangsu Province, ChinaMethods: The incidence rates of HBV in Jiangsu province from 2004 to 2014 were obtained from the National Notifiable Disease Reporting System (NNDRS). A stratified cluster random sampling method was used to select 3,002 participants aged 1-29 years across 13 HBV monitoring points throughout the province, which had been classified as either urban or rural. HBV serological markers were measured by Abbott microparticle enzyme immunoassay (MEIA) kits (Abbott Laboratories, Chicago, Illinois).Results: The incidence of hepatitis B decreased by approximately 71.44% in Jiangsu province between 2004 and 2014. Serological assessments showed that the prevalence of the HBsAg, anti-HBc, and anti-HBsin the 1-29 age group were 1.20%, 5.33%,and 66.89%, respectively. There was a significantly lower prevalence of HepB who were vaccinated than in unvaccinated subjects (0.46% vs 14.93%, p < .0001). Among these the ages of 1-29, the coverage rate drops from 97.7% to 56.6% with age,andthe timely rate among people aged 1-14 years was 90.93%.Conclusions: Since the HepB was integrated into the immunization programme in Jiangsu province,the rate of hepatitis B reported and the prevalence of HBsAg decreased significantly, and the coverage of HepB and the vaccination rate within 24 hours after birth have played an important role in reducing HBV infection.

12.
Nat Commun ; 12(1): 3983, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172745

RESUMO

Despite the well-established chemical processes for C-D bond formation, the toolbox of enzymatic methodologies for deuterium incorporation has remained underdeveloped. Here we describe a photodecarboxylase from Chlorella variabilis NC64A (CvFAP)-catalyzed approach for the decarboxylative deuteration of various carboxylic acids by employing D2O as a cheap and readily available deuterium source. Divergent protein engineering of WT-CvFAP is implemented using Focused Rational Iterative Site-specific Mutagenesis (FRISM) as a strategy for expanding the substrate scope. Using specific mutants, several series of substrates including different chain length acids, racemic substrates as well as bulky cyclic acids are successfully converted into the deuterated products (>40 examples). In many cases WT-CvFAP fails completely. This approach also enables the enantiocomplementary kinetic resolution of racemic acids to afford chiral deuterated products, which can hardly be accomplished by existing methods. MD simulations explain the results of improved catalytic activity and stereoselectivity of WT CvFAP and mutants.


Assuntos
Carboxiliases/química , Carboxiliases/metabolismo , Chlorella/enzimologia , Deutério/química , Carboxiliases/genética , Ácidos Carboxílicos/química , Ácidos Carboxílicos/metabolismo , Catálise , Descarboxilação , Óxido de Deutério/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Engenharia de Proteínas/métodos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
13.
Int Immunopharmacol ; 98: 107885, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34153669

RESUMO

OBJECTIVE: The purpose of this study was to observe the effect of hyperocclusion on the remodeling of gingival tissues and detect the related signaling pathways. DESIGN: Hyperocclusion models were established by tooth extraction in mice. The mice were sacrificed at 3, 7, 14, 28, or 56 days after the surgery, and the left mandibular first molars with gingival tissues were isolated and examinations were focused on the gingival tissues. Apoptotic cells were examined using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technology. Proliferating cells, p65, inflammatory cytokines, and ß-catenin were detected using immunohistochemical methods. RESULTS: A series of apoptosis and proliferation responses were triggered in stressed gingival tissues. It was observed that the levels of p65, proinflammatory factors including interleukin-1ß and tumor necrosis factor-α in extraction group were higher compared with those from mice with intact dentition, and peaked on days 14, 14 and 7 respectively. The expression of ß-catenin was increased under hyperocclusion situations, peaked on day 14, and declined to the initial levels over time. CONCLUSIONS: The results of this study suggest that hyperocclusion causes remodeling of the gingival tissues by activating a series of adaptive responses. Both nuclear factor kappa B and Wnt/ß-catenin signaling pathways may be responsible for those adaptive responses though the exact mechanism is not clear.

14.
Clin Lab ; 67(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34107630

RESUMO

BACKGROUND: We analyzed the 2019 external quality assessment (EQA) results to evaluate the analytical performance of maternal serum prenatal screening for Down Syndrome (DS) in the first trimester in China. METHODS: In each round, five lyophilized EQA samples with detailed clinical information were distributed to participants and used to test the concentration of human chorionic gonadotropin free beta subunits (free ß-HCG) and pregnancy-associated plasma protein-A (PAPP-A) to calculate the risk value of DS. The robust coefficient of variability (CV) was calculated or test results for free ß-HCG and PAPP-A using analytes and major measurement platforms. For DS risk values, the robust CV was calculated using a professional calculation platform. Failed EQA results were analyzed using serum marker testing results and DS risk values. RESULTS: EQA results were collected from 242 laboratories in round 1 and 239 laboratories in round 2. Total acceptable rates of testing results for free ß-HCG and PAPP-A ranged from 95.04% to 97.91%. Overall acceptable rates of DS risk values ranged from 97.52% to 97.90%. The proportion of laboratories exhibiting satisfactory performance was higher in round 2 than in round 1 for serum marker testing results and DS risk values. The robust CV for risk values for each sample were significantly higher than those of serum markers. Three EQA result failure types were found, including result reporting errors, serum marker concentration testing errors, and DS risk calculation errors. CONCLUSIONS: The analytical performance of maternal serum prenatal screening for DS in the first trimester in China can be improved further.


Assuntos
Síndrome de Down , Biomarcadores , China , Gonadotropina Coriônica Humana Subunidade beta , Síndrome de Down/diagnóstico , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Proteína Plasmática A Associada à Gravidez , Diagnóstico Pré-Natal
15.
Inorg Chem ; 60(13): 9345-9358, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34137256

RESUMO

Neuronal nitric oxide synthase (nNOS) is one of the three isoforms of nitric oxide synthase (NOS). The other two isoforms include inducible NOS (iNOS) and endothelial NOS (eNOS). These three isoforms of NOS are widely present in both human and other mammals and are responsible for the biosynthesis of NO. As an essential biological molecule, NO plays an essential role in neurotransmission, immune response, and vasodilation; however, the overproduction of NO can cause a series of diseases. Thus, the selective inhibition of three isoforms of NOS has been considered to be important in treating related diseases. The active sites of the three enzymes are highly conserved, causing the selective inhibition of the three enzymes to be a great challenge. (S)-2-Amino-5-(2-(methylthio)acetimidamido)pentanoic acid (1) has been experimentally proved to be a selective and time-dependent irreversible inhibitor of nNOS, and three pathways, including sulfide oxidation, oxidative dethiolation, and oxidative demethylation, have been suggested. In this work, we performed quantum mechanics/molecular mechanics calculations to verify the chemical conversion of inactivator 1. Although we agree with the previously suggested chemical transformation process, our calculations demonstrated that there are lower energy pathways to accomplish both oxidative dethiolation and oxidative demethylation. These three branching reactions are competitive, but only dethiolation and demethylation reactions can generate inhibitory intermediates. As a powerful time-dependent irreversible inhibitor of nNOS, the key sulfur atom and middle imine are all necessary. Our calculation results not only verified the chemical reaction of inhibitor 1 occurring in the enzymatic active site but also explained the inactivation mechanism of inhibitor 1. This is also the first verified example of the heme-enzyme-catalyzed S-demethylation mechanism.


Assuntos
Inibidores Enzimáticos/farmacologia , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Ácidos Pentanoicos/farmacologia , Cristalografia por Raios X , Teoria da Densidade Funcional , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Conformação Molecular , Simulação de Dinâmica Molecular , Óxido Nítrico Sintase Tipo I/metabolismo , Ácidos Pentanoicos/síntese química , Ácidos Pentanoicos/química
16.
J Appl Biomater Funct Mater ; 19: 22808000211023261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34102914

RESUMO

A slowly degradable bone scaffold can well maintain the balance between new bone regeneration and scaffold resorption, esp. for seniors or patients suffering from pathological diseases, because too fast degradation can lead to the loss of long-term biological stability and result in scaffold failure. In this present study, calcium phosphate silicate (CPS) and polydimethylsiloxane (PDMS) were blended in different ratios to formulate slurries for scaffold fabrication. The effects of crosslinked PDMS on the CPS material properties were first characterized and the most viable formulation of CPS-PDMS slurry was determined based on the aforementioned results to 3D fabricate scaffolds. The biocompatibility of CPS-PDMS was further evaluated based on the scaffold extract's cytotoxicity to osteoblast cells. Furthermore, real-time PCR was used to investigate the effects of scaffold extract to increase osteoblast proliferation. It is showed that the crosslinked PDMS interfered with CPS hydration and reduced both setting rate and compressive strength of CPS. In addition, CPS porosity was also found to increase with PDMS due to uneven water distribution as a result of increased hydrophobicity. Degradation and mineralization studies show that CPS-PDMS scaffold was slowly degradable and induced apatite formation. In addition, the in vitro analyses show that the CPS-PDMS scaffold did not exert any cytotoxic effect on osteoblast cells but could improve the cell proliferation via the TGFß/BMP signaling pathway. In conclusion, CPS-PDMS scaffold is proved to be slowly degradable and biocompatible. Further analyses are therefore needed to demonstrate CPS-PDMS scaffold applications in bone regeneration.

17.
Vaccine ; 39(26): 3509-3515, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33994238

RESUMO

BACKGROUND: Mumps outbreaks in adolescents who received two doses of measles-mumps-rubella vaccine (MMR) during childhood have been reported worldwide. In China, one dose of MMR administered in children aged among 18-24 months has a limited effect on the mumps epidemic. There are limited prospective studies evaluating the mumps immunity profile of children aged 3-7 years who received one dose of MMR. This study aimed to describe mumps immunity profile over a span of 4-years in kindergarten and primary school children. METHODS: An observational, prospective study on one-dose MMR in children aged 3-7 years who underwent blood sample collection in 2015, 2016, and 2018 was conducted from 2015 to 2018. The seropositivity and geometric mean concentration of mumps IgG antibodies over time were analyzed. RESULTS: A total of 3346 eligible children aged 3-7 years who underwent three rounds of blood sample collection were included. The overall seropositivity (79.6%) in 2015 was significantly higher than those recorded in 2016 (73.1%) and 2018 (71.4%). Approximately 11.6-15.9% of the participants were seropositive for mumps in 2015, and converted to negative in 2016. Meanwhile, 11.1-14.6% of the participants were seropositive for mumps in 2016, and the results converted to negative in 2018. Over 6.1-7.4% of the participants had asymptomatic infection from 2015 to 2016, while 9.0-9.9% of the participants were infected without clinical symptoms from 2016 to 2018. CONCLUSIONS: Kindergarten and primary school children who only received one dose of MMR were at higher risk of developing mumps. Waning immunity, seronegative conversion, and asymptomatic infection coexist in children who received one dose MMR. Determining the optimal age for administering the second dose of MMR in children should be prioritized to improve the control and prevention of mumps in China.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Anticorpos Antivirais , Infecções Assintomáticas/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Humanos , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba/epidemiologia , Caxumba/prevenção & controle , Estudos Prospectivos
18.
Artigo em Inglês | MEDLINE | ID: mdl-34009940

RESUMO

Innovations of transistors toward miniaturization and integration aggravate heat accumulation of central processing units (CPUs). Thermal interface materials (TIMs) are critical to remove the generated heat and to guarantee the device reliability. Herein, maltose-assisted mechanochemical exfoliation was proposed to prepare maltose-g-graphene as a structural motif of TIMs. Then, maltose-g-graphene/gelatin composite films with a bilayer structure were prepared by two-step vacuum filtration to construct effective thermally conductive pathways consisting of the directionally arranged and tightly packed maltose-g-graphene. The bilayer composite film exhibited a remarkable in-plane thermal conductivity (30.8 W m-1 K-1) and strong anisotropic ratio (∼8325%) at 40 wt % maltose-g-graphene addition. More intriguingly, the cooling effect on CPUs was significantly better for the bilayer composite films than commercial thermal pads as TIMs. The outstanding thermally conductive stability in resistance to instantaneous and prolonged thermal shocks as well as fatigue stability was gathered. Our work offers a valuable reference to design and fabricate high-performance TIMs for CPU cooling to surmount harsh application scenarios.

19.
J Magn Reson ; 326: 106959, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33711752

RESUMO

A 131Xe nuclear magnetic resonance (NMR) oscillator can be used in the measurement of rotation rates, CPT and Lorentz violation tests, etc. To improve the measurement precision of devices based on a 131Xe NMR oscillator, its characteristics need to be fully understood. Under the conditions where the Zeeman interaction is much larger than the quadrupolar interaction, the characteristics of the 131Xe NMR oscillator involving the magnetic resonance, free induction decay, and closed-loop oscillation are investigated both experimentally and theoretically. The main findings are as follows. The 131Xe NMR oscillator consists of six oscillators, three of which can be directly observed by a magnetometer. When the polarization of the 131Xe spin ensemble can be described by a spin temperature, the ensemble exhibits both spin orientation and spin alignment. The spin alignment breaks the symmetry of the three main oscillators. The free induction decay signal of 131Xe depends on parameters such as the spin alignment and the driving magnetic field, which make the measurement of the relaxation time difficult. In the closed-loop mode under self-excitation, the 131Xe NMR oscillator may oscillate with more than one frequency at certain feedback gain and phase. If the quadrupole splitting is much smaller than the spin relaxation rate, then the 131Xe oscillator can be described by the Bloch equations, and the 131Xe oscillator will have a large amplitude. The oscillation frequency of the closed-loop oscillator depends on the quadrupole splitting, polarization, and various relaxation times, which should be considered in designing a high-precision NMR sensor. The results are significant for optimizing and improving the performance of the 131Xe NMR oscillator as a sensor for precision measurement.

20.
Appl Opt ; 60(8): 2150-2157, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690309

RESUMO

Saccharomyces cerevisiae(S. cerevisiae) has been classically used as a treatment for diarrhea and diarrhea-related diseases. However, cases of the fungal infections caused by S. cerevisiae have been increasing in the last two decades among immunocompromised patients, while a long time was spent on S. cerevisiae isolation clinically so it was difficult to achieve timely diagnosis the diseases. Here, a novel approach for isolation and selection of S. cerevisiae is proposed by designing a microfluidic chip with an optically induced dielectrophoresis (ODEP) system. S. cerevisiae was isolated from the surroundings by ODEP due to different dielectrophoretic forces. Two special light images were designed and used to block and separate S. cerevisiae, respectively, and several manipulation parameters of ODEP were experimentally optimized to acquire the maximum isolation efficiency of S. cerevisiae. The results on the S. cerevisiae isolation declared that the purity of the S. cerevisiae selected by the method was up to 99.5%±0.05, and the capture efficiency was up to 65.0%±2.5 within 10 min. This work provides a general method to isolate S. cerevisiae as well as other microbial cells with high accuracy and efficiency and paves a road for biological research in which the isolation of high-purity cells is required.

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