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1.
Artigo em Inglês | MEDLINE | ID: mdl-36674265

RESUMO

The initial emission rights allocation is the key measure to achieve the goal of total amount control and deepen the emission trading system. Although many studies have focused on the modeling of initial emission rights allocation, such as using game theory and multi-objective optimization methods, few studies have observed the hierarchical relationship of mutual interference and restriction between watershed management agency and local governments in each subarea during allocation. This relationship directly affects the rationality of the results of regional emission rights allocation. In this study, a leader-follower hierarchical decision model (LFHDM) for allocating initial emission rights in a basin is developed. Based on the bilevel programming approach, the model simulates the interactive decision-making process between the watershed management agency of the upper-level model (LFHDM-U) and the local government of the lower-level model (LFHDM-L) in the allocation under total amount control. A case study of China's Yellow River Basin is conducted to demonstrate the feasibility and practicality of the model. Findings reveal that, compared with the single-level model, the developed LFHDM has higher satisfaction with the allocation scheme. Under different scenarios, the overall satisfaction of the configuration schemes of COD and NH3-N in each province and autonomous region remains above 0.9. In addition, the allocation volumes of COD and NH3-N in each province of the Yellow River Basin in planning year increase with the enhancement of allowable assimilative capacity of water bodies, but the interval gap of satisfaction with allocation schemes gradually narrows. It shows that when the allowable assimilation capacity of a water body is low, the decision-making of the allocation scheme needs to be more cautious. Moreover, for the Yellow River Basin, apart from Qinghai and Sichuan, the task of reducing water pollutants in other provinces in the next few years is very arduous. The average reduction of total COD and NH3-N in the basin is about 48% and 46%, respectively.


Assuntos
Poluentes da Água , Teoria do Jogo , Rios , Água , China
2.
N Engl J Med ; 388(3): 214-227, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36652353

RESUMO

BACKGROUND: The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. METHODS: In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-µg doses of the BNT162b2 vaccine were randomly assigned to receive 30 µg or 60 µg of BNT162b2, 30 µg or 60 µg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 µg (15 µg of BNT162b2 + 15 µg of monovalent BA.1) or 60 µg (30 µg of BNT162b2 + 30 µg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 µg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 µg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants. RESULTS: A total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 µg and 60 µg) and monovalent BA.1 (60 µg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 µg), with NT50 geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 µg) were also noninferior to BNT162b2 (30 µg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 µg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-µg bivalent BA.1 than with 30-µg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 µg). Adverse events were more common in the 30-µg monovalent-BA.1 (8.5%) and 60-µg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%). CONCLUSIONS: The candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 µg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.).


Assuntos
Vacina BNT162 , COVID-19 , SARS-CoV-2 , Vacinas Combinadas , Humanos , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacina BNT162/efeitos adversos , Vacina BNT162/imunologia , Vacina BNT162/uso terapêutico , COVID-19/genética , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Vacinação , Vacinas Combinadas/uso terapêutico , Pessoa de Meia-Idade
3.
Anal Chem ; 95(4): 2221-2228, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36635260

RESUMO

Stereochemical modifications (SCMs), mostly present in the form of d-amino acid substitution, have been increasingly identified from a wide range of neuropeptides and disease-associated biomarker proteins. Traditional mass spectrometry-based SCM identification has been effectively enhanced with technological and strategic advancements in ion mobility spectrometry. With the additional separation provided by ion mobility, SCM-induced structural changes can be probed both in theory and in practice, although the structural resolution for low-abundance SCMs still requires further improvement to enable accurate quantification or unambiguous identification of stereoisomers. Herein, we present a multi-component-enabled multidimensional ion mobility-mass spectrometry (3M-IM-MS) analytical workflow, based upon the metal-enhanced chiral amplification strategy we proposed previously (Nat. Commun., 2019, 5038). Notably, the 3M-IM-MS strategy comprises and features the powerful mathematical tools of continuous wavelet transform and Gaussian fitting-enabled peak splitting. Consequently, the resolving capability of ion mobility spectrometry for SCM analysis has been significantly enhanced, providing mobility profiles with baseline separation and more than fivefold improvement in resolving power and overall resolution. This study represents an alternative toward ultrahigh-resolution structural interrogation of mixtures with very small differences, featuring an important and long-lasting topic in chemical measurement.


Assuntos
Espectrometria de Mobilidade Iônica , Espectrometria de Mobilidade Iônica/métodos , Espectrometria de Massas/métodos
5.
Risk Anal ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653174

RESUMO

With the influence of climate change resulting in more extreme days, a rise in the number of work-related injuries could be expected. The literature has addressed the performance evaluation of a work-related injury insurance (WII) system via a two-stage structure with input/output correlation as well as the impact of extreme temperatures under different scenarios. This article thus evaluates the performance of a system comprised of operational and service sub-systems under three scenarios of extreme temperatures and proposes a hybrid two-stage dynamic data envelopment analysis (DEA) model with nondiscretionary variables for measuring integrated WII efficiency under the three scenarios. The results are as follows: (1) the poor performance of the operational and service sub-systems leads to the integrated WII system's low efficiency for 30 provinces in China during 2010-2019, except for Zhejiang, Hainan, and Qinghai. (2) Extreme temperatures must be considered when measuring WII efficiency and its stage efficiencies, or otherwise WII efficiency and operational efficiency will be underestimated in 19 provinces. (3) The negative impacts of extreme temperatures on the efficiency of the integrated WII system should be taken notice of, especially for Sichuan.

6.
Int J Biol Macromol ; 230: 123249, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36639079

RESUMO

To obtain lignin from lignocellulosic biomass, phenoxyethanol (EPH) was employed to construct a biphasic solvent system. The concentration of EPH in this biphasic solvent system was first studied to determine a pretreatment condition for fractionation of lignin. Then, the fractionation of lignin from rice straw was performed under the conditions of temperature 130 °C, cooking time 60 min and sulfuric acid concentration 0.1 M, in 70 % aqueous EPH solvent system. The results showed that 50.97 %, 49.52 % or 82.02 % of the removed lignin with the purity of 89.04 %, 91.30 % or 84.76 % was regenerated from EPH liquor using dimethyl carbonate (DMC), dimethoxymethane (DMM) or diethyl ether (DE) as precipitant, respectively. Additionally, the weight-average molecular weight (Mw) and dispersity index (D) of the regenerated lignin decreased to 4247-4809 g/mol and 1.26-1.60 compared with that of the original lignin (5654 g/mol and 4.78). Finally, the compositional and structural characteristics of lignin, e.g., molecular weight and molecular structure, were also investigated by DSC, HSQC and elemental analysis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36609756

RESUMO

As a critical way to realize the optimal allocation of water environment capacity resources in the basin, emission rights trading faces multiple uncertainties, making it extremely hard and challenging to formulate appropriate decisions and plans. Therefore, this study uses interval two-stage stochastic programming (ITSP) method to model the emission rights trading process with multiple uncertainties. It can promote the secondary optimal allocation of the emission rights between the demander and the supplier after the initial allocation. Externalities caused by environmental problems are internalized through the form of emission rights trading, thereby reducing the transaction costs and promoting the coordination and integrity of water pollution control among governments in a basin. Finally, the Yellow River basin is taken as an example for case analysis. The results show that the net revenue of emission rights system in the transaction status is better than that in the non-transaction status, and the average gap of net income reaches [171.031, 193.056] billion yuan. Under different reduction policies, the average water pollutant emission reduction in transaction status is [451.15, 628.34] thousand tons, which is generally less than [516.57, 670.05] thousand tons in non-transaction status. As policies get stricter and assimilative capacity of water bodies dwindles, reduction shrinks, leading to higher risks and economic loss from being unable to meet the discharge demand. When reduction policies are relatively loose and assimilative capacity is high, emission rights trading volume peaks. At this time, the trading volume of COD reached [29.05, 40.76] thousand tons, and that of NH3-N reached [3.74, 4.31] thousand tons. All these findings will offer insights for decision-makers on how to strike a balance between economic benefits and emission rights trading plans in the Yellow River basin.

8.
Clin Rheumatol ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36595110

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogeneous and chronic autoimmune disease. Aberrant DNA methylation occurs during various processes of SLE development regulating the mRNA expression of interrelated genes. This study aims to screen potential DNA methylation markers for SLE. METHODS: Gene expression and methylation datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between SLE patients and healthy controls were screened using the limma R package, and differentially methylated positions (DMPs) and regions (DMRs) were identified using dmpfinder and bumphunter (minfi). Additionally, the DNA methylation markers to distinguish SLE patients from healthy controls were explored through receiver operating characteristic (ROC) curves and logistic regression analyses. Finally, we validated the results of the bioinformatic analysis by pyrosequencing. RESULTS: In total, 91 DEGs, 90,092 DMPs, 15 DMRs, and 13 DMR-associated genes were identified. Through the integrative analysis of DEG- and DMR-associated genes, we identified five type I interferon (IFN)-related genes as key epigenetic-driven genes in SLE. GO enrichment analysis showed that the five SLE-associated epigenetic-driven genes were mainly enriched in the type I IFN signaling pathway involved in immune response and defense response to virus. Moreover, we identified two SLE-specific DNA methylation markers, three SLE without lupus nephritis (SLE-LN-)-specific DNA methylation markers, and two SLE with lupus nephritis (SLE-LN+)-specific DNA methylation markers by stepwise logistic regression. CONCLUSIONS: Overall, our study demonstrates potential DNA methylation markers of SLE, SLE-LN-, and SLE-LN+, which may help the diagnosis, boost the development of new epigenetic therapy, and contribute to individualized treatment. Key Points • This study identified five type I IFN-related genes as key epigenetic-driven genes in SLE, which support the importance of the type I IFN pathway in the pathogenesis of SLE • We identified novel DNA methylation biomarkers in SLE, SLE-LN-, and SLE-LN+ by a comprehensive analysis of bioinformatics methods and executed experimental validation, and binary logistic regression analysis showed that they have excellent potential • These results may provide new insights into the biological mechanisms of SLE, and identify reliable biomarkers for SLE, SLE-LN-, and SLE-LN+, which may contribute to diagnosis and individualized treatment.

9.
Talanta ; 253: 123982, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36206627

RESUMO

In this paper, a miniaturized kapok fiber-supported liquid extraction (mini-KF-SLE) method was proposed for selective extraction of pesticide residues in vegetable oils. The natural kapok fiber was used as an inert oil support material based on its hydrophobic and lipophilic properties, and the extraction device was conveniently constructed by loading 15 mg of kapok fiber at the lower middle part of a 1-mL pipette tip. The vegetable oil sample (150 mg) without any pretreatment was directly loaded, followed by the addition of 150 µL of acetonitrile (ACN) as the extractant. After static extraction for 30 min, the extractant was pipetted out with a pipettor. As the proof of concept, it was applied for extracting eight organochlorine pesticides (OCPs) from vegetable oils and the eluate was analyzed by gas chromatography-electron capture detector (GC-ECD). Under optimized conditions, the extraction recoveries of OCPs were calculated to be in ranges of 35.8-79.5%. The satisfied quantitation ability was verified by the established method with coefficients of determination (R2) being greater than 0.99. The limits of detection (LODs) were in ranges of 2.0-50.0 ng/g. The relative recoveries were in ranges of 78.3-117.0% with the inter-/intra-day relative standard deviation (RSD) both being less than 13.3%. The potential of mini-KF-SLE to extract other kinds of pesticides was further verified by the successful extracting three triazole pesticides in vegetable oils with good extraction recoveries (>41.4%). The proposed mini-KF-SLE in combination with instrument detection techniques has the great potential in the low-cost and high-throughput determination of various pesticide residues in vegetable oils.


Assuntos
Resíduos de Praguicidas , Óleos Vegetais
10.
Bioresour Technol ; 369: 128477, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36509300

RESUMO

A novel method based on pretreatment severity and solvent effects on delignification, was introduced to pretreat and fractionate lignocellulose in a 2-phenoxyethanol (EPH) biphasic solvent system. The combined severity factor (CSF) was used to regulate pretreatment severity, and the relative energy difference (RED) of solvent system to lignin was used to evaluate solvent effects. The combined action of pretreatment severity and solvent effects on delignification was first investigated by the response surface regression analysis on the pretreatment of Amorpha. Accordingly, pretreatment and fractionation of Amorpha, poplar and corn straw were then conducted under the optimized conditions. Results showed that >99 % lignin was removed after pretreatment with CSF 3.7845 in a solvent system with RED 0.9371, and 42.94 %, 39.41 % and 70.90 % lignin from Amorpha, poplar and corn straw were respectively regenerated from organosolv liquor after fractionation. Finally, the regenerated products were characterized by FTIR, TG and GPC analysis.


Assuntos
Lignina , Zea mays , Solventes , Biomassa , Hidrólise
11.
Eur J Radiol ; 158: 110639, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36463703

RESUMO

BACKGROUND: The histological sub-classes of brain tumors and the Ki-67 labeling index (LI) of tumor cells are major factors in the diagnosis, prognosis, and treatment management of patients. Many existing studies primarily focused on the classification of two classes of brain tumors and the Ki-67LI of gliomas. This study aimed to develop a preoperative non-invasive radiomics pipeline based on multiparametric-MRI to classify-three types of brain tumors, glioblastoma (GBM), metastasis (MET) and primary central nervous system lymphoma (PCNSL), and to predict their corresponding Ki-67LI. METHODS: In this retrospective study, 153 patients with malignant brain tumors were involved. The radiomics features were extracted from three types of MRI (T1-weighted imaging (T1WI), fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted imaging (CE-T1WI)) with three masks (tumor core, edema, and whole tumor masks) and selected by a combination of Pearson correlation coefficient (CORR), LASSO, and Max-Relevance and Min-Redundancy (mRMR) filters. The performance of six classifiers was compared and the top three performing classifiers were used to construct the ensemble learning model (ELM). The proposed ELM was evaluated in the training dataset (108 patients) by 5-fold cross-validation and in the test dataset (45 patients) by hold-out. The accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-Score, and the area under the receiver operating characteristic curve (AUC) indicators evaluated the performance of the models. RESULTS: The best feature sets and ELM with the optimal performance were selected to construct the tri-categorized brain tumor aided diagnosis model (training dataset AUC: 0.96 (95% CI: 0.93, 0.99); test dataset AUC: 0.93) and Ki-67LI prediction model (training dataset AUC: 0.96 (95% CI: 0.94, 0.98); test dataset AUC: 0.91). The CE-T1WI was the best single modality for all classifiers. Meanwhile, the whole tumor was the most vital mask for the tumor classification and the tumor core was the most vital mask for the Ki-67LI prediction. CONCLUSION: The developed radiomics models led to the precise preoperative classification of GBM, MET, and PCNSL and the prediction of Ki-67LI, which could be utilized in clinical practice for the treatment planning for brain tumors.

12.
Neuroendocrinology ; 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36481734

RESUMO

INTRODUCTION: Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity. At present, only limited options are available for the treatments of preeclampsia. Consequently, many patients need to terminate their pregnancy to relieve the disease. Soluble fms-like tyrosine kinase-1 (sFlt-1) is a decoy receptor of placental growth factor (PIGF) and vascular endothelial growth factor (VEGF) which can promote angiogenesis. Throughout pregnancy, the expression level of sFlt-1 continues to increase in both the mother with PE and her offspring. MATERIAL AND METHODS: In this experiment, we generated a zebrafish line expressing high levels of sFlt-1 and investigated changes in behavior and development of the nervous system. RESULTS: At 96 hours post-fertilization (hpf), the brain volume area of zebrafish in the experimental group (zFLT1+CasRx) was significantly smaller after injection than in the WT group (P<0.05) and the negative control group (CasRx) (P<0.05). At 96 hpf, compared with the WT group, the cerebral blood vessels in the CasRx control group and experimental group (zFLT1-sgRNA+CasRx) were significantly lower after injection (P<0.05). Compared with the CasRx control group, the track movement distance, and the mean track speed of zebrafish in the experimental group (zFLT1-sgRNA+CasRx) after the 6th injection were significantly decreased (P<0.05). CONCLUSIONS: the increased expression levels of sFlt-1 in zebrafish inhibited the development of the cerebral blood vessels, influenced brain volumes, and inhibited behavioral activities. Our data suggest that the elevation of sFlt-1 in the pathological state of PE can inhibit the development of the nervous system in offspring.

13.
J Transl Med ; 20(1): 588, 2022 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-36510245

RESUMO

BACKGROUND: Myotonic dystrophy type 1 (DM1), one of the most common forms of adult-onset muscular dystrophy, is caused by abnormally expanded CTG repeats in the 3' untranslated region of the DMPK gene. The CUG repeats transcribed from the expanded CTG repeats sequestrate a splicing factor, MBNL1, causing the clinical symptoms in DM1. Nowadays, only symptomatic treatments are available for DM1, and no rational therapy is available. Recently, upregulation of MBNL1 expression has been found to be one of the promising therapies for DM1. METHODS: All experiments were conducted in the C2C12 myoblasts and HSALR mice, a DM1 mouse model. Real-time PCR and western blot were used to detect the mRNA and protein level, respectively. The rotarod exercise, grip strength and hanging time were used to evaluate the muscle strength of mice. RESULTS: In this study, we demonstrated that calcitriol, an active form of vitamin D3, increased MBNL1 in C2C12 mouse myoblasts as well as in HSALR mice model for DM1. In HSALR mice model, calcitriol improved muscle strength, and corrected aberrant splicing in skeletal muscle. Besides, calcitriol reduced the number of central nuclei, and improved muscle histopathology in HSALR mice. In addition, we identified that calcitriol upregulated MBNL1 expression via activating the promoter of Mbnl1 in C2C12 myogenic cells. CONCLUSION: Our study suggests that calcitriol is a potential pharmacological strategy for DM1 that enhances MBNL1 expression.


Assuntos
Distrofia Miotônica , Camundongos , Animais , Distrofia Miotônica/tratamento farmacológico , Distrofia Miotônica/genética , Distrofia Miotônica/metabolismo , Calcitriol/farmacologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Mioblastos/metabolismo , Modelos Animais de Doenças , Músculo Esquelético/patologia , Processamento Alternativo , Proteínas de Ligação a DNA/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-36319918

RESUMO

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection mainly occurring in immunocompromised patients. Almost half of the 30 HIV-negative patients enrolled in this study from 2016-2020 in a Chinese single-center contracted 17 hematological malignancies, and 25 received long-term systemic corticosteroids. Only 4 patients received prophylaxis. The overall mortality was 30%. Patients with older age (> 43 years), dyspnea, and LDH > 404U/L had significantly higher risk of developing into a severe form. LDH > 424 U/L, PaO2 < 60 mmHg, monocyte < 0.2 × 10^9/L, and lymphocyte < 0.3 × 10^9/L were factors contributing to a poor survival outcome.

15.
J Burn Care Res ; 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402740

RESUMO

This work aims to elucidate the molecular mechanism of Qi Wei anti-burn Tincture (QW) on wound healing in burnt mice using metabolomics and molecular biology techniques. A scald model was first established in Kunming mice. After treatment, biochemical indicators for liver function and burnt skin tissues were then evaluated via biochemical detection and HE staining respectively. Liver tissues were further analyzed for differential metabolites, inflammatory factors, and mRNA levels of cytokines using metabolomics and molecular biology techniques. Involved metabolic pathways were also identified using software. Qi Wei anti-burn Tincture treatment did promote the healing of the burn wounds on Kunming mice with a downregulation of ALP, ALT, AST to normal levels. In mouse liver tissue, the contents of glutamine, aspartic acid, succinic acid and citrulline were significantly reduced, while the contents of 5-hydroxyproline, taurine, hypotaurine and glutamic acid significantly increased. These major differential compounds are involved in the arginine metabolic pathway, nitrogen excretion, and the metabolism of taurine and hypotaurine, suggesting that Qi Wei anti-burn Tincture reprogramed the above metabolic processes in the liver. Furthermore, the application of Qi Wei anti-burn Tincture increased the expression of TGF-ß1 and FGF-2, and reduced the levels of TNF-α, IL-1ß, IL-6 and reactive oxygen species in the liver of mice induced by burn injury. This study found that Qi Wei anti-burn Tincture treatment promoted metabolic pathway remodeling in liver, which might be a potential mechanism for Qi Wei anti-burn Tincture to treat burn wounds.

16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(11): 1270-1274, 2022 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-36317217

RESUMO

OBJECTIVE: To explore the genetic basis for a child featuring hypotonia, ataxia, and delayed development syndrome (HADDS). METHODS: Whole exome sequencing was carried out for the child. Candidate variant was verified by Sanger sequencing of the child and his parents. RESULTS: The child was found to harbor a de novo heterozygous c.625G>A (p.Arg209Trp) variant of the EBF3 gene, which has caused substitution of Arginine by Tryptophan. The variant may has impaired the binding affinity of EBF3 with DNA and altered its subcellular localization, and ultimately decreased the transcriptional activity of the EBF3 gene. CONCLUSION: The c.625G>A variant of the EBF3 gene probably underlay the pathogenesis of HADDS in this child. Above finding has expanded the spectrum of EBF3 variants and enriched the clinical manifestations of the HADDS.


Assuntos
Deficiência Intelectual , Hipotonia Muscular , Criança , Humanos , Ataxia/genética , Deficiência Intelectual/genética , Hipotonia Muscular/genética , Mutação , Síndrome , Fatores de Transcrição/genética , Masculino
17.
Front Psychol ; 13: 1029265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438328

RESUMO

Previous studies have indicated high perceived stress and its relationship with life satisfaction among healthcare workers. However, most of the existing studies have focused on the investigation and evaluation of the humanistic care abilities among nurses, but few studies revealed the levels of humanistic care ability among other healthcare workers including doctors and technicians. The study aimed to investigate the perceived stress and humanistic care abilities among Chinese healthcare workers. In addition, we further examined the mediating and moderating effects of social support and life satisfaction. A convenience sample of 955 health professionals from 29 hospitals in China was recruited to fill out the questionnaires about perceived stress, humanistic care ability, social support, and life satisfaction. The correlation and multivariate logistic regression analysis were carried out by SPSS 24.0. The Hayes SPSS macro program process (version 2.16.3) was used to analyze the significance of mediating and moderating model. The findings indicated that humanistic care ability was negatively associated with perceived stress and positively correlated with social support and life satisfaction. The effect of the path "perceived stress → social support → humanistic care ability" was -0.017, and the path "perceived stress → life satisfaction → social support → humanistic care ability" was -0.129. The current study contributed to a better understanding of humanistic care abilities and influential factors in Chinese healthcare workers. Thus, it may suggest studies on interventions to interventions to alleviate or eliminate the negative impact of perceived stress and improve humanistic care abilities.

18.
Int J Mol Sci ; 23(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36430644

RESUMO

Rice spotted-leaf mutants are ideal materials to study the molecular mechanism underlying programmed cell death and disease resistance in plants. LOC_Os07g04820 has previously been identified as the candidate gene responsible for the spotted-leaf phenotype in rice Spotted-leaf 26 (Spl26) mutant. Here, we cloned and validated that LOC_Os07g04820 is the locus controlling the spotted-leaf phenotype of Spl26 by reverse functional complementation and CRISPR/Cas9-mediated knockout of the mutant allele. The recessive wild-type spl26 allele (Oryza sativa spotted-leaf 26, Osspl26) is highly conservative in grass species and encodes a putative G-type lectin S-receptor-like serine/threonine protein kinase with 444 amino acid residuals. OsSPL26 localizes to the plasma membrane and can be detected constitutively in roots, stems, leaves, sheaths and panicles. The single base substitution from T to A at position 293 leads to phenylalanine/tyrosine replacement at position 98 in the encoded protein in the mutant and induces excessive accumulation of H2O2, leading to oxidative damage to cells, and finally, formation of the spotted-leaf phenotype in Spl26. The formation of lesions not only affects the growth and development of the plants but also activates the defense response and enhances the resistance to the bacterial blight pathogen, Xanthomonas oryzae pv. oryzae. Our results indicate that the gain-of-function by the mutant allele OsSpl26 positively regulates cell death and immunity in rice.


Assuntos
Oryza , Oryza/metabolismo , Mutação com Ganho de Função , Peróxido de Hidrogênio/metabolismo , Proteínas de Plantas/metabolismo , Imunidade Vegetal/genética
19.
Biomed Pharmacother ; 155: 113833, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271583

RESUMO

Patients with heart failure (HF) usually present with skeletal muscle diseases of varying severity, ranging from early fatigue on exercise to sarcopenia, sarcopenic obesity or cachexia, and frailty, which are significant predictors of HF prognosis. Abnormal mitochondrial metabolism has been identified as one of the earliest signs of skeletal muscle injury in HF and is associated with pathological alterations in muscle, manifested as muscle wasting, myocyte atrophy and apoptosis, fiber type shift, impaired contractile coupling, and muscle fat infiltration. In this review, we update the evidence for skeletal muscle mitochondrial remodeling in HF patients or animal models, including the impairments in mitochondrial ultrastructure, oxidative metabolism, electron transport chain (ETC), phosphorylation apparatus, phosphotransfer system, and quality control. We also focus on molecular regulatory mechanisms upstream of mitochondria, including circulating factors (e.g., RAAS, TNF-α IL-6, IGF-1, GH, ghrelin, adiponectin, NO) and molecular signals within myocytes (e.g., PGC-1α, PPARs, AMPK, SIRT1/3, ROS, and MuRF1). Besides the therapies targeting the signaling pathways mentioned above, such as AdipoRon and elamipretide, we further summarize other potential pharmacological approaches like inhibitors of sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4), as well as some natural products, which may have the beneficial effects on improving the skeletal muscle mitochondrial function of HF. Targeting myocyte mitochondrial biogenesis, oxidative metabolism, oxidative phosphorylation, and reduction of oxidative stress injury are promising future opportunities for the prevention and management of skeletal muscle myopathy in HF.


Assuntos
Produtos Biológicos , Insuficiência Cardíaca , Sarcopenia , Animais , Transportador 2 de Glucose-Sódio/metabolismo , Grelina/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Adiponectina/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias , Músculo Esquelético/metabolismo , Insuficiência Cardíaca/metabolismo , Produtos Biológicos/farmacologia , Dipeptidil Peptidases e Tripeptidil Peptidases , Glucose/metabolismo , Sódio/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-36264459

RESUMO

Take-away containers are the common food contact materials (FCMs) that are widely used in daily life. However, little is known regarding the effects of different food simulants on the pollution characteristics of microplastics derived from food containers, as well as the toxic effects of the chemical substances that are leached from them. Extracts were obtained by adding organic solvents into plastic containers (polypropylene, PP; polystyrene, PS) to simulate aqueous, alcoholic, and fatty environments. The extracted substances and their toxic effects were then assessed by counting and characterizing the resulting microplastics and performing bio-acute toxicity assays. The results demonstrated that the highest abundance of microplastics occurred in PS containers in fatty environments, which was likely due to the rough surface of the PS. In contrast, organic solvents seemed more conducive to the migration of substances. Furthermore, the PP and PS extracts in an alcohol and fatty environment have significant impacts on zebrafish embryo development, including arrhythmia, pericardial cysts, and spinal curvature.

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