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1.
Cell ; 186(22): 4788-4802.e15, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37741279

RESUMO

Gravity controls directional growth of plants, and the classical starch-statolith hypothesis proposed more than a century ago postulates that amyloplast sedimentation in specialized cells initiates gravity sensing, but the molecular mechanism remains uncharacterized. The LAZY proteins are known as key regulators of gravitropism, and lazy mutants show striking gravitropic defects. Here, we report that gravistimulation by reorientation triggers mitogen-activated protein kinase (MAPK) signaling-mediated phosphorylation of Arabidopsis LAZY proteins basally polarized in root columella cells. Phosphorylation of LAZY increases its interaction with several translocons at the outer envelope membrane of chloroplasts (TOC) proteins on the surface of amyloplasts, facilitating enrichment of LAZY proteins on amyloplasts. Amyloplast sedimentation subsequently guides LAZY to relocate to the new lower side of the plasma membrane in columella cells, where LAZY induces asymmetrical auxin distribution and root differential growth. Together, this study provides a molecular interpretation for the starch-statolith hypothesis: the organelle-movement-triggered molecular polarity formation.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Plastídeos , Arabidopsis/fisiologia , Proteínas de Arabidopsis/metabolismo , Sensação Gravitacional , Raízes de Plantas/metabolismo , Plastídeos/metabolismo , Amido/metabolismo , Proteínas de Membrana/metabolismo
2.
Int J Mol Sci ; 25(13)2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39000530

RESUMO

The fish gut microbiome is well known for its role in degrading nutrients to improve the host's digestion and absorption efficiency. In this study, we focused on the core physiological adaptability during the various reproductive stages of the black Amur bream (Megalobrama terminalis) to explore the interaction mechanisms among the fish host gut mucosal structure, gut enzyme activity, and gut microbial metabolism in the course of the host's reproductive cycle. Our findings showed that M. terminalis exhibited locomotion metabolic type (aids in sporting) in the reproductive stage, and a change to visceral metabolic type (aids in digestion) during non-reproductive and post-reproductive stage phases. The impact of metabolic type selection and energy demand during various reproductive stages on fish nutrition strategy and digestive function was substantial. Our resulted showed that mitochondria in intestinal epithelial cells of reproductive M. terminalis appeared autophagy phenomenon, and the digestive enzyme activities in the intestines of reproductive M. terminalis were lower than those in the non-reproductive and post-reproductive individuals. Moreover, these differences in nutrition strategy have a prominent impact on the gut microbiome of reproductive M. terminalis, compared to non-reproductive and post-reproductive samples. Our findings showed that reproductive females had lower levels of alpha diversity compared to non-reproductive and post-reproductive females. Our results also showed a greater functional variety and an increase in functional genes related to carbohydrate, lipid, amino acid, cofactors, and vitamin metabolic pathways in the NRS and PRS group. It is noteworthy that an enrichment of genes encoding putative enzymes implicated in the metabolism of taurine and hypotaurine was observed in the RS samples. Our findings illustrated that the stability and resilience of the gut bacterial community could be shaped in the wild fish host-microbiome interactions during reproductive life history.


Assuntos
Microbioma Gastrointestinal , Reprodução , Animais , Microbioma Gastrointestinal/fisiologia , Feminino , Cyprinidae/microbiologia , Cyprinidae/fisiologia , Cyprinidae/metabolismo , Água Doce/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia
3.
Glycobiology ; 33(6): 464-475, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37129515

RESUMO

PURPOSE: Sialic acid-bound immunoglobulin-like lectin 15 (Siglec15) has emerged as a novel therapeutic target in tumor immunotherapy. This study is designed to investigate the function and mechanism of Siglec15 in thyroid carcinoma (THCA). MATERIALS AND METHODS: The information on patients with THCA from TGCA and GEO database were used to analyze the expression of Siglec15 in THCA. THCA cells were treated with Siglec15-mFc, a recombinant fusion protein consisting of the extracellular domain of human Siglec15 and murine IgG Fc. THP-1 cells expressing human Siglec15 and its mutant were co-cultured with THCA cells to mimic the contact between Siglec15-expressing tumor-associated macrophages and THCA cells. Wound-healing assay and transwell migration assay were used to examine the migration abilities of BCPAP and C643 cells. Pull-down assay was performed to examine the interaction between Siglec15 and epidermal growth factor receptor (EGFR) on the cancer cells. Cycloheximide (CHX) assay was used to evaluate the stability of the protein. RESULTS: The expression of Siglec15 in thyroid carcinoma tissues is higher than in normal tissues. Siglec15 promotes the migration of THCA cells by binding to EGFR in a sialic acid-dependent manner and increases EGFR protein expression. Inhibition of the EGFR pathway blocks the effect of Siglec15 on the migration of THCA cells. CONCLUSIONS: Our findings reveals that Siglec15 promotes the migration of thyroid carcinoma cells by enhancing the EGFR protein stability.


Assuntos
Ácido N-Acetilneuramínico , Neoplasias da Glândula Tireoide , Humanos , Animais , Camundongos , Movimento Celular , Receptores ErbB/genética , Receptores ErbB/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Estabilidade Proteica
4.
Proc Natl Acad Sci U S A ; 117(28): 16324-16332, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601219

RESUMO

FadE, an acyl-CoA dehydrogenase, introduces unsaturation to carbon chains in lipid metabolism pathways. Here, we report that FadE5 from Mycobacterium tuberculosis (MtbFadE5) and Mycobacterium smegmatis (MsFadE5) play roles in drug resistance and exhibit broad specificity for linear acyl-CoA substrates but have a preference for those with long carbon chains. Here, the structures of MsFadE5 and MtbFadE5, in the presence and absence of substrates, have been determined. These reveal the molecular basis for the broad substrate specificity of these enzymes. FadE5 interacts with the CoA region of the substrate through a large number of hydrogen bonds and an unusual π-π stacking interaction, allowing these enzymes to accept both short- and long-chain substrates. Residues in the substrate binding cavity reorient their side chains to accommodate substrates of various lengths. Longer carbon-chain substrates make more numerous hydrophobic interactions with the enzyme compared with the shorter-chain substrates, resulting in a preference for this type of substrate.


Assuntos
Acil-CoA Desidrogenase/química , Acil-CoA Desidrogenase/metabolismo , Mycobacterium/enzimologia , Acil Coenzima A/metabolismo , Acil-CoA Desidrogenase/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Domínio Catalítico , Farmacorresistência Bacteriana/genética , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Modelos Moleculares , Mutação , Mycobacterium/efeitos dos fármacos , Mycobacterium/genética , Conformação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato
5.
Genomics ; 114(4): 110416, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35718089

RESUMO

The BBS2 gene plays a vital role in human obesity and fat deposition. However, little is known about it in beef cattle. Therefore, this study investigates the function of BBS2 in the fat deposition of beef cattle and screens the effective SNPs marker for meat quality traits in cattle breeding. The expression of BBS2 is negatively correlated with marbling ratios of beef cattle. Moreover, the knockdown of BBS2 promoted adipogenesis and lipid accumulation of bovine preadipocytes by stimulating PPARγ, FABP4, and FASN expression (P < 0.01). Four novel SNPs in the exons of BBS2 in Chinese Qinchuan cattle were identified and of which the g.24226239C > T (Q527), g.24223562G > A (V441I), and g.24227851A > G (Q627R) were significantly associated with the meat quality of Qinchuan cattle (P < 0.01, P < 0.05). The findings suggested that BBS2 could be used as a candidate gene for meat quality improvement in Qinchuan cattle. Furthermore, these genotypes can be exploited as molecular markers in future beef breeding projects.


Assuntos
Adipogenia , Carne , Adipogenia/genética , Animais , Bovinos/genética , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Análise de Sequência de DNA
6.
Clin Immunol ; 237: 108987, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35346864

RESUMO

Metabolic reprogramming of immune cells has been proven to be important for systemic lupus erythematosus (SLE). This study aims to understand the role of SLC7A5, an amino acid transporter, in SLE. We analyzed SLC7A5 mRNA expression of SLE patients compared to healthy controls using GEO database, and found that it was increased in CD4+ T cells and CD19+ B cells. We then confirmed the expression up-regulation using flow cytometry and found that the proportion of SLC7A5+ cells and its expression were increased in peripheral blood T and B cells from SLE patients. Importantly, SLC7A5 expression in T and B cells was positively correlated with blood urea nitrogen and serum creatinine. Therefore, we conclude that SLC7A5, up-regulating in circulating T and B cells, correlates with kidney function, suggesting its potential role in mediating renal damage in SLE, which provides novel insight into SLE pathogenesis and provides a potential biomarker for disease.


Assuntos
Rim , Transportador 1 de Aminoácidos Neutros Grandes , Lúpus Eritematoso Sistêmico , Antígenos CD19 , Linfócitos B , Citometria de Fluxo , Humanos , Rim/patologia , Transportador 1 de Aminoácidos Neutros Grandes/genética , Lúpus Eritematoso Sistêmico/complicações , Linfócitos T
7.
Int J Mol Sci ; 23(23)2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36499562

RESUMO

(1) Background: Huperzine A, a natural cholinesterase (AChE) inhibitor isolated from the Chinese herb Huperzia Serrata, has been used as a dietary supplement in the United States and a drug in China for therapeutic intervention on Alzheimer's disease (AD). This review aims to determine whether Huperzine A exerts disease-modifying activity through systematic analysis of preclinical studies on rodent AD models. (2) Methods: Sixteen preclinical studies were included based on specific criteria, and the methodological qualities were analyzed by SYRCLE's risk of bias tool. Some outcomes were meta-analyzed: latencies and time spent in quadrant of Morris water maze, soluble amyloid-ß (Aß) level measured by ELISA in the cortex and hippocampus, Aß plaque numbers measured by immunohistochemistry in hippocampus, choline acetyltransferase (ChAT) activity, and AChE activity. Finally, the mechanisms of Huperzine A on AD models were summarized. (3) Conclusions: The outcomes showed that Huperzine A displayed AChE inhibition, ChAT activity enhancement, memory improvement, and Aß decreasing activity, indicating the disease-modifying effect of Huperzine A. However, due to the uneven methodological quality, the results need to be rationally viewed, and extensively repeated.


Assuntos
Alcaloides , Doença de Alzheimer , Sesquiterpenos , Animais , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Roedores , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Peptídeos beta-Amiloides
8.
Int J Mol Sci ; 21(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941000

RESUMO

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It involves progressive impairment of cognitive function. A growing number of neuroprotective compounds have been identified with potential anti-AD properties through in vitro and in vivo models of AD. Quercetin, a natural flavonoid contained in a wide range of plant species, is repeatedly reported to exert neuroprotective effects in experimental animal AD models. However, a systematic analysis of methodological rigor and the comparison between different studies is still lacking. A systematic review uses a methodical approach to minimize the bias in each independent study, providing a less biased, comprehensive understanding of research findings and an objective judgement of the strength of evidence and the reliability of conclusions. In this review, we identified 14 studies describing the therapeutic efficacy of quercetin on animal AD models by electronic and manual retrieval. Some of the results of the studies included were meta-analyzed by forest plot, and the methodological quality of each preclinical trial was assessed with SYRCLE's risk of bias tool. Our results demonstrated the consistent neuroprotective effects of quercetin on different AD models, and the pharmacological mechanisms of quercetin on AD models are summarized. This information eliminated the bias of each individual study, providing guidance for future tests and supporting evidence for further implementation of quercetin into clinical trials. However, the limitations of some studies, such as the absence of sample size calculations and low method quality, should also be noted.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Quercetina , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Humanos , Fármacos Neuroprotetores/farmacocinética , Fármacos Neuroprotetores/uso terapêutico , Quercetina/farmacocinética , Quercetina/uso terapêutico
9.
Biochem Biophys Res Commun ; 510(1): 116-121, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30665717

RESUMO

Argininosuccinate lyase (ASL) participates in arginine synthesis through catalysing a reversible reaction in which argininosuccinate (AS) converts into arginine and fumarate. ASL from Mycobacterium tuberculosis is essential for its growth. In this work, the crystal structure of the apo form of MtbASL was determined and reveals a tetrameric structure that is essential for its activity since the active sites are formed by residues from three different monomers. Subsequently, we determined the crystal structure of MtbASL-sulfate complex, and the ligand mimics the negatively charged intermediate. The complex structure and mutagenesis studies indicate that residues S282 and H161 might act as a catalytic dyad. A major conformational change in the MtbASL-SO4 complex structure could be observed upon sulfate binding, and this movement facilitates the interaction between substrate and the residues involved in catalysis. A different conformational change in the C-terminal domain could be observed in the MtbASL-SO4 complex compared with that in other homologues. This difference may be responsible for the lower activity of MtbASL, which is related to the slow growth rate of M. tuberculosis. The C-terminal domain is a potential allosteric site upon inhibitor binding. The various conformational changes and the diversity of the sequence of the potential allosteric site across the homologues might provide clues for designing selective inhibitors against M. tuberculosis.


Assuntos
Argininossuccinato Liase/química , Mutagênese Sítio-Dirigida , Mycobacterium tuberculosis/enzimologia , Sítio Alostérico , Arginina/biossíntese , Argininossuccinato Liase/genética , Biocatálise , Domínio Catalítico , Cristalografia por Raios X , Ligação Proteica , Conformação Proteica/efeitos dos fármacos , Sulfatos/metabolismo , Sulfatos/farmacologia
10.
Pharmacol Res ; 150: 104476, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605783

RESUMO

Alzheimer's disease (AD) is a progressive dementia caused by degeneration of the central nervous system with a high incidence in the elderly. Resveratrol is a natural compound contained in a wide range of plant species, including grapes. Recent studies have shown positive effects of resveratrol in animal models of AD; however, whether these results justify clinical trials is uncertain. Furthermore, there are multiple theories about the mechanism(s) by which resveratrol works and knowing how it works can suggest targets for future drug development. So far, systematic evaluation of both of these aspects is lacking. In this study, we selected 19 studies describing the efficacy of resveratrol in rodent AD models by electronic and manual retrieval. The method quality of the study were analyzed by the SYRCLE's risk of bias tool and the experimental data were retrieved and meta-analyzed using forest plot. Analysis of these studies demonstrates the consistent neuroprotective effects of resveratrol in AD models and offers insights into the possible pharmacological mechanisms. This information eliminates the bias of each study, providing supporting evidence for the implementation of clinical trials. However, the limits of studies were also noticed: low method quality, lack of sample size calculation and high risks of bias.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Resveratrol/uso terapêutico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Modelos Animais de Doenças , Proteínas tau/metabolismo
11.
Macromol Rapid Commun ; 39(6): e1700572, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29314369

RESUMO

A versatile platform allowing capture and detection of normal and dysfunctional cells on the same patterned surface is important for accessing the cellular mechanism, developing diagnostic assays, and implementing therapy. Here, an original and effective method for fabricating binary polymer brushes pattern is developed for controlled cell adhesion. The binary polymer brushes pattern, composed of poly(N-isopropylacrylamide) (PNIPAAm) and poly[poly(ethylene glycol) methyl ether methacrylate] (POEGMA) chains, is simply obtained via a combination of surface-initiated photopolymerization and surface-activated free radical polymerization. This method is unique in that it does not utilize any protecting groups or procedures of backfilling with immobilized initiator. It is demonstrated that the precise and well-defined binary polymer patterns with high resolution are fabricated using this facile method. PNIPAAm chains capture and release cells by thermoresponsiveness, while POEGMA chains possess high capability to capture dysfunctional cells specifically, inducing a switch of normal red blood cells (RBCs) arrays to hemolytic RBCs arrays on the pattern with temperature. This novel platform composed of binary polymer brush pattern is smart and versatile, which opens up pathways to potential applications as microsensors, biochips, and bioassays.


Assuntos
Polímeros/química , Resinas Acrílicas/efeitos adversos , Resinas Acrílicas/química , Resinas Acrílicas/farmacologia , Adesão Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Metacrilatos/efeitos adversos , Metacrilatos/química , Metacrilatos/farmacologia , Microscopia Eletrônica de Varredura , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polímeros/efeitos adversos , Polímeros/farmacologia , Propriedades de Superfície , Temperatura
12.
Anal Chem ; 89(19): 10141-10146, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-28837331

RESUMO

The principle of the mole-ratio method utilizing magnetophoretic velocimetry was demonstrated for the first time. The feasibility of the magnetophoretic mole-ratio method was studied for the determination of the stoichiometry of the complexes formed between a hydrophobic phosphate ligand adsorbed in mesoporous hydrophobic silica particles and paramagnetic metal ions of Co(II), Tb(III), and Dy(III) in aqueous solutions. The present method is a nonspectroscopic method and carried out by a simple magnetic device.

13.
Support Care Cancer ; 24(3): 1019-24, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26245496

RESUMO

PURPOSE: Our aim is to test the validity, reliability, and acceptability of the Chinese version of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Bone Metastases 22 (EORTC QLQ-BM22) module to assess health-related quality of life (HRQOL) in patients with bone metastases in China. METHODS: Patients with histological confirmation of malignancy and bone metastases from Tianjin Cancer Institution and Hospital from June 2013 to April 2014 were enrolled in this study. All patients self-administered the EORTC QLQ-BM22 and the EORTC QLQ-C30. The Karnofsky Performance Scale (KPS) was performed to evaluate scores. The reliability and validity tests of the questionnaires were based on Cronbach's α coefficients, Pearson correlation test, and Wilcoxon rank sum nonparametric test. RESULTS: Internal consistency reliabilities of all the four scales were acceptable. Scales measuring similar HRQOL aspects were found to correlate with one another between EORTC QLQ-BM22 and EORTC QLQ-C30, but differences still existed. Significant differences were demonstrated in the scores of all four subscales of the QLQ-BM22 between the two KPS subgroups (KPS ≤ 80; KPS > 80). Meanwhile, the compliance for item completion of the QLQ-BM22 was satisfactory. CONCLUSIONS: The Chinese version of EORTC QLQ-BM22 is a reliable and valid instrument, which is appropriate for measuring the HRQOL of patients with bone metastases in China.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/secundário , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Inquéritos e Questionários , Estudos de Validação como Assunto , Adulto Jovem
14.
J Pharm Policy Pract ; 17(1): 2306867, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357548

RESUMO

Purpose: This study described pharmaceutical and medical resource accessibility of COVID-19 treatment in Shenzhen, China during the peak of COVID-19 infection from December 2022 to January 2023, and examined its influence on clinical outcomes. Methods: We surveyed Shenzhen residents on COVID-19-related topics using electronic questionnaires. We conducted descriptive statistical analyses and multiple regressions including logistic and Tobit models to explore the impacts of resource constraints on patient outcomes. Resource utilisation and attempts to seek medical care were also described for severity-stratified subgroups. Results: 76.8% of respondents reported experiencing COVID-19 symptoms between December 7, 2022 and January 29, 2023. Of those who attempted to purchase medication, 72.8% reported drug shortage. 49% of those seeking medical treatment experienced difficulties. Compared with those who did not experience drug shortages, those who did had an odds ratio of 1.959 (95% CI: 1.159 ∼3.313) of presenting with moderate to severe symptoms. Compared with those without difficulties in seeking medical treatment, those who did had an average of 0.39 (95% CI: 0.110 ∼0.670) more days absent from work. Conclusion: Shenzhen residents with COVID-19 symptoms from December 2022 to January 2023 experienced a certain degree of pharmaceutical and medical resource constraints, which might have compromised their prognosis.

15.
Vaccine X ; 19: 100508, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38903607

RESUMO

Objective: To investigate the real-world effectiveness of COVID-19 vaccine boosters during China's Omicron wave. Methods: In January 2023, we surveyed Shenzhen, China residents via online questionnaires to investigate their COVID-19 symptoms and vaccination history. The outcomes of interest included fever, other COVID-19-related symptoms, severity of symptoms, whether early onset (before December 23, 2022) and duration. Respondents were categorized as no booster, one booster 6mo ago, one booster within 6mo, or two boosters based on dose count and vaccination timing. We used multivariable logistic regressions and Tobit models to assess COVID-19 vaccine booster impacts. Results: Compared to the no booster group, two booster recipients had a lower fever risk (OR = 0.35, 95 %CI = 0.16-0.76) but not lower risks of COVID-19-related symptoms (OR = 0.74, 95 %CI = 0.26-2.06) and self-reported severe symptoms (OR = 0.47, 95 %CI = 0.19-1.15). Nor did the two booster recipients had a shorter illness duration (marginal effect = -0.79 days, 95 %CI = -1.65-0.07) and a lower risk of symptom onset delay (OR = 0.48, 95 %CI = 0.19-1.23). Compared to the no booster group, both one booster within six months (OR = 2.17, 95 %CI = 1.34-3.52) and one booster six months ago (OR = 1.30, 95 %CI = 0.92-1.82) did not reduce the risks of fever and symptoms (one booster within six months: OR = 1.57, 95 %CI = 0.84-2.90; one booster six months ago: OR = 1.23, 95 %CI = 0.79-1.93). Regardless of timing, one booster did not reduce illness duration (within six months: marginal effect = 0.25 days, 95 %CI = -0.20-0.70; six months ago: marginal effect = 0.27 days, 95 %CI = -0.08-0.62). However, receiving one booster within six months delayed symptom onset (OR = 0.54, 95 %CI = 0.34-0.86), while one booster six months ago did not (OR = 1.03, 95 %CI = 0.74-1.44). Conclusions: Receiving two booster doses reduced the onset of fever during the Omicron outbreak in mainland China.

16.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167287, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38862095

RESUMO

Intestinal barrier dysfunction characterized by the functional loss of the intestinal epithelium's tight junction (TJ) barrier is a key factor in the pathogenesis of ulcerative colitis (UC). Although rapamycin, an mTOR (mechanistic target of rapamycin) inhibitor, has shown promise in inducing clinical remission and mucosal healing in inflammatory bowel disease, its underlying mechanism remains elusive. Thus, this study investigated the role of the mTOR pathway in regulating the intestinal barrier. To investigate the molecular mechanism regulating the intestinal barrier, specific intestinal epithelial phenazine biosynthesis-like domain-containing protein (PBLD)-deficient (PBLDIEC-/-) mice and control wild-type (WT) mice were intraperitoneally injected with rapamycin or MHY1485. To determine the relevance of the findings for UC, we analyzed transcriptome data and single-cell expression profiles from public databases and intestinal mucosal tissues obtained from patients with active UC or colon cancer. We observed that mTOR activation in the intestinal epithelium of patients with active UC. Moreover, in vivo, rapamycin markedly increased the expressions of PBLD and TJ proteins and reduced intestinal inflammation in mice with dextran sulfate sodium-induced enteritis. However, the therapeutic efficacy of rapamycin was notably reduced in PBLDIEC-/- mice. In vitro, rapamycin influenced PBLD expression by modulating the nuclear transcription of transcription factor EB (TFEB). Angiomotin (AMOT) could directly bind to PBLD, and rapamycin could not effectively increase the expression of TJ proteins after the knockdown of PBLD or AMOT. In summary, the administration of rapamycin is a potential treatment for UC, and targeting the mTOR/PBLD/AMOT axis is a potential novel approach for UC treatment.

17.
Sci Rep ; 14(1): 3215, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332186

RESUMO

Children are generally susceptible to COVID-19, and infection with COVID-19 may cause serious harm to children. COVID-19 vaccination is an effective way to prevent infection at present, and many factors affect children's COVID-19 vaccination. This study aimed to explore the effects of perceived social support and health literacy on hesitancy towards first and second vaccine dose. This cross-sectional study was conducted in the Minhang District of Shanghai, China, in October 2022. A total of 1150 parents of preschool children from 10 kindergartens participated. The survey encompassed four sections, capturing data on sociodemographic attributes, health literacy, perceived social support, and parental COVID-19 vaccine hesitancy. Health literacy was measured using a self-designed questionnaire consisting of four dimensions. Perceived social support was assessed using the MSPSS questionnaire. Hierarchical multiple logistic regression was used to examine the relationship between the independent variables and parental hesitancy towards the first and second doses of COVID-19 vaccine. Parental hesitancy rate for the first dose of the COVID-19 vaccine was 69.6%, and for the second dose, it was 33.1%. The final integrated model showed that parental hesitancy towards the first and the second dose of COVID-19 vaccine was associated with parental educational level, allergy in children, information decision-making and information comprehension ability, perceived social support from family and friends. Health literacy and perceived social support are influence factors for parental hesitancy towards COVID-19 vaccine for preschool children. The findings will provide insights for future intervention studies on COVID-19 vaccine hesitancy and inform the development of vaccination policies.


Assuntos
COVID-19 , Letramento em Saúde , Humanos , Pré-Escolar , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , China/epidemiologia , Apoio Social , Pais , Vacinação
18.
Artigo em Inglês | MEDLINE | ID: mdl-38821004

RESUMO

BACKGROUND: Poisonings caused by plant toxins and mycotoxins occur frequently, which do great harm to human health and social public health safety. When a poisoning incident occurs, biological samples are commonly be used to conduct the detection of toxic substances and their metabolites for targeted clinical treatment and incident analysis. OBJECTIVE: To establish an efficient and accurate analysis method of 39 phytotoxins and mycotoxins in blood and urine by high performance liquid chromatography quadrupole tandem orbitrap mass spectrometry (HPLC-Orbitrap MS). METHOD: After 3 mL of methanol being added to 1 mL blood and urine respectively for extraction and protein precipitation, the supernatant was injected into HPLC-Orbitrap MS for analysis. The phytotoxins and mycotoxins were separated by Hypersil GOLD PFP column with gradient elution using methanol-5 mmol/L ammonium acetate as mobile phase. The data were collected in ESI positive ion mode using Full MS/dd-MS2 for mass spectrometry detection. RESULT: The mass database of 39 phytotoxins and mycotoxins was developed, and accurate qualitative analysis can be obtained by matching with the database using the proposed identification criteria. Limit of detections (LODs) were 1.34 × 10-4 âˆ¼ 1.92 ng/mL and 1.92 × 10-4 âˆ¼ 9.80 ng/mL for blood and urine samples, respectively. Limits of quantification (LOQ) of toxins in blood and urine ranged from 4.47 × 10-4 âˆ¼ 6.32 ng/mL and 6.39 × 10-4 âˆ¼ 32.67 ng/mL, respectively. Intra-day relative standard deviations (RSDs) were 0.79 % âˆ¼ 10.90 %, and inter-day RSDs were 1.08 % âˆ¼ 18.93 %. The recoveries can reach 90 % âˆ¼ 110 % with matrix matching calibration curves. CONCLUSION: The established method is simple and rapid to operate, which can complete the sample analysis within 30 min, providing technical support for clinical poisoning treatment and public health poisoning analysis.


Assuntos
Limite de Detecção , Micotoxinas , Micotoxinas/urina , Micotoxinas/sangue , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes , Modelos Lineares , Espectrometria de Massas em Tandem/métodos
19.
Nanoscale ; 16(29): 14130-14142, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39011614

RESUMO

Recently, water resources have become scarce due to the growing global population and human impact on the environment, coupled with the effects of climate change. For solving the problem of global freshwater shortage and increasing the value of discarded polyphenylene sulfide (PPS) filter bags, in this study, balsa wood was used as the base of a photothermal solar evaporator, chitosan solution was used as the binder, and the main photothermal conversion materials used were polyphenylene sulfide (CP) carbide and copper sulfide. In order to create synergistic photothermal conversion materials, freeze-drying and in situ precipitation were used to deposit the photothermal conversion materials on top of the balsa wood. The prepared CP/CuS-wood evaporator has excellent water evaporation performance and light conversion capability, with a water evaporation rate of 2.68 kg m-2 h-1 and a photothermal conversion efficiency of 93.2% under simulated one solar intensity irradiation. In addition, the evaporator can effectively remove organic dyes such as methylene blue and methyl orange. The evaporator's durability and seawater desalination capability have also been confirmed through seawater desalination experiments and outdoor tests. Studies have shown that solar interface photothermal evaporators are a viable solution for desalination and wastewater treatment. This eco-friendly, economically viable and stable photothermal evaporator mentioned in this paper has pioneering features and will be a new paradigm for desalination and wastewater treatment.

20.
Clin Appl Thromb Hemost ; 29: 10760296231175654, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37365833

RESUMO

Obstructive sleep apnea (OSA) has been associated with the initiation and progression of cardiovascular disease. This study aimed to explore the relationship between the severity of OSA and the risk stratification of acute pulmonary embolism (PE). In this single-center cohort study, patients diagnosed with PE were evaluated for OSA via polygraphy monitoring. The simplified PE severity index (sPESI) and the number of patients requiring systemic thrombolysis were used to determine the severity of the disease. Echocardiography was performed on all participants. All patients were divided into 2 groups (OSA group and non-OSA group), and the patients in OSA group were then divided into 3 groups based on the severity of OSA. Patients with severe OSA had a significantly higher number of patients with sPESI ≥ 1 (P = .005). A higher proportion of patients with severe OSA require systemic thrombolysis (P = .010). Patients with apnea-hypopnea index (AHI) > 30/h had a much higher fibrinogen (P = .004) and D-dimer (P = .040) level than those in the non-OSA group. The levels of creatinine were significantly higher in patients with OSA (P = .040). Echocardiography showed a significant difference in left ventricular ejection fraction (LVEF) between patients in non-OSA and severe OSA groups (P = .035). And brain natriuretic peptide (BNP) also exhibited a progressive worsening related to the deepest desaturation and oxygen desaturation index. OSA, especially with AHI > 30/h, is correlated with the severity and prognosis of acute PE. This might be attributed to the prothrombotic effect, renal impairment, and cardiac dysfunction in patients with severe OSA.


Assuntos
Embolia Pulmonar , Apneia Obstrutiva do Sono , Humanos , Estudos de Coortes , Volume Sistólico , Função Ventricular Esquerda , Polissonografia , Apneia Obstrutiva do Sono/complicações , Medição de Risco
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