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1.
Drug Resist Updat ; 72: 101019, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984225

RESUMO

This report expands on our previous research, highlighting a unique inverse correlation between MYC expression in tumor cells and immune cells during the development of EGFR-TKI resistance. It is observed that MYC expression and fatty acid oxidation (FAO) metabolism in tissue-resident memory (TRM) CD8 + T cells are significantly impaired. These findings offer new insights into the mechanisms of TKI resistance. Although the study is preliminary, it suggests caution when interpreting the effectiveness of MYC inhibitors in reversing TKI resistance, especially when immune factors are not considered.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Ácidos Graxos/uso terapêutico , Mutação
2.
Small ; 20(8): e2306382, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37828635

RESUMO

Amelioration of nickel-cobalt layered double hydroxides (NiCo-LDH) with a high specific theoretical capacitance is of great desire for high-power supercapacitors. Herein, a molybdenum (Mo) doping strategy is proposed to improve the charge-storage performance of NiCo-LDH nanosheets growing on carbon cloth (CC) via a rapid microwave process. The regulation of the electronic structure and oxygen vacancy of the LDH is consolidated by the density functional theory (DFT) calculation, which demonstrates that Mo doping narrows the band gap, reduces the formation energy of hydroxyl vacancies, and promotes ionic and charge transfer as well as electrolyte adsorption on the electrode surface. The optimal Mo-doped NiCo-LDH electrode (MoNiCo-LDH-0.05/CC) has an amazing specific capacity of 471.1 mA h g-1 at 1 A g-1 , and excellent capacity retention of 84.8% at 32 A g-1 , far superior to NiCo-LDH/CC (258.3 mA h g-1 and 76.4%). The constructed hybrid supercapacitor delivers an energy density of 103.3 W h kg-1 at a power density of 750 W kg-1 and retains the cycle retention of 85.2% after 5000 cycles. Two assembled devices in series can drive thirty LED lamps, revealing a potential application prospect of the rationally synthesized MoNiCo-LDH/CC as an energy-storage electrode material.

3.
Epidemiology ; 35(4): 559-567, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38534181

RESUMO

BACKGROUND: Artificial light at night, a well-recognized circadian clock disrupter, causes disturbances in endocrine homeostasis. However, the association of artificial light at night with polycystic ovary syndrome (PCOS) is still unknown. This study examines the effects of outdoor artificial light at night on sex hormones, glucose homeostasis markers, and PCOS prevalence in Anhui Province, China. METHODS: We recruited 20,633 women of reproductive age from Anhui Medical University Reproductive Medicine Center. PCOS was diagnosed according to Rotterdam criteria. We estimated long-term (previous year) and short-term (previous month) artificial light at night values for residential addresses using 500 m resolution satellite imagery. We fitted multivariable models, using both linear and logistic regression, to estimate the association of artificial light at night with sex hormones, glucose homeostasis markers, and PCOS prevalence. RESULTS: Both long-term and short-term exposure to outdoor artificial light at night were negatively associated with follicle-stimulating hormone and luteinizing hormone levels, while positively associated with testosterone, fasting insulin, homeostasis model assessment-insulin resistance, and homeostasis model assessment-insulin resistance-ß levels. The second-highest quintile of artificial light at night was associated with increased PCOS prevalence (odds ratio [OR long-term ] = 1.4; 95% confidence interval [CI] = 1.2, 1.6 and OR short-term = 1.3; 95% CI = 1.1, 1.5) compared with the lowest quintile. In addition, prevalence of PCOS was linearly associated with long-term exposure to artificial light at night, but nonlinearly associated with short-term exposure. This association was more evident in younger, obese or overweight, moderately educated, rural women, and for the summer and fall seasons. CONCLUSION: Outdoor artificial light at night may be a novel risk factor for PCOS.


Assuntos
Hormônio Foliculoestimulante , Homeostase , Resistência à Insulina , Hormônio Luteinizante , Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/epidemiologia , Adulto , China/epidemiologia , Hormônio Luteinizante/sangue , Adulto Jovem , Hormônio Foliculoestimulante/sangue , Glicemia/análise , Iluminação/efeitos adversos , Testosterona/sangue , Prevalência , Adolescente , Insulina/sangue , Modelos Logísticos
4.
Environ Res ; 258: 119462, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38908664

RESUMO

Extreme weather is becoming more frequent due to drastic changes in the climate. Despite this, the body of research focused on the association between temperature extreme events and sperm quality remains sparse. In this study, we elucidate the impact of exposure to environmental temperature extremes on sperm quality. Data for this investigation were derived from the Anhui Prospective Assisted Reproduction Cohort, encompassing the period from 2015 to 2020. Parameters such as sperm concentration, total sperm count, total motility, progressive motility, total motile sperm count, and progressive motile sperm count were quantified from semen samples. We assessed the exposure of participants to temperature extremes during the 0-90 days prior to sampling. This investigation encompassed 15,112 participants, yielding 28,267 semen samples. Our research findings indicate that exposure to low temperature extreme for three consecutive days (at the first percentile threshold) has a detrimental correlation with sperm count parameters and concentration. Similar trends were observed with the second percentile threshold, where significant adverse effects typically manifested after a four-day exposure sequence. Analysis of high temperature extreme showed that exposure at the 98th percentile had adverse effects on all six sperm quality parameters, and the sperm count parameter was particularly sensitive to high temperature, showing significant results immediately after three days of exposure. When considering even more temperature extreme (99th percentile), the negative consequences were more pronounced on the sperm count parameter. Additionally, progressive motility showed a stronger negative response. In summary, parameters associated with sperm count are particularly vulnerable to temperature extremes exposure. Exposure to high temperature extremes environments may also be associated with a decrease in sperm concentration and vitality. The findings of this study suggest that male population should pay attention to avoid exposure to temperature extreme environment, which has important significance for improving the quality of human fertility.


Assuntos
Contagem de Espermatozoides , Espermatozoides , Temperatura , Masculino , Humanos , China , Estudos Prospectivos , Adulto , Motilidade dos Espermatozoides , Análise do Sêmen , Exposição Ambiental/efeitos adversos
5.
Int Arch Occup Environ Health ; 97(3): 313-329, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38403848

RESUMO

OBJECTIVES: This study aimed to reveal the short-term impact of meteorological factors on the mortality risk in hypertensive patients, providing a scientific foundation for formulating pertinent prevention and control policies. METHODS: In this research, meteorological factor data and daily death data of hypertensive patients in Hefei City from 2015 to 2018 were integrated. Time series analysis was performed using distributed lag nonlinear model (DLNM) and generalized additive model (GAM). Furthermore, we conducted stratified analysis based on gender and age. Relative risk (RR) combined with 95% confidence interval (95% CI) was used to represent the mortality risk of single day and cumulative day in hypertensive patients. RESULTS: Single-day lag results indicated that high daily mean temperature (T mean) (75th percentile, 24.9 °C) and low diurnal temperature range (DTR) (25th percentile, 4.20 °C) levels were identified as risk factors for death in hypertensive patients (maximum effective RR values were 1.144 and 1.122, respectively). Extremely high levels of relative humidity (RH) (95th percentile, 94.29%) reduced the risk of death (RR value was 0.893). The stratified results showed that the elderly and female populations are more susceptible to low DTR levels, whereas extremely high levels of RH have a more significant protective effect on both populations. CONCLUSION: Overall, we found that exposure to low DTR and high T mean environments increases the risk of death for hypertensive patients, while exposure to extremely high RH environments significantly reduces the risk of death for hypertensive patients. These findings contribute valuable insights for shaping targeted prevention and control strategies.


Assuntos
Hipertensão , Conceitos Meteorológicos , Humanos , Feminino , Idoso , Temperatura , Fatores de Tempo , China/epidemiologia , Fatores de Risco , Hipertensão/epidemiologia
6.
Drug Resist Updat ; 66: 100910, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36571924

RESUMO

Acquired resistance to tyrosine kinase inhibitors (TKIs) is reportedly inevitable in lung cancers harboring epidermal growth factor receptor (EGFR) mutations, emphasizing the need for novel approaches to predict EGFR-TKI resistance for clinical monitoring and patient management. This study identified a significant increase in eomesodermin (EOMES)+CD8+ T cells in the TKI-resistant patients, which was correlated with poor survival. The increase in EOMES+CD8+ T cells was further confirmed in both tissue samples and peripheral blood of patients with TKIs resistance. The integrated analysis of pseudotime and Gene set variation showed that the increase in EOMES+CD8+ T cells may be attributed to TRM T cell conversion and metabolic reprogramming. Overall, this work suggested an association between the increased number of EOMES+CD8+ T cells and acquired TKI drug resistance, supporting the utility of EOMES+CD8+ T cells as a biomarker for TKI treatment response.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Pulmonares , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas com Domínio T/genética , Proteínas com Domínio T/uso terapêutico
7.
Ecotoxicol Environ Saf ; 284: 116915, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39178764

RESUMO

Fine particulate matter (PM2.5) may disrupt women's reproductive hormones, posing potential reproductive risks. However, the exact compositions of PM2.5 responsible for these effects remain unclear. Our investigation explored the long-term impacts of PM2.5 constituents on reproductive hormones, based on a large longitudinal assisted reproductive cohort study in Anhui, China. We included 24,396 reproductive hormone samples from 19,845 women attending assisted reproductive technologies (ART) between 2014 and 2020. Using high-resolution gridded data (1-km resolution), we calculated the residence-specified PM2.5 constituents during the year before the month of hormone testing. Relationships between PM2.5 constituents [organic matter (OM), chloride (Cl-), sulfate (SO42-), ammonium (NH4+), black carbon, and nitrate] and reproductive hormones were investigated using the linear mixed model with subject-specific intercepts. The constituent-proportion model and the constituent-residual model were also constructed. Additionally, cubic spline analysis was used to examine the potential non-linear exposure-response relationship. We found that per interquartile range (IQR) increment in OM was associated with a 5.31 % (3.74 %, 6.89 %) increase in estradiol, and per IQR increment in Cl- and NH4+ were associated with 13.56 % (7.63 %, 19.82 %) and 9.07 % (4.35 %, 14.01 %) increases in luteinizing hormone. Conversely, per IQR increment in OM and Cl- were associated with -7.27 % (-9.34 %, -5.16 %) and -8.52 % (-10.99 %, -5.98 %) decreases in progesterone, and per IQR increment in SO42- was associated with a -9.15 % (-10.31 %, -7.98 %) decrease in testosterone. These associations were held in both proportional and residual models. Moreover, exposure-response curves for estradiol and progesterone with PM2.5 constituents exhibited approximately U-shaped. These results suggested that specific PM2.5 constituents might disrupt reproductive hormone homeostasis in women attending ART, providing new evidence for formulating PM2.5 pollution reduction strategies that could benefit women's reproductive health.


Assuntos
Poluentes Atmosféricos , Estradiol , Material Particulado , Técnicas de Reprodução Assistida , Material Particulado/análise , Feminino , Humanos , Estudos Longitudinais , Adulto , China , Poluentes Atmosféricos/análise , Homeostase/efeitos dos fármacos , Progesterona , Exposição Ambiental , Hormônio Luteinizante
8.
J Am Chem Soc ; 145(9): 5252-5260, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36848482

RESUMO

The quantitative profiling of residue reactivity in proteins promotes the discovery of covalent druggable targets for precise therapy. Histidine (His) residues, accounting for more than 20% of the active sites in enzymes, have not been systematically characterized for their reactivity, due to lack of labeling probes. Herein, we report a chemical proteomics platform for the site-specific quantitative analysis of His reactivity by combination of acrolein (ACR) labeling and reversible hydrazine chemistry enrichment. Based on this platform, in-depth characterization of His residues was conducted for the human proteome, in which the rich content of His residues (>8200) was quantified, including 317 His hyper-reactive residues. Intriguingly, it was observed that the hyper-reactive residues were less likely to be the sites for phosphorylation, and the possible mechanism of this antagonistic effect still needs to be evaluated in further research. Based on the first comprehensive map of His residue reactivity, many more residues could be adopted as the bindable sites to disrupt the activities of a diverse number of proteins; meanwhile, ACR derivatives could also be used as a novel reactive warhead in the development of covalent inhibitors.


Assuntos
Acroleína , Proteoma , Humanos , Histidina , Fosforilação , Proteômica
9.
Clin Exp Pharmacol Physiol ; 50(1): 28-38, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36059120

RESUMO

The aberrant expression of secretory mucin MUC5AC has been documented during the tumourigenesis and progression of various cancers. However, little is currently known on the function of MUC5AC in lung adenocarcinoma. The present study focused on the tumour-promoting role of MUC5AC and its regulatory mechanisms in lung adenocarcinoma. Firstly, MUC5AC expression was evaluated in NSCLC tissue microarrays by immunohistochemistry. Kaplan-Meier analysis were used to clarify the prognostic value of MUC5AC. Subsequently, small interfering RNA and small hairpin RNA were used to knockdown MUC5AC in lung ADC cell lines to elucidate its role in tumorigenesis and progression of lung adenocarcinoma via in vitro functional assays and xenograft mouse models. Finally, the regulatory mechanisms underlying p53/Sp1/MUC5AC axis were identified through dual-luciferase report. We found that MUC5AC was upregulated in lung ADC tissues and cell lines, especially in KRAS-mutant cases and correlated with poor prognosis. MUC5AC gene silencing resulted in reduced cell proliferation, invasion and migration. Furthermore, knockdown of MUC5AC led to reversion of the epithelial-mesenchymal transition. Additionally, downregulation of MUC5AC reduced tumourigenesis in mouse models. Finally, we found an antagonistic role between Sp1 and p53 in the regulation of MUC5AC gene expression. Our findings suggest that high MUC5AC expression promotes tumourigenesis and progression of lung ADC. Both p53 gene inactivation and Sp1 overexpression in lung ADC may enhance MUC5AC expression, especially in KRAS-mutated cases. Given the paucity of efficient drug-targeted approaches of KRAS-driven lung ADCs, therapies directed at downstream effectors such as MUC5AC could have huge prospects.


Assuntos
Adenocarcinoma de Pulmão , Proteína Supressora de Tumor p53 , Humanos , Animais , Camundongos , Proteína Supressora de Tumor p53/genética , Adenocarcinoma de Pulmão/genética , Fator de Transcrição Sp1/genética , Mucina-5AC/genética
10.
Gastroenterology ; 161(5): 1601-1614.e23, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34303658

RESUMO

BACKGROUND & AIMS: Promoted by pancreatitis, oncogenic KrasG12D triggers acinar cells' neoplastic transformation through acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia. Anterior gradient 2 (Agr2), a known inhibitor of p53, is detected at early stage of pancreatic ductal adenocarcinoma (PDAC) development. RNA polymerase II (RNAPII) is a key nuclear enzyme; regulation of its nuclear localization in mammalian cells represents a potential therapeutic target. METHODS: A mouse model of inflammation-accelerated KrasG12D-driven ADM and pancreatic intraepithelial neoplasia development was used. Pancreas-specific Agr2 ablation was performed to access its role in pancreatic carcinogenesis. Hydrophobic hexapeptides loaded in liposomes were developed to disrupt Agr2-RNAPII complex. RESULTS: We found that Agr2 is up-regulated in ADM-to-pancreatic intraepithelial neoplasia transition in inflammation and KrasG12D-driven early pancreatic carcinogenesis. Genetic ablation of Agr2 specifically blocks this metaplastic-to-neoplastic process. Mechanistically, Agr2 directs the nuclear import of RNAPII via its C-terminal nuclear localization signal, undermining the ATR-dependent p53 activation in ADM lesions. Because Agr2 binds to the largest subunit of RNAPII in a peptide motif-dependent manner, we developed a hexapeptide to interfere with the nuclear import of RNAPII by competitively disrupting the Agr2-RNAPII complex. This novel hexapeptide leads to dysfunction of RNAPII with concomitant activation of DNA damage response in early neoplastic lesions; hence, it dramatically compromises PDAC initiation in vivo. Moreover, the hexapeptide sensitizes PDAC cells and patient-derived organoids harboring wild-type p53 to RNAPII inhibitors and first-line chemotherapeutic agents in vivo. Of note, this therapeutic effect is efficient across various cancer types. CONCLUSIONS: Agr2 is identified as a novel adaptor protein for nuclear import of RNAPII in mammalian cells. Also, we provide genetic evidence defining Agr2-dependent nuclear import of RNAPII as a pharmaceutically accessible target for prevention and treatment in PDAC in the context of wild-type p53.


Assuntos
Carcinoma in Situ/enzimologia , Carcinoma Ductal Pancreático/enzimologia , Mucoproteínas/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias Pancreáticas/enzimologia , RNA Polimerase II/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Antineoplásicos/farmacologia , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica , Metaplasia , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Mucoproteínas/genética , Mutação , Oligopeptídeos/farmacologia , Proteínas Oncogênicas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Polimerase II/genética , Proteína Supressora de Tumor p53/genética
11.
Prev Med ; 157: 107007, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35247440

RESUMO

BACKGROUND: This study aimed to identify latent class profiles of sexual minority adolescents (Men Sexually attracted to Men, Women Sexually attracted to Women, and Bisexual) with elevated suicidal ideation. METHODS: Data were collected from 18 secondary schools in China. Sub-group classifications were identified using variables associated with suicidal ideation in sexual minority adolescents, including parental relationship quality, electronic equipment time, school bullying, and sleep quality using the Chinese version of the Pittsburgh Sleep Quality Index to measure sleep. Anxiety was measured using the Generalized Anxiety Disorder 7 (GAD-7), depression was measured using the Patient Health Questionnaire 9 (PHQ-9), hypomania using the Hypomanic Checklist-32 (HCL-32), positive coping style was identified using the Trait Coping Style Questionnaire, and self-efficacy was measured by the General Self-Efficacy Scale. RESULTS: Four distinctive profiles were derived from the data. Compared to "low-risk" group (Class 3), the "adolescent with mood problems" group (Class 2) had a 9.81 times higher risk of suicidal ideation; the those who classified as "severe bullied adolescent" (Class 4) had a 9.26 times higher risk of suicidal ideation. and the "adolescents with low self-efficacy" group (Class 1) had a 4.48 times higher risk of suicidal ideation. CONCLUSIONS: Sexual minority adolescents with mood problems have the highest risk of suicidal ideation, followed by adolescents frequently being bullied at school. Interventions aimed at reducing suicide risk among sexual minority adolescents may benefit from attending to such profile factors identified in this study to develop targeted clinical care.


Assuntos
Bullying , Minorias Sexuais e de Gênero , Suicídio , Adolescente , Bissexualidade , Feminino , Humanos , Masculino , Fatores de Risco , Ideação Suicida
12.
Nanotechnology ; 33(48)2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-35834909

RESUMO

Nanoantenna fusion photonics and nanotechnology can manipulate light through the ultra-thin structure composed of sub-wavelength antennas, and meet the important requirements for miniaturized optical components, completely changing the field of optics. However, the device design process is still time-consuming and consumes computing resources. Besides, the professional knowledge requirements of engineers are also high. Relying on the algorithm's inference ability and excellent computing ability, artificial intelligence has great potential in the fields of material design, material screening, and device performance prediction. However, the deep learning (DL) requires a mass of data. Therefore, this article proposes a method for the forward and inverse design of nanoantenna based on DL. Compared with the previous work, the network uses a two-dimensional matrix as input, which has a simple structure and is more suitable for the advantages of deep netural network. Simultaneously, the small datasets can be used to achieve higher accuracy. In the forward prediction, 100% of the data error is less than 0.007; in the inverse prediction, the data with error less than 0.05 accounted for 90%, 99.8% and 100% of the length, height, and width's datasets. It demonstrates that the method can improve the automation of the design process and reduce the consumption of computer resources.

13.
Bull Environ Contam Toxicol ; 110(1): 12, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36512146

RESUMO

The widespread occurrence of cyanobacteria blooms damages the water ecosystem and threatens the safety of potable water and human health. Exogenous L-lysine significantly inhibits the growth of a dominant cyanobacteria Microcystis aeruginosa in freshwater. However, the molecular mechanism of how lysine inhibits the growth of M. aeruginosa is unclear. In this study, both non-target and target metabolomic analysis were performed to investigate the effects of algicide L-lysine. The results showed that 8 mg L- 1 lysine most likely disrupts the metabolism of amino acids, especially the arginine and proline metabolism. According to targeted amino acid metabolomics analysis, only 3 amino acids (L-arginine, ornithine, and citrulline), which belong to the ornithine-ammonia cycle (OAC) in arginine metabolic pathway, showed elevated levels. The intracellular concentrations of ornithine, citrulline, and arginine increased by 115%, 124%, and 19.4%, respectively. These results indicate that L-lysine may affect arginine metabolism and OAC to inhibit the growth of M. aeruginosa.


Assuntos
Cianobactérias , Herbicidas , Microcystis , Humanos , Microcystis/metabolismo , Lisina/toxicidade , Lisina/metabolismo , Citrulina/metabolismo , Ecossistema , Herbicidas/metabolismo , Cianobactérias/metabolismo , Ornitina/toxicidade , Ornitina/metabolismo , Arginina/química , Arginina/metabolismo , Amônia , Microcistinas/metabolismo
14.
BMC Public Health ; 21(1): 2249, 2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895204

RESUMO

BACKGROUNDS: Various family factors have been identified in association with school bullying and the involvement of children and adolescents in bullying behaviors. METHODS: A total of 11,919 participants (female = 6671, mean age = 15) from 22 middle schools in Suzhou City, China completed the questionnaire. The associations between structural family factors (family socio-economic status, living arrangement, number of siblings, whether they were local residents/migrants, had an urban/rural hukou [a household registration system in China], parental and maternal education levels, and other various bullying-related constructs (i.e. bullying witnessing, bullying involvement, bystander intervention, and fear of being bullied) were all examined. Odds ratios (ORs) adjusted for covariates were calculated for the four bullying-related constructs (bullying witness, bullying involvement, bystander intervention, and reactions to being bullied) using structural family factors. RESULTS: The result showed that all demographic household characteristics were associated with bullying at school except for being from a single-child family. Adolescents from rural families witnessed more bullying incidents than those from local families (OR = 1.35, 95% CI: [1.09, 1.68]). Adolescents who come from migrant families (OR = 1.12, 95% CI: [1.07, 1.43]) with a rural hukou (OR = 1.31, 95% CI: [1.00, 1.74]) and low parental education levels (OR = 1.42, 95% CI: [1.01, 2.57]) were more likely to be bullies. Adolescents who came from migrant families (OR = 1.37, 95% CI: [1.03, 1.82]), with low maternal education levels (OR = 1.42, 95% CI: [1.06, 1.91]) engaged in more negative bystander intervention behaviors. Furthermore, adolescents with less educated mothers experienced a higher fear of being bullied (never versus sometimes: OR = 1.33, 95% CI: [1.00, 1.85]; never versus usually OR = 1.39, 95% CI: [1.01, 1.20]). CONCLUSIONS: A systematic examination of the relationship between school bullying and demographic household characteristics may be used to inform school policies on bullying, such as training management on the importance of paying attention to adolescents from disadvantage household backgrounds. Identifying demographic factors that may predict bullying can also be used to prevent individuals from becoming involved in bullying and reduce the related negative consequences from being bullied.


Assuntos
Bullying , Vítimas de Crime , Adolescente , Escolaridade , Feminino , Humanos , Pais , Instituições Acadêmicas , Inquéritos e Questionários
15.
Angew Chem Int Ed Engl ; 60(20): 11143-11147, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33644946

RESUMO

While two-dimensional infrared (2D-IR) spectroscopy is uniquely suitable for monitoring femtosecond (fs) to picosecond (ps) water dynamics around static protein structures, its utility for probing enzyme active-site dynamics is limited due to the lack of site-specific 2D-IR probes. We demonstrate the genetic incorporation of a novel 2D-IR probe, m-azido-L-tyrosine (N3Y) in the active-site of DddK, an iron-dependent enzyme that catalyzes the conversion of dimethylsulfoniopropionate to dimethylsulphide. Our results show that both the oxidation of active-site iron to FeIII , and the addition of denaturation reagents, result in significant decrease in enzyme activity and active-site water motion confinement. As tyrosine residues play important roles, including as general acids and bases, and electron transfer agents in many key enzymes, the genetically encoded 2D-IR probe N3Y should be broadly applicable to investigate how the enzyme active-site motions at the fs-ps time scale direct reaction pathways to facilitating specific chemical reactions.


Assuntos
Azidas/metabolismo , Liases de Carbono-Enxofre/metabolismo , Compostos Férricos/metabolismo , Tirosina/análogos & derivados , Azidas/química , Liases de Carbono-Enxofre/química , Domínio Catalítico , Compostos Férricos/química , Estrutura Molecular , Espectrofotometria Infravermelho , Tirosina/química , Tirosina/metabolismo
16.
Analyst ; 145(17): 5870-5877, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32662497

RESUMO

Extracellular vesicles (EVs) are cell-derived vesicles which encapsulate a variety of molecules. Numerous studies have demonstrated EVs as signaling mediators of intercellular communication and are heavily involved under physiological and pathological conditions. In translational medicine, EVs have been used for disease diagnosis and treatment monitoring. EVs as natural nanocarriers for drug delivery and therapeutic EVs are also under intense investigation. While still in its infancy, relevant EV studies have been growing. For EV-centered research to thrive, a few fundamental unanswered questions, such as EV biogenesis, EV secretion rate (SR), EV content sorting mechanisms, etc. require further investigation. In this study, we measured the SR of EVs derived from 6 cancerous cell lines. Several factors that may interfere with EV secretion, isolation, and storage were also investigated. Our results show that the SR of EVs derived from various cancer cells was significantly different, indicating a heterogeneous EV secretion behavior among cell types. Moreover, 5 different drugs that interfere with cellular metabolism significantly influenced EV release. In addition, we found that (1) more EVs can be harvested at 24 h compared to 48 h of serum-free cell culture with a similar degree of FBS contamination; (2) filtration of the cell culture supernatant with a 0.22 µm filter causes ∼70% loss of EVs; (3) the isolation efficiency of EVs with the prevalent ultracentrifugation is only ∼14%; (4) storage at 4 °C for 3 days causes ∼21% loss of EVs. Overall, our findings provide a guideline for proper EV collection and storage in laboratory settings.


Assuntos
Vesículas Extracelulares , Movimento Celular , Organelas , Soro , Ultracentrifugação
17.
BMC Pregnancy Childbirth ; 20(1): 537, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933502

RESUMO

BACKGROUND: Post-partum depression (PPD) is a growing mental health concern worldwide. There is little evidence in the Chinese context of the relationship between paternal PPD and maternal PPD. Given the growing global concerns this relationship requires further exploration. METHODS: A survey was conducted with 950 total couples from March 2017 to December 2018. The study was conducted using a standardized questionnaire that included basic demographic information, information on the relationship between the mother-in-law and daughter-in-law, marital satisfaction (both maternal and paternal), and PPD symptoms. Structural Equation Modelling (SEM) analysis was used to explore the underlying mechanism for PPD symptoms in mothers and fathers. RESULTS: In 4.4% of the couples both the wife and the husband showed depressive symptoms. Maternal marital satisfaction showed a significant mediating effect on paternal PPD (B = -0.114, p < 0.01), and there was a direct effect of maternal PPD on paternal PPD (B = 0.31, p < 0.001). CONCLUSIONS: This is the first study to investigate the possible correlation between maternal PPD, mother-in-law and daughter-in-law relationship satisfaction, maternal marital satisfaction, paternal marital satisfaction, and paternal PPD. It is important for future PPD interventions to target both maternal and paternal mental health, as well as the mechanisms identified that can lead to PPD.


Assuntos
Depressão Pós-Parto/epidemiologia , Pai/psicologia , Modelos Estatísticos , Mães/psicologia , Adulto , Correlação de Dados , Relações Familiares , Feminino , Humanos , Masculino , Satisfação Pessoal , Autorrelato , Adulto Jovem
18.
Mol Cancer ; 18(1): 53, 2019 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-30925925

RESUMO

Exosomes are cell-derived vesicles of 30 to 150 nm that contain diverse proteins, nucleic acids, and lipids. These vesicles facilitate effective intercellular communication and trigger profound environmental changes. In recent years, many studies have identified diverse roles for exosomes in tumor metastasis, a major cause of cancer-related deaths; furthermore, circulating tumor-derived exosomes can drive the initiation and progression of metastasis and determine the specific target organs affected. Fortunately, our growing understanding of exosomes and relevant modification technology have provided new ideas for potential treatment of tumor metastases. Here we review recent advances concerning the role of exosomes in metastasis, focusing on their regulatory mechanisms and therapeutic targeting in advanced cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Exossomos/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Animais , Comunicação Celular , Humanos , Metástase Neoplásica , Neoplasias/patologia , Microambiente Tumoral
19.
Int Wound J ; 15(2): 237-242, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29193653

RESUMO

This study aimed to investigate the incidence and risk factors of deep surgical site infection (DSSI) during hospitalisation after closed tibial plateau fractures treated with open reduction and internal fixation (ORIF). We performed this retrospective study at a university-affiliated hospital with an advanced trauma centre. The data of adult patients with closed tibial plateau fractures treated with ORIF from January 2012 to February 2017 were extracted from the electronic medical records. Demographics, injury-related and surgery-related variables of DSSI and non-DSSI groups were compared by univariate test. Multivariate logistic analysis models were used to investigate the independent risk factors. In total, 676 patients with complete data met the inclusion criteria and were included, and of them, 17 developed DSSI (2.51%) during hospitalisation. Approximately 60% (9/17) of DSSI was caused by Staphylococcus aureus. Compared to the non-DSSI group, DSSI patients had a significantly longer stay in hospital (25.8 vs 15.2 days). Independent risk factors of DSSI identified by multivariate analysis were higher BMI (>26.0) (OR, 1.58; 95% CI, 1.09 to 3.27; P = 0.032), prolonged surgical duration (>138 min) (OR, 4.26; 95% CI, 1.54 to 11.19; P = 0.005) and current smoking (OR, 3.42; 95% CI, 1.47 to 8.62; P = 0.01). A relatively low incidence rate of DSSI (2.51%) was found in this study, and several significant risk factors were identified. Smoking cessation programmes should be implemented immediately after hospitalisation, especially for obesity and morbid obesity patients. Detailed and comprehensive preoperative assessment and a considerate operative plan should be guaranteed to reduce surgical duration.


Assuntos
Fixação Interna de Fraturas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Infecção da Ferida Cirúrgica/etiologia , Fraturas da Tíbia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia
20.
Inflammopharmacology ; 25(2): 203-210, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28190128

RESUMO

OBJECTIVE: In the present study, DNA methylation level of CD4+ T cells exposed to ultraviolet B (UVB) was investigated and its potential mechanisms were also explored. METHODS: CD4+ T cells from 12 cases of healthy subjects and 33 cases of SLE patients were isolated and exposed to different dosages (0, 50, 100 mJ/cm2) of UVB. Further, SLE patients were divided into two groups: active SLE group (22 cases, SLEDAI scores >4) and inactive SLE group (11 cases, SLEDAI scores ≤4). DNA methylation was evaluated by the Methylamp™ Global DNA Methylation Quantification Ultra Kit. The mRNA and protein expression levels of DNA methyltransferases (DNMT1 and DNMT3A) were detected by real-time PCR and western blot, respectively. RESULTS: The levels of DNA methylation and DNMT3A mRNA in SLE patients were significantly decreased compared with those in healthy subjects at baseline. After different dosages of ultraviolet irradiation (0, 50 and 100 mJ/cm2), DNA methylation levels of CD4+ T cells were all reduced in a dose-dependent manner in three subgroups. Additionally, 100 mJ/cm2 ultraviolet irradiation in active SLE group contributed to a significant decrease of both DNA methylation and DNMT3A mRNA levels in CD4+ T cells. UVB exposure had no significant effects on expression levels of DNMT1 mRNA and protein and DNMT3A protein. CONCLUSION: UVB decreases DNA methylation level of CD4+ T cells in SLE patients probably via inhibiting DNMT3A mRNA expression level, which needs to be further explored.


Assuntos
Linfócitos T CD4-Positivos/efeitos da radiação , DNA (Citosina-5-)-Metiltransferases/efeitos da radiação , Metilação de DNA/efeitos da radiação , Lúpus Eritematoso Sistêmico , Raios Ultravioleta , Adulto , Linfócitos T CD4-Positivos/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/fisiologia , DNA Metiltransferase 3A , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Raios Ultravioleta/efeitos adversos
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