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1.
Patient Prefer Adherence ; 18: 1907-1918, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296427

RESUMO

Purpose: Our study aimed to explore the current status of patient participation in medication safety from the perspectives of general practitioners (GPs), pharmacists, and outpatients in Beijing, China. Patients and Methods: A qualitative study using semi-structured in-depth individual interviews with GPs, pharmacists, and outpatients. Subjects were identified by purposive sampling until code saturation. Semi-structured qualitative interviews were conducted with GPs, pharmacists, and patients from community health service centers in three urban districts of Beijing, China. The interviews were transcribed verbatim and the text was analysed using thematic analysis techniques including familiarising with data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report. Results: A total of eight GPs, seven pharmacists, and 18 outpatients were interviewed. Data analysis led to the generation of five key themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. Patients participated in medication safety in multiple ways. However, insufficient knowledge about medication safety, lack of awareness of the patient's role in ensuring medication safety, shortage of consultation lengths, and being misled by some information were problems with patient participation in medication safety. Conclusion: This exploratory study contributes to our initial understanding of patient participation in medication safety. There were still many issues and barriers in the process of patient participation. Appropriate policies and measures, such as providing various forms of patient education, ensuring sufficient physician-patient communication, giving full play to the role of pharmacists, and making judicious use of digital health tools should be taken to improve medication safety by fully utilising the role of patients.


Medication safety is a significant concern around the world. Patient participation in the medication process is effective in reducing the incidence of medication errors and improving medication safety. However, the role of outpatients with chronic conditions in ensuring medication safety is often neglected. This study aims to explore the perspectives and experiences of GPs, pharmacists, and outpatients by qualitative interviews in Beijing, China. The study involved a series of interviews with eight GPs, seven pharmacists, and 18 outpatients living with noncommunicable diseases. The interview revealed five themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. The findings might help propose suggestions for patient participation in medication safety. Integrating these findings into future studies can help healthcare professionals formulate interventions and better support patients in participating in the medication process.

2.
Wei Sheng Yan Jiu ; 53(5): 701-707, 2024 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-39308100

RESUMO

OBJECTIVE: Understanding urban-rural differences in the risk of aggregation of adolescents' health-risk behaviors in the Wuling Mountain Area. METHODS: From March to May 2023, 7901 adolescents from junior to junior high school and senior high school grades in 32 middle schools in 8 counties(districts) in the Wuling Mountain Area were selected as survey respondents using the multi-stage stratified random cluster sampling method, with the age of the survey respondents being(14.82±1.50) years old. There were 4047 male students(51.22%) and 3854 female students(48.78%), 5126(64.88%) in junior high school and 2775(35.12%) in senior high school.2513(31.81%) in rural schools and 5388(68.19%) in urban schools. The Questionnaire on Health Risky Behaviors of Youth in Wuling Mountain Area was used to investigate 9 health risky behaviors of youth, such as partial feeding, smoking, and drinking alcohol. The χ~2 test was used to test the difference between urban and rural adolescents' risky health behaviors and their multivariate aggregation incidence rates, and to calculate the relative risk(RR) and the actual expected ratio(O/E). RESULTS: The incidence of bivariate to quintivariate cluster of adolescent health-risk behaviors was lower in all rural schools than in urban schools(χ~2 were 60.73, 34.97, 16.89, and 9.14, P<0.05). Rural school adolescents had the highest RR value for alcohol consumption behavior(18.02), while urban school adolescents had the highest RR value for insomnia behavior(15.05). In the bivariate cluster model, the O/E values for "smoking+alcohol consumption" were highest in both rural(8.18) and urban(6.14) school adolescents. In the trivariate cluster model, the O/E values for "smoking+alcohol consumption+fighting" were highest in both rural(28.41) and urban(18.15) school adolescents. In the quadrivariate cluster model, the O/E values for "smoking+alcohol consumption+insomnia+experiencing school bullying" were highest in rural school adolescents(95.10), while the O/E values for "smoking+alcohol consumption+fighting+experiencing school bullying" were highest in urban school adolescents(42.97). In the quintivariate cluster model, the O/E values for "smoking+alcohol consumption+fighting+insomnia+experiencing school bullying" were highest in both rural(309.57) and urban(129.28) school adolescents. CONCLUSION: Adolescents in urban schools in the Wuling Mountain Area are more prone to clustering harmful health behaviors compared to those in rural schools, and there are differences in the clustering risks of harmful health behaviors and their diverse clustering patterns between urban and rural areas.


Assuntos
Consumo de Bebidas Alcoólicas , Comportamentos de Risco à Saúde , População Rural , População Urbana , Adolescente , Humanos , Masculino , Feminino , População Rural/estatística & dados numéricos , China/epidemiologia , População Urbana/estatística & dados numéricos , Inquéritos e Questionários , Consumo de Bebidas Alcoólicas/epidemiologia , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Fumar/epidemiologia , Comportamento do Adolescente/psicologia , Assunção de Riscos , Estudos de Amostragem
3.
Sci Rep ; 14(1): 20855, 2024 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242798

RESUMO

This study aims to investigate the relationship between bullying victimization and mobile phone addiction (MPA) among college students, taking into consideration the mediating role of self-control and the moderating role of physical activity. A self-report survey was administered to college students from 4 universities in Guangxi, Liaoning, and Hunan provinces in China. Participants were asked to report their experiences of bullying victimization, level of MPA, self-control, and physical activity. Descriptive statistics, correlation analysis, and regression analysis were conducted to analyze the data. Mediation and moderation models were subsequently established to examine the relationships between variables. The results indicated a positive correlation between bullying victimization and MPA among college students. Additionally, bullying victimization was negatively correlated with self-control. Bullying victimization significantly predicted MPA, and self-control partially mediated this relationship. Furthermore, physical activity moderated the association between bullying victimization and self-control among college students. The findings suggest that self-control plays a partial mediating role in the relationship between bullying victimization and MPA among college students. Moreover, physical activity weakens the association between bullying victimization and self-control. Therefore, promoting physical activity to reduce MPA among college students who have experienced bullying victimization is highly recommended.


Assuntos
Bullying , Telefone Celular , Vítimas de Crime , Exercício Físico , Autocontrole , Estudantes , Humanos , Masculino , Feminino , Estudantes/psicologia , Bullying/psicologia , Universidades , Adulto Jovem , Vítimas de Crime/psicologia , Autocontrole/psicologia , China/epidemiologia , Adulto , Comportamento Aditivo/psicologia , Adolescente , Inquéritos e Questionários , Autorrelato
4.
Asian J Androl ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39091129

RESUMO

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.

6.
Int Heart J ; 65(4): 730-737, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39085112

RESUMO

Sodium tanshinone IIA sulfonate (STS), which is extracted from a Chinese medicinal herb, possesses many pharmacologic functions, such as coronary dilation, anti-inflammatory properties, and antiapoptotic and antioxidant effects. It remains unknown whether STS can protect cardiomyocytes injured after radiation therapy. An in vitro Sprague-Dawley (SD) rat neonatal cardiomyocyte system was established. Primary cardiomyocytes (PCMs) from neonatal SD rats were isolated under sterile conditions. PCM cells were divided into a control group (0 Gy/hour) and 5 experimental radiation therapy groups (0.25 Gy/hour, 0.5 Gy/hour, 1 Gy/hour, 2 Gy/hour, and 4 Gy/hour). Cell viability, the content of malondialdehyde (MDA), the lactate dehydrogenase (LDH) leakage rate, and superoxide dismutase (SOD) and glutathione (GSH) activities were recorded separately in each group after 7 days of culture. Western blot was used to detect the levels of p38, caspase-3 protein, and X protein (BAX) associated with B-cell lymphoma 2 (Bcl-2) in PCMs. X-rays inhibited cell growth, decreased cell viability, and induced an oxidative stress response in PCMs. STS and SB203580 (the inhibitor of P38 mitogen-activated protein kinase pathway) alleviated X-ray-induced damage to PCMs. An enzyme-linked immunosorbent assay showed that X-rays increased the cTnT level. STS and SB203580 ameliorated the X-ray-induced increase in cTnT leakage. X-rays enhanced the expression of p38/p-p38 and caspase-3 while reducing the expression of Bcl-2/BAX in PCMs, as demonstrated by western blotting. STS and SB203580 mitigated the changes in protein expression triggered by X-ray radiation. In conclusions, STS was shown to exert significant cardioprotective, anti-inflammatory, and antioxidant effects in PCMs by inhibiting the p38 mitogen-activated protein kinase pathway.


Assuntos
Miócitos Cardíacos , Fenantrenos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos da radiação , Ratos , Fenantrenos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Células Cultivadas , Animais Recém-Nascidos , Sobrevivência Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Antioxidantes/farmacologia
7.
J Vis Exp ; (207)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829106

RESUMO

Human lifespan is considerably long, while mouse models can simulate the entire human lifespan in a relatively short period, with one year of mouse life roughly equivalent to 40 human years. Intracytoplasmic sperm injection (ICSI) is a commonly used assisted reproductive technology in clinical practice. However, given its relatively recent emergence about 30 years ago, the long-term effects of this technique on human development remain unclear. In this study, we established the ICSI combined with embryo transfer (ET) method using a mouse model. The results demonstrated that normal mouse sperm, after undergoing in vitro culture and subsequent ICSI, exhibited a fertilization rate of 89.57% and a two-cell rate of 87.38%. Following ET, the birth rate of offspring was approximately 42.50%. Furthermore, as the mice aged, fluctuations in glucose metabolism levels were observed, which may be associated with the application of the ICSI technique. These findings signify that the mouse ICSI-ET technique provides a valuable platform for evaluating the impact of sperm abnormalities on embryo development and their long-term effects on offspring health, particularly concerning glucose metabolism. This study provides important insights for further research on the potential effects of the ICSI technique on human development, emphasizing the necessity for in-depth investigation into the long-term implications of this technology.


Assuntos
Glicemia , Transferência Embrionária , Injeções de Esperma Intracitoplásmicas , Animais , Injeções de Esperma Intracitoplásmicas/métodos , Transferência Embrionária/métodos , Camundongos , Feminino , Masculino , Glicemia/análise , Glicemia/metabolismo , Gravidez
8.
Water Res ; 260: 121900, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38870862

RESUMO

Membrane science is the key strategy to solve water shortage in the future, and its essence is energy and mass transfer. Due to the complexity and variety of the internal structure of membrane, the energy transfer theory of membrane is still a black box theory. Herein, a new fluid mechanics principle is introduced to establish the energy fluid theory of membrane, which is translated into the energy formula: such as the initial total pressure difference (ΔP), the flow rate of fluid exiting the membrane (v1 and v2), fluid density (ρ), and energy consumption by salt resistance (NSR): { [Formula: see text] +12ρv23}. The theoretical framework is not only helpful for the data analysis of the energy transfer process of membranes, but also helps to allow for more in-depth and specific theoretical research. For instance, the relationship between NSR and the concentration difference (C) of salt can be expressed as NSR = aCb (a-product constant, b-exponential constant, R2>0.99). Hence, the basic theory can not only be widely applied to a variety of membranes with complex internal structure, but also have a profound impact on the application and research of membrane science.


Assuntos
Membranas Artificiais , Modelos Teóricos
9.
Front Immunol ; 15: 1391524, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835778

RESUMO

Background: Cervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity. Methods: Using advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively. Results: 55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined. Conclusion: Our findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies.


Assuntos
Biomarcadores Tumorais , Imunoterapia , Proteômica , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/diagnóstico , Biomarcadores Tumorais/sangue , Proteômica/métodos , Prognóstico , Imunoterapia/métodos , Pessoa de Meia-Idade , Adulto
10.
Psychol Health Med ; 29(9): 1602-1618, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38770920

RESUMO

This study aims to investigate the mediating effect of anxiety and inhibitory control in the relationship between physical activity and Internet addiction (IA) among adolescents. A total of 951 adolescents from western China completed a self-report survey assessing physical activity, anxiety, inhibitory control, and IA. Descriptive analysis, correlation analysis, and mediation analysis were conducted using SPSS software and the Process plug-in. Controlling for age, gender, and only child status, the findings revealed a negative association between physical activity and anxiety, inhibitory control, and IA. Moreover, anxiety were positively correlated with inhibitory control and IA. Additionally, anxiety exhibited a positive association with inhibitory control. Notably, physical activity directly and negatively predicted IA in adolescents, while also indirectly predicting it through anxiety and inhibitory control. This study contributes to a deeper understanding of the mechanisms that underlie the complex effects of physical activity on IA among adolescents.


Assuntos
Ansiedade , Exercício Físico , Inibição Psicológica , Transtorno de Adição à Internet , Humanos , Adolescente , Feminino , China/epidemiologia , Masculino , Transtorno de Adição à Internet/psicologia , Transtorno de Adição à Internet/epidemiologia , Exercício Físico/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Comportamento do Adolescente/psicologia , Autorrelato , Criança
11.
Science ; 384(6695): eadj4857, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38696569

RESUMO

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.


Assuntos
Linfócitos B , Centro Germinativo , Linfócitos do Interstício Tumoral , Neoplasias , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/genética , Linfócitos do Interstício Tumoral/imunologia , Linfócitos B/imunologia , Centro Germinativo/imunologia , Imunoterapia , Transcriptoma , Análise de Célula Única , Epigênese Genética , Imunidade Humoral , Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos B/imunologia
12.
BMC Psychiatry ; 24(1): 410, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816793

RESUMO

BACKGROUND: Childhood psychological abuse (CPA) are highly correlated with depression among college students, but the underlying mechanisms between variables need further exploration. This study aims to investigate internet addiction as a mediating factor and alexithymia as a moderating factor, in order to further elucidate the potential risk factors between CPA and depression among college students. METHODS: A self-report survey was conducted among 1196 college students from four universities in three provinces in China. The survey included measures of CPA, internet addiction, alexithymia, and depression. Descriptive and correlational analyses were performed on these variables, and a moderated mediation model was constructed. RESULTS: CPA was positively correlated with depression among college students, as well as internet addiction with alexithymia. Internet addiction partially mediated the relationship between CPA and depression among college students, while alexithymia strengthened the relationships among the paths in the moderated mediation model. CONCLUSION: This study provides further insights into the psychological mechanisms underlying the relationship between CPA and depression among college students. Internet addiction serves as a mediating factor in this relationship, while alexithymia may enhance the strength of the relationships among the three variables.


Assuntos
Sintomas Afetivos , Depressão , Transtorno de Adição à Internet , Estudantes , Humanos , Masculino , Estudantes/psicologia , Feminino , Adulto Jovem , Universidades , China/epidemiologia , Depressão/psicologia , Transtorno de Adição à Internet/psicologia , Adulto , Sintomas Afetivos/psicologia , Adolescente , Análise de Mediação , Autorrelato , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Fatores de Risco
13.
Sci Rep ; 14(1): 9781, 2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684733

RESUMO

There is a certain relationship between alexithymia and depression, but further investigation is needed to explore their underlying mechanisms. The aims of this study was to explore the mediating role of internet addiction between alexithymia and depression and the moderating role of physical activity. A total of 594 valid responses were included in the analysis, with a mean age of 18.72 years (SD = 1.09). The sample comprised 250 males (42.09%) and 344 females (57.91%). These responses were utilized for descriptive analysis, correlation analysis, regression analysis, and the development of mediation and moderation models. Alexithymia showed positive correlations with depression and internet addiction, and physical activity was negatively correlated with internet addiction and depression. Internet addiction partially mediated the relationship between alexithymia and depression, while physical activity weakened the association between internet addiction and depression, acting as a moderator. Our findings suggest that excessive Internet engagement may mediate the relationship between alexithymia and depression as an emotional regulatory coping strategy, and that physical activity attenuates the predictive effect of Internet addiction on depression.


Assuntos
Sintomas Afetivos , Depressão , Exercício Físico , Transtorno de Adição à Internet , Humanos , Transtorno de Adição à Internet/epidemiologia , Depressão/epidemiologia , Depressão/etiologia , Depressão/prevenção & controle , Sintomas Afetivos/complicações , Sintomas Afetivos/epidemiologia , Exercício Físico/psicologia , China/epidemiologia , Estudantes , Correlação de Dados , Masculino , Feminino , Adolescente , Adulto Jovem , Análise de Regressão
14.
Cell ; 187(6): 1422-1439.e24, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38447573

RESUMO

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.


Assuntos
Apresentação de Antígeno , Neoplasias , Neutrófilos , Animais , Humanos , Camundongos , Antígenos de Neoplasias , Leucina/metabolismo , Neoplasias/imunologia , Neoplasias/patologia , Neutrófilos/metabolismo , Linfócitos T , Análise da Expressão Gênica de Célula Única
15.
J Agric Food Chem ; 72(11): 5636-5644, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38457784

RESUMO

The evaluation of toxicity and environmental behavior of bioactive lead molecules is helpful in providing theoretical support for the development of agrochemicals, in line with the sustainable development of the ecological environment. In previous work, some acethydrazide structures have been demonstrated to exhibit excellent and broad-spectrum fungicidal activity; however, its environmental compatibility needs to be further elucidated if it is to be identified as a potential fungicide. In this project, the toxicity of fungicidal acethydrazide lead compounds F51, F58, F72, and F75 to zebrafish was determined at 10 µg mL-1 and 1 µg mL-1. Subsequently, the toxic mechanism of compound F58 was preliminarily explored by histologic section and TEM observations, which revealed that the gallbladder volume of common carp treated with compound F58 increased, accompanied by a deepened bile color, damaged plasma membrane, and atrophied mitochondria in gallbladder cells. Approximately, F58-treated hepatocytes exhibited cytoplasmic heterogeneity, with partial cellular vacuolation and mitochondrial membrane rupture. Metabolomics analysis further indicated that differential metabolites were enriched in the bile formation-associated steroid biosynthesis, primary bile acid biosynthesis, and taurine and hypotaurine metabolism pathways, as well as in the membrane function-related glycerophospholipid metabolism, linolenic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism pathways, suggesting that the acethydrazide F58 may have acute liver toxicity to common carp. Finally, the hydrolysis dynamics of F58 was investigated, with the obtained half-life of 5.82 days. The above results provide important guiding significance for the development of new green fungicides.


Assuntos
Fungicidas Industriais , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Fungicidas Industriais/toxicidade , Fungicidas Industriais/metabolismo , Hidrólise , Bile , Metabolômica
16.
Mol Ther ; 32(5): 1387-1406, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38414247

RESUMO

Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics; however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice. Moreover, several key ferroptosis regulator genes were altered in cisplatin-damaged cochlear explants based on RNA sequencing, implying the induction of ferroptosis. Ferroptosis-related Gpx4 and Fsp1 knockout mice were established to investigate the specific mechanisms associated with ferroptosis in cochleae. Severe outer hair cell loss and progressive damage of synapses in inner hair cells were observed in Atoh1-Gpx4-/- mice. However, Fsp1-/- mice showed no significant hearing phenotype, demonstrating that Gpx4, but not Fsp1, may play an important role in the functional maintenance of HCs. Moreover, findings showed that FDA-approved luteolin could specifically inhibit ferroptosis and alleviate cisplatin-induced ototoxicity through decreased expression of transferrin and intracellular concentration of ferrous ions. This study indicated that ferroptosis inhibition through the reduction of intracellular ferrous ions might be a potential strategy to prevent cisplatin-induced hearing loss.


Assuntos
Cisplatino , Ferroptose , Perda Auditiva , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Animais , Cisplatino/efeitos adversos , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Camundongos , Perda Auditiva/induzido quimicamente , Perda Auditiva/genética , Perda Auditiva/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Modelos Animais de Doenças , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Espécies Reativas de Oxigênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Células Ciliadas Auditivas Externas/metabolismo , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Células Ciliadas Auditivas Externas/patologia , Ototoxicidade/etiologia , Ototoxicidade/metabolismo , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos
17.
Chinese Journal of School Health ; (12): 509-513, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016870

RESUMO

Objective@#To understand the potential categories of health risk behaviors among adolescents in the Wuling Mountain Area and their association with school connectedness, so as to provide reference for formulating classified and effective intervention measures.@*Methods@#From March to June 2023, 3 386 middle and high school students from eight schools in the Wuling Mountain Area were selected using the multistage stratified cluster random sampling method. A basic information questionnaire, health risk behaviors questionnaire, and school connectedness scale were utilized for the survey. The latent classes of adolescent health risk behaviors in the Wuling Mountain Area were investigated by using latent class analysis, while an multinomial Logistic regression model was employed to analyze the association between latent classes and school connectedness.@*Results@#Adolescent health risk behaviors in the Wuling Mountains Area were classified into three latent classes: high risk class of episodic behaviors ( 5.64 %), high risk class of implicit behaviors (26.90%), and low risk class of implicit behaviors (67.45%). Gender, ethnicity, and family type revealed significant differences in the distribution of the three latent classes ( χ 2=117.91, 22.55, 21.51, P <0.05). The results of the regression model analysis showed that, with the low risk class as the reference category, high school connectedness scores were associated with the high risk class of episodic behaviors ( OR=0.89, 95%CI = 0.88- 0.91) and the high risk class of implicit behaviors ( OR=0.90, 95%CI =0.89-0.91)( P <0.05).@*Conclusions@#The characteristics of adolescent health risk behavior classes in the Wuling Mountain Area are obvious. The high risk class of episodic behaviors and the high risk class of implicit behaviors are negatively correlated with school connectedness. Corresponding measures should be taken to enhance adolescents sense of belonging in school and reduce the aggregation and co occurrence of health risk behaviors.

18.
J Agric Food Chem ; 71(46): 17988-17998, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37916897

RESUMO

Structure optimization based on natural products has become an effective way to develop new green fungicides. In this project, thirty-two novel NPs-derived hydrazide compounds were designed and synthesized by introducing the bioactive hydrazide substructure into sinapic acid and mycophenolic acid. The fungicidal bioassays indicated that the obtained hydrazide compounds showed excellent and selective fungicidal activity against specific pathogens, especially compounds C8, D7, and D8 with EC50 values of 0.63, 0.56, and 0.43 µg mL-1 against M. oryzae, respectively. SAR indicated that the introduction of 4-fluoro, 4-chloro, and 2,4-difluoro groups was conducive to improving the fungicidal activity, while the extension of the hydrazide bridge would affect the selectivity for inhibitory activity. Subsequently, the effects of hydrazide compounds on rice seedling and zebrafish growth were also investigated. The fungicidal mechanism implied that treatment with compound B4 would cause significant changes in metabolites of plasma membrane-related linolenic acid metabolism, arachidonic acid metabolism, and α-linolenic acid metabolism pathways, which further led to the wrinkled hyphae and the blurred plasma membrane and cytoplasm. Finally, the frontier molecular orbitals and charge distribution were calculated to analyze the differences in bioactivity from a structural perspective. These results provide important guidance for the development and practical application of novel fungicides.


Assuntos
Fungicidas Industriais , Animais , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Relação Estrutura-Atividade , Ácido Micofenólico/farmacologia , Peixe-Zebra
19.
iScience ; 26(9): 107705, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37680466

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-ß and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by antagonizing the RLR-mediated antiviral signaling pathway. Mechanically, we found that the poly-U-specific endonuclease domain (EndoU) of Nsp15 directly associates with the kinase domain (KD) of TBK1 to interfere TBK1 interacting with IRF3 and the flowing TBK1-mediated IRF3 phosphorylation. Furthermore, Nsp15 also prevented nuclear translocation of phosphorylated IRF3 via binding to the nuclear import adaptor karyopherin α1 (KPNA1) and promoting it autophagy-dependent degradation. These findings collectively reveal a novel mechanism by which Nsp15 antagonizes host's innate immune response.

20.
Nat Commun ; 14(1): 6014, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37758708

RESUMO

The twisted stacking of two layered crystals has led to the emerging moiré physics as well as intriguing chiral phenomena such as chiral phonon and photon generation. In this work, we identified and theoretically formulated a non-trivial twist-enabled coupling mechanism in twisted bilayer photonic crystal (TBPC), which connects the bound state in the continuum (BIC) mode to the free space through the twist-enabled channel. Moreover, the radiation from TBPC hosts an optical vortex in the far field with both odd and even topological orders. We quantitatively analyzed the twist-enabled coupling between the BIC mode and other non-local modes in the photonic crystals, giving rise to radiation carrying orbital angular momentum. The optical vortex generation is robust against geometric disturbance, making TBPC a promising platform for well-defined vortex generation. As a result, TBPCs not only provide a new approach to manipulating the angular momentum of photons, but may also enable novel applications in integrated optical information processing and optical tweezers. Our work broadens the field of moiré photonics and paves the way toward the novel application of moiré physics.

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