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1.
Front Plant Sci ; 13: 923183, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774802

RESUMO

Longan (Dimocarpus longan Lour.) is a tropical/subtropical fruit tree of significant economic importance. Floral induction is an essential process for longan flowering and plays decisive effects on the longan yield. Due to the instability of flowering, it is necessary to understand the molecular mechanisms of floral induction in longan. In this study, mRNA and long noncoding RNA (lncRNA) transcriptome sequencing were performed using the apical buds of fruiting branches as materials. A total of 7,221 differential expressions of mRNAs (DEmRNAs) and 3,238 differential expressions of lncRNAs (DElncRNAs) were identified, respectively. KEGG enrichment analysis of DEmRNAs highlighted the importance of starch and sucrose metabolic, circadian rhythms, and plant hormone signal transduction pathways during floral induction. Combining the analysis of weighted gene co-expression network (WGCNA) and expression pattern of DEmRNAs in the three pathways, specific transcriptional characteristics at each stage during floral induction and regulatory network involving co-expressed genes were investigated. The results showed that sucrose metabolism and auxin signal transduction may be crucial for the growth and maturity of autumn shoots in September and October (B1-B2 stage); starch and sucrose metabolic, circadian rhythms, and plant hormone signal transduction pathways participated in the regulation of floral bud physiological differentiation together in November and December (B3-B4 stage) and the crosstalk among three pathways was also found. Hub genes in the co-expression network and key DEmRNAs in three pathways were identified. The circadian rhythm genes FKF1 and GI were found to activate SOC1gene through the photoperiod core factor COL genes, and they were co-expressed with auxin, gibberellin, abscisic acid, ethylene signaling genes, and sucrose biosynthesis genes at B4 stage. A total of 12 hub-DElncRNAs had potential for positively affecting their distant target genes in three putative key pathways, predominantly in a co-transcriptional manner. A hypothetical model of regulatory pathways and key genes and lncRNAs during floral bud induction in longan was proposed finally. Our studies will provide valuable clues and information to help elucidate the potential molecular mechanisms of floral initiation in longan and woody fruit trees.

3.
Front Psychiatry ; 13: 888055, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669272

RESUMO

Background: Aggression is common among individuals with methamphetamine use disorder (MAUD) and constitutes a serious public health issue. The current study aimed to examine associations of methamphetamine-use characteristics and childhood trauma with aggression in men with MAUD. Methods: This cross-sectional study was conducted from December 2017 to August 2018. MAUD patients recruited from a compulsory drug rehabilitation center (n = 360) and healthy comparison subjects (n = 604) completed a survey that measured aggression and childhood trauma, using the Chinese version of Buss-Perry Aggressive Questionnaire (AQ-CV), and the short form of Childhood Trauma Questionnaire (CTQ-SF), respectively. MAUD patients also provided information on methamphetamine-use characteristics such as the age of MAUD onset, MAUD severity, and co-occurring alcohol use disorder (AUD) and tobacco use disorder (TUD) using standard or self-designed questionnaires. Chi-square tests and t-tests were used to compare childhood trauma and aggression between the MAUD and comparison groups. Multiple linear regressions were conducted to determine correlates of overall aggression and its five sub-scales among the MAUD group. Results: The MAUD group had higher childhood trauma and aggression scores than the comparison group. Within the MAUD group, age of MAUD onset, having severe MAUD, co-occurring AUD, co-occurring TUD, and childhood trauma were associated with overall aggression, with slightly different correlates found for its five sub-scales. Conclusions: Our study shows a high level of childhood trauma and aggression in the MAUD group. Both methamphetamine-use characteristics (age of MAUD onset, severe MAUD, co-occurring AUD/TUD) and childhood trauma were associated with aggression in MAUD. Our findings provide useful information on potential risk factors for aggression and inform future longitudinal research to establish causal relationships between these factors and aggression to guide further prevention and treatment programs.

4.
J Pers Med ; 12(6)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35743796

RESUMO

Intellectual disability (ID) and autism spectrum disorder (ASD) are complex neurodevelopmental disorders with high heritability. To search for the genetic deficits in two siblings affected with ID and ASD in a family, we first performed a genome-wide copy number variation (CNV) analysis using chromosomal microarray analysis (CMA). We found a 3.7 Mb microdeletion at 22q13.3 in the younger sister. This de novo microdeletion resulted in the haploinsufficiency of SHANK3 and several nearby genes involved in neurodevelopment disorders. Hence, she was diagnosed with Phelan-McDermid syndrome (PMS, OMIM#606232). We further performed whole-genome sequencing (WGS) analysis in this family. We did not detect pathogenic mutations with significant impacts on the phenotypes of the elder brother. Instead, we identified several rare, likely pathogenic variants in seven genes implicated in neurodevelopmental disorders: KLHL17, TDO2, TRRAP, EIF3F, ATP10A, DICER1, and CDH15. These variants were transmitted from his unaffected parents, indicating these variants have only moderate clinical effects. We propose that these variants worked together and led to the clinical phenotypes in the elder brother. We also suggest that the combination of multiple genes with moderate effects is part of the genetic mechanism of neurodevelopmental disorders.

5.
Viruses ; 14(6)2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35746803

RESUMO

The global spread of SARS-CoV-2 and its variants poses a serious threat to human health worldwide. Recently, the emergence of Omicron has presented a new challenge to the prevention and control of the COVID-19 pandemic. A convenient and reliable in vitro neutralization assay is an important method for validating the efficiency of antibodies, vaccines, and other potential drugs. Here, we established an effective assay based on a pseudovirus carrying a full-length spike (S) protein of SARS-CoV-2 variants in the HIV-1 backbone, with a luciferase reporter gene inserted into the non-replicate pseudovirus genome. The key parameters for packaging the pseudovirus were optimized, including the ratio of the S protein expression plasmids to the HIV backbone plasmids and the collection time for the Alpha, Beta, Gamma, Kappa, and Omicron pseudovirus particles. The pseudovirus neutralization assay was validated using several approved or developed monoclonal antibodies, underscoring that Omicron can escape some neutralizing antibodies, such as REGN10987 and REGN10933, while S309 and ADG-2 still function with reduced neutralization capability. The neutralizing capacity of convalescent plasma from COVID-19 convalescent patients in Wuhan was tested against these pseudoviruses, revealing the immune evasion of Omicron. Our work established a practical pseudovirus-based neutralization assay for SARS-CoV-2 variants, which can be conducted safely under biosafety level-2 (BSL-2) conditions, and this assay will be a promising tool for studying and characterizing vaccines and therapeutic candidates against Omicron-included SARS-CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/terapia , Humanos , Imunização Passiva , Testes de Neutralização/métodos , Pandemias , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus
6.
Front Psychiatry ; 13: 913640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693962

RESUMO

Background: Few studies have analyzed opioid consumption and the average daily dose and duration for different patients in hospital settings in China. The aim of this study was to measure the status of and trends in prescribed opioids and the prescribing patterns at the Second Xiangya Hospital. Methods: The data were obtained from the prescribed medicine database of the inpatient department. We included patients who were >18 years old and received any level of opioid analgesic between 2012 and 2017. The international Anatomical Therapeutic Chemical Classification/Defined Daily Dose (ATC/DDD) methodology was used to standardize the consumption rates. All opioid units were converted into morphine equivalents (MEs) to analyze the specific opioid usage. Results: The consumption of prescribed opioids increased from 3.16 to 3.74 DDD/100 bed-days (+18.3%) from 2012 to 2017. Both cancer and noncancer patients had similar administration routes and median daily dosages in MEs, but cancer patients had longer treatment durations (median: 5 days vs. 1 day, respectively). The median average daily dose and treatment duration for all patients were 15 MEs/day and 2 days, respectively, for oral administration, 100 MEs/day and 1 day for parenteral administration, and 47.14 MEs/day and 5 days for both oral and parenteral administration. Conclusion: Although there was a tendency toward an increase in opioid consumption, the overall level of consumption in the Second Xiangya Hospital remained relatively low. Thus, it is urgently necessary to increase the availability of opioids and alter prescription habits for them in order adopt the current concept of pain management developed by the World Health Organization (WHO).

7.
Artigo em Inglês | MEDLINE | ID: mdl-35681966

RESUMO

OBJECTIVES: This study examined the prevalence of anxiety, depression, and job burnout among frontline healthcare workers (HCWs) across six Southeast Asian countries (Indonesia, Malaysia, Philippines, Singapore, Thailand, Vietnam) during the COVID-19 pandemic in 2021. We also investigated the associated risk and protective factors. METHODS: Frontline HCWs (N = 1381) from the participating countries participated between 4 January and 14 June 2021. The participants completed self-reported surveys on anxiety (GAD-7), depression (PHQ-8), and job burnout (PWLS). Multivariate logistic regressions were performed with anxiety, depression, and job burnout as outcomes and sociodemographic and job characteristics and HCW perceptions as predictors. RESULTS: The average proportion of HCWs reporting moderate anxiety, moderately severe depression, and job burnout across all countries were 10%, 4%, and 20%, respectively. Working longer hours than usual (Odds ratio [OR] = 1.82; 3.51), perceived high job risk (1.98; 2.22), and inadequate personal protective equipment (1.89; 2.11) were associated with increased odds of anxiety and job burnout while working night shifts was associated with increased risk of depression (3.23). Perceived good teamwork was associated with lower odds of anxiety (0.46), depression (0.43), and job burnout (0.39). CONCLUSION: Job burnout remains a foremost issue among HCWs. Potential opportunities to improve HCW wellness are discussed.


Assuntos
Esgotamento Profissional , COVID-19 , Ansiedade/epidemiologia , Ansiedade/psicologia , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , COVID-19/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Pessoal de Saúde/psicologia , Humanos , Pandemias , Equipamento de Proteção Individual , SARS-CoV-2
8.
J Org Chem ; 87(13): 8599-8610, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704791

RESUMO

An iron-promoted oxidative tandem alkylation/cyclization of ynones with 4-alkyl-substituted 1,4-dihydropyridines for the efficient synthesis of 2-alkylated indenones is described. The process occurs via oxidative homolysis of a C-C σ-bond in 1,4-dihydropyridines to generate an alkyl radical followed by the addition of C-C triple bonds in ynones and intramolecular cyclization. A wide range of alkyl radicals could be efficiently transferred to generate a series of synthetically useful 2-alkylated indenones with excellent selectivity under mild conditions.

9.
Eur J Med Chem ; 238: 114445, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35580424

RESUMO

As a recently discovered DNA repair enzyme, tyrosyl-DNA phosphodiesterase 2 (TDP2) can specifically repair topoisomerase 2 (TOP2)-mediated DNA damage, resulting in cancer cell resistance to TOP2 inhibitors. Its inhibitors can enhance the anticancer efficacy of TOP2 inhibitors. In this work, we report the discovery of natural product myrtucommulone E as selective TDP2 inhibitor and its first enantioselective total synthesis through a pivotal CPA-catalyzed Michael addition reaction. A series of myrtucommulone E analogues were asymmetrically synthesized and evaluated for TDP2 and TDP1 inhibitions, and cytotoxicity. Analogue (+)-29 shows good TDP2 inhibition potency (5.4 ± 0.25 µM), but no TDP1 inhibition at 100 µM concentration, and can significantly enhance the cytotoxicity of TOP2 inhibitor etoposide in both DU145 (CI = 0.26) and DT40 hTDP2 cells (CI = 0.48).


Assuntos
Proteínas de Ligação a DNA , Diester Fosfórico Hidrolases , DNA Topoisomerases Tipo II , Diester Fosfórico Hidrolases/genética , Estereoisomerismo , Inibidores da Topoisomerase II/farmacologia
10.
Front Microbiol ; 13: 901912, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602061

RESUMO

Cronobacter sakazakii is a common foodborne pathogen, and the mortality rate of its infection is as high as 40-80%. SdiA acts as a quorum sensing regulator in many foodborne pathogens, but its role in C. sakazakii remains unclear. Here, we further determined the effect of the sdiA gene in C. sakazakii pathogenicity. The SdiA gene in C. sakazakii was knocked out by gene editing technology, and the biological characteristics of the ΔsdiA mutant of C. sakazakii were studied, followed by transcriptome analysis to elucidate its effects. The results suggested that SdiA gene enhanced the drug resistance of C. sakazakii but diminished its motility, adhesion and biofilm formation ability and had no effect on its growth. Transcriptome analysis showed that the ΔsdiA upregulated the expression levels of D-galactose operon genes (including dgoR, dgoK, dgoA, dgoD and dgoT) and flagella-related genes (FliA and FliC) in C. sakazakii and downregulated the expression levels of related genes in the type VI secretion system (VasK gene was downregulated by 1.53-fold) and ABC transport system (downregulated by 1.5-fold), indicating that SdiA gene was related to the physiological metabolism of C. sakazakii. The results were useful for clarifying the pathogenic mechanism of C. sakazakii and provide a theoretical basis for controlling bacterial infection.

11.
BMJ Open ; 12(5): e054566, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35580967

RESUMO

BACKGROUND: Chronic Sciatica is a disabling condition causing considerable medical, social and financial implications. Currently, there is no recognised long-term effective treatment to alleviate sciatica. Acupuncture has been widely used for treating chronic pains with persistent analgesic effects. We aim to evaluate the efficacy and safety of acupuncture for chronic sciatica with follow-up in 52 weeks. METHODS AND ANALYSIS: This is a multicenter randomised sham-controlled trial. A total of 216 patients with chronic sciatica will be enrolled and randomly assigned to the acupuncture or sham acupuncture group. There will be 10 treatment sessions applied in 4 weeks with frequency decreased over time. Patients will complete follow-ups during 52 weeks. The primary outcomes are changes in leg pain intensity and disability from baseline to week 4. Secondary outcomes include back pain intensity, frequency and bothersomeness, quality of life, and global perceived effect. Adverse events will be recorded in detail. ETHICS AND DISSEMINATION: Ethical approval of this trial was granted from the ethics committee of Beijing University of Chinese Medicine and all study centres (No. 2020BZYLL0803). Written informed consent will be obtained from enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100044585 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 24 March 2021); preresults.


Assuntos
Terapia por Acupuntura , Ciática , Terapia por Acupuntura/métodos , Humanos , Estudos Multicêntricos como Assunto , Medição da Dor , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Ciática/terapia , Resultado do Tratamento
12.
Foods ; 11(10)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35627040

RESUMO

Browning and lignification often occur in fresh-cut apple processing, leading to quality deterioration and limiting the shelf life of products. In this study, 0.8% (v/v) phytic acid was used to improve the quality and shelf life of fresh-cut apples. From the results, the browning was inhibited by the phytic acid treatment and the browning index (BI) of the control fruit was 1.62 times that of phytic acid treatment at 2 d of storage. The lignin content in phytic acid-treated fruit significantly decreased at 2, 4, and 6 d of storage compared to the control. Phytic acid treatment also reduced H2O2 and malonaldehyde (MDA) contents, which may indicate lighter membrane damage to apples. Compared with the control, the polyphenol oxidase (PPO) and peroxidase (POD) activities decreased while superoxide dismutase (SOD) and catalase (CAT) activities increased in phytic acid-treated fruit. Consistent with the lignin content, the activities of phenylpropane metabolism-related enzymes phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate: CoA ligase (4CL) were inhibited by phytic acid treatment. In conclusion, phytic acid alleviated the browning and lignification of fresh-cut apples by reducing PPO and POD activities, maintaining cell membrane integrity, and inhibiting phenylpropane metabolism.

13.
Epidemics ; 39: 100581, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35636311

RESUMO

We present a country specific method to calculate the COVID-19 vaccination coverage needed for herd immunity by considering age structure, age group-specific contact patterns, relative infectivity and susceptibility of children to adults, vaccination effectiveness and seroprevalence prior to vaccination. We find that across all six countries, vaccination of adults age 60 and above has little impact on Reff and this is could be due to the smaller number of contacts between this age group and the rest of the population according to the contact matrices used. If R0 is above 6, herd immunity by vaccine alone is unattainable for most countries either if vaccination is only available for adults or that vaccine effectiveness is lower at 65% against symptomatic infections. In this situation, additional control measures, booster shots, if they improve protection against infection, or the extension of vaccination to children, are required. For a highly transmissible variant with R0 up to 8, herd immunity is possible for all countries and for all four scenarios of varying relative infectivity and susceptibility of children compared to adults, if vaccine effectiveness is very high at 95% against symptomatic infections and that high vaccination coverage is achieved for both adults and children. In addition, we show that the effective reproduction number will vary between countries even if the same proportion of the population is vaccinated, depending on the demographics, the contact rates and the previous pre-vaccination seroprevalence in the country. This therefore means that care must be taken in extrapolating population level impacts of certain vaccine coverages from one country to another.


Assuntos
COVID-19 , Imunidade Coletiva , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Criança , Humanos , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Vacinação/métodos , Cobertura Vacinal
14.
Peptides ; 153: 170811, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35594964

RESUMO

A group of long-acting, peptide-based, and selective GLP-1R/CCK-2R dual agonizts were identified by rational design. Guided by sequence analysis, structural elements of the CCK-2R agonist moiety were engineered into the GLP-1R agonist Xenopus GLP-1, resulting in hybrid peptides with potent GLP-1R/CCK-2R dual activity. Further modifications with fatty acids resulted in novel metabolically stable peptides, among which 3d and 3 h showed potent GLP-1R and CCK-2R activation potencies and comparable stability to semaglutide. In food intake tests, 3d and 3 h also showed a potent reduction in food intake, superior to that of semaglutide. Moreover, the acute hypoglycemic and insulinotropic activities of 3d and 3 h were better than that of semaglutide and ZP3022. Importantly, the limited pica response following 3d and 3 h administration in SD rats preliminarily indicated that the food intake reduction effects of 3d and 3 h are independent of nausea/vomiting. In a 35-day study in db/db mice, every two days administration of 3d and 3 h increased islet areas and numbers, insulin contents, ß-cell area, ß-cell proliferation, as well as improved glucose tolerance, and decreased HbA1c, to a greater extent than ZP3022 and semaglutide. In a 21-day study in DIO mice, once-weekly administration of 3d and 3 h significantly induced body weight loss, improved glucose tolerance, and normalized lipid metabolism, to a greater extent than semaglutide. The current study showed the antidiabetic and antiobesity potentials of GLP-1R/CCK-2R dual agonizts that warrant further investigation.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Peptídeos , Receptor de Colecistocinina B , Animais , Fármacos Antiobesidade/farmacologia , Colecistocinina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Glucose , Hipoglicemiantes/farmacologia , Camundongos , Peptídeos/química , Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor de Colecistocinina B/agonistas , Receptor de Colecistocinina B/efeitos dos fármacos , Receptor de Colecistocinina B/metabolismo
15.
Sex Health ; 19(3): 212-223, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35491538

RESUMO

BACKGROUND: HIV self-testing (HIVST) is a potential strategy to overcome challenges of HIV testing among men who have sex with men (MSM). However, for resource-limited settings, technology and diagnostic devices are lagging. Hence, we estimated the status and correlates of HIVST among MSM in resource-limited settings in China to inform the development of HIVST to reach United Nations Programme on HIV and AIDS (UNAIDS) targets to end HIV by 2030. METHODS: A cross-sectional study was conducted among MSM in Nanning, Guangxi, China, between August 2019 and January 2020. The HIVST status was collected and data on social network features, sociodemographic information, risk behaviours, etc. were compared between prior- and non-HIVST MSM. Logistic regression analyses were conducted to examine the correlates of HIVST. RESULTS: The prevalence of HIVST among 446 MSM was 40.4% (95% confidence interval [CI] 35.8-44.9%). The main component of sociocentric network contains more prior-HIVST MSM (38.3%) than non-HIVST MSM (28.6%, P =0.031). More MSM with individual features such as substance use during anal sex (22.8% vs 15.4%, P =0.049) and multiple sexual partners (76.1% vs 59.4%, P <0.001) were detected among prior-HIVST MSM. In multivariable analysis, prior HIVST was associated with the strong strength of ego-alter ties in the egocentric network (adjusted odds ratio [aOR] 1.72; 95% CI 1.09-2.71), HIV-infected partners (aOR, 7.17; 95% CI, 1.40-36.60), and vaginal intercourse (aOR, 0.38; 95% CI, 0.17-0.85). CONCLUSIONS: HIVST coverage among MSM in resource-limited settings is suboptimal. Integrating social networks into testing services may be viable to promote HIVST in MSM within resource-limited settings.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , China/epidemiologia , Estudos Transversais , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV , Homossexualidade Masculina , Humanos , Masculino , Autoteste
16.
Foods ; 11(8)2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35454747

RESUMO

Rice-crayfish system has been extensively promoted in China in recent years. However, the presence of toxic elements in soil may threaten the quality of agricultural products. In this study, eight toxic elements were determined in multi-medium including soil, rice, and crayfish from the rice-crayfish system (RCS) and conventional rice culture (CRC) area. Crayfish obtained a low level of toxic element content, and mercury (Hg) in rice from RCS showed the highest bioavailability and mobility. Health risk assessment, coupled with Monte Carlo simulation, revealed that the dietary exposure to arsenic (As) and Hg from rice and crayfish consumption was the primary factor for non-carcinogenic risk, while Cd and As were the dominant contributors to the high carcinogenic risk of rice intake for adults and children, respectively. Based on the estimated probability distribution, the probabilities of the total cancer risk (TCR) of rice intake for children from RCS were lower than that from CRC.

17.
BMC Public Health ; 22(1): 797, 2022 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449098

RESUMO

INTRODUCTION: This study aimed to investigate sexual orientation disclosure and mental health among young men who have sex with men (YMSMs). To this end, we constructed a chained multimediator model of sexual minority stigma, sexual minority identity, social support, and resilience, with the moderator of sexual orientation disclosure. METHODS: We conducted a cross-sectional survey of 345 YMSMs in Nanning, China. Bivariate analysis was used to evaluate factors associated with sexual orientation disclosure. Sexual minority stigma was used to predict identity, with social support as the step 1 mediator and resilience as the step 2 mediator. Sexual minority identity was analyzed using a chained moderated mediation model; sexual orientation disclosure was included as a moderator in all models to control its confounding effect. RESULTS: The average age of YMSMs was 20.0 ± 1.3 years. Bivariate analysis indicated that YMSMs who disclosed sexual orientation may have experienced less stigma (15.49 ± 3.02 vs 16.21 ± 2.74), obtained more social support (65.98 ± 11.18 vs 63.19 ± 11.13), had strong psychological resilience (37.40 ± 8.57 vs 35.39 ± 7.73), and had a more positive self-identity (104.12 ± 21.10 vs 95.35 ± 16.67); differences between subgroups were statistically significant (p < 0.05). Sexual minority stigma, perceived stigma, and enacted stigma were significantly associated with social support and resilience. The association between sexual minority stigma and sexual minority identity was significantly mediated by social support (indirect effect [95% CI] = - 3.307 [- 4.782, - 1.907]). Resilience significantly mediated the same association for identity (- 2.544 [- 4.052, - 1.114]). The chained relationship from sexual minority stigma to social support, resilience, and identity was also significant, with an indirect effect of - 0.404 [- 0.621, - 0.249]. CONCLUSION: Among YMSMs in China, sexual minority stigma affects sexual minority identity through social support and resilience. Given the psychological effects of stigma, social support and resilience must be considered to better promote positive self-identity and mental health among YMSMs.


Assuntos
Minorias Sexuais e de Gênero , Adolescente , Adulto , Estudos Transversais , Revelação , Feminino , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Identificação Social , Estigma Social , Apoio Social , Adulto Jovem
18.
Bioorg Chem ; 123: 105789, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35429714

RESUMO

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme that repairs DNA lesions caused by the trapping of DNA topoisomerase IB (TOP1)-DNA break-associated crosslinks. TDP1 inhibitors have synergistic effect with TOP1 inhibitors in cancer cells and can overcome cancer cell resistance to TOP1 inhibitors. Here, we report the synthesis of 11-aminoalkoxy substituted benzophenanthridine derivatives as selective TDP1 inhibitors and show that six compounds 14, 16, 18, 20, 25 and 27 exhibit high TDP1 inhibition potency. The most potent TDP1 inhibitor 14 (IC50 = 1.7 ±â€¯0.24 µM) induces cellular TDP1cc formation and shows synergistic effect with topotecan in four human cancer cell lines MCF-7, A549, H460 and HepG2.


Assuntos
Diester Fosfórico Hidrolases , Inibidores da Topoisomerase I , Benzofenantridinas , DNA Topoisomerases Tipo I/metabolismo , Humanos , Diester Fosfórico Hidrolases/metabolismo , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/farmacologia
19.
Comput Intell Neurosci ; 2022: 1549275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371244

RESUMO

In order to improve the operation effect of farmer cooperatives, this paper combines the intelligent data sampling technology to analyze the ecological circle operation mode of farmer cooperatives. Moreover, this paper strives to promote the ecosphere business model, accelerate regional development, build agricultural pastoral complex projects and in-depth study TI-ADC modeling, error estimation, mismatch compensation, and other technologies, and carry out engineering realization. In addition, this paper uses technology to analyze intelligent data and builds a system structure based on the actual needs of the farmer cooperative ecosphere management. Finally, this paper analyzes the structure and flow of the data processing layer. The test results show that the ecosystem business model of farmer cooperatives based on intelligent data sampling technology proposed in this paper has good results.


Assuntos
Ecossistema , Fazendeiros , Comércio , Engenharia , Humanos , Tecnologia
20.
Signal Transduct Target Ther ; 7(1): 139, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35478188

RESUMO

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Anticorpos Monoclonais/genética , Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , COVID-19/prevenção & controle , Vacinas contra COVID-19/genética , Microscopia Crioeletrônica , Epitopos , Humanos , Camundongos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Proteínas do Envelope Viral
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