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PURPOSE: Toludesvenlafaxine is a recently developed antidepressant that belongs to the triple reuptake inhibitor class. Despite the in vitro evidence that toludesvenlafaxine inhibits the reuptake of serotonin (5-HT), norepinephrine (NE) and dopamine (DA), there is no in vivo evidence that toludesvenlafaxine binds to DAT and increases DA level, a mechanism thought to contribute to its favorable clinical performance. METHODS: Positron emission tomography/computed tomography (PET/CT) was used to examine the DAT binding capacity in healthy rats and human subjects and microdialysis was used to examine the striatal DA level in rats. [18F]FECNT and [11C]CFT were used as PET/CT radioactive tracer for rat and human studies, respectively. RESULTS: In rats, 9 mg/kg of toludesvenlafaxine hydrochloride (i.v.) followed by an infusion of 3 mg/kg via minipump led to the binding rate to striatum DAT at 3.7 - 32.41% and to hypothalamus DAT at 5.91 - 17.52% during the 45 min scanning period. 32 mg/kg oral administration with toludesvenlafaxine hydrochloride significantly increased the striatal DA level with the AUC0 - 180 min increased by 63.9%. In healthy volunteers, 160 mg daily toludesvenlafaxine hydrochloride sustained-release tablets for 4 days led to an average occupancy rates of DAT at 8.04% ± 7.75% and 8.09% ± 7.00%, respectively, in basal ganglion 6 h and 10 h postdose. CONCLUSION: These results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine. GOV IDENTIFIERS: NCT05905120. Registered 14 June 2023. (retrospectively registered).
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Succinato de Desvenlafaxina , Proteínas da Membrana Plasmática de Transporte de Dopamina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Ratos , Humanos , Animais , Masculino , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Adulto , Ligação Proteica , Ratos Sprague-Dawley , Feminino , Dopamina/metabolismoRESUMO
The prediction of three-dimensional (3D) protein structure from amino acid sequences has stood as a significant challenge in computational and structural bioinformatics for decades. Recently, the widespread integration of artificial intelligence (AI) algorithms has substantially expedited advancements in protein structure prediction, yielding numerous significant milestones. In particular, the end-to-end deep learning method AlphaFold2 has facilitated the rise of structure prediction performance to new heights, regularly competitive with experimental structures in the 14th Critical Assessment of Protein Structure Prediction (CASP14). To provide a comprehensive understanding and guide future research in the field of protein structure prediction for researchers, this review describes various methodologies, assessments, and databases in protein structure prediction, including traditionally used protein structure prediction methods, such as template-based modeling (TBM) and template-free modeling (FM) approaches; recently developed deep learning-based methods, such as contact/distance-guided methods, end-to-end folding methods, and protein language model (PLM)-based methods; multi-domain protein structure prediction methods; the CASP experiments and related assessments; and the recently released AlphaFold Protein Structure Database (AlphaFold DB). We discuss their advantages, disadvantages, and application scopes, aiming to provide researchers with insights through which to understand the limitations, contexts, and effective selections of protein structure prediction methods in protein-related fields.
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Inteligência Artificial , Proteínas , Conformação Proteica , Modelos Moleculares , Proteínas/química , Algoritmos , Biologia Computacional/métodos , Bases de Dados de Proteínas , Software , Dobramento de ProteínaRESUMO
OBJECTIVE: Environmental contaminants such as cadmium (Cd) may have a deleterious impact on sperm and reduce male fertility by compromising the blood-testis barrier (BTB). Hence, the effects of the traditional Chinese medicine Qiangjing tablet (QJP) on sperm quality and BTB alterations induced by Cd in mouse testes were examined. METHODS: Adult KM mice challenged with Cd chloride were examined, QJP was administered to mice as an oral drug by gavage, and the experiments lasted 2 weeks. Testicular and epididymal weights, sperm quality, anti-sperm antibodies (AsAb), hormone levels, and histology were evaluated. Changes in the levels of N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin and their mRNAs were evaluated. The effects of QJP on the PI3K/Akt/Rictor pathway were evaluated. RESULTS: CdCl2 decreased reproductive organ weight, sperm quality, and testosterone (T) levels; increased AsAb, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; induced structural damage in testicles with BTB disruption; increased BTB permeability; and decreased N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin expression. After treatment, QJP blocked the effects of Cd on reproductive organ weight, sperm quality, and T; mitigated germinal epithelium compartment alterations; decreased AsAb, FSH, and LH levels; and preserved BTB ultrastructure and function. In addition, QJP induced increases in N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin levels and the expression of their mRNAs through the PI3K/Akt/Rictor pathway. After the application of JRAB2011, the levels of a specific mTORC2 suppressor, Rictor, and the BTB-protective effect of QJP were greatly reduced. CONCLUSIONS: We demonstrated the effect of QJP against Cd-induced damage to the BTB, and the results indicate that QJP may play a significant role in opposing the effects of Cd through the PI3K/Akt/Rictor pathway.
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Barreira Hematotesticular , Fosfatidilinositol 3-Quinases , Camundongos , Masculino , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cádmio/metabolismo , Actinas/metabolismo , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/farmacologia , Ocludina/metabolismo , Medicina Tradicional Chinesa , Testículo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Caderinas/metabolismo , Hormônio Foliculoestimulante/metabolismo , Claudinas/metabolismo , EspermatogêneseRESUMO
BACKGROUND: Human papillomavirus (HPV) vaccine has immense research value in the prevention of related tumours. A huge body of work has been published in this field, which may pose difficulties for researchers aiming to investigate all the available information. However, bibliometrics can provide deep insights into this research field. OBJECTIVE: We aimed to study HPV vaccine development, visually analyse the development status, trends, research hotspots, and frontiers of this field, and provide a reference for research on it. METHODS: Articles were acquired from the Web of Science Core Collection. VOS viewer and CiteSpace software were used to analyse publication growth, country/region, institution, journal distribution, author, reference, and keywords, and collected burst keyword words to display research hotspots. RESULTS: A total of 4831 references were obtained, and the annual number of publications increased fluctuating over the past decade. The United States of America ranked at the top in terms of percentage of articles. The institution with the highest number of research publications in this field was the Centers for Disease Control and Prevention. The most productive and frequently cited authors was Lauri E Markowitz. The journal with the most publications in this field was Vaccine, and the most influential journal was Paediatrics. The most frequently cited reference was 'A 9-Valent HPV Vaccine against Infection and Intraepithelial Neoplasia in Women'. Burst detection analysis of top keywords showed that 'national immunisation survey', 'social media', and 'hesitancy' are the current research frontiers in this field. CONCLUSION: This study provides useful information for acquiring knowledge on HPV vaccine. Research on solving the hesitation of HPV vaccination will become an academic trend in this field, which can offer guidance for more extensive and in-depth studies in the future.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Feminino , Humanos , Criança , Papillomavirus Humano , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Vacinação , Imunização , BibliometriaRESUMO
The aim of this study was to thoroughly document the effects of multiple intervention and control methods to mitigate the ongoing coronavirus disease 2019 (COVID-19) outbreak in Pudong New Area, Shanghai. After identification of the first confirmed case of COVID-19 in Pudong on January 21, 2020, the local Center for Disease Control and Prevention (CDC) launched a case investigation involving isolation, close-contact (CC) tracing and quarantine of persons with a potential exposure risk to prevent and control transmission. Epidemiological features of cases detected by three different strategies were compared to assess the impact of these active surveillance measures. As of February 16, 2020, a total of 108 confirmed COVID-19 cases had been identified in Pudong, Shanghai. Forty-five (41.67%) cases were identified through active surveillance measures, with 22 (20.37%) identified by CC tracing and 23 (21.30%) by quarantine of potential exposure populations (PEPs). The average interval from illness onset to the first medical visit was 1 day. Cases identified by CC tracing and PEPs were quarantined for 0.5 and 1 day before illness onset, respectively. The time intervals from illness onset to the first medical visit and isolation among actively screened cases were 2 days (p = .02) and 3 days (p = .00) shorter, respectively, than those among self-admission cases. Our study highlights the importance of active surveillance for potential COVID-19 cases, as demonstrated by shortened time intervals from illness onset to both the first medical visit and isolation. These measures contributed to the effective control of the COVID-19 outbreak in Pudong, Shanghai.
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COVID-19/epidemiologia , COVID-19/prevenção & controle , Vigilância da População/métodos , Adulto , COVID-19/transmissão , China/epidemiologia , Busca de Comunicante/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quarentena/estatística & dados numéricos , SARS-CoV-2 , Fatores de TempoRESUMO
Nonconventional luminogens with persistent room temperature phosphoresce (p-RTP) are attracting increasing attention owing to their momentous significance and diverse technical applications in optoelectronic and biomedical. So far, the p-RTP emission of some amorphous powders or single crystals has been studied in depth. The p-RTP emission of amorphous and fully crystalline states and their emission properties are widely divergent, while the difference of their p-RTP emission mechanism is still controversial. The relevance between crystallinity change and p-RTP properties is rarely studied. Furthermore, there is almost no research on the photoluminescence (PL) property change and emission mechanism under the crystal form transformation of semi-crystalline polymer. Herein, microcrystalline cellulose (MCC) is chosen as a model compound to explore its crystallinity and the change in luminescence during the crystal form transformation to make up for this gap. By precisely adjusting the crystallinity and crystal cellulose conversion of MCC, the changing trend of quantum efficiency, and p-RTP lifetime is consistent with the change of crystallinity, and the cellulose I may be more beneficial to PL emission than cellulose II. Clustering-triggered emission mechanism can reasonably explain these interesting photophysical processes, which also can be supported by single-crystal analysis and theoretical calculations.
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Celulose , LuminescênciaRESUMO
BACKGROUND: Cognitive deficits are common in patients with schizophrenia (SCZ). Abnormal serum total bilirubin (TBIL) levels have been involved in cognitive deficits associated with neuropsychiatric diseases such as mild cognitive impairment and subcortical ischemic vascular disease. However, this relationship has not yet been fully investigated in patients with SCZ. Therefore, the aim of this study was to investigate the association between the serum TBIL concentration and cognitive deficits in SCZ patients and to determine whether a sex difference exists in the association. METHODS: A total of 455 participants were eligible and included in this cross-sectional study. Cognition was evaluated using the Montreal Cognitive Assessment. Serum TBIL concentration was measured with an automatic biochemistry analyzer according to the routine protocol in the hospital medical laboratory. RESULTS: Serum TBIL levels were lower in the cognition impairment group than in the cognition normal group in male patients. In contrast, serum TBIL levels tended to be increased in the cognition impairment group in female patients, although the difference was not significant. Further stepwise multiple regression analysis stratified by sex showed that serum TBIL was independently and positively associated with cognitive function in male patients but not in female patients. Moreover, the association between serum TBIL level and cognitive function was also identified by the propensity score matching (PSM) method in male patients, but not in female patients. CONCLUSION: These findings suggest that lower serum TBIL levels may be associated with cognitive impairment in male SCZ patients.
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Esquizofrenia , Bilirrubina , Cognição , Estudos Transversais , Feminino , Humanos , Masculino , Esquizofrenia/complicações , Caracteres SexuaisRESUMO
OBJECTIVE: Model-based meta-analysis was used to describe the time-course and dose-effect relationships of antidepressants and also simultaneously investigate the impact of various factors on drug efficacy. METHODS: This study is a reanalysis of a published network meta-analysis. Only placebo-controlled trials were included in this study. The change rate in depression rating scale scores from baseline was used as an efficacy indicator because a continuous variable is more likely to reflect subtle differences in efficacy between drugs. RESULTS: A total 230 studies containing 64 346 patients were included in the analysis. The results showed that the number of study sites (single or multi-center) and the type of setting (inpatient or noninpatient) are important factors affecting the efficacy of antidepressants. After deducting the placebo effect, the maximum pure drug efficacy value of inpatients was 18.4% higher than that of noninpatients, and maximum pure drug efficacy value of single-center trials was 10.2% higher than that of multi-central trials. Amitriptyline showed the highest drug efficacy. The remaining 18 antidepressants were comparable or had little difference. Within the approved dose range, no significant dose-response relationship was observed. However, the time-course relationship is obvious for all antidepressants. In terms of safety, with the exception of amitriptyline, the dropout rate due to adverse events of other drugs was not more than 10% higher than that of the placebo group. CONCLUSION: The number of study sites and the type of setting are significant impact factors for the efficacy of antidepressants. Except for amitriptyline, the other 18 antidepressants have little difference in efficacy and safety.
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Antidepressivos/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Doença Aguda , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Metanálise em RedeRESUMO
This study examined randomized controlled trial data for blonanserin and risperidone in Chinese schizophrenia patients (N = 264). Data related to historical changes in the Positive and Negative Syndrome Scale (PANSS) were used to successfully construct a longitudinal Emax model. Results: (a) The efficacy of the two drugs was similar after week 8, showing a small difference in PANSS reduction. (b) Using the model, we predicted that each 5-point increase in the baseline FPOS (positive score in PANSS five-factor subscales) leads to a decrease in the PANSS total scores at week 8 for 2 points in patients administered blonanserin. (c) The effect of blonanserin on prolactin (PRL) elevation was less. The model was used to predict that prolactin elevations in patients administered risperidone were 2.41-fold of those in patients administered blonanserin. (d) Model quantitation showed that gender is a risk factor for prolactin elevation. Prolactin elevations in female patients were 2.95-fold of the value in male patients administered the same drug. The model demonstrated Blonanserin has similar antischizophrenic efficacy and less serum prolactin rising compared to risperidone in Chinese patients.
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Modelos Estatísticos , Piperazinas/uso terapêutico , Piperidinas/uso terapêutico , Prolactina/sangue , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/sangue , Fatores Sexuais , Adulto JovemRESUMO
Atypical antipsychotics exert remarkable long-term efficacy on the personal and social functions of schizophrenic patients. However, quantitative information on the social function of schizophrenic patients treated with atypical antipsychotics is scarce in the current clinical guidelines. In this study, we established pharmacodynamic models to quantify the time-efficacy relationship of three antipsychotic drugs based on the data from a real-world study conducted in China. A total of 373 schizophrenic patients who received antipsychotic monotherapy with olanzapine (n = 144), risperidone (n = 160), or aripiprazole (n = 69) were selected from a three-year prospective, multicenter study. The follow-up times were 13, 26, 52, 78, 104, 130, and 156 weeks after baseline. A time-efficacy model was developed with nonlinear mixed effect method based on changes in Personal and Social Performance (PSP) score compared with the baseline level. Crucial pharmacodynamic parameters, including maximum efficacy and drug onset time, were used to distinguish the efficacy of the three drugs. We quantified the time course of PSP improvement in patients after treatment with these three antipsychotics: olanzapine, risperidone, and aripiprazole reached an Emax value of 80.3%, 68.2%, and 23.9% at weeks 56.7, 29.2, and 36.8, respectively. General psychotic symptoms, onset frequency, and illness course were identified as significant factors affecting the efficacy of these drugs. The newly constructed models provide an evidence of the benefit of long-term maintenance therapy with atypical antipsychotics in individualized schizophrenia treatment in China.
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Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Prospectivos , Adulto JovemRESUMO
An ideal proppant showing super-hydrophobicity and enough strength to bear high closure stress is revolutionary for the effective exploration of gas or oil in shale. Here, the ideal proppants were obtained by wrapping specially treated phenol formaldehyde resins around the cover of the traditional ceramsites. The resin coating is patterned with innumerable fluorine-modified silica nanoparticles, whose thickness is controllable. Benefitting from the low surface energy of fluorine, nano-roughness structures from nano-silica, and the adhesive action of the resin, the modified proppant exhibits awesome properties. The nanoparticle-patterned resin gives the ceramic proppants a water contact angle of 157.8° that has been proved to be stable after being treated in strong acid, thus dramatically accelerating the fracture conductivity for oil by 150% whereas totally preventing water passing through. Besides, it is the resin that reduces the crushing rate of the proppants by 52% and decreases the density of the proppants to 1.63 g/cm³.
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BACKGROUND: Nucleus Accumbens (NAc) is a vital brain region for the process of reward and stress, whereas microRNA plays a crucial role in depression pathology. However, the abnormality of NAc miRNA expression during the stress-induced depression and antidepressant treatment, as well as its biological significance, are still unknown. METHODS: We performed the small RNA-sequencing in NAc of rats from three groups: control, chronic unpredictable mild stress (CUMS), and CUMS with an antidepressant, Escitalopram. We applied an integrative pipeline for analyzing the miRNA expression alternation in different model groups, including differential expression analysis, co-expression analysis, as well as a subsequent pathway/network analysis to discover both miRNA alteration pattern and its biological significance. RESULT: A total of 423 miRNAs were included in analysis.18/8 differential expressing (DE) miRNA (adjusted p < 0.05, |log2FC| > 1) were observed in controls Vs. depression/depression Vs. treatment, 2 of which are overlapping. 78% (14/18) of these miRNAs showed opposite trends of alteration in stress and treatment. Two micro RNA, miR-10b-5p and miR-214-3p, appeared to be hubs in the regulation networks and also among the top findings in both differential analyses. Using co-expression analysis, we found a functional module that strongly correlated with stress (R = 0.96, P = 0.003), and another functional module with a moderate correlation with anhedonia (R = 0.89, P = 0.02). We also found that predicted targets of these miRNAs were significantly enriched in the Ras signaling pathway, which is associated with both depression, anhedonia, and antidepressant treatment. CONCLUSION: Escitalopram treatment can significantly reverse NAc miRNA abnormality induced by chronic stress. However, the novel miRNA alteration that is absent in stress pathology also emerges, which means that antidepressant treatment is unlikely to bring miRNA expression back to the same level as the controls. Also, the Ras-signaling pathway may be involved in explaining the depression disease etiology, the clinical symptom, and treatment response of stress-induced depression.
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Citalopram/farmacologia , Depressão/genética , Expressão Gênica , MicroRNAs/genética , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Estresse Psicológico/genética , Animais , Antidepressivos/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Masculino , Ratos , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas ras/genéticaRESUMO
PURPOSE: The purpose of this study is to investigate the efficacy, safety, and tolerability of agomelatine and paroxetine in Chinese Han patients with major depressive disorder (MDD). METHODS: A 8-week, double-blind, randomized, parallel study was conducted in 14 medical centers in mainland China from December 2011 to September 2012. A total of 264 subjects with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD were randomly assigned to receive agomelatine 25-50 mg/d (n = 132) or paroxetine 20-40 mg/d (n = 132). The primary efficacy was evaluated by the decrease of Hamilton Depression Rating Scale (HAM-D17) scores. The secondary measurements of efficacy included Hamilton Anxiety Rating Scale, Montgomery-Asberg Depression Rating Scale, Sheehan Disability Scale, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. The laboratory test abnormity, and observed and self-reported adverse events were all assessed as the measurements of safety and tolerability. RESULTS: Both the agomelatine and paroxetine groups showed significant improvement from baseline to the end point (P < 0.05) without between-group differences (P > 0.05). The mean decrease of HAM-D17 of agomelatine group was not inferior to the paroxetine group over the 8-week treatment (agomelatine 15.26 ± 6.44 vs paroxetine 14.87 ± 5.89, δ = 2.0; µA-µB 95% confidence interval, -1.13 to 1.91). The percentage of responders at the last postbaseline assessment was similar in the 2 groups on both HAM-D17 (agomelatine 66.15% vs paroxetine 63.49%) and Clinical Global Impressions-Improvement (agomelatine 79.09% vs paroxetine 80.36%). The anxiety (Hamilton Anxiety Rating Scale) and sleep symptoms (sleep items of HAM-D17) of the patients were improved significantly in the 2 groups at week 8 without between-group differences (P > 0.05). The incidence of overall adverse events was similar in the 2 groups (agomelatine 49.62% vs paroxetine 56.15%, P > 0.05). The incidence of adverse events in skin and subcutaneous tissue was higher in the paroxetine group than in the agomelatine group (none in agomelatine and 4.62% in paroxetine, P = 0.0144). CONCLUSIONS: Agomelatine showed equivalent antidepressant efficacy to paroxetine in treating MDD patients after 8 weeks of treatment with an acceptable safety.
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Acetamidas/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Paroxetina/uso terapêutico , Adolescente , Adulto , Idoso , Antidepressivos/efeitos adversos , Povo Asiático , China , Transtorno Depressivo Maior/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paroxetina/efeitos adversos , Escalas de Graduação Psiquiátrica , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Backgrounds: Observational studies suggest that air pollutants, including particulate matter and nitrogen compounds, could elevate asthma and allergic rhinitis health risks. Nevertheless, the exact nature of the causal relationship between air pollution and asthma and allergic rhinitis remains unknown. This study utilizes the Mendelian randomization (MR) technique to explore the potential causal links between air pollution components (PM2.5, PM2.5-10, PM10, NO2, and nitrogen dioxide) and the incidence of allergic rhinitis and asthma. Methods: A MR study utilized summary statistics from GWAS that are publicly accessible. The inverse variance weighting (IVW) approach served as the foundational analysis technique. To ensure robustness, supplementary methodologies such as the weighted median, MR-Egger regression, simple mode, and weighted model were also applied. Heterogeneity was evaluated using Cochran's Q test, and the presence of pleiotropy was determined through MR-Egger regression. The MR-PRESSO test was employed for outlier detection, and the analysis's sensitivity was scrutinized via a leave-one-out strategy. Results: The IVW technique showed a strong correlation between PM10 and asthma (OR = 0.625, 95% CI = 0.396-0.988, p = 0.044). No significant associations were found between asthma and other air pollutants such as PM2.5, PM2.5-10, NO2, or nitrogen dioxide. Similarly, allergic rhinitis showed no causal relationships with any studied air pollution metrics. Pleiotropy was absent in the findings. Sensitivity analyses, employing the leave-one-out method, confirmed the stability of these results, unaffected by individual single nucleotide polymorphisms (SNPs). Conclusion: This Mendelian randomization study establishes a causal link between PM10 exposure and asthma, suggesting that interventions to reduce air pollution may decelerate the adverse progression of asthma.
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Poluição do Ar , Asma , Análise da Randomização Mendeliana , Material Particulado , Rinite Alérgica , Asma/genética , Asma/epidemiologia , Asma/etiologia , Humanos , Rinite Alérgica/genética , Rinite Alérgica/epidemiologia , Rinite Alérgica/etiologia , Poluição do Ar/efeitos adversos , Material Particulado/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Exposição Ambiental/efeitos adversos , CausalidadeRESUMO
Magnetically responsive soft smart materials have garnered significant academic attention due to their flexibility, remote controllability, and reconfigurability. However, traditional soft materials used in the construction of these magnetically responsive systems typically exhibit low density and poor thermal and electrical conductivities. These limitations result in suboptimal performance in applications such as medical radiography, high-performance electronic devices, and thermal management. To address these challenges, magnetically responsive gallium-based liquid metals have emerged as promising alternatives. In this review, we summarize the methodologies for achieving magnetically responsive liquid metals, including the integration of magnetic agents into the liquid metal matrix and the utilization of induced Lorentz forces. We then provide a comprehensive discussion of the key physicochemical properties of these materials and the factors influencing them. Additionally, we explore the advanced and potential applications of magnetically responsive liquid metals. Finally, we discuss the current challenges in this field and present an outlook on future developments and research directions.
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This study aimed to summarize the characteristics of the top 100 most-cited publications on Peyronie's disease (PD) research and to analyse past and current research hotspots and trends. The SCI-E database of the Web of Science Core Collection (WoSCC) provided us with the top 100 most-cited publications in PD research, from which we took the following information: general trend of publication, year of publication, nation/region, institution, journal, author, and keywords. VOSviewer (version 1.6.18) and Excel (version 2016) were used for information analysis. Through a standardized search, we ultimately found 1019 papers in the field of PD research, from which we extracted the 100 articles that had received the highest citations. The articles were published between 1949 and 2016. The United States is a major contributor to PD research (n = 67). The University of California, Los Angeles, was the institution with the largest number of articles (n = 11). These articles were published in 16 journals, with the largest number appearing in the Journal of Urology (n = 47). The author with the most articles was Levine LA (n = 9). Gelbard MK's articles had the highest citation frequency (n = 1158). Erectile dysfunction (n = 19) was the keyword with the highest frequency, indicating that PD-related erectile dysfunction was the leading focus of research in this field. Most of the keywords that have appeared in the past decade are related to the clinical treatment of PD. Therefore, we believe that improving patients' erectile function to the greatest extent in clinical treatment is the frontier and hot spot of future research.
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Disfunção Erétil , Induração Peniana , Urologia , Masculino , Humanos , Bibliometria , Bases de Dados FactuaisRESUMO
SCOPE: l-Theanine (l-Thea) is an amino acid which is naturally present in tea leaves. It has been associated with possible health advantages, including obesity prevention, but the underlying molecular mechanisms have not been elucidated. METHODS AND RESULTS: A multiomics approach is utilized to examine the mechanism by which l-Thea exerts its antiobesity effects. This study reveals that l-Thea administration significantly ameliorates high-fat diet (HFD)-induced obesity in rats by improving body weight and hyperlipidemia. l-Thea mitigates HFD-induced inflammation and reverses hepatic and colonic damage, and intestinal barrier. This research verifies that the preventive effect of l-Thea on obesity in rats induced by an HFD with colitis is accomplished by suppressing the phosphorylation of important proteins in the NF-κB/mitogen-activated protein kinase (MAPK) pathways. Metabolome analysis reveals that l-Thea regulates HFD-induced metabolic disorders, specifically through modulation of steroid hormone biosynthesis. Microbiome analysis reveals that l-Thea mitigates HFD-induced dysbiosis by increasing the relative abundance of obesity-associated probiotic bacteria, including Blautia coccoides and Lactobacillus murinus, while simultaneously suppressing the abundance of pathogenic bacteria. CONCLUSIONS: l-Thea alleviates colitis generated by an HFD by restoring the integrity of the intestinal barrier, suppressing inflammation through regulation of MAPK/NF-κB signaling pathways, and enhancing microbial metabolism in colon.
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Colo , Dieta Hiperlipídica , Obesidade , Animais , Masculino , Ratos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Disbiose , Microbioma Gastrointestinal/efeitos dos fármacos , Glutamatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Bisphenol A (BPA) is a prevalent endocrine disruptor found in natural environments. Exposure to BPA has been associated with male infertility. The natural phytochemical icariin (ICA) has demonstrated significant promise for the treatment of male infertility. However, its effectiveness is limited due to its low bioavailability, poor water solubility, and insufficient targeting abilities. Herein, novel nanoparticles are generated from the natural silk fibroin, which are used to load ICA. The efficient drug delivery system (ICA-SNPs) result in significantly focused drug distribution to spermatogonium, enhancing the anti-infertility properties of ICA, and can effectively mitigate spermatogenesis dysfunction induced by BPA, control serum sex hormone levels, and enhance testicular ultrastructure. Additionally, the ICA-SNPs restore spermatogenesis dysfunction primarily via the hormone biosynthesis, spermatogonium meiosis process, and glycerophospholipid metabolism.
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Compostos Benzidrílicos , Fibroínas , Flavonoides , Infertilidade Masculina , Nanopartículas , Fenóis , Masculino , Humanos , Espermatogênese , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/tratamento farmacológicoRESUMO
BACKGROUND: JX11502MA is a potent partial agonist of dopamine D2 and D3 receptors, with a preferential binding profile for D3 receptors in vitro, potentially for treating schizophrenia. METHODS: A first-in-human, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. The subjects were randomly assigned to receive JX11502MA and placebo capsules with seven ascending dose groups: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 6 mg, and 8 mg. The PK profiles of JX11502MA and its metabolites were evaluated, along with a safety and tolerability assessment. RESULTS: Considering the safety of participants, the dose escalation was halted at 3 mg. Following single-dose administration, JX11502MA exhibited rapid absorption with a median Tmax ranging from 1 to 1.75 h. The terminal half-life of JX11502MA ranged from 73.62 to 276.85 h. The most common treatment-emergent adverse events (TEAEs) for subjects receiving JX11502MA were somnolence (56.3%), dizziness (18.8%), nausea (21.9%), vomiting (18.8%), and hiccups (18.8%). CONCLUSIONS: JX11502MA was generally well tolerated at a single dose of 0.25 to 3 mg. The PK profiles and safety characteristics in this study indicated that JX11502MA has the potential to be a favorable treatment option for patients with schizophrenia. TRIAL REGISTRATION: https://clinicaltrials.gov (identifier: NCT05233657).
Assuntos
Receptores de Dopamina D2 , Receptores de Dopamina D3 , Humanos , Área Sob a Curva , China , Relação Dose-Resposta a Droga , Método Duplo-Cego , Voluntários Saudáveis , População do Leste Asiático , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D3/agonistasRESUMO
Currently, research predominantly focuses on evaluating clinical effects at specific time points while neglecting underlying patterns within the treatment process. This study aims to analyze the dynamic alterations in PANSS total scores and prolactin levels in patients with schizophrenia treated with risperidone, along with the influencing covariates. Using data from an 8-week randomized, double-blind, multicenter clinical trial, a population pharmacodynamic model was established for the PANSS total scores of and prolactin levels in patients treated with risperidone. The base model employed was the Emax model. Covariate selection was conducted using a stepwise forward inclusion and backward elimination approach. A total of 144 patients were included in this analysis, with 807 PANSS total scores and 531 prolactin concentration values. The PANSS total scores of the patients treated with risperidone decreased over time, fitting a proportionally parameterized sigmoid Emax model with covariates including baseline score, course of the disease, gender, plasma calcium ions, and lactate dehydrogenase levels. The increase in prolactin levels conformed to the ordinary Emax model, with covariates encompassing course of the disease, gender, weight, red blood cell count, and triglyceride levels. The impacts of the baseline scores and the course of the disease on the reduction of the PANSS scores, as well as the influence of gender on the elevation of prolactin levels, each exceeded 20%. This study provides valuable quantitative data regarding PANSS total scores and prolactin levels among patients undergoing risperidone treatment across various physiological conditions.