Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 96
Filtrar
1.
Sci Total Environ ; 951: 175527, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153617

RESUMO

The Yangtze River Estuary (YRE) is one of the areas in China most severely affected by harmful algal blooms (HABs). This study explored the distributive patterns of HABs in the YRE and how they are influenced by the El Niño-Southern Oscillation (ENSO) and other environmental factors. Quantitative real-time PCR (qPCR) was employed to detect and quantify the four predominant HAB species in the YRE, Karenia mikimotoi, Margalefidinium polykrikoides, Prorocentrum donghaiense, and Heterosigma akashiwo. Additionally, the study analyzed how turbidity, pH, salinity, and temperature influence these algae. Distribution of the four HAB species in the YRE area shows clear geographical variations: K. mikimotoi is predominantly found in the northwest and central sea areas, M. polykrikoides (East Asian Ribotype, EAR) is mainly distributed in the southeastern part, P. donghaiense is abundant in the northern regions, and H. akashiwo is especially prevalent at stations S26 and S27 in the northeastern part of the study area. HABs dominated by H. akashiwo and P. donghaiense were observed in the northeastern sea area of the YRE on July 22, 2020. Our study reveals that K. mikimotoi, M. polykrikoides (EAR), and P. donghaiense are mainly affected by turbidity, pH, and salinity, while temperature predominantly influences the blooms of H. akashiwo. Moreover, runoff in the YRE has a certain correlation with ENSO events, which may also impact the nutrient content of the region. The findings of this study illustrate the distributive patterns of the four HAB species under various ecological conditions in the YRE and emphasize the importance of establishing practical cases for future warning systems. To better understand how climate change affects HABs, exploring the link between ENSO and HABs is essential.


Assuntos
Mudança Climática , Monitoramento Ambiental , Estuários , Proliferação Nociva de Algas , China , Rios , Dinoflagellida , Salinidade
2.
Materials (Basel) ; 17(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39203127

RESUMO

Mixing cement with seawater will cause the hydration process of cement to be different from that of ordinary cement, which will significantly affect cement's mechanical properties and durability. This article investigates the effects of chloride ion concentration, curing temperature, and nano-metakaolin content on the evolution process of Friedel's salts and ettringite (AFt) crystals in cement pastes. The study was conducted using X-ray diffraction (XRD), thermal analysis (TG), scanning electron microscopy (SEM), and mercury-intrusion porosimetry (MIP). The results show that chlorine salt can increase the production of Friedel's salt and ettringite, and the delayed AFt production increases by up to 27.95% after the addition of chlorine salt, which has an adverse effect on cement-based materials. Increasing the curing temperature and increasing the nano-metakaolin dosage increased the generation of Friedel's salt and decreased the delayed AFt generation, which resulted in a decrease in the length and diameter of the AFt crystals. After 28 days of high-temperature curing and the addition of nano-metakaolin, Friedel's salt production increased by 13.40% and 14.34%, respectively, and ettringite production decreased by 9.68% and 7.93%, respectively. Increasing the curing temperature and adding nano-metakaolin can reduce the adverse effect of delayed ettringite increases due to chloride ion binding.

3.
J Affect Disord ; 363: 249-257, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39029702

RESUMO

BACKGROUND: Major depressive disorder (MDD) is progressively recognized as a stress-related disorder characterized by aberrant brain network dynamics, encompassing both structural and functional domains. Yet, the intricate interplay between these dynamic networks and their molecular underpinnings remains predominantly unexplored. METHODS: Both structural and functional networks were constructed using multimodal neuroimaging data from 183 MDD patients and 300 age- and gender-matched healthy controls (HC). structural-functional connectivity (SC-FC) coupling was evaluated at both the connectome- and nodal-levels. Methylation data of five HPA axis key genes, including NR3C1, FKBP5, CRHBP, CRHR1, and CRHR2, were analyzed using Illumina Infinium Methylation EPIC BeadChip. RESULTS: We observed a significant reduction in SC-FC coupling at the connectome-level in patients with MDD compared to HC. At the nodal level, we found an imbalance in SC-FC coupling, with reduced coupling in cortical regions and increased coupling in subcortical regions. Furthermore, we identified 23 differentially methylated CpG sites on the HPA axis, following adjustment for multiple comparisons and control of age, gender, and medication status. Notably, three CpG sites on NR3C1 (cg01294526, cg19457823, and cg23430507), one CpG site on FKBP5 (cg25563198), one CpG site on CRHR1 (cg26656751), and one CpG site on CRHR2 (cg18351440) exhibited significant associations with SC-FC coupling in MDD patients. CONCLUSIONS: These findings provide valuable insights into the connection between micro-scale epigenetic changes in the HPA axis and SC-FC coupling at macro-scale connectomes. They unveil the mechanisms underlying increased susceptibility to MDD resulting from chronic stress and may suggest potential pharmacological targets within the HPA-axis for MDD treatment.


Assuntos
Encéfalo , Conectoma , Metilação de DNA , Transtorno Depressivo Maior , Epigênese Genética , Humanos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Masculino , Adulto , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Proteínas de Ligação a Tacrolimo/genética , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipotálamo-Hipofisário/metabolismo , Receptores de Hormônio Liberador da Corticotropina/genética , Imageamento por Ressonância Magnética , Sistema Hipófise-Suprarrenal/fisiopatologia , Receptores de Glucocorticoides/genética , Estudos de Casos e Controles
4.
J Coll Physicians Surg Pak ; 34(7): 805-810, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978245

RESUMO

OBJECTIVE: To investigate the variability in the expression profile of genes associated with polymyositis (PM), explore the potential molecular mechanisms underlying PM, and predict novel targets for intervention. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Rheumatology, Taizhou Municipal Hospital, Taizhou, China, from August to November 2023. METHODOLOGY: Three microarray datasets (GSE3112, GSE39454, and GSE128470) were extracted from the gene expression omnibus (GEO). The analysis of this research involved identifying the differentially expressed genes (DEGs) in PM compared to normal samples. Enrichment analysis, gene-microRNA, gene-transcription factor (TF), and protein-protein interaction (PPI) network studies were conducted to identify hub genes and relevant pathways. Additionally, the drug-gene interaction database (DGIdb) was used to predict therapeutic medications. RESULTS: Eighty-eight DEGs were identified. The enrichment analysis results highlighted the significant involvement of downregulated DEGs in antigen processing and presentation. Based on the PPI networks, seven hub genes with high connectivity degrees were selected including a cluster of differentiation 74 (CD74), human leukocyte antigen (HLA)-DPA1, HLA-B, guanylate-binding protein 1 (GBP1), recombinant 2', 5'-oligoadenylate synthetase 1 (OAS1), HLA-C, and HLA-E. CONCLUSION: This research screened-out core genes, projected prospective therapeutic medications, discovered DEGs between PM and normal samples, and offered fresh perspectives for additional research into the possible mechanism and therapeutic targets of PM. KEY WORDS: Polymyositis, DEGs, Hub genes, Bioinformatics, Potential therapeutic agents.


Assuntos
Perfilação da Expressão Gênica , Polimiosite , Mapas de Interação de Proteínas , Humanos , Polimiosite/genética , Polimiosite/tratamento farmacológico , Redes Reguladoras de Genes , Biologia Computacional , MicroRNAs/genética , Bases de Dados Genéticas , Transcriptoma
5.
Sci Total Environ ; 946: 174332, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38950630

RESUMO

Cathodic electroactive bacteria (C-EAB) which are capable of accepting electrons from solid electrodes provide fresh avenues for pollutant removal, biosensor design, and electrosynthesis. This review systematically summarized the burgeoning applications of the C-EAB over the past decade, including 1) removal of nitrate, aromatic derivatives, and metal ions; 2) biosensing based on biocathode; 3) electrosynthesis of CH4, H2, organic carbon, NH3, and protein. In addition, the mechanisms of electron transfer by the C-EAB are also classified and summarized. Extracellular electron transfer and interspecies electron transfer have been introduced, and the electron transport mechanism of typical C-EAB, such as Shewanella oneidensis MR-1, has been combed in detail. By bringing to light this cutting-edge area of the C-EAB, this review aims to stimulate more interest and research on not only exploring great potential applications of these electron-accepting bacteria, but also developing steady and scalable processes harnessing biocathodes.


Assuntos
Eletrodos , Transporte de Elétrons , Bactérias/metabolismo , Shewanella/metabolismo , Fontes de Energia Bioelétrica , Técnicas Biossensoriais/métodos
6.
Angew Chem Int Ed Engl ; 63(39): e202409986, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923276

RESUMO

The utilization of hybrid aqueous electrolytes has significantly broadened the electrochemical and temperature ranges of aqueous batteries, such as aqueous zinc and lithium-ion batteries, but the design principles for extreme operating conditions remain poorly understood. Here, we systematically unveil the ternary interaction involving salt-water-organic co-solvents and its intricate impacts on both the atomic-level and macroscopic structural features of the hybrid electrolytes. This highlights a distinct category of micelle-like structure electrolytes featuring organic-enriched phases and nanosized aqueous electrolyte aggregates, enabled by appropriate low donor number co-solvents and amphiphilic anions. Remarkably, the electrolyte enables exceptional high solubility, accommodating up to 29.8 m zinc triflate within aqueous micelles. This configuration maintains an intra-micellar salt-in-water setup, allowing for a broad electrochemical window (up to 3.86 V), low viscosity, and state-of-the-art ultralow-temperature zinc ion conductivity (1.58 mS cm-1 at -80 °C). Building upon the unique nature of the inhomogeneous localized aggregates, this micelle-like electrolyte facilitates dendrite-free Zn plating/stripping, even at -80 °C. The assembled Zn||PANI battery showcases an impressive capacity of 71.8 mAh g-1 and an extended lifespan of over 3000 cycles at -80 °C. This study opens up a promising approach in electrolyte design that transcends conventional local atomic solvation structures, broadening the water-in-salt electrolyte concept.

7.
Asian J Psychiatr ; 97: 104092, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823081

RESUMO

BACKGROUND: Early life stress (ELS) significantly increases the risk of mood disorders and affects the neurodevelopment of the primary cortex. HYPOTHESIS: Modulating the primary cortex through neural intervention can ameliorate the impact of ELS on brain development and consequently alleviate its effects on mood disorders. METHOD: We induced the chronic unpredictable mild stress (CUMS) model in adolescent rats, followed by applying repetitive transcranial magnetic stimulation (rTMS) to their primary cortex in early adulthood. To assess the applicability of primary cortex rTMS in humans, we recruited individuals aged 17-25 with mood disorders who had experienced ELS and performed primary cortex rTMS on them. Functional magnetic resonance imaging (fMRI) and depression-related behavioral and clinical symptoms were conducted in both rats and human subjects before and after the rTMS. RESULTS: In animals, fMRI analysis revealed increased activation in the primary cortex of CUMS rats and decrease subcortical activation. Following the intervention of primary cortex rTMS, the abnormal functional activity was reversed. Similarly, in mood disorders patients with ELS, increased activation in the primary cortex and decreased activation in the frontal cortex were observed. During rTMS intervention, similar neuroimaging improvements were noted, particularly decreased activation in the primary cortex. This suggests that targeted rTMS in the primary cortex can reverse the abnormal neuroimaging. CONCLUSION: This cross-species translational study has identified the primary cortex as a key region in mood disorders patients with ELS. Targeting the primary cortex with rTMS can correct abnormal functional activity while improving symptoms. Our study provides translational evidence for therapeutics targeting the ELS factor of mood disorders patients.


Assuntos
Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Transtornos do Humor , Estresse Psicológico , Estimulação Magnética Transcraniana , Animais , Estimulação Magnética Transcraniana/métodos , Ratos , Estresse Psicológico/terapia , Estresse Psicológico/fisiopatologia , Adulto , Masculino , Humanos , Adulto Jovem , Adolescente , Transtornos do Humor/terapia , Transtornos do Humor/fisiopatologia , Feminino , Ratos Sprague-Dawley , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem
8.
Front Pharmacol ; 15: 1407989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38769996

RESUMO

Osteosarcoma (OS) is notorious for its high malignancy, and conventional chemotherapy drugs, while killing tumor cells, often inflict significant harm on the patient's body. The tumor microenvironment of OS is characterized by high levels of hydrogen peroxide (H2O2). Leveraging this feature, we have developed Mg-ZIF nanoparticles, which incorporate magnesium (Mg) to confer robust peroxidase (POD)-like enzymatic activity. These Mg-ZIF nanozymes can generate highly lethal superoxide anions within tumor cells in a responsive manner, thereby achieving effective tumor destruction. Both in vitro and in situ OS models have corroborated the anti-tumor efficacy of Mg-ZIF nanozymes, while also validating their biosafety. The design of Mg-ZIF nanozymes opens a new avenue for the treatment of OS, offering a promising therapeutic strategy.

9.
Psychol Med ; : 1-11, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804091

RESUMO

BACKGROUND: Mood disorders are characterized by great heterogeneity in clinical manifestation. Uncovering such heterogeneity using neuroimaging-based individual biomarkers, clinical behaviors, and genetic risks, might contribute to elucidating the etiology of these diseases and support precision medicine. METHODS: We recruited 174 drug-naïve and drug-free patients with major depressive disorder and bipolar disorder, as well as 404 healthy controls. T1 MRI imaging data, clinical symptoms, and neurocognitive assessments, and genetics were obtained and analyzed. We applied regional gray matter volumes (GMV) and quantile normative modeling to create maturation curves, and then calculated individual deviations to identify subtypes within the patients using hierarchical clustering. We compared the between-subtype differences in GMV deviations, clinical behaviors, cell-specific transcriptomic associations, and polygenic risk scores. We also validated the GMV deviations based subtyping analysis in a replication cohort. RESULTS: Two subtypes emerged: subtype 1, characterized by increased GMV deviations in the frontal cortex, cognitive impairment, a higher genetic risk for Alzheimer's disease, and transcriptionally associated with Alzheimer's disease pathways, oligodendrocytes, and endothelial cells; and subtype 2, displaying globally decreased GMV deviations, more severe depressive symptoms, increased genetic vulnerability to major depressive disorder and transcriptionally related to microglia and inhibitory neurons. The distinct patterns of GMV deviations in the frontal, cingulate, and primary motor cortices between subtypes were shown to be replicable. CONCLUSIONS: Our current results provide vital links between MRI-derived phenotypes, spatial transcriptome, genetic vulnerability, and clinical manifestation, and uncover the heterogeneity of mood disorders in biological and behavioral terms.

10.
Animals (Basel) ; 14(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38539976

RESUMO

This study aimed to investigate whether a dietary 25-OHD3 addition improved the performance, egg quality, blood indexes, antioxidant status, jejunal morphology, and tibia quality of aged laying hens compared to a dietary VD3 addition. A total of 270 Hy-Line Brown laying hens at 55 wk of age were randomly assigned to three dietary treatments with six replicates (15 birds per replicate with 3 birds per cage). Chickens were fed a corn-soybean meal diet supplementation of 4000 IU/kg VD3 (control group), 50 µg/kg 25-OHD3 and 2000 IU/kg VD3 (experimental group 1), or 50 µg/kg 25-OHD3 and 4000 IU/kg VD3 (experimental group 2) for 12 weeks. The results demonstrated that 25-OHD3 caused a significant increase in the laying rate, especially in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group; the laying rate reached the maximum compared with other groups after 12 weeks (p < 0.05). However, there were no significant effects on the average egg weight, average daily feed intake, or feed-to-egg ratio (p > 0.05). A dietary supplementation of 50 µg/kg 25-OHD3 and 2000 IU/kg VD3 provided an improved eggshell strength, thick albumen height, and Haugh unit after 12 weeks (p < 0.05). Further analysis of the blood indexes showed that alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, calcium, and phosphorus were enhanced significantly in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group, while the content of total bilirubin decreased significantly (p < 0.05). In addition, the 25-OHD3 addition in diets improved the calcium and phosphorus contents in the serum (p < 0.05). The concentrations of 25-OHD3, parathyroid hormones, follicle-stimulating hormone, and progesterone were increased in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group, and the levels of cortisol, calcitonin, bone gla protein, and endotoxin in the serum reached a minimum in the 50 µg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05), which constitutes an advantage for the aged laying hens. The antioxidant enzyme activities and free radical scavenging abilities in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group increased markedly, and the MDA level decreased significantly in the 50 µg/kg 25-OHD3 + 4000 IU/kg VD3 group (p < 0.05). Improvements in jejunal morphology and intestinal integrity resulted in an increased villi-length-to-crypt-depth ratio in the 50 µg/kg 25-OHD3 + 2000 IU/kg VD3 group (p < 0.05). Dietary 50 µg/kg 25-OHD3 and 2000 IU/kg VD3 additions improved the tibia quality, including fresh tibia weight, strength, mineral content (Ca), and trabeculae area (p < 0.05). Taken together, compared with the dietary VD3 addition, dietary supplementation of 25-OHD3 supported a stable physiological status for sustained egg production, egg quality, and bone quality in late-phase laying hens, and the addition levels of 50 µg/kg 25-OHD3 and 2000 IU/kg VD3 had the best effect. Therefore, this could provide a theoretical basis for the use of 25-OHD3 as a substitute forVD3.

11.
iScience ; 27(4): 109474, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38551000

RESUMO

Abnormal accumulation of hydrogen peroxide (H2O2) in the tumor microenvironment is associated with altered metabolism, abnormal proliferation of tumor cells, and changes in the tumor microenvironment. Based on this phenomenon, we have developed manganese-doped zeolitic imidazolate frameworks (Mn-ZIF) nanozymes, which exhibit superior peroxidase (POD)-like activity and enhanced cytotoxicity. Inside the tumor, the H2O2 is catalyzed by Mn-ZIF nanozymes through the Fenton reaction to generate more potent hydroxyl radicals (·OH), further increasing the local reactive oxygen species (ROS) levels in tumor cells and inducing tumor cell death. Meanwhile, the removal of H2O2 in the tumor microenvironment reduces tumor proliferation. We have confirmed the anti-tumor effect of these particles in an in situ osteosarcoma (OS) model, providing a direction for the future design of hybrid nanozyme drug delivery systems.

12.
BMC Psychiatry ; 24(1): 187, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448895

RESUMO

BACKGROUND: Depression and anxiety are common and disabling mental health problems in children and young adults. Group cognitive behavioral therapy (GCBT) is considered that an efficient and effective treatment for these significant public health concerns, but not all participants respond equally well. The aim of this study was to examine the predictive ability of heart rate variability (HRV), based on sensor data from consumer-grade wearable devices to detect GCBT effectiveness in early intervention. METHODS: In a study of 33 college students with depression and anxiety, participants were randomly assigned to either GCBT group or a wait-list control (WLC) group. They wore smart wearable devices to measure their physiological activities and signals in daily life. The HRV parameters were calculated and compared between the groups. The study also assessed correlations between participants' symptoms, HRV, and GCBT outcomes. RESULTS: The study showed that participants in GCBT had significant improvement in depression and anxiety symptoms after four weeks. Higher HRV was associated with greater improvement in depressive and anxious symptoms following GCBT. Additionally, HRV played a noteworthy role in determining how effective GCBT was in improve anxiety(P = 0.002) and depression(P = 0.020), and its predictive power remained significant even when considering other factors. CONCLUSION: HRV may be a useful predictor of GCBT treatment efficacy. Identifying predictors of treatment response can help personalize treatment and improve outcomes for individuals with depression and anxiety. TRIAL REGISTRATION: The trial has been retrospectively registered on [22/06/2023] with the registration number [NCT05913349] in the ClinicalTrials.gov. Variations in heart rate variability (HRV) have been associated with depression and anxiety, but the relationship of baseline HRV to treatment outcome in depression and anxiety is unclear. This study predicted GCBT effectiveness using HRV measured by wearable devices. 33 students with depression and anxiety participated in a trial comparing GCBT and wait-list control. HRV parameters from wearables correlated with symptoms (PHQ, PSS) and GCBT effectiveness. Baseline HRV levels are strongly associated with GCBT treatment outcomes. HRV may serve as a useful predictor of efficacy of GCBT treatment,facilitating personalized treatment approaches for individuals with depression and anxiety.


Assuntos
Terapia Cognitivo-Comportamental , Dispositivos Eletrônicos Vestíveis , Criança , Adulto Jovem , Humanos , Frequência Cardíaca , Projetos de Pesquisa , Ansiedade/terapia
13.
Nanomicro Lett ; 16(1): 145, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441811

RESUMO

Aqueous Zn-ion batteries (AZIBs) have attracted increasing attention in next-generation energy storage systems due to their high safety and economic. Unfortunately, the side reactions, dendrites and hydrogen evolution effects at the zinc anode interface in aqueous electrolytes seriously hinder the application of aqueous zinc-ion batteries. Here, we report a critical solvation strategy to achieve reversible zinc electrochemistry by introducing a small polar molecule acetonitrile to form a "catcher" to arrest active molecules (bound water molecules). The stable solvation structure of [Zn(H2O)6]2+ is capable of maintaining and completely inhibiting free water molecules. When [Zn(H2O)6]2+ is partially desolvated in the Helmholtz outer layer, the separated active molecules will be arrested by the "catcher" formed by the strong hydrogen bond N-H bond, ensuring the stable desolvation of Zn2+. The Zn||Zn symmetric battery can stably cycle for 2250 h at 1 mAh cm-2, Zn||V6O13 full battery achieved a capacity retention rate of 99.2% after 10,000 cycles at 10 A g-1. This paper proposes a novel critical solvation strategy that paves the route for the construction of high-performance AZIBs.

14.
Opt Lett ; 49(3): 434-437, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300025

RESUMO

Single-frequency fiber lasers (SFFLs), 1083 nm, have been extensively applied in 4He optical pumping magnetometers (OPMs) for magnetic field detection. However, the sensitivity and accuracy of OPMs are constrained by the frequency stability of SFFLs. Focusing on this concern, the frequency-stabilized performance of the 1083 nm SFFLs is successfully improved by externally tailoring the laser linewidth to match the spectral width of the error signal in saturated absorption spectroscopy. Thereinto, a high-intensity error signal of saturated absorption is generated as a large number of 4He atoms with a wide range of velocities interacting with the 1083 nm laser. Consequently, the root mean square value of the fluctuating frequency after locking is effectively decreased from 24.6 to 13.6 kHz, which achieves a performance improvement of 44.7%. Such a strategy can provide a technical underpinning for effectuating an absolute frequency stabilization with higher precision based on atomic and molecular absorption spectroscopy techniques.

15.
Lancet Reg Health West Pac ; 42: 100925, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38357391

RESUMO

Background: The efficacy and safety of the oral Janus kinase inhibitor peficitinib were investigated in Asian patients with rheumatoid arthritis (RA). Methods: In this double-blind, phase 3 study, patients from mainland China, Korea, and Taiwan with RA and an inadequate response/intolerance to methotrexate were randomized (1:1:1) to once-daily placebo (N = 128), peficitinib 100 mg (N = 129), or 150 mg (N = 128) in combination with non-biologic DMARDs. At Week 24, patients receiving placebo switched to peficitinib 100 mg or 150 mg. American College of Rheumatology (ACR) 20 response at Week 24/early termination (ET) was the primary endpoint. Adverse events (AEs) were assessed. The study was registered at ClinicalTrials (NCT03660059). Findings: 385 patients were included in the analysis. ACR20 responses were statistically significantly higher in both peficitinib 100 mg (56.6%) and 150 mg (56.3%) groups versus placebo (24.2%); Odds Ratio (95% confidence interval, CI) 4.14 (2.42, 7.08) and 4.07 (2.38, 6.96), respectively (both P < 0.001) at Week 24/ET. The incidence rate of herpes zoster related disease (herpes zoster and varicella) was higher in patients who received peficitinib versus placebo, but no dose dependency was observed (incidence rate/100 patient-years (95% CI): peficitinib 6.7 (4.32, 10.37); placebo 3.7 (0.93, 14.88). Interpretation: In Asian patients with RA and an inadequate response/intolerance to methotrexate, peficitinib 100 mg and 150 mg demonstrated superiority to placebo in the reduction of RA symptoms and was well tolerated. No additional benefit was observed with use of the higher peficitinib dose in this study population of predominantly Chinese patients. Funding: Astellas Pharma.

16.
Transl Psychiatry ; 14(1): 17, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195555

RESUMO

Several lines of evidence support the involvement of transcriptomic and epigenetic mechanisms in the brain structural deficits of major depressive disorder (MDD) separately. However, research in these two areas has remained isolated. In this study, we proposed an integrative strategy that combined neuroimaging, brain-wide gene expression, and peripheral DNA methylation data to investigate the genetic basis of gray matter abnormalities in MDD. The MRI T1-weighted images and Illumina 850 K DNA methylation microarrays were obtained from 269 patients and 416 healthy controls, and brain-wide transcriptomic data were collected from Allen Human Brain Atlas. The between-group differences in gray matter volume (GMV) and differentially methylated CpG positions (DMPs) were examined. The genes with their expression patterns spatially related to GMV changes and genes with DMPs were overlapped and selected. Using principal component regression, the associations between DMPs in overlapped genes and GMV across individual patients were investigated, and the region-specific correlations between methylation status and gene expression were examined. We found significant associations between the decreased GMV and DMPs methylation status in the anterior cingulate cortex, inferior frontal cortex, and fusiform face cortex regions. These DMPs genes were primarily enriched in the neurodevelopmental and synaptic transmission process. There was a significant negative correlation between DNA methylation and gene expression in genes associated with GMV changes of the frontal cortex in MDD. Our findings suggest that GMV abnormalities in MDD may have a transcriptomic and epigenetic basis. This imaging-transcriptomic-epigenetic integrative analysis provides spatial and biological links between cortical morphological deficits and peripheral epigenetic signatures in MDD.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/genética , Epigenômica , Multiômica , Encéfalo/diagnóstico por imagem , Perfilação da Expressão Gênica
17.
Angew Chem Int Ed Engl ; 63(11): e202317957, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38270335

RESUMO

Weak adsorption of gas reactants and strong binding of intermediates present a significant challenge for most transition metal oxides, particularly in the realm of CO2 photoreduction. Herein, we demonstrate that the adsorption can be fine-tuned by phase engineering of oxide catalysts. An oxygen vacancy mediated topological phase transition in Ni-Co oxide nanowires, supported on a hierarchical graphene aerogel (GA), is observed from a spinel phase to a rock-salt phase. Such in situ phase transition empowers the Ni-Co oxide catalyst with a strong internal electric field and the attainment of abundant oxygen vacancies. Among a series of catalysts, the in situ transformed spinel/rock-salt heterojunction supported on GA stands out for an exceptional photocatalytic CO2 reduction activity and selectivity, yielding an impressive CO production rate of 12.5 mmol g-1 h-1 and high selectivity of 96.5 %. This remarkable performance is a result of the robust interfacial coupling between two topological phases that optimizes the electronic structures through directional charge transfer across interfaces. The phase transition process induces more Co2+ in octahedral site, which can effectively enhance the Co-O covalency. This synergistic effect balances the surface activation of CO2 molecules and desorption of reaction intermediates, thereby lowering the energetic barrier of the rate-limiting step.

18.
CNS Neurosci Ther ; 30(3): e14427, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37721197

RESUMO

AIMS: Neurodevelopmental impairments are closely linked to the basis of adolescent major psychiatric disorders (MPDs). The visual cortex can regulate neuroplasticity throughout the brain during critical periods of neurodevelopment, which may provide a promising target for neuromodulation therapy. This cross-species translational study examined the effects of visual cortex repetitive transcranial magnetic stimulation (rTMS) on neurodevelopmental impairments in MPDs. METHODS: Visual cortex rTMS was performed in both adolescent methylazoxymethanol acetate (MAM) rats and patients with MPDs. Functional magnetic resonance imaging (fMRI) and brain tissue proteomic data in rats and fMRI and clinical symptom data in patients were analyzed. RESULTS: The regional homogeneity (ReHo) analysis of fMRI data revealed an increase in the frontal cortex and a decrease in the posterior cortex in the MAM rats, representing the abnormal neurodevelopmental pattern in MPDs. In regard to the effects of rTMS, similar neuroimaging changes, particularly reduced frontal ReHo, were found both in MAM rats and adolescent patients, suggesting that rTMS may reverse the abnormal neurodevelopmental pattern. Proteomic analysis revealed that rTMS modulated frontal synapse-associated proteins, which may be the underpinnings of rTMS efficacy. Furthermore, a positive relationship was observed between frontal ReHo and clinical symptoms after rTMS in patients. CONCLUSION: Visual cortex rTMS was proven to be an effective treatment for adolescent MPDs, and the underlying neural and molecular mechanisms were uncovered. Our study provides translational evidence for therapeutics targeting the neurodevelopmental factor in MPDs.


Assuntos
Transtornos Mentais , Córtex Visual , Humanos , Adolescente , Animais , Ratos , Estimulação Magnética Transcraniana/métodos , Proteômica , Córtex Pré-Frontal , Córtex Visual/diagnóstico por imagem , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/terapia , Imageamento por Ressonância Magnética
19.
Neurosci Bull ; 40(6): 683-694, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38141109

RESUMO

Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence. The methylazoxymethanol acetate (MAM) animal model, in which disruption in neurodevelopmental processes is induced, mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective. We conducted longitudinal structural magnetic resonance imaging (MRI) scans during childhood, adolescence, and adulthood in MAM rats to identify specific brain regions and critical windows for intervention. Then, the effect of repetitive transcranial magnetic stimulation (rTMS) intervention on the target brain region during the critical window was investigated. In addition, the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders (diagnosed with major depressive disorder or bipolar disorder) to evaluate its clinical translational potential. The results demonstrated that, compared to the control group, the MAM rats exhibited significantly lower striatal volume from childhood to adulthood (all P <0.001). In contrast, the volume of the hippocampus did not show significant differences during childhood (P >0.05) but was significantly lower than the control group from adolescence to adulthood (both P <0.001). Subsequently, rTMS was applied to the occipital cortex, which is anatomically connected to the hippocampus, in the MAM models during adolescence. The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group (P <0.01), while the volume of the striatum remained unchanged (P >0.05). In the clinical trial, adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline (P <0.01), and these volumetric changes were associated with improvement in depressive symptoms (r = - 0.524, P = 0.018). These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for early-onset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms.


Assuntos
Modelos Animais de Doenças , Hipocampo , Imageamento por Ressonância Magnética , Acetato de Metilazoximetanol , Estimulação Magnética Transcraniana , Animais , Hipocampo/patologia , Estimulação Magnética Transcraniana/métodos , Masculino , Adolescente , Feminino , Ratos , Humanos , Acetato de Metilazoximetanol/análogos & derivados , Transtorno Depressivo Maior/terapia , Transtornos Mentais/terapia , Pesquisa Translacional Biomédica , Ratos Sprague-Dawley , Transtorno Bipolar/terapia
20.
Proc Inst Mech Eng H ; 238(1): 33-44, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38156406

RESUMO

Gastrointestinal surgery using a stapler is usually associated with tissue damage, anastomosis leakage, bleeding, and other complications, which is one of the effective methods for treating digestive tract cancer. The cutting properties of staples and the tissue damage occurring in the process of stapling porcine esophageal and gastric tissues have been evaluated and a new type of stapler has been designed. Since different structural and mechanical properties esophageal and gastric tissues layers, the puncturing force exhibits a fluctuating trend. Compressive stress caused by the bending of the staple legs can lead to the destruction of the vascular network inside the tissue, tissue deforms and tears. Finally, a staple with an internal incision arc (IIA) tip is designed, which meeting the performance requirements.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Grampeamento Cirúrgico , Suínos , Animais , Grampeamento Cirúrgico/efeitos adversos , Grampeamento Cirúrgico/métodos , Trato Gastrointestinal , Anastomose Cirúrgica/métodos , Desenho de Equipamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA