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1.
Phys Med Biol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593827

RESUMO

BACKGROUND: Radiomics and deep learning techniques have become integral in meningioma grading. The combination of these approaches holds the potential to enhance classification accuracy. Given the frequent occurrence of peritumoral edema (PTE) in meningiomas, investigating the potential value of PTE requires further research. Objectives: To address the challenge of meningioma grading, this study introduces a unique approach that integrates radiomics and deep learning techniques. The primary focus is on the development of a Transfer Learning-based Meningioma Feature Extraction Model (MFEM), leveraging both Vision Transformer (ViT) and Convolutional Neural Network (CNN) architectures. Furthermore, the study explores the potential significance of the peritumoral edema (PTE) region in enhancing the grading process. Materials and Methods: A retrospective study was conducted involving 98 meningioma patients, with 60 classified as low-grade meningiomas and 38 as high-grade meningiomas. PTE was observed in 51.02% of low-grade meningiomas patients and 89.47% of high-grade meningiomas patients. Magnetic resonance images were acquired using a GE Signa HDxt 1.5T MRI scanner, incorporating T2-weighted Fluid-Attenuated Inversion Recovery (T2 Flair) sequences. A Transfer Learning-based Meningioma Feature Extraction Model (MFEM) was constructed by combining ViT and CNN models to extract deep features from the Transformer layer, alongside radiomics features. These were then utilized as input for a machine learning classifier to accurately grade meningiomas. Results: The proposed method demonstrated excellent grading accuracy and robustness on the meningioma dataset, offering valuable guidance for treatment decisions. The approach achieved 92.86% accuracy, 93.44% precision, 95% sensitivity, and 89.47% specificity. Conclusion: The radiomics and deep learning-based approach presented in this study offers a reliable method for preoperative meningioma grading. This innovative method not only enhances accuracy but also reduces observer subjectivity, thereby contributing to improved clinical decision-making. .

2.
Small ; : e2310702, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38660707

RESUMO

Disordered MOFs seamlessly amalgamate the robust stability and pore tunability inherent in crystalline MOFs with the advantages derived from abundant defects and active sites present in amorphous structures. This study pioneers the use of the interference-oriented attachment (IOA) mechanism to meticulously craft the morphology and crystal growth of MIL-101(Cr) (Cr-MOF), resulting in the successful synthesis of a high-level disordered Cr-MOF boasting an enhanced array of active sites and exceptional electrochemical properties. The correlation between disordered structures and the electrochemical properties of MOFs are elucidated using the lattice distortion index and fractal dimension. The high-level disordered MOF electrode showcases a remarkable fluoride sieving effect, outperforming conventional fluoride removal materials with a remarkable fluoride adsorption capacity of 41.04 mgNaF gelectrodes -1. First-principles calculations, in conjunction with relevant experiments, provided further validation that the disordered structure significantly enhances the defluorination performance of the material. This study introduces a novel approach for the direct bottom-up synthesis of high-level disordered MOFs, showcasing their potential for applications in electrochemical water treatment.

3.
Front Public Health ; 12: 1329234, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463162

RESUMO

China's rural residents have basically solved the problem of subsistence, but due to aging, the prevalence of sarcopenia (abbreviated as sarcopenia) has been increasing year by year, especially the skeletal muscle health of the rural older residents has not been sufficiently paid attention to, so analyses of the impact of income level on the skeletal muscle health of the older people in rural areas of China are of great practical significance. Based on the annual data of the China Health and Nutrition Survey (CHNS) in 2006, 2009, and 2011, we introduced the mediator variable of dietary knowledge and used the Probit model regression, mediation effect model, and instrumental variable regression to assess the skeletal muscle health status of the rural older people in China and explore the mechanism of the influence of the income level on the skeletal muscle health of the rural older residents in China. The primary objectives of this study were to evaluate the impact of income level on the skeletal muscle health status of older adults living in rural areas of China and to investigate the underlying mechanisms. By analyzing the findings of this study, our aim is to establish a correlation between the economic status and skeletal muscle health of older adults in rural communities, as well as elucidate the influence of income level and dietary knowledge on their skeletal muscle health. Through the attainment of these objectives, we hope to provide valuable insights and recommendations for enhancing skeletal muscle health among the rural older population in China. Based on our research findings, it can be inferred that there was a significant association between the financial status of rural older adults and their skeletal muscle health. Additionally, the prevalence of sarcopenia was lower among individuals with higher income levels, and there was a negative correlation between the prevalence of sarcopenia and the level of dietary knowledge among rural older individuals. The knowledge of dietary knowledge level of rural older people plays a mediating role in the income level and the prevalence of sarcopenia. Moreover, with the change in income level and the increase in age, the change in skeletal muscle health status showed obvious heterogeneity, in which the effect on the relatively younger (65-70 years old) samples was greater. Therefore, sustained income growth remains an effective way to improve the skeletal muscle health of older rural residents. At the same time, improving dietary knowledge and dietary quality among the older people is important in preventing a decline in muscle strength and physical function and in preventing the onset of sarcopenia.


Assuntos
Sarcopenia , Humanos , Idoso , Sarcopenia/epidemiologia , População Rural , Músculo Esquelético/fisiologia , Dieta , Força Muscular/fisiologia
4.
Compr Psychiatry ; 131: 152462, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38354586

RESUMO

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) has been documented to be effective in treating obsessive-compulsive disorder (OCD). However, the neurobiological basis of MBCT remains largely elusive, which makes it clinically challenging to predict which patients are more likely to respond poorly. Hence, identifying biomarkers for predicting treatment outcomes holds both scientific and clinical values. This prognostic study aims to investigate whether pre-treatment brain morphological metrics can predict the effectiveness of MBCT, compared with psycho-education (PE) as an active placebo, among patients with OCD. METHODS: A total of 32 patients with OCD were included in this prognostic study. They received magnetic resonance imaging (MRI) brain scans before treatment. Subsequently, 16 patients received 10 weeks of MBCT, while the other 16 patients underwent a 10-week PE program. The effectiveness of the treatments was primarily assessed by the reduction rate of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score before and after the treatment. We investigated whether several predefined OCD-associated brain morphological metrics, selected based on prior published studies by the ENIGMA Consortium, could predict the treatment effectiveness. RESULTS: Both the MBCT and PE groups exhibited substantial reductions in Y-BOCS scores over 10 weeks of treatment, with the MBCT group showing a larger reduction. Notably, the pallidum total volume was associated with treatment effectiveness, irrespective of the intervention group. Specifically, a linear regression model utilizing the pre-treatment pallidum volume to predict the treatment effectiveness suggested that a one-cubic-centimeter increase in pallidum volume corresponded to a 22.3% decrease in the Y-BOCS total score reduction rate. CONCLUSIONS: Pallidum volume may serve as a promising predictor for the effectiveness of MBCT and PE, and perhaps, other treatments with the shared mechanisms by MBCT and PE, among patients with OCD.


Assuntos
Terapia Cognitivo-Comportamental , Atenção Plena , Transtorno Obsessivo-Compulsivo , Humanos , Atenção Plena/métodos , Globo Pálido , Terapia Cognitivo-Comportamental/métodos , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/terapia , Transtorno Obsessivo-Compulsivo/psicologia , Resultado do Tratamento
5.
Nat Commun ; 15(1): 1125, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321032

RESUMO

Congenital vertebral malformation, affecting 0.13-0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.


Assuntos
Anormalidades Musculoesqueléticas , Coluna Vertebral , Humanos , Coluna Vertebral/anormalidades , Anormalidades Musculoesqueléticas/genética , Alelos , Exoma , Proteínas com Domínio T/genética
6.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385872

RESUMO

Drug discovery and development constitute a laborious and costly undertaking. The success of a drug hinges not only good efficacy but also acceptable absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties. Overall, up to 50% of drug development failures have been contributed from undesirable ADMET profiles. As a multiple parameter objective, the optimization of the ADMET properties is extremely challenging owing to the vast chemical space and limited human expert knowledge. In this study, a freely available platform called Chemical Molecular Optimization, Representation and Translation (ChemMORT) is developed for the optimization of multiple ADMET endpoints without the loss of potency (https://cadd.nscc-tj.cn/deploy/chemmort/). ChemMORT contains three modules: Simplified Molecular Input Line Entry System (SMILES) Encoder, Descriptor Decoder and Molecular Optimizer. The SMILES Encoder can generate the molecular representation with a 512-dimensional vector, and the Descriptor Decoder is able to translate the above representation to the corresponding molecular structure with high accuracy. Based on reversible molecular representation and particle swarm optimization strategy, the Molecular Optimizer can be used to effectively optimize undesirable ADMET properties without the loss of bioactivity, which essentially accomplishes the design of inverse QSAR. The constrained multi-objective optimization of the poly (ADP-ribose) polymerase-1 inhibitor is provided as the case to explore the utility of ChemMORT.


Assuntos
Aprendizado Profundo , Humanos , Desenvolvimento de Medicamentos , Descoberta de Drogas , Inibidores de Poli(ADP-Ribose) Polimerases
7.
Biomed Eng Lett ; 14(2): 341-353, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374903

RESUMO

Deep learning-based methods have recently shown great promise in medical image segmentation task. However, CNN-based frameworks struggle with inadequate long-range spatial dependency capture, whereas Transformers suffer from computational inefficiency and necessitate substantial volumes of labeled data for effective training. To tackle these issues, this paper introduces CI-UNet, a novel architecture that utilizes ConvNeXt as its encoder, amalgamating the computational efficiency and feature extraction capabilities. Moreover, an advanced attention mechanism is proposed to captures intricate cross-dimensional interactions and global context. Extensive experiments on two segmentation datasets, namely BCSD, and CT2USforKidneySeg, confirm the excellent performance of the proposed CI-UNet as compared to other segmentation methods.

8.
J Dent Sci ; 19(1): 631-636, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303828

RESUMO

The main outcome measure assessed in previous studies on photodynamic therapy (PDT) for oral precancerous lesions (OPL) is clinical response based on the alteration in lesion size after treatment. However, the primary and secondary outcome measures of the interventions for OPL should be malignant transformation and recurrence. Thus, the objective of this short communication is to summarize the evidence on PDT in preventing the recurrence and malignant transformation of OPL. There were 16 eligible studies which addressed the issue of OPL patients who received PDT with recurrence outcome, and the pooled recurrence rate (95% confidence interval) was analyzed to be 20.1% (16.2-24.6%). Notably, only 1 study reported that 7.5% of malignant transformation rate for OPL received PDT. These should be interpreted with caution due to low-level evidence, such as differences in study design, clinical and pathological features of patients enrolled, limited sample size, short follow-up time. Given few evaluated the effect of PDT on malignant transformation, we highlight that this primary outcome measure of OPL needs to be investigated in further well-designed longitudinal studies with adequate follow-up periods.

9.
J Dent Sci ; 19(1): 620-625, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303850

RESUMO

In 2020, Fanconi anemia (FA) was classified as a syndrome with insufficient epidemiological evidence in the oral potentially malignant disorder (OPMD) group by the WHO Collaborating Centre. The paucity of case reports on FA-associated OPMD limits evidence-based management, and such cases have not been analyzed collectively in detail. Hence, the objective of this short communication is to summarize the evidence on the onset and progression of OPMD in FA patients, so as to better understand the natural history of oral cancer development in patients affected by FA. A total of 11 eligible papers containing 1332 FA patients are involved in onset and progression of OPMD in FA patients. Of these, 186 (14.0%) were diagnosed with OPMD. With available data from 4 follow-up studies, 30 (41.1%) of 73 FA patients compatible with OPMD further developed into OSCC at young age (10-30 years old). The evidence on FA with malignant potential comprise clinical epidemiology, oral cytology abnormalities, DNA aneuploidy, loss of autofluorescence, loss of heterozygosity, high-risk human papillomavirus infection, DNA mutations in saliva and plasma samples. Collectively, these can consummate the evidence on FA as a syndrome that may potentiate cancer development in oral cavity mentioned by the WHO. Importantly, it highlights close surveillance is instrumental for FA patients with OPMD to early detect oral cancer.

10.
Plant Biotechnol J ; 22(5): 1325-1334, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38213067

RESUMO

Cytoplasmic male sterility (CMS), encoded by the mitochondrial open reading frames (ORFs), has long been used to economically produce crop hybrids. However, the utilization of CMS also hinders the exploitation of sterility and fertility variation in the absence of a restorer line, which in turn narrows the genetic background and reduces biodiversity. Here, we used a mitochondrial targeted transcription activator-like effector nuclease (mitoTALENs) to knock out ORF138 from the Ogura CMS broccoli hybrid. The knockout was confirmed by the amplification and re-sequencing read mapping to the mitochondrial genome. As a result, knockout of ORF138 restored the fertility of the CMS hybrid, and simultaneously manifested a cold-sensitive male sterility. ORF138 depletion is stably inherited to the next generation, allowing for direct use in the breeding process. In addition, we proposed a highly reliable and cost-effective toolkit to accelerate the life cycle of fertile lines from CMS-derived broccoli hybrids. By applying the k-mean clustering and interaction network analysis, we identified the central gene networks involved in the fertility restoration and cold-sensitive male sterility. Our study enables mitochondrial genome editing via mitoTALENs in Brassicaceae vegetable crops and provides evidence that the sex production machinery and its temperature-responsive ability are regulated by the mitochondria.


Assuntos
Brassica , Infertilidade Masculina , Masculino , Humanos , Brassica/genética , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição , Melhoramento Vegetal , Mitocôndrias/genética , Fertilidade/genética , Infertilidade das Plantas/genética
11.
Sensors (Basel) ; 24(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38203159

RESUMO

Most navigation aids for visually impaired individuals require users to pay close attention and actively understand the instructions or feedback of guidance, which impose considerable cognitive loads in long-term usage. To tackle the issue, this study proposes a cognitive burden-free electronic travel aid for individuals with visual impairments. Utilizing human instinctive compliance in response to external force, we introduce the "Aerial Guide Dog", a helium balloon aerostat drone designed for indoor guidance, which leverages gentle tugs in real time for directional guidance, ensuring a seamless and intuitive guiding experience. The introduced Aerial Guide Dog has been evaluated in terms of directional guidance and path following in the pilot study, focusing on assessing its accuracy in orientation and the overall performance in navigation. Preliminary results show that the Aerial Guide Dog, utilizing Ultra-Wideband (UWB) spatial positioning and Measurement Unit (IMU) angle sensors, consistently maintained minimal deviation from the targeting direction and designated path, while imposing negligible cognitive burdens on users while completing the guidance tasks.


Assuntos
Aeronaves , Animais de Trabalho , Animais , Cães , Humanos , Projetos Piloto , Eletrônica , Cognição
12.
Stem Cells Int ; 2024: 3361794, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283119

RESUMO

Objective: Periodontitis is a chronic inflammatory disease that causes loss of periodontal support tissue. Our objective was to investigate the mechanism by which METTL3-mediated N6-methyladenosine modification regulates the osteogenic differentiation through lncRNA in periodontal mesenchymal stem cells in patients with periodontitis (pPDLSCs). Material and Methods. We carried out a series of experiments, including methylated RNA immunoprecipitation-PCR, quantitative real-time polymerase chain reaction, and western blotting. The expressions of alkaline phosphatase (ALP), Runx2, Col1, Runx2 protein level, ALP staining, and Alizarin red staining were used to demonstrate the degree of osteogenic differentiation. Results: We found that METTL3 was the most significantly differentially expressed methylation-related enzyme in pPDLSCs and promoted osteogenic differentiation of pPDLSCs. METTL3 regulated the stability and expression of lncRNA CUTALP, while lncRNA CUTALP promoted osteogenic differentiation of pPDLSCs by inhibiting miR-30b-3p. At different time points of osteogenic differentiation, lncRNA CUTALP expression was positively correlated with Runx2, while miR-30b-3p showed the opposite pattern. The attenuated osteogenic differentiation induced by METTL3 knockdown was recovered by lncRNA CUTALP overexpression. The attenuated osteogenic differentiation induced by lncRNA CUTALP knockdown could be reversed by the miR-30b-3p inhibitor. Conclusions: In summary, METTL3/lncRNA CUTALP/miR-30b-3p/Runx2 is a regulatory network in the osteogenic differentiation of pPDLSCs.

13.
Nanomaterials (Basel) ; 14(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38251145

RESUMO

In this work, a bimetallic sulfide-coupled graphene hybrid was designed and constructed for capacitive energy storage. The hybrid structure involved decorating copper-cobalt-sulfide (CuCo2S4) nanoparticles onto graphene layers, with the nanoparticles anchored within the graphene layers, forming a hybrid energy storage system. In this hybrid structure, rGO can work as the substrate and current collector to support the uniform distribution of the nanoparticles and provides efficient transportation of electrons into and out of the electrode. In the meantime, CuCo2S4-active materials are expected to offer an evident enhancement in electrochemical activities, due to the rich valence change provided by Cu and Co. Benefiting from the integrated structure of CuCo2S4 nanoparticles and highly conductive graphene substrates, the prepared CuCo2S4@rGO electrode exhibited a favorable capacitive performance in 1 M KOH. At 1 A g-1, CuCo2S4@rGO achieved a specific capacitance of 410 F g-1. The capacitance retention at 8 A g-1 was 70% of that observed at 1 A g-1, affirming the material's excellent rate capability. At the current density of 5 A g-1, the electrode underwent 10,000 charge-discharge cycles, retaining 98% of its initial capacity, which indicates minimal capacity decay and showcasing excellent cycling performance.

14.
Autophagy ; 20(2): 416-436, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37733896

RESUMO

Crizotinib, a small-molecule tyrosine kinase inhibitor targeting ALK, MET and ROS1, is the first-line drug for ALK-positive metastatic non-small cell lung cancer and is associated with severe, sometimes fatal, cases of cardiac failure, which increases the risk of mortality. However, the underlying mechanism remains unclear, which causes the lack of therapeutic strategy. We established in vitro and in vivo models for crizotinib-induced cardiotoxicity and found that crizotinib caused left ventricular dysfunction, myocardial injury and pathological remodeling in mice and induced cardiomyocyte apoptosis and mitochondrial injury. In addition, we found that crizotinib prevented the degradation of MET protein by interrupting autophagosome-lysosome fusion and silence of MET or re-activating macroautophagy/autophagy flux rescued the cardiomyocytes death and mitochondrial injury caused by crizotinib, suggesting that impaired autophagy activity is the key reason for crizotinib-induced cardiotoxicity. We further confirmed that recovering the phosphorylation of PRKAA/AMPK (Ser485/491) by metformin re-activated autophagy flux in cardiomyocytes and metformin rescued crizotinib-induced cardiomyocyte injury and cardiac complications. In summary, we revealed a novel mechanism for crizotinib-induced cardiotoxicity, wherein the crizotinib-impaired autophagy process causes cardiomyocyte death and cardiac injury by inhibiting the degradation of MET protein, demonstrated a new function of impeded autophagosome-lysosome fusion in drugs-induced cardiotoxicity, pointed out the essential role of the phosphorylation of PRKAA (Ser485/491) in autophagosome-lysosome fusion and confirmed metformin as a potential therapeutic strategy for crizotinib-induced cardiotoxicity.Abbreviations and Acronyms: AAV: adeno-associated virus; ACAC/ACC: acetyl-Co A carboxylase; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATG5: autophagy related 5; ATG7: autophagy related 7; CHX: cycloheximide; CKMB: creatine kinase myocardial band; CQ: chloroquine; c-PARP: cleaved poly (ADP-ribose) polymerase; DAPI: 4'6-diamidino-2-phenylindole; EF: ejection fraction; FOXO: forkhead box O; FS: fractional shortening; GSEA: gene set enrichment analysis; H&E: hematoxylin and eosin; HF: heart failure; HW: TL: ratio of heart weight to tibia length; IR: ischemia-reperfusion; KEGG: Kyoto encyclopedia of genes and genomes; LAMP2: lysosomal-associated membrane protein 2; LDH: lactate dehydrogenase; MCMs: mouse cardiomyocytes; MMP: mitochondrial membrane potential; mtDNA: mitochondrial DNA; MYH6: myosin, heavy peptide 6, cardiac muscle, alpha; MYH7: myosin, heavy peptide 7, cardiac muscle, beta; NPPA: natriuretic peptide type A; NPPB: natriuretic peptide type B; PI: propidium iodide; PI3K: phosphoinositide 3-kinase; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; qPCR: quantitative real-time PCR; SD: standard deviation; SRB: sulforhodamine B; TKI: tyrosine kinase inhibitor; WGA: wheat germ agglutinin.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metformina , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/genética , Fosforilação , Macroautofagia , Crizotinibe/metabolismo , Autofagossomos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Cardiotoxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Peptídeos/metabolismo , Miosinas/metabolismo , Lisossomos/metabolismo , Monofosfato de Adenosina , Receptores Proteína Tirosina Quinases/metabolismo
15.
Int J Mol Med ; 53(2)2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38063273

RESUMO

Cytokines are the main regulators of innate and adaptive immunity, mediating communications between the cells of the immune system and regulating biological functions, including cell motility, differentiation, growth and apoptosis. Cytokines and cytokine receptors have been used in the treatment of tumors and autoimmune diseases, and to intervene in cytokine storms. Indeed, the use of monoclonal antibodies to block cytokine­receptor interactions, as well as antibody­cytokine fusion proteins has exhibited immense potential for the treatment of tumors and autoimmune diseases. Compared with these traditional types of antibodies, nanobodies not only maintain a high affinity and specificity, but also have the advantages of high thermal stability, a high capacity for chemical manipulation, low immunogenicity, good tissue permeability, rapid clearance and economic production. Thus, nanobodies have extensive potential for use in the diagnosis and treatment of cytokine­related diseases. The present review summarizes the application of nanobodies in cytokine­mediated immunotherapy and immunoimaging.


Assuntos
Doenças Autoimunes , Neoplasias , Anticorpos de Domínio Único , Humanos , Citocinas , Anticorpos de Domínio Único/uso terapêutico , Anticorpos Monoclonais , Neoplasias/terapia , Imunoterapia/métodos
16.
Redox Biol ; 69: 102996, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103341

RESUMO

Diabetic encephalopathy (DE) is a common central nervous system complication of diabetes mellitus without effective therapy currently. Recent studies have highlighted synaptic mitochondrial damages as a possible pathological basis for DE, but the underlying mechanisms remain unclear. Our previous work has revealed that phosphatidate phosphatase Lipin1, a critical enzyme involved with phospholipid synthesis, is closely related to the pathogenesis of DE. Here, we demonstrate that Lipin1 is significantly down-regulated in rat hippocampus of DE. Knock-down of Lipin1 within hippocampus of normal rats induces dysregulation of homeostasis in synaptic mitochondrial dynamics with an increase of mitochondrial fission and a decrease of fusion, then causes synaptic mitochondrial dysfunction, synaptic plasticity deficits as well as cognitive impairments, similar to that observed in response to chronic hyperglycemia exposure. In contrast, an up-regulation of Lipin1 within hippocampus in the DE model ameliorates this cascade of dysfunction. We also find that the effect of Lipin1 that regulating mitochondrial dynamics results from maintaining appropriate phospholipid components in the mitochondrial membrane. In conclusion, alterations in hippocampal Lipin1 contribute to hippocampal synaptic mitochondrial dysfunction and cognitive deficits observed in DE. Targeting Lipin1 might be a potential therapeutic strategy for the clinical treatment of DE.


Assuntos
Encefalopatias , Diabetes Mellitus , Hipoglicemia , Doenças Mitocondriais , Animais , Ratos , Hipocampo/metabolismo , Dinâmica Mitocondrial , Fosfatidato Fosfatase/genética , Fosfatidato Fosfatase/metabolismo , Fosfolipídeos
17.
Mater Horiz ; 11(5): 1223-1233, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38126361

RESUMO

2D transition metal carbides and carbonitrides (MXenes) have emerged as promising electrode materials for electrochemistry ion capture but always suffer from severe layer-restacking and irreversible oxidation that restrains their electrochemical performance. Here we design a dual strategy of microstructure tailoring and heterostructure construction to synthesize a unique 3D grape string-like heterostructure consisting of Ti3C2Tx MXene hollow microspheres wrapped by fungi-derived N-doping carbon nanoribbons (denoted as GMNC). The 3D grape string-like heterostructure effectively avoids the aggregation of Ti3C2Tx MXene sheets and enhances the stability of MXenes, providing abundant active sites for ion capture, and an interconnected conductive bionic nanofiber network for high-rate electron transport. In consequence, GMNC achieves a superior adsorption capacity for sodium ions (Na+) in capacitive deionization (CDI) (162.37 mg gNaCl-1) with an ultra-high instantaneous adsorption rate (30.52 mg g-1 min-1) at an applied voltage of 1.6 V and satisfactory cycle stability over 100 cycles, which is a strong performer among the state-of-the-art values for MXene-based CDI electrodes. In addition, in situ electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D) measurement combined with density functional theory (DFT) reveals the mechanisms of the Na+ capture process in the GMNC heterostructure. This work opens a new avenue for designing high-performance MXenes with a 3D hierarchical heterostructure for advanced electrochemical applications.

18.
Gut Microbes ; 15(2): 2290320, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38059752

RESUMO

Women's health encompasses life-course healthcare, and mounting evidence emphasizes the pivotal contribution of gut microbiota. Therefore, understanding the temporal dynamics of gut microbiota and how age influences disease-gut microbiota associations is essential for improving women's health. By analyzing metagenomic data from 3625 healthy women, we revealed significant effects of age on gut microbiota and age-dependent patterns in microbial features, such as relative abundance, Shannon index, and microbial network properties. Additionally, declining trends in the predictive accuracy of gut microbiota for age groups were shown using iterative sub-sampling based random forest (ISSRF) model. Age-specific species markers were also identified, many of which were shared across age groups. To investigate the influence of age on disease-gut microbiota associations, metagenomic data from 681 women with various disease conditions and 491 matched healthy controls were collected. A substantial proportion of species markers for inflammatory bowel disease (IBD), type 2 diabetes (T2D), atherosclerotic cardiovascular disease (ACVD), and impaired glucose tolerance (IGT) differed in relative abundance across age groups, and were also age-specific species markers. Besides, the microbiota-based probabilities of IBD and ACVD were positively correlated with age. Furthermore, the age specificity of disease-gut microbiota associations was explored using the ISSRF model. Associations between IBD and gut microbiota were age-specific, with reduced stability of disease species markers in childhood and adolescence, possibly due to decrease in the effect size between patients and controls. Our findings provided valuable insights into promoting healthy aging and developing personalized healthcare strategies for women.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Microbiota , Adolescente , Humanos , Feminino , Saúde da Mulher
19.
Plants (Basel) ; 12(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38068596

RESUMO

Flower bud formation in the apple tree life cycle is associated with multiple biological processes. To explore the physiological and molecular mechanisms underlying the protein and metabolite changes in buds with different flowering capabilities, axillary buds with no flowering (Ab), long-shoot buds with a low flowering rate (Lb), and spur buds with a higher flowering rate than the Lb (Sb) were analyzed using a Tandem Mass Tag™ proteomic technique in combination with nLC-MS/MS analyses. We identified 471 (88 up- and 383 down-regulated), 459 (176 up- and 283 down-regulated), and 548 (387 up- and 161 down-regulated) differentially expressed proteins in Sb vs. Lb, Sb vs. Ab, and Lb vs. Ab, respectively, that were involved in carbohydrate, amino acid and lipid transport, and metabolism. Additionally, 110 (91 increased and 19 decreased), 89 (71 increased and 18 decreased), and 99 (37 increased and 62 decreased) metabolites having significantly different levels were identified in Sb vs. Lb, Sb vs. Ab, and Lb vs. Ab, respectively. The identified metabolites were related to amino acids and their isoforms, sugars and polyols, and organic acids, and occurred at significantly greater levels in the Sbs than the other buds. Thus, flower bud formation is a complex process that involves various biochemical materials and signals, such as carbohydrates, amino acids and their isoforms, and organic acids.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38153965

RESUMO

Introduction: Postoperative pain control is a challenge in enhanced recovery after surgery (ERAS). The current study reviewed the efficacy and safety of incorporating acupoint stimulation for postoperative pain control in ERAS. Methods: Ten databases for relevant randomized controlled trials (RCTs) published in English or Mandarin Chinese were searched from 1997 to 2022. The quality of each article was appraised using the Cochrane Collaboration Risk of Bias Criteria and the modified Jadad Scale. The primary outcome was pain control, measured using the visual analog scale 24 h after surgery. Results: Eleven trials met the eligibility criteria and were included in the study. Acupoint stimulation was found more effective than control treatments in terms of pain intensity (standardized mean difference [SMD] -0.94; 95% confidence interval [CI] -1.35 to -0.53), analgesic drug consumption (SMD -1.87; 95% CI -2.98 to -0.75), postoperative nausea (PON; SMD 0.31; 95% CI 0.13 to 0.73), postoperative vomiting (POV; SMD 0.57; 95% CI 0.11 to 2.92), and PON and POV (PONV; SMD 0.29; 95% CI 0.16 to 0.53). The Zusanli (ST36) and Neiguan (PC6) were the most-used acupoints in the included trials (8/11). The reported adverse reaction was only one case of bruising. Discussion: Acupoint stimulation improved pain control in patients undergoing ERAS more than control treatments. The findings provide an evidence-based premise for incorporating acupoint stimulation into ERAS strategies. More rigorous RCTs are needed in the future.

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