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1.
Med Eng Phys ; 125: 104117, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38508797

RESUMO

This study aims to establish an effective benign and malignant classification model for breast tumor ultrasound images by using conventional radiomics and transfer learning features. We collaborated with a local hospital and collected a base dataset (Dataset A) consisting of 1050 cases of single lesion 2D ultrasound images from patients, with a total of 593 benign and 357 malignant tumor cases. The experimental approach comprises three main parts: conventional radiomics, transfer learning, and feature fusion. Furthermore, we assessed the model's generalizability by utilizing multicenter data obtained from Datasets B and C. The results from conventional radiomics indicated that the SVM classifier achieved the highest balanced accuracy of 0.791, while XGBoost obtained the highest AUC of 0.854. For transfer learning, we extracted deep features from ResNet50, Inception-v3, DenseNet121, MNASNet, and MobileNet. Among these models, MNASNet, with 640-dimensional deep features, yielded the optimal performance, with a balanced accuracy of 0.866, AUC of 0.937, sensitivity of 0.819, and specificity of 0.913. In the feature fusion phase, we trained SVM, ExtraTrees, XGBoost, and LightGBM with early fusion features and evaluated them with weighted voting. This approach achieved the highest balanced accuracy of 0.964 and AUC of 0.981. Combining conventional radiomics and transfer learning features demonstrated clear advantages over using individual features for breast tumor ultrasound image classification. This automated diagnostic model can ease patient burden and provide additional diagnostic support to radiologists. The performance of this model encourages future prospective research in this domain.


Assuntos
Neoplasias da Mama , 60570 , Humanos , Feminino , Estudos Retrospectivos , Ultrassonografia Mamária , Aprendizado de Máquina , Neoplasias da Mama/diagnóstico por imagem
2.
Quant Imaging Med Surg ; 14(2): 2034-2048, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415149

RESUMO

Background: In recent years, computer-aided diagnosis (CAD) systems have played an important role in breast cancer screening and diagnosis. The image segmentation task is the key step in a CAD system for the rapid identification of lesions. Therefore, an efficient breast image segmentation network is necessary for improving the diagnostic accuracy in breast cancer screening. However, due to the characteristics of blurred boundaries, low contrast, and speckle noise in breast ultrasound images, breast lesion segmentation is challenging. In addition, many of the proposed breast tumor segmentation networks are too complex to be applied in practice. Methods: We developed the attention gate and dilation U-shaped network (GDUNet), a lightweight, breast lesion segmentation model. This model improves the inverted bottleneck, integrating it with tokenized multilayer perceptron (MLP) to construct the encoder. Additionally, we introduce the lightweight attention gate (AG) within the skip connection, which effectively filters noise in low-level semantic information across spatial and channel dimensions, thus attenuating irrelevant features. To further improve performance, we innovated the AG dilation (AGDT) block and embedded it between the encoder and decoder in order to capture critical multiscale contextual information. Results: We conducted experiments on two breast cancer datasets. The experiment's results show that compared to UNet, GDUNet could reduce the number of parameters by 10 times and the computational complexity by 58 times while providing a double of the inference speed. Moreover, the GDUNet achieved a better segmentation performance than did the state-of-the-art medical image segmentation architecture. Conclusions: Our proposed GDUNet method can achieve advanced segmentation performance on different breast ultrasound image datasets with high efficiency.

3.
J Imaging Inform Med ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381383

RESUMO

The purpose of this study was to fuse conventional radiomic and deep features from digital breast tomosynthesis craniocaudal projection (DBT-CC) and ultrasound (US) images to establish a multimodal benign-malignant classification model and evaluate its clinical value. Data were obtained from a total of 487 patients at three centers, each of whom underwent DBT-CC and US examinations. A total of 322 patients from dataset 1 were used to construct the model, while 165 patients from datasets 2 and 3 formed the prospective testing cohort. Two radiologists with 10-20 years of work experience and three sonographers with 12-20 years of work experience semiautomatically segmented the lesions using ITK-SNAP software while considering the surrounding tissue. For the experiments, we extracted conventional radiomic and deep features from tumors from DBT-CCs and US images using PyRadiomics and Inception-v3. Additionally, we extracted conventional radiomic features from four peritumoral layers around the tumors via DBT-CC and US images. Features were fused separately from the intratumoral and peritumoral regions. For the models, we tested the SVM, KNN, decision tree, RF, XGBoost, and LightGBM classifiers. Early fusion and late fusion (ensemble and stacking) strategies were employed for feature fusion. Using the SVM classifier, stacking fusion of deep features and three peritumoral radiomic features from tumors in DBT-CC and US images achieved the optimal performance, with an accuracy and AUC of 0.953 and 0.959 [CI: 0.886-0.996], a sensitivity and specificity of 0.952 [CI: 0.888-0.992] and 0.955 [0.868-0.985], and a precision of 0.976. The experimental results indicate that the fusion model of deep features and peritumoral radiomic features from tumors in DBT-CC and US images shows promise in differentiating benign and malignant breast tumors.

4.
Med Eng Phys ; 124: 104101, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38418029

RESUMO

With the advancement of deep learning technology, computer-aided diagnosis (CAD) is playing an increasing role in the field of medical diagnosis. In particular, the emergence of Transformer-based models has led to a wider application of computer vision technology in the field of medical image processing. In the diagnosis of thyroid diseases, the diagnosis of benign and malignant thyroid nodules based on the TI-RADS classification is greatly influenced by the subjective judgment of ultrasonographers, and at the same time, it also brings an extremely heavy workload to ultrasonographers. To address this, we propose Swin-Residual Transformer (SRT) in this paper, which incorporates residual blocks and triplet loss into Swin Transformer (SwinT). It improves the sensitivity to global and localized features of thyroid nodules and better distinguishes small feature differences. In our exploratory experiments, SRT model achieves an accuracy of 0.8832 with an AUC of 0.8660, outperforming state-of-the-art convolutional neural network (CNN) and Transformer models. Also, ablation experiments have demonstrated the improved performance in the thyroid nodule classification task after introducing residual blocks and triple loss. These results validate the potential of the proposed SRT model to improve the diagnosis of thyroid nodules' ultrasound images. It also provides a feasible guarantee to avoid excessive puncture sampling of thyroid nodules in future clinical diagnosis.


Assuntos
Recuperação Demorada da Anestesia , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassonografia , Diagnóstico por Computador/métodos
5.
Parasit Vectors ; 17(1): 20, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229193

RESUMO

BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that can infect a wide range of warm-blooded animals, including humans. It poses significant health risks, particularly in immunocompromised individuals and during pregnancy, leading to severe disease manifestations. The liver, being a crucial organ involved in immune response and metabolic regulation, plays a critical role in the host's defense against T. gondii infection. METHODS: In this study, we utilized RNA sequencing to investigate the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the liver of mice infected with T. gondii. By employing this method, we obtained a comprehensive overview of the alterations in gene expression occurring in the liver during infection. RESULTS: By comparing the infected groups to the control groups, we identified numerous differentially expressed lncRNAs DElncRNAs and DEmRNAs at two stages of infection. Specifically, at the acute infection stage, we found 628 DElncRNAs, and 6346 DEmRNAs. At the chronic infection stage, we identified 385 DElncRNAs and 2513 DEmRNAs. Furthermore, we identified 1959 commonly expressed DEmRNAs, including IL27, Nos2, and Cxcr2, across two infection stages. Enrichment and co-location analyses revealed pathways linked to immune and inflammatory responses during T. gondii infection. Notably, through co-location analysis, our analysis revealed several DElncRNAs, including Gm29156, Gm29157, and Gm28644, which are potentially implicated in the progression of liver inflammation induced by T. gondii. Additionally, functional enrichment analysis disclosed stage-specific characteristics of liver inflammation and immune response, alongside changes in metabolic regulation and immunosuppression pathways. CONCLUSIONS: Our findings provide valuable insights into the expression patterns of lncRNAs and mRNAs in the liver at different stages of T. gondii infection. We identified potential regulatory factors and pathways implicated in liver inflammation, thereby enhancing our understanding of the molecular mechanisms underlying liver inflammation and immune responses during T. gondii infection. These findings could contribute to the development of targeted therapeutic strategies for liver inflammation in the context of T. gondii infection.


Assuntos
RNA Longo não Codificante , Toxoplasma , Toxoplasmose , Humanos , Animais , Camundongos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Toxoplasmose/genética , Perfilação da Expressão Gênica/métodos , Toxoplasma/genética , Fígado , Inflamação
6.
J Fungi (Basel) ; 10(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38248952

RESUMO

Most reported members of Microascaceae that have been reported originate from the terrestrial environment, where they act as saprobes or plant pathogens. However, our understanding of their species diversity and distribution in the marine environment remains vastly limited, with only 22 species in nine genera having been reported so far. A survey of the fungal diversity in intertidal areas of China's mainland has revealed the discovery of several Microascaceae strains from 14 marine algae and 15 sediment samples. Based on morphological characteristics and LSU-ITS-tef1-tub2 multilocus phylogeny using Bayesian inference and maximum likelihood methods, 48 strains were identified as 18 species belonging to six genera. Among these, six new species were discovered: Gamsia sedimenticola, Microascus algicola, M. gennadii, Scedosporium ellipsosporium, S. shenzhenensis, and S. sphaerospermum. Additionally, the worldwide distribution of the species within this family across various marine habitats was briefly reviewed and discussed. Our study expands the knowledge of species diversity and distribution of Microascaceae in the marine environment.

7.
Adv Sci (Weinh) ; 11(7): e2305761, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063803

RESUMO

Pentamethyl cyanine dyes are promising fluorophores for fluorescence sensing and imaging. However, advanced biomedical applications require enhanced control of their excited-state properties. Herein, a synthetic approach for attaching aryl substituents at the C2' position of the thio-pentamethine cyanine (TCy5) dye structure is reported for the first time. C2'-aryl substitution enables the regulation of both the twisted intramolecular charge transfer (TICT) and photoinduced electron transfer (PET) mechanisms to be regulated in the excited state. Modulation of these mechanisms allows the design of a nitroreductase-activatable TCy5 fluorophore for hypoxic tumor photodynamic therapy and fluorescence imaging. These C2'-aryl TCy5 dyes provide a tunable platform for engineering cyanine dyes tailored to sophisticated biological applications, such as photodynamic therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes , Corantes Fluorescentes/química , Imagem Óptica/métodos
8.
Animal ; 17(12): 101021, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38061178

RESUMO

As important environmental factors, the light spectra and tank colours have not received sufficient attention. Most fishes have the ability to perceive environment, distinguish colours, and exhibit preferences or aversions towards different environments, which can provide a reference for the design of their rearing environment. Tiger puffer (Takifugu rubripes) is an important mariculture species in China and East Asia, but its preference for illumination spectra and tank colours is unclear. This study focuses on the preferences of juvenile tiger puffers for different spectra and tank background colours in different rearing backgrounds and body sizes. The experiments were conducted in a preference testing device, and the behavioural videos were recorded and analysed using a motion behaviour tracking system (EthoVision XT 12). The results show that the puffers showed preference for short-wavelength lights ((i.e., cyan, green, etc.), avoidance of long-wavelength light (i.e., red) and less stay time in the full light spectrum and dark. For tank colours, the puffers showed a preference for light background colours (i.e., white), and avoidance of deep background colours (i.e., dark, red, etc.). Fish body sizes and original breeding environment could significantly affect the selective preference of juvenile puffer (P < 0.05). Large puffers preferred green tank colour than small ones, while small ones preferred grey and red. The puffers reared in green light and grey tank for 3 months preferred green light spectrum and green tank colour compared with those reared in full spectrum and grey tank, while the fish reared in full spectrum preferred grey tank colour and area without light. It was also found that the movement rate of juvenile puffers was affected by the light spectra and tank colours and was positively correlated with light wavelength (P < 0.05). Therefore, for tiger puffer breeding, short-wavelength light spectrums (cyan, green, etc.) and light-coloured tank backgrounds (white) are recommended. Long-wavelength Light-emitting diodes and dark tank colours should be avoided in breeding. This study would provide a reference basis for fish light spectra and background colour preference studies, as well as for the improvement of breeding welfare and production efficiency of juvenile tiger puffer.


Assuntos
Luz , Takifugu , Animais , Cor , Tamanho Corporal , China
9.
Med Phys ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38063140

RESUMO

BACKGROUND: Accurate and automated segmentation of thoracic organs-at-risk (OARs) is critical for radiotherapy treatment planning of thoracic cancers. However, this has remained a challenging task for four major reasons: (1) thoracic OARs have diverse morphologies; (2) thoracic OARs have low contrast with the background; (3) boundaries of thoracic OARs are blurry; (4) class imbalance issue caused by small organs. PURPOSE: To overcome the above challenges and achieve accurate and automated segmentation of thoracic OARs on thoracic CT. METHODS: A novel cascaded framework based on mixed attention and multiscale information for thoracic OARs segmentation, called Cascaded-TOARNet. This cascaded framework comprises two stages: localization and segmentation. During the localization stage, TOARNet locates each organ to crop the regions of interest (ROIs). During the segmentation stage, TOARNet accurately segments the ROIs, and the segmentation results are merged into a complete result. RESULTS: We evaluated our proposed method and other common segmentation methods on two public datasets: the AAPM Thoracic Auto-Segmentation Challenge dataset and the Segmentation of Thoracic Organs at Risk (SegTHOR) dataset. Our method demonstrated superior performance, achieving a mean Dice score of 92.6% on the SegTHOR dataset and 90.8% on the AAPM dataset. CONCLUSIONS: This segmentation method holds great promise as an essential tool for enhancing the efficiency of thoracic radiotherapy planning.

10.
Front Public Health ; 11: 1250572, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37927881

RESUMO

Aiming to investigate the health risk impact of PM2.5 pollution on a heavily populated province of China. The exposure response function was used to assess the health risk of PM2.5 pollution. Results shows that the total number of premature deaths and diseases related to PM2.5 pollution in Shandong might reach 159.8 thousand people based on the new WHO (2021) standards. The health effects of PM2.5 pollution were more severe in men than in women. Five of the 16 cities in Shandong had higher health risks caused by PM2.5 pollution, including LinYi, HeZe, JiNing, JiNan, and WeiFang. PM2.5 pollution resulted in nearly 7.4 billions dollars in healthy economic cost, which accounted for 0.57% of GDP in Shandong in 2021. HeZe, LiaoCheng, ZaoZhuang, and LinYi were the cities where the health economic loss was more than 1% of the local GDP, accounted for 1.30, 1.26, 1.08, and 1.04%. Although the more rigorous assessment criteria, the baseline concentration was lowered by 30 µg/m3 compared to our previous study, there was no significant increase in health risks and economic losses. China's air quality improvement strategy may already be having a positive effect.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Masculino , Feminino , Humanos , Melhoria de Qualidade , Poluição Ambiental , Medição de Risco , China/epidemiologia , Material Particulado , Poluição do Ar/efeitos adversos , Poluentes Atmosféricos/efeitos adversos
11.
BMJ Open ; 13(11): e073058, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37996234

RESUMO

INTRODUCTION: Osteoarthritis (OA) is one of the main causes of mobility impairment in the elderly worldwide. Therefore, total knee arthroplasty (TKA) is often performed and is one of the most successful surgery and has resulted in substantial quality-of-life gains for people with end-stage arthritis. There is still room for improvement in the standard treatment process in the preoperative, intraoperative and postoperative period of TKA. Telerehabilitation has the potential to become a positive alternative to face-to-face rehabilitation nowadays. But it remains unclear how well telemedicine interventions cover the entire surgical pathway (preoperation, intraoperation, postoperation). This study aims to explore the effectiveness of Joint Cloud (JC, an online management platform) compared with existing standard process in regulating functional recovery, pain management, muscle strength changes and other health-related outcomes in patients undergoing total knee arthroplasty preoperation, intraoperation and postoperation. METHODS AND ANALYSIS: A randomised controlled trial was designed to compare the online management platform (JC) with standard process (SP) in patients undergoing TKA. A total of 186 TKA patients will be randomly assigned to the intervention (n=93) or control (n=93) group. Patients in the intervention group will receive access to the 'JC' mini-program. This mini-program provides popular science information (eg, information about OA and TKA), functional exercise information and communication channels. Patients evaluate their condition and functional level through standardised digital questionnaires. The control group of patients will not accept any functions of this mini-program. The primary outcome is knee functional recovery, and the secondary outcomes are pain management, isometric knee extensor muscle strength, patient satisfaction and cost-benefit analysis. Assessments will be performed 1 month and 3 days before surgery (T0) and 1 month and 3 months after surgery. Data analysis will be performed according to the intent-to-treat (ITT) principle. Repeated measures of linear mixed models and parametric and non-parametric testing will be used for statistical analysis. ETHICS AND DISSEMINATION: The study was reviewed and approved by the Tianjin Hospital Medical Ethics Review Committee on 10 February 2023 (2022YLS155). Test data are considered highly sensitive but are available upon request. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2300068486.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Idoso , Artroplastia do Joelho/reabilitação , Osteoartrite do Joelho/cirurgia , Estudos Prospectivos , Articulação do Joelho/cirurgia , Satisfação do Paciente , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Curr Med Imaging ; 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37860999

RESUMO

BACKGROUND: Breast cancer is one of the leading causes of mortality among women. In addition, 1 in 8 women and 1 in 833 men will be diagnosed with breast cancer in 2022. The detection of breast cancer can not only lower treatment costs but also increase survival rates. Due to increased cancer awareness, more women are undergoing breast cancer screening, leading to more cases being diagnosed worldwide, but doctors' ability to analyze these images is limited. As a result, they get overloaded leading to misinterpretations. The advent of computer-aided diagnosis (CAD) minimized man's involvement and achieved good results. CAD helps medical doctors automatically detect and analyze abnormalities found in the breast. Such abnormalities may be benign or malignant tumors. OBJECTIVE: The goal of this study is to evaluate the effectiveness of using seven layers to classify breast cancer as either benign or malignant using mammograms. MATERIALS AND METHODS: The open-source MIAS dataset of 322 images was used for our study, of which 207 were normal images and 115 were abnormal images. The proposed CNN model convolves an image into seven layers that extract features from the input images, and these features are used to classify breast cancer as malignant or benign. RESULTS: The proposed CNN used a limited data set and achieved the best result compared to previous work. The method achieved results with a 0.39% loss, 99.89% accuracy, 99.85% precision, 99.89% recall, 99.87% F1-score, and an area under the curve noted to be 100.0%. CONCLUSION: CNN uses a small amount of data to determine abnormalities; the method will assist a medical doctor in determining whether or not a specific patient has cancer.

13.
Biomaterials ; 302: 122365, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37890436

RESUMO

Prodrug is a potential regime to overcome serious adverse events and off-target effects of chemotherapy agents. Among various prodrug activators, hypoxia stands out owing to the generalizability and prominence in tumor micro-environment. However, existing hypoxia activating prodrugs generally face the limitations of stringent structural requirements, the lack of feedback and the singularity of therapeutic modality, which is imputed to the traditional paradigm that recognition groups must be located at the terminus of prodrugs. Herein, a multifunctional nano-prodrug Mal@Cy-NTR-CB has been designed. In this nano-prodrug, a self-destructive tether is introduced to break the mindset, and achieves the activation by hypoxia of chemotherapy based on Chlorambucil (CB), whose efficacy can be augmented and traced by photodynamic therapy (PDT) and fluorescence from Cyanine dyes (Cy). In addition, Maleimide (Mal) carried by the nano-shells can regulate glutathione (GSH) content, preventing 1O2 scavenging, so as to realize PDT sensitization. Experiments demonstrate that Mal@Cy-NTR-CB specifically responds to hypoxic tumors, and achieve synchronous activation, enhancement and feedback of chemotherapy and PDT, inhibiting the tumor growth effectively. This study broadens the design ideas of activatable prodrugs and provides the possibility of multifunctional nano-prodrugs to improve the generalization and prognosis in precision oncology.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Pró-Fármacos , Humanos , Neoplasias/tratamento farmacológico , Pró-Fármacos/química , Medicina de Precisão , Hipóxia/tratamento farmacológico , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/uso terapêutico , Nanopartículas/química , Microambiente Tumoral
14.
Nature ; 624(7992): 611-620, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37907096

RESUMO

Ageing is a critical factor in spinal-cord-associated disorders1, yet the ageing-specific mechanisms underlying this relationship remain poorly understood. Here, to address this knowledge gap, we combined single-nucleus RNA-sequencing analysis with behavioural and neurophysiological analysis in non-human primates (NHPs). We identified motor neuron senescence and neuroinflammation with microglial hyperactivation as intertwined hallmarks of spinal cord ageing. As an underlying mechanism, we identified a neurotoxic microglial state demarcated by elevated expression of CHIT1 (a secreted mammalian chitinase) specific to the aged spinal cords in NHP and human biopsies. In the aged spinal cord, CHIT1-positive microglia preferentially localize around motor neurons, and they have the ability to trigger senescence, partly by activating SMAD signalling. We further validated the driving role of secreted CHIT1 on MN senescence using multimodal experiments both in vivo, using the NHP spinal cord as a model, and in vitro, using a sophisticated system modelling the human motor-neuron-microenvironment interplay. Moreover, we demonstrated that ascorbic acid, a geroprotective compound, counteracted the pro-senescent effect of CHIT1 and mitigated motor neuron senescence in aged monkeys. Our findings provide the single-cell resolution cellular and molecular landscape of the aged primate spinal cord and identify a new biomarker and intervention target for spinal cord degeneration.


Assuntos
Senescência Celular , Quitinases , Microglia , Neurônios Motores , Primatas , Medula Espinal , Animais , Humanos , Biomarcadores/metabolismo , Quitinases/metabolismo , Microglia/enzimologia , Microglia/metabolismo , Microglia/patologia , Neurônios Motores/metabolismo , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Primatas/metabolismo , Reprodutibilidade dos Testes , Análise da Expressão Gênica de Célula Única , Medula Espinal/metabolismo , Medula Espinal/patologia
15.
Parkinsons Dis ; 2023: 7427136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37791037

RESUMO

Parkinson's disease (PD) is a complex syndrome with many elements, such as chronic inflammation, oxidative stress, mitochondrial dysfunction, loss of dopaminergic neurons, build-up of alpha-synuclein (α-syn) in cells, and energy depletion in neurons, that drive the disease. We and others have shown that treatment with mimetics of the growth factor glucagon-like peptide 1 (GLP-1) can normalize energy utilization, neuronal survival, and dopamine levels and reduce inflammation. Liraglutide is a GLP-1 analogue that recently showed protective effects in phase 2 clinical trials in PD patients and in Alzheimer disease patients. We have developed a novel dual GLP-1/GIP receptor agonist that can cross the blood-brain barrier and showed good protective effects in animal models of PD. Here, we test liraglutide against the dual GLP-1/GIP agonist DA5-CH (KP405) in the A53T tg mouse model of PD which expresses a human-mutated gene of α-synuclein. Drug treatment reduced impairments in three different motor tests, reduced levels of α-syn in the substantia nigra, reduced the inflammation response and proinflammatory cytokine levels in the substantia nigra and striatum, and normalized biomarker levels of autophagy and mitochondrial activities in A53T mice. DA5-CH was superior in almost all parameters measured and therefore may be a better drug treatment for PD than liraglutide.

16.
Sci Adv ; 9(41): eadf4170, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37824625

RESUMO

Femtosecond laser-driven photoemission source provides an unprecedented femtosecond-resolved electron probe not only for atomic-scale ultrafast characterization but also for free-electron radiation sources. However, for conventional metallic electron source, intense lasers may induce a considerable broadening of emitting energy level, which results in large energy spread (>600 milli-electron volts) and thus limits the spatiotemporal resolution of electron probe. Here, we demonstrate the coherent ultrafast photoemission from a single quantized energy level of a carbon nanotube. Its one-dimensional body can provide a sharp quantized electronic excited state, while its zero-dimensional tip can provide a quantized energy level act as a narrow photoemission channel. Coherent resonant tunneling electron emission is evidenced by a negative differential resistance effect and a field-driven Stark splitting effect. The estimated energy spread is ~57 milli-electron volts, which suggests that the proposed carbon nanotube electron source may promote electron probe simultaneously with subangstrom spatial resolution and femtosecond temporal resolution.

17.
Opt Express ; 31(19): 31661-31669, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710680

RESUMO

Introducing phase transition materials to random systems provides a promising route to create new optoelectronic functionalities of random lasers. Here, a phase transition random laser with switchable lasing modes is reported, which is designed with a thermoresponsive hydrogel as scattering medium. By manipulating the phase transition in hydrogel, random lasing modes can be switched reversibility between incoherent and coherent random lasing. The phenomenon derives from the changing of light scattering properties in different phase states, thus affecting the optical feedback path of random lasing. Besides, based on its controllable and easily detectable time-domain characteristics, the phase transition random laser is applied in information encoding and transmission. It is the first time that the transition from coherent to incoherent random lasing is observed by varying the sample phase states. This work will inspire the design and application of novel random lasers in photoelectric device.

18.
Drug Des Devel Ther ; 17: 2639-2655, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37667787

RESUMO

From a clinical perspective, local anesthetics have rather widespread application in regional blockade for surgery, postoperative analgesia, acute/chronic pain control, and even cancer treatments. However, a number of disadvantages are associated with traditional local anesthetic agents as well as routine drug delivery administration ways, such as neurotoxicity, short half-time, and non-sustained release, thereby limiting their application in clinical practice. Successful characterization of drug delivery systems (DDSs) for individual local anesthetic agents can support to achieve more efficient drug release and prolonged duration of action with reduced systemic toxicity. Different types of DDSs involving various carriers have been examined, including micromaterials, nanomaterials, and cyclodextrin. Among them, nanotechnology-based delivery approaches have significantly developed in the last decade due to the low systemic toxicity and the greater efficacy of non-conventional local anesthetics. Multiple nanosized materials, including polymeric, lipid (solid lipid nanoparticles, nanostructured lipid carriers, and nanoemulsions), metallic, inorganic non-metallic, and hybrid nanoparticles, offer a safe, localized, and long-acting solution for pain management and tumor therapy. This review provides a brief synopsis of different nano-based DDSs for local anesthetics with variable sizes and structural morphology, such as nanocapsules and nanospheres. Recent original research utilizing nanotechnology-based delivery systems is particularly discussed, and the progress and strengths of these DDSs are highlighted. A specific focus of this review is the comparison of various nano-based DDSs for local anesthetics, which can offer additional indications for their further improvement. All in all, nano-based DDSs with unique advantages provide a novel direction for the development of safer and more effective local anesthetic formulations.


Assuntos
Anestesia Local , Anestésicos Locais , Manejo da Dor , Sistemas de Liberação de Medicamentos , Lipídeos
19.
Angew Chem Int Ed Engl ; 62(41): e202308513, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37607898

RESUMO

We report a supramolecular naphthalene diimide (NDI) radical anion with efficient NIR-II photothermal conversion for E. coli-responsive photothermal therapy. The supramolecular radical anion (NDI-2CB[7])⋅- , which is obtained from the E. coli-induced in situ reduction of NDI-2CB[7] neutral complex, formed by the host-guest interaction between an NDI derivative and cucurbit[7]uril (CB[7]), exhibits unexpectedly strong NIR-II absorption and remarkable photothermal conversion capacity in aqueous solution. The NIR-II absorption is caused by the self-assembly of NDI radical anions to form supramolecular dimer radicals in aqueous solution, which is supported by theoretically predicted spectra. The (NDI-2CB[7])⋅- demonstrates excellent NIR-II photothermal antimicrobial activity (>99 %). This work provides a new approach for constructing NIR-II photothermal agents and non-contact treatments for bacterial infections.


Assuntos
Escherichia coli , Terapia Fototérmica , Ânions , Imidas/farmacologia
20.
Sci Rep ; 13(1): 13213, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37580391

RESUMO

The increase in the aging population has seriously affected our society. Neurodegenerative diseases caused by aging of the brain significantly impact the normal life of the elderly, and delaying brain aging is currently the focus of research. SIRT1 is a viable therapeutic target, and there is mounting evidence that it plays a significant role in the aging process. Mesenchymal stem cell-derived exosomes (MSC-Exos) have gained widespread interest as nanotherapeutic agents because of their ability to be injected at high doses to reduce the immune response. The present study focused on the ameliorative effect of MSC-Exos on aging mice and the potential mechanisms of this effect on cognitive impairment and brain aging. In this study, we first tested the neuroprotective effects of MSC-Exos in vitro on H2O2-induced oxidative damage in BV2 cells. An in vivo SAMP8 rapid senescence mouse model showed that MSC-Exos significantly increased SIRT1 gene expression in senescent mice. In addition, MSC-Exos also had an anti-apoptotic effect and reduced oxidative stress in the brains of SAMP8 senescent mice. In conclusion, MSC-Exos may exert neuroprotective effects and help prevent brain senescence in SAMP8 mice by activating the SIRT1 signaling pathway.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Fármacos Neuroprotetores , Sirtuína 1 , Animais , Camundongos , Envelhecimento , Encéfalo/metabolismo , Exossomos/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fármacos Neuroprotetores/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo
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