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1.
J Proteome Res ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225497

RESUMEN

Intracerebral hemorrhage (ICH) could trigger inflammatory responses. However, the specific role of inflammatory proteins in the pathological mechanism, complications, and prognosis of ICH remains unclear. In this study, we investigated the expression of 92 plasma inflammation-related proteins in patients with ICH (n = 55) and healthy controls (n = 20) using an Olink inflammation panel and discussed the relation to the severity of stroke, clinical complications, 30-day mortality, and 90-day outcomes. Our result showed that six proteins were upregulated in ICH patients compared with healthy controls, while seventy-four proteins were downregulated. In patients with ICH, seven proteins were increased in the severe stroke group compared with the moderate stroke group. In terms of complications, two proteins were downregulated in patients with pneumonia, while nine proteins were upregulated in patients with sepsis. Compared with the survival group, three proteins were upregulated, and one protein was downregulated in the death group. Compared with the good outcome group, eight proteins were upregulated, and four proteins were downregulated in the poor outcome group. In summary, an in-depth exploration of the differential inflammatory factors in the early stages of ICH could deepen our understanding of the pathogenesis of ICH, predict patient prognosis, and explore new treatment strategies.

2.
Cerebrovasc Dis ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043146

RESUMEN

INTRODUCTION: The traditional Chinese medicine (TCM) herbal compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) by reducing brain edema, hematoma absorption, and enhancement of the immune system. We outline the statistical analysis plan (SAP) for the Chinese Herbal medicine in Acute INtracerebral haemorrhage (CHAIN) study. DESIGN: CHAIN is a multicenter, prospective, randomized, double-blind, placebo-controlled trial being undertaken at 20-30 hospitals in China. After the completion of eligibility checks, patients are randomly allocated to FYTF-919 (100 mL per day, oral) or matching placebo over 28 days. A sample size of 1504 patients is estimated to provide 90% power (α 0.05) for a 0.06 absolute improvement in the primary outcome of utility-weighted modified Rankin scale scores at 90 days, analyzed by general linear regression. METHODS: The statistical analysis plan was developed by the study statistician, principal investigators, international experts, and the study project manager. The plan provides details for analyzing baseline characteristics, patient management, and outcomes. It includes provisions for covariate adjustments, subgroup analysis, the handling missing data, and in the conduct of sensitivity analyzes. RESULTS: A predefined statistical analysis plan was established for CHAIN, facilitating transparent and verifiable analysis. CONCLUSIONS: The CHAIN statistical analysis plan was prospectively developed with a focus on maintaining high-quality standards of internal validity to minimise potential analysis biases. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05066620).

3.
Cerebrovasc Dis ; 53(4): 501-508, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39250890

RESUMEN

INTRODUCTION: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. This study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. METHODS: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20-30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day × 28 d, oral) or matching placebo. A sample size of 1,504 patients is estimated to provide 90% power (α 0.05) to detect a ≥20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-5L scale at different time points over 6 months of follow-up. The key safety measure is serious adverse events. CONCLUSION: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH.


Asunto(s)
Hemorragia Cerebral , Medicamentos Herbarios Chinos , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Hemorragia Cerebral/tratamiento farmacológico , Resultado del Tratamiento , Estudios Prospectivos , China , Factores de Tiempo , Recuperación de la Función , Estudios Multicéntricos como Asunto , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedad Aguda , Evaluación de la Discapacidad , Estado Funcional , Adulto
4.
Bioorg Chem ; 147: 107416, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705107

RESUMEN

BACKGROUND: Intracerebral hemorrhage (ICH) is a debilitating condition characterized by the rupture of cerebral blood vessels, resulting in profound neurological deficits. A significant challenge in the treatment of ICH lies in the brain's limited capacity to regenerate damaged blood vessels. This study explores the potential synergistic effects of Ginsenoside Rh2 and Chrysophanol in promoting angiogenesis following ICH in a rat model. METHODS: Network pharmacology was employed to predict the potential targets and pathways of Ginsenoside Rh2 and Chrysophanol for ICH treatment. Molecular docking was utilized to assess the binding affinity between these compounds and their respective targets. Experimental ICH was induced in male Sprague-Dawley rats through stereotactic injection of type VII collagenase into the right caudate putamen (CPu). The study encompassed various methodologies, including administration protocols, assessments of neurological function, magnetic resonance imaging, histological examination, observation of brain tissue ultrastructure, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, Western blot analysis, and statistical analyses. RESULTS: Network pharmacology analysis indicated that Ginsenoside Rh2 and Chrysophanol may exert their therapeutic effects in ICH by promoting angiogenesis. Results from animal experiments revealed that rats treated with Ginsenoside Rh2 and Chrysophanol exhibited significantly improved neurological function, reduced hematoma volume, and diminished pathological injury compared to the Model group. Immunofluorescence analysis demonstrated enhanced expression of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31, signifying augmented angiogenesis in the peri-hematomal region following combination therapy. Importantly, the addition of a VEGFR2 inhibitor reversed the increased expression of VEGFR2 and CD31. Furthermore, Western blot analysis revealed upregulated expression of angiogenesis-related factors, including VEGFR2, SRC, AKT1, MAPK1, and MAPK14, in the combination therapy group, but this effect was abrogated upon VEGFR2 inhibitor administration. CONCLUSION: The synergistic effect of Ginsenoside Rh2 and Chrysophanol demonstrated a notable protective impact on ICH injury in rats, specifically attributed to their facilitation of angiogenesis. Consequently, this research offers a foundation for the utilization of Ginsenosides Rh2 and Chrysophanol in medical settings and offers direction for the advancement of novel pharmaceuticals for the clinical management of ICH.


Asunto(s)
Hemorragia Cerebral , Ginsenósidos , Ratas Sprague-Dawley , Animales , Ginsenósidos/farmacología , Ginsenósidos/química , Masculino , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Ratas , Antraquinonas/farmacología , Antraquinonas/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Relación Estructura-Actividad , Angiogénesis
5.
Zhongguo Zhong Yao Za Zhi ; 49(17): 4723-4733, 2024 Sep.
Artículo en Zh | MEDLINE | ID: mdl-39307820

RESUMEN

Zhongfeng Xingnao Decoction(ZFXN) has been utilized for treating intracerebral hemorrhage(ICH) in China, while the pharmacological mechanism of ZFXN remains unclear. Exploring the pharmacological roles of ZFXN is critical for guiding the treatment of cerebrovascular diseases. In this study, a rat model of ICH was constructed by injection of Ⅶ collagenase in the right caudate nucleus. SD rats were randomly assigned into five groups, and the neurological function of rats was evaluated based on the Bederson score. Magnetic resonance imaging(MRI) was used to assess the volume of ICH. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to observe the pathological and ultrastructural changes in the brain tissue. The levels of reactive oxygen species(ROS) were measured by flow cytometry. The immunofluorescence assay was employed to detect the expression of glutathione peroxidase 4(GPX4) in neurons surrounding the hematoma. Finally, Western blot was employed to determine the expression of ferroptosis-related proteins upstream frameshift 1(UPF1), ferroportin(FPN), acyl-CoA ligase 4(ACSL4), cyclooxyge-nase-2(COX-2), GPX4, NADPH oxidase 1(NOX1), and solute carrier family 7 member 11(SLC7A11) after ICH. Compared with the model(ICH) group, ZFXN treatment for 5 days attenuated neurological dysfunction, reduced the hematoma volume, and alleviated the pathological changes induced by ICH. Meanwhile, ZFXN lowered the levels of Fe~(2+) and oxidative stress and up-regulated the expression of proteins inhibiting ferroptosis. ZFXN improved the prognosis of ICH in rats by inhibiting neuronal ferroptosis, which provided a valuable guide for the clinical application of ZFXN. ZFXN may inhibit ferroptosis by promoting the expression of SLC7A11 and FPN.


Asunto(s)
Hemorragia Cerebral , Medicamentos Herbarios Chinos , Ferroptosis , Neuronas , Ratas Sprague-Dawley , Animales , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Ferroptosis/efectos de los fármacos , Ratas , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/etiología , Especies Reactivas de Oxígeno/metabolismo , Humanos
6.
BMC Psychiatry ; 23(1): 314, 2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-37143014

RESUMEN

BACKGROUND: Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. Acupuncture (AC), as a minimally invasive technique, has become a popular choice for improving depression symptoms. However, it is still unclear which therapy is associated with the best outcomes for PSD. In this review, we aimed to explore the impact of AC in alleviating symptoms of PSD and to evaluate the difference in effectiveness between AC combined with pharmacotherapies and various non-pharmacotherapies. METHODS: Six databases and three clinical trials registration platforms were searched from inception to March 2023. Randomized clinical trial comparing needle-based AC with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies, and collected data using a pre-made form. A Bayesian network meta-analysis was conducted to assess and compare different techniques using RStudio 3.6.0 with the package 'GEMTC' V.0.8.1. The primary outcome was the efficacy for PSD assessed by scales measuring depressive symptoms. The secondary outcomes were effectiveness for neurological function and the quality of life. The ranking probabilities for all treatment interventions was performed using the Surface Under the Cumulative Ranking curve (SUCRA). The risk of bias was assessed by using the Revised Cochrane Risk of Bias tool 2. RESULTS: Sixty-two studies, involving 5308 participants published from 2003 to 2022, were included. The results showed that compared with western medicine (WM) (defined as pharmacotherapy for PSD), AC alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, AC alone or plus other therapies could significantly decrease scores on the Hamilton Depression Rating scale. According to result of SUCRA, AC plus RTMS had the highest probability of improving depressive symptoms with a probability of 49.43%. CONCLUSIONS: The results of this study indicate that AC alone or combined with other therapies appears to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison to WM, AC alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms of PSD. Also, AC with RTMS seems to be the most effective with the highest probability. REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database in November 2020 and updated in July 2021. The registration number is CRD42020218752.


Asunto(s)
Terapia por Acupuntura , Accidente Cerebrovascular , Humanos , Depresión/etiología , Depresión/terapia , Metaanálisis en Red , Teorema de Bayes , Calidad de Vida , Terapia por Acupuntura/métodos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Mol Plant Microbe Interact ; 35(6): 440-449, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35196108

RESUMEN

Phytophthora capsici is a broad-host range oomycete pathogen that can cause severe phytophthora blight disease of pepper and hundreds of other plant species worldwide. Natural resistance against P. capsici is inadequate, and it is very difficult to control by most of existing chemical fungicides. Therefore, it is urgent to develop alternative strategies to control this pathogen. Recently, host-induced or spray-induced gene silencing of essential or virulent pathogen genes provided an effective strategy for disease controls. Here, we demonstrate that P. capsici can effectively take up small interfering RNAs (siRNAs) from the environment. According to RNA-seq and quantitative reverse transcription PCR analysis, we identified four P. capsici RXLR effector genes that are significantly up-regulated during the infection stage. Transient overexpression and promote-infection assays indicated that RXLR1 and RXLR4 could promote pathogen infection. Using a virus-induced gene silencing system in pepper plants, we found that in planta-expressing RNA interference (RNAi) constructs that target RXLR1 or RXLR4 could significantly reduce pathogen infection, while co-interfering RXLR1 and RXLR4 could confer a more enhanced resistance to P. capsici. We also found that exogenously applying siRNAs that target RXLR1 or RXLR4 could restrict growth of P. capsici on the pepper and Nicotiana benthamiana leaves; when targeting RXLR1 and RXLR4 simultaneously, the control effect was more remarkable. These data suggested that RNAi-based gene silencing of RXLR effectors has great potential for application in crop improvement against P. capsici and also provides an important basis for the development of RNA-based antioomycete agents.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Asunto(s)
Capsicum , Phytophthora infestans , Capsicum/genética , Silenciador del Gen , Enfermedades de las Plantas/genética , Interferencia de ARN , Nicotiana/genética
8.
Sensors (Basel) ; 22(10)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35632122

RESUMEN

In this article, we employed a satellite-enabled Internet of Remote Things (IoRT) network as a promising solution to retrieve data in the most remote areas of interest, where public networks are absent. This article presents a system network based on the satellite-enabled IoRT, a new paradigm that defines a network where each environmental monitoring device can autonomously establish a network with a remote data center. The Xingyun satellite constellation was employed for data retrieval on the Tibetan Plateau (TP). The monitoring system was mainly composed of a ground Internet of Things (IoT) terminal that was built with satellite transceivers, environmental monitoring devices, and system software. We deployed five of these newly developed terminals in harsh areas to monitor environmental variables, and accordingly, air temperature and relative humidity, precipitation, snow depth, land surface temperature, tree stemflow rate, and photosynthetically active radiation were retrieved with the satellite-enabled IoRT network. Field experiments were conducted to evaluate the performance of the proposed system network, and the results indicated that the average time delay with and without the packet creation mode reached 32 and 32.7 s, respectively, and the average packet loss rate with and without the packet creation mode reached 5.63% and 4.48%, respectively. The successful implementation of the satellite-enabled IoRT network for the rapid retrieval of monitoring data in remote glacier, forestland, and canyon areas at very high altitudes on the TP provides an entirely new and revolutionary data retrieval means for backhauling data from remote areas of interest.

9.
Sensors (Basel) ; 21(16)2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34450871

RESUMEN

River basin cyberinfrastructure with the Internet of Things (IoT) as the core has brought watershed data science into the big data era, greatly improving data acquisition and sharing efficiency. However, challenges in analyzing, processing, and applying very large quantities of observational data remain. Given the observational needs in watershed research, we studied the construction of river basin cyberinfrastructure and developed an integrated observational data control system (IODCS). The IODCS is an important platform for processing large quantities of observational data, including automated collection, storage, analysis, processing, and release. This paper presents various aspects of the IODCS in detail, including the system's overall design, function realization, big data analysis methods, and integrated models. We took the middle reaches of the Heihe River Basin (HRB) as the application research area to show the performance of the developed system. Since the system began operation, it has automatically received, analyzed, and stored more than 1.4 billion observational data records, with an average of more than 14 million observational data records processed per month and up to 21,011 active users. The demonstrated results show that the IODCS can effectively leverage the processing capability of massive observational data and provide a new perspective for facilitating ecological and hydrological scientific research on the HRB.


Asunto(s)
Conservación de los Recursos Naturales , Ríos , Macrodatos , China , Hidrología
10.
Nano Lett ; 20(2): 1383-1387, 2020 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-31891508

RESUMEN

Living organisms utilize spatially organized enzyme complexes to carry out signal transduction and metabolic pathways in an efficient and specific way. Herein, inspired by natural enzyme complexes, we report the polymerization-induced coassembly (PICA) of enzyme-polymer conjugates into comicelles with tunable and enhanced cascade activity by using the cascade reaction implemented by glucose oxidase (GOX) and horseradish peroxidase (HRP) as a model system. Notably, the cascade activity of GOX/HRP-polymer comicelles monotonically increases with the GOX/HRP ratio. The cascade activity of GOX/HRP-polymer comicelles is up to 4.9 times higher than that of free GOX and HRP mixtures at the same GOX/HRP ratio. We further demonstrate that our system can quickly detect glucose in contrast with a commercially available glucose assay kit. These findings provide a new and general method of PICA for the controlled construction of artificial enzyme complexes with tunable and enhanced activity in enzyme cascades for advanced biomedical applications.


Asunto(s)
Enzimas Inmovilizadas/química , Glucosa Oxidasa/química , Glucosa/aislamiento & purificación , Peroxidasa de Rábano Silvestre/química , Biocatálisis , Glucosa/química , Humanos , Redes y Vías Metabólicas/efectos de los fármacos , Polimerizacion , Polímeros/química
11.
BMC Plant Biol ; 20(1): 256, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493221

RESUMEN

BACKGROUND: Plant transcription factors (TFs) are key transcriptional regulators to manipulate the regulatory network of host immunity. However, the globally transcriptional reprogramming of plant TF families in response to pathogens, especially between the resistant and susceptible host plants, remains largely unknown. RESULTS: Here, we performed time-series RNA-seq from a resistant pepper line CM334 and a susceptible pepper line EC01 upon challenged with Phytophthora capsici, and enrichment analysis indicated that WRKY family most significantly enriched in both CM334 and EC01. Interestingly, we found that nearly half of the WRKY family members were significantly up-regulated, whereas none of them were down-regulated in the two lines. These induced WRKY genes were greatly overlapped between CM334 and EC01. More strikingly, most of these induced WRKY genes were expressed in time-order patterns, and could be mainly divided into three subgroups: early response (3 h-up), mid response (24 h-up) and mid-late response (ML-up) genes. Moreover, it was found that the responses of these ML-up genes were several hours delayed in EC01. Furthermore, a total of 19 induced WRKY genes were selected for functional identification by virus-induced gene silencing. The result revealed that silencing of CaWRKY03-6, CaWRKY03-7, CaWRKY06-5 or CaWRKY10-4 significantly increase the susceptibility to P. capsici both in CM334 and EC01, indicating that they might contribute to pepper's basal defense against P. capsici; while silencing of CaWRKY08-4 and CaWRKY01-10 significantly impaired the disease resistance in CM334 but not in EC01, suggesting that these two WRKY genes are prominent modulators specifically in the resistant pepper plants. CONCLUSIONS: These results considerably extend our understanding of WRKY gene family in pepper's resistance against P. capsici and provide potential applications for genetic improvement against phytophthora blight.


Asunto(s)
Capsicum/metabolismo , Phytophthora , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismo , Capsicum/genética , Capsicum/inmunología , Capsicum/microbiología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia , Enfermedades de las Plantas/inmunología , Proteínas de Plantas/genética , Factores de Transcripción/genética
12.
Sensors (Basel) ; 20(19)2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33023175

RESUMEN

Recently, wireless sensor networks (WSNs) have been extensively deployed to monitor environments. Sensor nodes are susceptible to fault generation due to hardware and software failures in harsh environments. Anomaly detection for the time-series streaming data of sensor nodes is a challenging but critical fault diagnosis task, particularly in large-scale WSNs. The data-driven approach is becoming essential for the goal of improving the reliability and stability of WSNs. We propose a data-driven anomaly detection approach in this paper, named median filter (MF)-stacked long short-term memory-exponentially weighted moving average (LSTM-EWMA), for time-series status data, including the operating voltage and panel temperature recorded by a sensor node deployed in the field. These status data can be used to diagnose device anomalies. First, a median filter (MF) is introduced as a preprocessor to preprocess obvious anomalies in input data. Then, stacked long short-term memory (LSTM) is employed for prediction. Finally, the exponentially weighted moving average (EWMA) control chart is employed as a detector for recognizing anomalies. We evaluate the proposed approach for the panel temperature and operating voltage of time-series streaming data recorded by wireless node devices deployed in harsh field conditions for environmental monitoring. Extensive experiments were conducted on real time-series status data. The results demonstrate that compared to other approaches, the MF-stacked LSTM-EWMA approach can significantly improve the detection rate (DR) and false rate (FR). The average DR and FR values with the proposed approach are 95.46% and 4.42%, respectively. MF-stacked LSTM-EWMA anomaly detection also achieves a better F2 score than that achieved by other methods. The proposed approach provides valuable insights for anomaly detection in WSNs by detecting anomalies in the time-series status data recorded by wireless sensor nodes.

13.
Sensors (Basel) ; 20(5)2020 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-32131393

RESUMEN

Intelligent fault diagnosis algorithms based on machine learning and deep learning techniques have been widely used in industrial applications and have obtained much attention as well as achievements. In real industrial applications, working loads of machines are always changing. Hence, directly applying the traditional algorithms will cause significant degradation of performance with changing conditions. In this paper, a novel domain adaptation method, named generative transfer learning (GTL), is proposed to tackle this problem. First, raw datasets were transformed to time-frequency domain based on short-time Fourier transformation. A domain discriminator was then built to distinguish whether the data came from the source or the target domain. A target domain classification model was finally acquired by the feature extractor and the classifier. Experiments were carried out for the fault diagnosis of a wind turbine gearbox. The t-distributed stochastic neighbor embedding technique was used to visualize the output features for checking the effectiveness of the proposed algorithm in feature extraction. The results showed that the proposed GTL could improve classification rates under various working loads. Compared with other domain adaptation algorithms, the proposed method exhibited not only higher accuracy but faster convergence speed as well.

14.
J Am Chem Soc ; 140(33): 10435-10438, 2018 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-30084632

RESUMEN

Conjugating a hydrophilic and protein-resistant polymer to a protein is a widely used strategy to extend the in vivo half-life of the protein; however, the benefit of the half-life extension is usually limited by the bioactivity decrease. Herein we report a supramolecular self-assembly strategy of site-specific in situ polymerization induced self-assembly (SI-PISA) to address the dilemma. An amphiphilic block copolymer (POEGMA-PHPMA) was directly grown from the C-terminus of an important therapeutic protein interferon-α (IFN) to in situ form IFN-POEGMA-PHPMA conjugate micelles. Notably, the in vitro bioactivity of the micelles was 21.5-fold higher than that of the FDA-approved PEGylated interferon-α PEGASYS. Particularly, the in vivo half-life of the micelles (83.8 h) was 1.7- and 100-fold longer than those of PEGASYS (49.5 h) and IFN (0.8 h), respectively. In a tumor-bearing mouse model, the micelles completely suppressed tumor growth with 100% animal survival, whereas at the same dose, PEGASYS and IFN were much less effective. These findings suggest that SI-PISA is promising as a next-generation technology to remarkably enhance the pharmacological performance of therapeutic proteins with short circulation half-lives.


Asunto(s)
Interferón-alfa/química , Micelas , Polietilenglicoles/química , Polimerizacion , Ácidos Polimetacrílicos/química , Animales , Xenoinjertos , Ratones , Proteínas Recombinantes/química
15.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(7): 821-826, 2016 07.
Artículo en Zh | MEDLINE | ID: mdl-30634209

RESUMEN

OBJECTIVE: To study the safety of using Chinese drugs for breaking blood expelling stasis (CDBBES) in hypertension patients with intracerebral hemorrhage within 6 h, and to observe whether they would result in hematoma enlargement. METHODS: A prospective randomized double-blind controlled clinical study was employed. Totally 128 cerebral hemorrhage patients within 6 h were recruited from 8 research centers from October 2013 to March 2015, and finally 76 of them were included. These patients were assigned to 3 groups by simple random sampling, group A, B, and C. Patients in group A (26 cases) took whole CDBBES recipe (containing leeches and equivalent insects). Those in group B (25 cases) took CDBBES recipe (removing leech and gradfly). Those in group C (25 cases) took placebos. Medication lasted for 10 successive days. The hematoma enlargement rate within 24 h, the occurrence of adverse reactions and adverse events were observed. To guarantee the safety of this trial, an interim analysis of first level unblinding was used. RESULTS: The hematoma enlargement rate was 11. 5% (3/26) in group A, 16. 0% (4/25) in group B, and 20. 0% (5/25) in group C. There was no statistical difference in the hematoma enlargement rate among the 3 groups (X² =0. 823, P =0. 682). Adverse reactions and adverse events occurred in 7 cases, 1 patient with acute myocardial infarction, 1 with chest op- pression and palpitation, 2 with diarrhea in group A. No patient had adverse reaction or adverse event in group B. And diarrhea occurred in 3 patients of group C. CONCLUSION: The interim analysis of first level unblinding showed that hematoma enlargement within 6 h was not resulted from using CDBBES.


Asunto(s)
Hemorragia Cerebral , Hematoma , Hipertensión , Medicina Tradicional China , Hemorragia Cerebral/tratamiento farmacológico , Método Doble Ciego , Hematoma/tratamiento farmacológico , Humanos , Hipertensión/complicaciones , Estudios Prospectivos
16.
Heliyon ; 10(16): e36092, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39247290

RESUMEN

Despite advances in deep learning for plant leaf disease recognition, accurately distinguishing morphological features under varying environmental conditions continues to pose significant challenges. Traditional deep learning models often fail to effectively merge local and global information, especially in small-scale datasets, impairing performance and elevating training costs. Focusing on citrus diseases, we propose an improved FasterViT Model, an advanced hybrid CNN-ViT framework that builds upon the FasterViT model. The proposed model seamlessly integrates CNN's rapid local learning capabilities with ViT's global information processing strength, thereby effectively extracting complex textures and morphological features from images. Cross-stage alternating Mixup and Cutout methods are strategically employed to enhance model robustness and generalization capabilities, particularly valuable for fast learning on small-scale datasets by simulating a more diverse training environment. Triplet Attention and AdaptiveAvgPool mechanisms are utilized to reduce training costs and optimize training performance. The proposed model is tested on both our specially constructed small-scale citrus disease dataset called in-field small dataset and the comprehensive PlantVillage dataset. The experimental results demonstrated that the model exhibits the capability of fast learning and adaptation to small sample training in plant disease detection tasks, and demonstrates the effectiveness of our improvement approach in improving model accuracy and reducing training costs. Additionally, its exemplary performance in transfer learning scenarios underscores its adaptability and broad applicability. This study not only highlights the efficacy of the improved FasterViT model in addressing the complexities of plant disease image recognition but also pioneers a new paradigm for developing efficient, scalable, and robust classification systems.

17.
Chem Sci ; 15(31): 12589-12597, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39118621

RESUMEN

Azulene, known for its unique electronic properties and structural asymmetry, serves as a promising building block for the design of novel non-benzenoid polycyclic aromatic hydrocarbons (PAHs). Herein, we present the synthesis, characterization, and physical properties of three diazulene-fused heptacyclic aromatic hydrocarbons, 8,17-dioctyldiazuleno[2,1-a:2',1'-h]anthracene (trans configuration), 16,18-dioctyldiazuleno[2,1-a:1',2'-j]anthracene (cis configuration) and 3,18-dioctyldiazuleno[2,1-a:1',2'-i]phenanthrene (zigzag configuration). Three compounds are configurational isomers with different fusing patterns of aromatic rings. All three isomers exhibit pronounced aromaticity, as revealed by nuclear magnetic resonance spectroscopy and theoretical calculations. They exhibit characteristics of both azulene and benzenoid PAHs and are much more stable than their all-benzene analogues. The optical and electrochemical properties of these three isomers were investigated through UV-vis absorption spectra and cyclic voltammetry, revealing distinct behaviors influenced by their molecular configurations. Furthermore, the isomer in trans configuration exhibits promising semiconducting properties with a hole mobility of up to 0.22 cm2 V-1 s-1, indicating its potential in organic electronics applications.

18.
Biology (Basel) ; 13(3)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38534455

RESUMEN

Phytophthora blight of pepper is a notorious disease caused by the oomycete pathogen Phytophthora capsici, which poses a great threat to global pepper production. MicroRNA (miRNA) is a class of non-coding small RNAs that regulate gene expressions by altering the translation efficiency or stability of targeted mRNAs, which play important roles in the regulation of a plant's response to pathogens. Herein, time-series mRNA-seq libraries and small RNA-seq libraries were constructed using pepper roots from the resistant line CM334 and the susceptible line EC01 inoculated with P. capsici at 0, 6, 24, and 48 h post-inoculation, respectively. For mRNA-seq analysis, a total of 2159 and 2971 differentially expressed genes (DEGs) were identified in CM334 and EC01, respectively. For miRNA-seq analysis, 491 pepper miRNAs were identified, including 330 known miRNAs and 161 novel miRNAs. Among them, 69 and 88 differentially expressed miRNAs (DEMs) were identified in CM334 and EC01, respectively. Examination of DEMs and their targets revealed 22 regulatory networks, predominantly featuring up-regulated miRNAs corresponding to down-regulated target genes. Notably, these DEM-DEG regulatory networks exhibited significant overlap between CM334 and EC01, suggesting that they might contribute to pepper's basal defense against P. capsici. Furthermore, five selected DEMs (miR166, miR1171, miR395, miR530 and miRN2) and their target genes underwent qRT-PCR validation, confirming a consistent negative correlation in the expression patterns of miRNAs and their targets. This comprehensive analysis provides novel insights into the regulatory networks of miRNAs and their targets, offering valuable contributions to our understanding of pepper's defense mechanisms against P. capsici.

19.
Commun Biol ; 7(1): 465, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632312

RESUMEN

High temperature and humidity in the environment are known to be associated with discomfort and disease, yet the underlying mechanisms remain unclear. We observed a decrease in plasma glucagon-like peptide-1 levels in response to high-temperature and humidity conditions. Through 16S rRNA gene sequencing, alterations in the gut microbiota composition were identified following exposure to high temperature and humidity conditions. Notably, changes in the gut microbiota have been implicated in bile acid synthesis. Further analysis revealed a decrease in lithocholic acid levels in high-temperature and humidity conditions. Subsequent in vitro experiments demonstrated that lithocholic acid increases glucagon-like peptide-1 secretion in NCI-H716 cells. Proteomic analysis indicated upregulation of farnesoid X receptor expression in the ileum. In vitro experiments revealed that the combination of lithocholic acid with farnesoid X receptor inhibitors resulted in a significant increase in GLP-1 levels compared to lithocholic acid alone. In this study, we elucidate the mechanism by which reduced lithocholic acid suppresses glucagon-like peptide 1 via farnesoid X receptor activation under high-temperature and humidity condition.


Asunto(s)
Microbioma Gastrointestinal , Péptido 1 Similar al Glucagón , Animales , Ratones , Péptido 1 Similar al Glucagón/genética , Péptido 1 Similar al Glucagón/metabolismo , Humedad , Proteómica , ARN Ribosómico 16S , Temperatura , Factores de Transcripción , Ácidos y Sales Biliares , Ácido Litocólico
20.
Front Neurorobot ; 17: 1193823, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37600466

RESUMEN

Introduction: A hot cell is generally deployed with a teleoperation power manipulator to complete tests, operations, and maintenance. The position and pose of the manipulator are mostly acquired through radiation-resistant video cameras arranged in the hot cell. In this paper, deep learning-based target detection technology is used to establish an experimental platform to test the methods for target detection and pose estimation of teleoperation power manipulators using two cameras. Methods: In view of the fact that a complex environment affects the precision of manipulator pose estimation, the dilated-fully convolutional one-stage object detection (dilated-FCOS) teleoperation power manipulator target detection algorithm is proposed based on the scale of the teleoperation power manipulator. Model pruning is used to improve the real-time performance of the dilated-FCOS teleoperation power manipulator target detection model. To improve the detection speed for the key points of the teleoperation power manipulator, the keypoint detection precision and model inference speed of different lightweight backbone networks were tested based on the SimpleBaseline algorithm. MobileNetv1 was selected as the backbone network to perform channel compression and pose distillation on the upsampling module so as to further optimize the inference speed of the model. Results and discussion: Compared with the original model, the proposed model was experimentally proven to reach basically the same precision within a shorter inference time (only 58% of that of the original model). The experimental results show that the compressed model basically retains the precision of the original model and that its inference time is 48% of that of the original model.

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