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1.
Proc Natl Acad Sci U S A ; 119(33): e2118501119, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35943985

RESUMO

Pain and itch are distinct sensations arousing evasion and compulsive desire for scratching, respectively. It's unclear whether they could invoke different neural networks in the brain. Here, we use the type 1 herpes simplex virus H129 strain to trace the neural networks derived from two types of dorsal root ganglia (DRG) neurons: one kind of polymodal nociceptors containing galanin (Gal) and one type of pruriceptors expressing neurotensin (Nts). The DRG microinjection and immunosuppression were performed in transgenic mice to achieve a successful tracing from specific types of DRG neurons to the primary sensory cortex. About one-third of nuclei in the brain were labeled. More than half of them were differentially labeled in two networks. For the ascending pathways, the spinothalamic tract was absent in the network derived from Nts-expressing pruriceptors, and the two networks shared the spinobulbar projections but occupied different subnuclei. As to the motor systems, more neurons in the primary motor cortex and red nucleus of the somatic motor system participated in the Gal-containing nociceptor-derived network, while more neurons in the nucleus of the solitary tract (NST) and the dorsal motor nucleus of vagus nerve (DMX) of the emotional motor system was found in the Nts-expressing pruriceptor-derived network. Functional validation of differentially labeled nuclei by c-Fos test and chemogenetic inhibition suggested the red nucleus in facilitating the response to noxious heat and the NST/DMX in regulating the histamine-induced scratching. Thus, we reveal the organization of neural networks in a DRG neuron type-dependent manner for processing pain and itch.


Assuntos
Galanina , Gânglios Espinais , Rede Nervosa , Neurotensina , Nociceptores , Dor , Prurido , Animais , Galanina/metabolismo , Gânglios Espinais/ultraestrutura , Herpesvirus Humano 1 , Camundongos , Camundongos Transgênicos , Rede Nervosa/ultraestrutura , Neurotensina/metabolismo , Nociceptores/metabolismo , Dor/fisiopatologia , Prurido/fisiopatologia , Núcleo Solitário/ultraestrutura
2.
J Am Chem Soc ; 146(28): 19239-19248, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38949598

RESUMO

Advanced in vitro diagnosis technologies are highly desirable in early detection, prognosis, and progression monitoring of diseases. Here, we engineer a multiplex protein biosensing strategy based on the tunable liquid confinement self-assembly of multi-material heterochains, which show improved sensitivity, throughput, and accuracy compared to standard ELISA kits. By controlling the material combination and the number of ligand nanoparticles (NPs), we observe robust near-field enhancement as well as both strong electromagnetic resonance in polymer-semiconductor heterochains. In particular, their optical signals show a linear response to the coordination number of the semiconductor NPs in a wide range. Accordingly, a visible nanophotonic biosensor is developed by functionalizing antibodies on central polymer chains that can identify target proteins attached to semiconductor NPs. This allows for the specific detection of multiple protein biomarkers from healthy people and pancreatic cancer patients in one step with an ultralow detection limit (1 pg/mL). Furthermore, rapid and high-throughput quantification of protein expression levels in diverse clinical samples such as buffer, urine, and serum is achieved by combining a neural network algorithm, with an average accuracy of 97.3%. This work demonstrates that the heterochain-based biosensor is an exemplary candidate for constructing next-generation diagnostic tools and suitable for many clinical settings.


Assuntos
Técnicas Biossensoriais , Aprendizado de Máquina , Humanos , Técnicas Biossensoriais/métodos , Biomarcadores/análise , Nanopartículas/química , Semicondutores , Ensaios de Triagem em Larga Escala , Neoplasias Pancreáticas , Polímeros/química
3.
Am J Epidemiol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38872336

RESUMO

Non-optimal ambient temperatures are risk factors for myocardial infarction (MI) and urban-rural temperature differences in the context of climate change may have caused and will lead to differential association between temperature and MI. We collected daily mean temperature and daily MI deaths from 1 January 2016 to 31 December 2020 in Anhui Province, China. A distributed lag nonlinear model was performed to estimate the area-specific association of heat and cold (defined as the 2.5th and 97.5th percentile of the daily mean temperature) with MI mortality; the random-effects meta-analysis was then used to pool the effects of cold and heat. We found the risk of MI death due to cold was higher in rural areas [relative risk (RR): 1.13, 95% confidence interval (CI): 1.02-1.26, lag0) than in urban areas (RR: 0.99, 95% CI: 0.80-1.21, lag0), whereas the risk of MI death associated with heat was higher in urban areas (RR: 1.14, 95% CI: 1.03-1.27, lag0) than in rural areas (RR: 1.04, 95% CI: 0.99-1.10, lag0). Our findings may help to develop targeted protective strategies to reduce the adverse effects of cold and heat on cardiovascular disease.

4.
Fungal Genet Biol ; 170: 103864, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38199492

RESUMO

Methyl jasmonate (MeJA)-regulated postharvest quality retention of Agaricus bisporus fruiting bodies is associated with arginine catabolism. However, the mechanism of MeJA-regulated arginine catabolism in edible mushrooms is still unclear. This study aimed to investigate the regulatory modes of MeJA on the expression of arginine catabolism-related genes and proteins in intact and different tissues of A. bisporus mushrooms during storage. Results showed that exogenous MeJA treatment activated endogenous JA biosynthesis in A. bisporus mushrooms, and differentially and tissue-specifically regulated the expression of arginine catabolism-related genes (AbARG, AbODC, AbSPE-SDH, AbSPDS, AbSAMDC, and AbASL) and proteins (AbARG, AbSPE-SDH, AbASL, and AbASS). MeJA caused no significant change in AbASS expression but resulted in a dramatic increase in AbASS protein level. Neither the expression of the AbSAMS gene nor the AbSAMS protein was conspicuously altered upon MeJA treatment. Additionally, MeJA reduced the contents of arginine and ornithine and induced the accumulation of free putrescine and spermidine, which was closely correlated with MeJA-regulated arginine catabolism-related genes and proteins. Hence, the results suggested that the differential and tissue-specific regulation of arginine catabolism-related genes and proteins by MeJA contributed to their selective involvement in the postharvest continuing development and quality retention of button mushrooms.


Assuntos
Agaricus , Agaricus/genética , Acetatos/farmacologia , Ciclopentanos/farmacologia , Oxilipinas/farmacologia
5.
Int J Med Sci ; 21(1): 95-106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164361

RESUMO

Evidence presented that osteoporosis is closely related to the dysfunction of bone mesenchymal stem cells (BMSCs). But most studies are insufficient to reveal what actually happens to the osteoporotic BMSCs. In this study, BMSCs were harvested from ovariectomized and sham-operated rats. After checking the characteristics of rat models and stem cells, the BMSCs were carried out for RNA sequencing. Part of the findings were verified that seven mRNAs (Abi3bp, Aifm3, Ccl11, Cdkn1c, Chst10, Id2, Vcam1) were significantly up-regulated in osteoporotic BMSCs while seven mRNAs (Cep63, Fgfr3, Myc, Omd, Pou2f1, Smarcal1, Timm10b) were down-regulated. In addition, potential miRNA-mRNA and lncRNA-mRNA regulatory networks were illustrated. The changes in osteoporotic BMSCs covered a large set of biological processes, including cell viability, differentiation, immunoreaction, bone repairment and estrogen defect. This study enriched the pathophysiological mechanisms of BMSCs and osteporosis, as well as provided dozens of attractive RNA targets for further treatment.


Assuntos
Células-Tronco Mesenquimais , Osteoporose , Ratos , Animais , Osteoporose/genética , Osteoporose/terapia , Diferenciação Celular/genética , Análise de Sequência de RNA , RNA Mensageiro , Osteogênese/genética , Células Cultivadas
6.
Anal Chem ; 95(31): 11769-11776, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37489945

RESUMO

Biomolecular markers, particularly circulating microRNAs (miRNAs) play an important role in diagnosis, monitoring, and therapeutic intervention of cancers. However, existing detection strategies remain intricate, laborious, and far from being developed for point-of-care testing. Here, we report a portable colorimetric sensor that utilizes the hetero-assembly of nanostructures driven by base pairing and recognition for direct detection of miRNAs. Following hybridization, two sizes of nanoparticles modified with single-strand DNA can be robustly assembled into heterostructures with strong optical resonance, exhibiting distinct structure colors. Particularly, the large nanoparticles are first arranged into nanochains to enhance scattering signals of small nanoparticles, which allows for sensitive detection and quantification of miRNAs without the requirement of target extraction, amplification, and fluorescent labels. Furthermore, we demonstrate the high specificity and single-base selectivity of testing different miRNA samples, which shows great potential in the diagnosis, staging, and monitoring of cancers. These heterogeneous assembled nanostructures provide an opportunity to develop simple, fast, and convenient tools for miRNAs detection, which is suitable for many scenarios, especially in low-resource setting.


Assuntos
Técnicas Biossensoriais , MicroRNA Circulante , MicroRNAs , Nanoestruturas , MicroRNAs/genética , Hibridização de Ácido Nucleico , Corantes , Limite de Detecção
7.
Small ; 19(28): e2301162, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36988021

RESUMO

Rapid and ultra-sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for early screening and management of COVID-19. Currently, the real-time reverse transcription polymerase chain reaction (rRT-PCR) is the primary laboratory method for diagnosing SARS-CoV-2. It is not suitable for at-home COVID-19 diagnostic test due to the long operating time, specific equipment, and professional procedures. Here an all-printed photonic crystal (PC) microarray with portable device for at-home COVID-19 rapid antigen test is reported. The fluorescence-enhanced effect of PC amplifies the fluorescence intensity of the labeled probe, achieving detection of nucleocapsid (N-) protein down to 0.03 pg mL-1 . A portable fluorescence intensity measurement instrument gives the result (negative or positive) by the color of the indicator within 5 s after inserting the reacted PC microarray test card. The N protein in inactivated virus samples (with cycle threshold values of 26.6-40.0) can be detected. The PC microarray provides a general and easy-to-use method for the timely monitoring and eventual control of the global coronavirus pandemic.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Proteínas do Nucleocapsídeo/análise , Proteínas do Nucleocapsídeo/genética , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
8.
Planta ; 258(2): 45, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37462779

RESUMO

MAIN CONCLUSION: We review the application and the molecular regulation of anthocyanins in colorful Brassica crops, the creation of new germplasm resources, and the development and utilization of colorful Brassica crops. Brassica crops are widely cultivated: these include oilseed crops, such as rapeseed, mustards, and root, leaf, and stem vegetable types, such as turnips, cabbages, broccoli, and cauliflowers. Colorful variants exist of these crop species, and asides from increased aesthetic appeal, these may also offer advantages in terms of nutritional content and improved stress resistances. This review provides a comprehensive overview of pigmentation in Brassica as a reference for the selection and breeding of new colorful Brassica varieties for multiple end uses. We summarize the function and molecular regulation of anthocyanins in Brassica crops, the creation of new colorful germplasm resources via different breeding methods, and the development and multifunctional utilization of colorful Brassica crop types.


Assuntos
Brassica napus , Brassica , Brassica/genética , Antocianinas , Melhoramento Vegetal
9.
Brief Bioinform ; 22(5)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-33866367

RESUMO

Although synonymous mutations do not alter the encoded amino acids, they may impact protein function by interfering with the regulation of RNA splicing or altering transcript splicing. New progress on next-generation sequencing technologies has put the exploration of synonymous mutations at the forefront of precision medicine. Several approaches have been proposed for predicting the deleterious synonymous mutations specifically, but their performance is limited by imbalance of the positive and negative samples. In this study, we firstly expanded the number of samples greatly from various data sources and compared six undersampling strategies to solve the problem of the imbalanced datasets. The results suggested that cluster centroid is the most effective scheme. Secondly, we presented a computational model, undersampling scheme based method for deleterious synonymous mutation (usDSM) prediction, using 14-dimensional biology features and random forest classifier to detect the deleterious synonymous mutation. The results on the test datasets indicated that the proposed usDSM model can attain superior performance in comparison with other state-of-the-art machine learning methods. Lastly, we found that the deep learning model did not play a substantial role in deleterious synonymous mutation prediction through a lot of experiments, although it achieves superior results in other fields. In conclusion, we hope our work will contribute to the future development of computational methods for a more accurate prediction of the deleterious effect of human synonymous mutation. The web server of usDSM is freely accessible at http://usdsm.xialab.info/.


Assuntos
Algoritmos , Biologia Computacional/métodos , Aprendizado de Máquina , Modelos Genéticos , Proteínas/genética , Mutação Silenciosa , Humanos , Proteínas/química , Reprodutibilidade dos Testes
10.
J Transl Med ; 21(1): 543, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37580725

RESUMO

BACKGROUND: The ventral tegmental area (VTA) contains heterogeneous cell populations. The dopaminergic neurons in VTA play a central role in reward and cognition, while CamKIIα-positive neurons, composed mainly of glutamatergic and some dopaminergic neurons, participate in the reward learning and locomotor activity behaviors. The differences in brain-wide functional and structural networks between these two neuronal subtypes were comparatively elucidated. METHODS: In this study, we applied a method combining Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and fMRI to assess the cell type-specific modulation of whole-brain neural networks. rAAV encoding the cre-dependent hM3D was injected into the right VTA of DAT-cre or CamKIIα-cre transgenic rats. The global brain activities elicited by DREADD stimulation were then detected using BOLD-fMRI. Furthermore, the cre-dependent antegrade transsynaptic viral tracer H129ΔTK-TT was applied to label the outputs of VTA neurons. RESULTS: We found that DREADD stimulation of dopaminergic neurons induced significant BOLD signal changes in the VTA and several VTA-related regions including mPFC, Cg and Septum. More regions responded to selective activation of VTA CamKIIα-positive neurons, resulting in increased BOLD signals in VTA, Insula, mPFC, MC_R (Right), Cg, Septum, Hipp, TH_R, PtA_R, and ViC_R. Along with DREADD-BOLD analysis, further neuronal tracing identified multiple cortical (MC, mPFC) and subcortical (Hipp, TH) brain regions that are structurally and functionally connected by VTA dopaminergic and CamKIIα-positive neurons. CONCLUSIONS: Our study dissects brain-wide structural and functional networks of two neuronal subtypes in VTA and advances our understanding of VTA functions.


Assuntos
Imageamento por Ressonância Magnética , Área Tegmentar Ventral , Ratos , Animais , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/fisiologia , Imageamento por Ressonância Magnética/métodos , Encéfalo , Neurônios Dopaminérgicos/fisiologia
11.
BMC Cancer ; 23(1): 828, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670252

RESUMO

BACKGROUND: The goal was to investigate the feasibility of the registration generative adversarial network (RegGAN) model in image conversion for performing adaptive radiation therapy on the head and neck and its stability under different cone beam computed tomography (CBCT) models. METHODS: A total of 100 CBCT and CT images of patients diagnosed with head and neck tumors were utilized for the training phase, whereas the testing phase involved 40 distinct patients obtained from four different linear accelerators. The RegGAN model was trained and tested to evaluate its performance. The generated synthetic CT (sCT) image quality was compared to that of planning CT (pCT) images by employing metrics such as the mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM). Moreover, the radiation therapy plan was uniformly applied to both the sCT and pCT images to analyze the planning target volume (PTV) dose statistics and calculate the dose difference rate, reinforcing the model's accuracy. RESULTS: The generated sCT images had good image quality, and no significant differences were observed among the different CBCT modes. The conversion effect achieved for Synergy was the best, and the MAE decreased from 231.3 ± 55.48 to 45.63 ± 10.78; the PSNR increased from 19.40 ± 1.46 to 26.75 ± 1.32; the SSIM increased from 0.82 ± 0.02 to 0.85 ± 0.04. The quality improvement effect achieved for sCT image synthesis based on RegGAN was obvious, and no significant sCT synthesis differences were observed among different accelerators. CONCLUSION: The sCT images generated by the RegGAN model had high image quality, and the RegGAN model exhibited a strong generalization ability across different accelerators, enabling its outputs to be used as reference images for performing adaptive radiation therapy on the head and neck.


Assuntos
Tomografia Computadorizada de Feixe Cônico Espiral , Humanos , Cabeça , Pescoço , Benchmarking , Tomografia Computadorizada de Feixe Cônico
12.
Clin Exp Pharmacol Physiol ; 50(6): 463-475, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36809521

RESUMO

Osteosarcoma (OS) is the most common bone tumour with a high risk of metastatic progression and recurrence after treatment. Circular RNA hsa_circ_0000591 (circ_0000591) plays a compelling role in OS aggressiveness. However, the function and regulatory mechanism of circ_0000591 need to be further elucidated. As a subject of this study, a differential circRNA circ_0000591 was screened by circRNA microarray expression profiling (GSE96964). Expression changes of circ_0000591 were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Effects of circ_0000591 silencing on OS cell viability, proliferation, colony formation, apoptosis, invasion, and glycolysis were determined via functional experiments. The mechanism by which circ_0000591 functions as a molecular sponge for miRNAs was predicted using bioinformatics analysis and validated using dual-luciferase reporter and RNA pull-down assays. Xenograft assay was done to validate the function of circ_0000591. Circ_0000591 was strongly expressed in OS samples and cells. Silencing of circ_0000591 lessened cell viability, repressed cell proliferation, invasion, glycolysis, and promoted cell apoptosis. Importantly, circ_0000591 regulated HK2 expression by serving as a miR-194-5p molecular sponge. MiR-194-5p silencing impaired circ_0000591 downregulation-mediated suppression of OS cell malignancy and glycolysis. HK2 overexpression weakened the inhibiting impacts of miR-194-5p on OS cell malignancy and glycolysis. Also, circ_0000591 silencing decreased xenograft tumour growth in vivo. Circ_0000591 drove OS glycolysis and growth by upregulating HK2 by sequestering miR-194-5p. The study highlighted the tumour-promoting function of circ_0000591 in OS.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Humanos , RNA Circular , Proliferação de Células , Glicólise , Linhagem Celular Tumoral
13.
BMC Public Health ; 23(1): 461, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36899365

RESUMO

BACKGROUND: A universal set of disability weights(DWs) is mainly based on the survey of North America, Australia and Europe, whereas the participants in Asia was limited. The debate hasn't yet settled whether a universal DW is desirable or useful.The focus of the debate is its representativenes-s.After all, the DWs come from people's subjective evaluation of pain, and they may vary according to cultural background.The differences of the DWs could have implications for the magnitude or ranking of disease burdens.The DWs of Anhui Province has not been completely presented.This paper aims to obtain the DWs suitable for the general population of Anhui Province of China, and attempts to explore the differences between different DWs by comparing the DWs with the similar-cultural background and the DWs with cross-cultural background. METHODS: A web-based survey was conducted to estimate the DWs for 206 health states of Anhui province in 2020. Paired comparison (PC) data were analyzed and anchored by probit regression and fitting loess model. We compared the DWs in Anhui with other provinces in China and those in Global burden of disease (GBD) and Japan. RESULTS: Compared with Anhui province, the proportion of health states which showed 2 times or more differences ranged from 1.94% (Henan) to 11.17% (Sichuan) in China and domestic provinces. It was 19.88% in Japan and 21.51% in GBD 2013 respectively. In Asian countries or regions, most of the health states with top 15 DWs belonged to the category of mental, behavioral, and substance use disorders. But in GBD, most were infectious diseases and cancer. The differences of DWs in neighboring provinces were smaller than other geographically distant provinces or countries. CONCLUSION: PC responses were largely consistent across very distinct settings,but the exceptions do need to be faced squarely.The differences of DWs among similar-cultural regions were smaller than cross-cultural regions. There is an urgent need for relevant gold standards.


Assuntos
Pessoas com Deficiência , Neoplasias , Humanos , Efeitos Psicossociais da Doença , Inquéritos e Questionários , Carga Global da Doença
14.
Med Teach ; : 1-8, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910012

RESUMO

INTRODUCTION: Due to policy changes in the context of COVID-19 pandemic, online teaching has become the main form of class in many Chinese universities. Flipped classroom has been widely used in other disciplines, but there is a dearth of evidence available about the use in online teaching of emergency medicine. This study aimed to develop a flipped classroom for online emergency medicine teaching and evaluate its effectiveness by comparing it with traditional lecture-based online teaching. METHODS: A total of 62 clinical medical undergraduates from Jinan University participated in this study from September to December in 2022. An online flipped classroom approach was developed (FC group, n = 31). Traditional lecture-based online teaching was applied as a contrast (LBT group, n = 31). The undergraduates completed examinations and questionnaires at the end of the course. A course experience questionnaire and course examination score were used to evaluate the effectiveness of the flipped classroom approach. RESULTS: Regarding the five dimensions of the course experience questionnaire, the scores for good teaching (3.47 ± 0.50 vs. 2.34 ± 0.48, p < .001), appropriate assessment (3.31 ± 0.68 vs. 2.95 ± 0.71, p = .043) and generic skills (3.16 ± 0.60 vs. 2.72 ± 0.39, p < .001) were higher for the FC group than for the LBT group. There was no significant difference between the two groups in clear goals and standards, and appropriate workload. The undergraduates in the FC group showed significantly higher overall satisfaction than those in the LBT group (3.52 ± 0.1.03 vs. 2.87 ± 0.92, p = .012). The examination scores (77.936 ± 11.573 vs. 70.484 ± 7.434, p < .001), especially the scores for questions related to case analysis (33.032 ± 5.363 vs. 26.968 ± 7.657, p < .001), were significantly higher in the FC group than in the LBT group. CONCLUSIONS: The flipped classroom for online teaching was efficient in improving undergraduates' emergency medical academic performance and promoting the development of clinical case analysis ability. These findings provide an alternative flipped classroom approach for online teaching of emergency medicine.

15.
Chem Soc Rev ; 51(7): 2583-2600, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35262144

RESUMO

Borenium ions are strong Lewis acids because of the positive charge on boron. While their high reactivity had long restricted their role in organic synthesis to stoichiometric reagents, in the past ten years the introduction of suitable supporting ligands, such as N-heterocyclic carbenes, has enabled them to function as competent catalysts for various organic transformations involving the activation of strong covalent bonds, such as H-H, Si-H, B-H, C-H and C-C bonds. This review provides an overview of the recent advances in borenium-catalysed reactions with emphasis on catalyst synthesis, methodology development and mechanistic insight.

16.
Sensors (Basel) ; 23(9)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37177635

RESUMO

In 2016, Google proposed a congestion control algorithm based on bottleneck bandwidth and round-trip propagation time (BBR). The BBR congestion control algorithm measures the network bottleneck bandwidth and minimum delay in real-time to calculate the bandwidth delay product (BDP) and then adjusts the transmission rate to maximize throughput and minimize latency. However, relevant research reveals that BBR still has issues such as RTT unfairness, high packet loss rate, and deep buffer performance degradation. This article focuses on its most prominent RTT fairness issue as a starting point for optimization research. Using fluid models to describe the data transmission process in BBR congestion control, a fairness optimization strategy based on pacing gain is proposed. Triangular functions, inverse proportional functions, and gamma correction functions are analyzed and selected to construct the pacing gain model, forming three different adjustment functions for adaptive adjustment of the transmission rate. Simulation and real experiments show that the three optimization algorithms significantly improve the fairness and network transmission performance of the original BBR algorithm. In particular, the optimization algorithm that employs the gamma correction function as the gain model exhibits the best stability.

17.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36834687

RESUMO

Doxorubicin (DOX)-related cardiotoxicity has been recognized as a serious complication of cancer chemotherapy. Effective targeted strategies for myocardial protection in addition to DOX treatment are urgently needed. The purpose of this paper was to determine the therapeutic effect of berberine (Ber) on DOX-triggered cardiomyopathy and explore the underlying mechanism. Our data showed that Ber markedly prevented cardiac diastolic dysfunction and fibrosis, reduced cardiac malondialdehyde (MDA) level and increased antioxidant superoxide dismutase (SOD) activity in DOX-treated rats. Moreover, Ber effectively rescued the DOX-induced production of reactive oxygen species (ROS) and MDA, mitochondrial morphological damage and membrane potential loss in neonatal rat cardiac myocytes and fibroblasts. This effect was mediated by increases in the nuclear accumulation of nuclear erythroid factor 2-related factor 2 (Nrf2) and levels of heme oxygenase-1 (HO-1) and mitochondrial transcription factor A (TFAM). We also found that Ber suppressed the differentiation of cardiac fibroblasts (CFs) into myofibroblasts, as indicated by decreased expression of α-smooth muscle actin (α-SMA), collagen I and collagen III in DOX-treated CFs. Pretreatment with Ber inhibited ROS and MDA production and increased SOD activity and the mitochondrial membrane potential in DOX-challenged CFs. Further investigation indicated that the Nrf2 inhibitor trigonelline reversed the protective effect of Ber on both cardiomyocytes and CFs after DOX stimulation. Taken together, these findings demonstrated that Ber effectively alleviated DOX-induced oxidative stress and mitochondrial damage by activating the Nrf2-mediated pathway, thereby leading to the prevention of myocardial injury and fibrosis. The current study suggests that Ber is a potential therapeutic agent for DOX-induced cardiotoxicity that exerts its effects by activating Nrf2.


Assuntos
Berberina , Traumatismos Cardíacos , Animais , Ratos , Apoptose , Berberina/farmacologia , Cardiotoxicidade/metabolismo , Doxorrubicina/farmacologia , Fibrose , Traumatismos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
18.
Int J Mol Sci ; 24(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37373312

RESUMO

Rapeseed has the ability to absorb cadmium in the roots and transfer it to aboveground organs, making it a potential species for remediating soil cadmium (Cd) pollution. However, the genetic and molecular mechanisms underlying this phenomenon in rapeseed are still unclear. In this study, a 'cadmium-enriched' parent, 'P1', with high cadmium transport and accumulation in the shoot (cadmium root: shoot transfer ratio of 153.75%), and a low-cadmium-accumulation parent, 'P2', (with a cadmium transfer ratio of 48.72%) were assessed for Cd concentration using inductively coupled plasma mass spectrometry (ICP-MS). An F2 genetic population was constructed by crossing 'P1' with 'P2' to map QTL intervals and underlying genes associated with cadmium enrichment. Fifty extremely cadmium-enriched F2 individuals and fifty extremely low-accumulation F2 individuals were selected based on cadmium content and cadmium transfer ratio and used for bulk segregant analysis (BSA) in combination with whole genome resequencing. This generated a total of 3,660,999 SNPs and 787,034 InDels between these two segregated phenotypic groups. Based on the delta SNP index (the difference in SNP frequency between the two bulked pools), nine candidate Quantitative trait loci (QTLs) from five chromosomes were identified, and four intervals were validated. RNA sequencing of 'P1' and 'P2' in response to cadmium was also performed and identified 3502 differentially expressed genes (DEGs) between 'P1' and 'P2' under Cd treatment. Finally, 32 candidate DEGs were identified within 9 significant mapping intervals, including genes encoding a glutathione S-transferase (GST), a molecular chaperone (DnaJ), and a phosphoglycerate kinase (PGK), among others. These genes are strong candidates for playing an active role in helping rapeseed cope with cadmium stress. Therefore, this study not only sheds new light on the molecular mechanisms of Cd accumulation in rapeseed but could also be useful for rapeseed breeding programs targeting this trait.


Assuntos
Brassica napus , Cádmio , Humanos , Brassica napus/genética , Melhoramento Vegetal , Locos de Características Quantitativas , Análise de Sequência de RNA
19.
J Am Chem Soc ; 144(51): 23286-23291, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36524876

RESUMO

Non-metal-catalyzed C-H borylation of arenes represents a sustainable and environment-friendly approach for the functionalization of arenes. Despite its promise as an alternative to traditional transition-metal systems, its substrate scope is generally limited to electron-rich arenes, thus hindering its application in organic synthesis. Herein, we report the development of a borenium-ion catalyst which can borylate unactivated arenes under ambient conditions with 4-chlorocatecholborane (HBcatCl) as borylation reagent. This metal-free catalytic system is suitable for the borylation of C-H bonds in sterically encumbered positions, which has been a challenging task for transition-metal systems. Additionally, this catalytic system allows para-selective one-pot borylation of phenols, which has not been achieved by using transition-metal systems. Our mechanistic investigations and computational studies support a synergistic activation of the H-BcatCl bond by the arene substrate and the borenium-ion catalyst. This generates a Wheland intermediate and a neutral hydroborane species and is followed by deprotonation of the Wheland intermediate with the hydroborane species. The latter step of C-H bond cleavage is likely the rate-limiting step.

20.
Exp Eye Res ; 218: 109009, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35276185

RESUMO

Accumulated clinical evidence has shown that Posner-Schlossman syndrome (PSS) is most likely the result of recurrent human cytomegalovirus (HCMV) infection in the anterior chamber (AC). Establishing an animal model is necessary to investigate the pathogenesis of PSS. In this study, we constructed a mouse model of (PSS) by injecting murine cytomegalovirus (MCMV) into the AC of BALB/c mice. Twenty-five BALB/c mice were divided into 5 groups. Smith strain MCMV expressing enhanced green fluorescent protein (EGFP) was passaged with mouse embryonic fibroblast (MEF). Right eyes in the 4 experiment groups received AC injection of 1 µL of virus solution with concentrations of 103,104,105,106 pfu/mL respectively, and the control group received only PBS. PSS-like signs (mutton-fat keratic precipitates (KP), pupil dilation, IOP elevation and corneal edema) were recorded 0-28 days post-injection (DPI). Sections of eyeballs from another 9 mice harvested on 0,10 and 28 DPI were examined to locate KP and the fluorescence signal of the virus. Reversible PSS-like signs except KP were observed in 20% and 60% mice of 104 and 105 groups while no PSS-like signs in the control and 103 group; 80% in the 106 group with partially unreversible signs till 28DPI. Much More fluorescent signals of virus in the iris and KP were found on 10DPI than 28 DPI, while no fluorescent signals and KP on 0DPI. The extent of PSS-like signs (pupil dilation, IOP elevation and corneal edema) was virus concentration-dependent (Spearman correlation coefficient, r = 0.830, = 0.475, = 0.662, p < 0.0001, <0.05, <0.001, respectively, n = 25). Success rate of PSS model (mice with PSS-like signs) was also virus concentration-dependent (Chi-square trend test, χ2 = 6.828, df = 1, p < 0.01, n = 25). Our results indicate that AC injection of 1 µL MEF passaged MCMV (Smith strain) of 104-106 pfu/mL in BALB/c mice can be used to construct a mouse model of PSS. MCMV can infect iris tissue and replicate in it and then establish latency. This might account for the recurrent and self-limited nature of PSS.


Assuntos
Edema da Córnea , Infecções por Citomegalovirus , Glaucoma de Ângulo Aberto , Muromegalovirus , Animais , Câmara Anterior/patologia , Citomegalovirus , Modelos Animais de Doenças , Fibroblastos/patologia , Camundongos , Camundongos Endogâmicos BALB C
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