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OBJECTIVE: This study aims to elucidate the mechanism of action and impact of the "Xuanshen Yishen Mixture" (XYM) on hypertension. METHODS: Active components were identified and potential targets were predicted using the Traditional Chinese Medicine Systems Pharmacology database. Hypertension-related targets were collected from GeneCards, DRUGBANK, OMIM, TTD, and PharmaGKB databases. Intersections of disease and drug targets were visualized using the R package "VennDiagram". A protein-protein interaction network was established via the STRING database. GO function enrichment and KEGG pathway analyses were conducted using "clusterProfiler", while "Cytoscape" was used to construct a "drug-component-target" network. Additionally, data from 60 patients with essential hypertension from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were retrospectively analyzed. Patients were divided into a control group (n = 30) and an XYM group (n = 30) based on treatment regimen. RESULTS: Sixty active ingredients and 98 related targets were identified from Uncaria, Radix Scrophulariae, and Epimedium in hypertension treatment. Key active components such as quercetin, kaempferol, yohimbine, and beta-sitosterol were pinpointed, with PTGS2, PTGS1, AR, DPP4, and F2 as crucial targets. KEGG pathway analysis highlighted significant pathways including IL-17 signaling, TNF signaling, Relaxin signaling, and HIF-1 signaling. Clinical data indicated that XYM's therapeutic effects are comparable to those of valsartan, which significantly reduced diastolic and systolic blood pressure and demonstrated good biosafety. CONCLUSIONS: Uncaria, Radix Scrophulariae, and Epimedium effectively mitigate hypertension through multiple components, targets, and pathways. Additionally, DPP4, IL-17, and TNF-α are identified as potential therapeutic targets for traditional Chinese medicine preparations in hypertension treatment. This study provides a foundation for further investigation into XYM's mechanisms in hypertension management.
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Synaptic potentiation has been linked to learning in sensory cortex, but the connection between this potentiation and increased sensory-evoked neural activity is not clear. Here, we used longitudinal in vivo Ca2+ imaging in the barrel cortex of awake mice to test the hypothesis that increased excitatory synaptic strength during the learning of a whisker-dependent sensory-association task would be correlated with enhanced stimulus-evoked firing. To isolate stimulus-evoked responses from dynamic, task-related activity, imaging was performed outside of the training context. Although prior studies indicate that multiwhisker stimuli drive robust subthreshold activity, we observed sparse activation of L2/3 pyramidal (Pyr) neurons in both control and trained mice. Despite evidence for excitatory synaptic strengthening at thalamocortical and intracortical synapses in this brain area at the onset of learning-indeed, under our imaging conditions thalamocortical axons were robustly activated-we observed that L2/3 Pyr neurons in somatosensory (barrel) cortex displayed only modest increases in stimulus-evoked activity that were concentrated at the onset of training. Activity renormalized over longer training periods. In contrast, when stimuli and rewards were uncoupled in a pseudotraining paradigm, stimulus-evoked activity in L2/3 Pyr neurons was significantly suppressed. These findings indicate that sensory-association training but not sensory stimulation without coupled rewards may briefly enhance sensory-evoked activity, a phenomenon that might help link sensory input to behavioral outcomes at the onset of learning.
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Neocórtex , Córtex Somatossensorial , Vibrissas , Animais , Vibrissas/fisiologia , Neocórtex/fisiologia , Camundongos , Córtex Somatossensorial/fisiologia , Masculino , Células Piramidais/fisiologia , Camundongos Endogâmicos C57BL , Feminino , Aprendizagem por Associação/fisiologiaRESUMO
BACKGROUND: Lentil is a significant legume that are consumed as a staple food and have a significant economic impact around the world. The purpose of the present research on lentil was to assess the hydrothermal time model's capacity to explain the dynamics of Lens culinaris L. var. Markaz-09 seed germination, as well as to ascertain the germination responses at various sub-optimal temperatures (T) and water potentials (Ψ). In order to study lentil seed germination (SG) behavior at variable water potentials (Ψs) and temperatures (Ts). A lab experiment employing the hydrothermal time model was created. Seeds were germinated at six distinct temperatures: 15 0С, 20 0С, 25 0С, 30 0С, 35 0С, and 40 0С, with five Ψs of 0, -0.3, -0.6, -0.9, and - 1.2 MPa in a PEG-6000 (Polyethylene glycol 6000) solution. RESULTS: The results indicated that the agronomic parameters like Germination index (GI), Germination energy (GE), Timson germination index (TGI), were maximum in 25 0C at (-0.9 MPa) and lowest at 40 0C in 0 MPa. On other hand, mean germination time (MGT) value was highest at 15 0C in -1.2 MPa and minimum at 40 0C in (-0.6 MPa) while Mean germination rate (MGR) was maximum at 40 0C in (0 MPa) and minimum at 15 0C in (-0.6 MPa). CONCLUSIONS: The HTT model eventually defined the germination response of Lens culinaris L. var. Markaz-09 (Lentil) for all Ts and Ψs, allowing it to be employed as a predictive tool in Lens culinaris L. var. Markaz-09 (Lentil) seed germination simulation models.
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Germinação , Lens (Planta) , Sementes , Temperatura , Germinação/fisiologia , Sementes/fisiologia , Sementes/crescimento & desenvolvimento , Lens (Planta)/fisiologia , Lens (Planta)/crescimento & desenvolvimento , Água/metabolismo , Modelos Biológicos , Pressão OsmóticaRESUMO
The primary and initial manifestations of hypertension encompass arterial hypoelasticity and histiocyte senescence. Oxidative stress plays a pivotal role in the progression of senescence. Elevated intracellular oxidative stress levels will directly induce cell damage, disrupt normal physiological signal transduction, which can cause mitochondrial dysfunction to accelerate the process of senescence. Alizarin, an anthraquinone active ingredient isolated from Rubia cordifolia L., has a variety of pharmacological effects, including antioxidant, anti-inflammatory and anti-platelet. Nevertheless, its potential in lowering blood pressure (BP) and mitigating hypertension-induced vascular senescence remains uncertain. In this study, we used spontaneously hypertensive rats (SHR) and human umbilical vein endothelial cells (HUVECs) to establish a model of vascular senescence in hypertension. Our aim was to elucidate the mechanisms underpinning the vascular protective effects of Alizarin. By assessing systolic blood pressure (SBP) and diastolic blood pressure (DBP), H&E staining, SA-ß-Gal staining, vascular function, oxidative stress levels, calcium ion concentration and mitochondrial membrane potential, we found that Alizarin not only restored SBP and increased endothelium-dependent relaxation (EDR) in SHR, but also inhibited oxidative stress-induced mitochondrial damage and significantly delayed the vascular senescence effect in hypertension, and the mechanism may be related to the activation of VEGFR2/eNOS signaling pathway.
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Antraquinonas , Anti-Hipertensivos , Senescência Celular , Células Endoteliais da Veia Umbilical Humana , Hipertensão , Mitocôndrias , Óxido Nítrico Sintase Tipo III , Estresse Oxidativo , Ratos Endogâmicos SHR , Transdução de Sinais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Estresse Oxidativo/efeitos dos fármacos , Animais , Humanos , Ratos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Antraquinonas/farmacologia , Senescência Celular/efeitos dos fármacos , Anti-Hipertensivos/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Hipertensão/metabolismo , Hipertensão/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Pressão Sanguínea/efeitos dos fármacos , Ratos Endogâmicos WKYRESUMO
Purpose of current study was to determine physicochemical, triglyceride composition, and functional groups of wild adlay accessions (brown, black, yellow, grey, green, off white, and purple) to find out its scope as cereal crop. Triglycerides, minerals and functional groups were determined through Gas chromatography, spectrophotometer and Fourier Transform Infrared (FTIR) spectrophotometer respectively. Results revealed variation among bulk densities, specific densities, percent empty spaces, and corresponding grain counts per 10 g of sample are useful in distinguishing brown, black, yellow, grey, green, off white, and purple wild adlay accessions. Specific density and grain count per 10 g sample was significantly related. No statistical relationship exists among the pronounced physical characteristics. Brown adlay expressed the highest protein, fat, and fiber contents 15.82%, 4.76% and 2.37% respectively. Protein, fat, ash, and fiber percent contents were found comparable to cultivated adlay. Spectrophotometric analysis revealed macro elements including phosphorus, potassium, calcium, and sodium in the range 0.3% - 2.2% and micro elements boron, iron, copper, zinc, and manganese in the range 1.6 mg/kg - 20.8 mg/kg. Gas chromatography showed polyunsaturated fatty acids (PUFA) constitute the primary fraction (39% ± 7.2) of wild adlay triglycerides. Linoleic and palmitic acids were present as prominent fatty acids, 43.5% ±1.4 and 26.3% ±1.4 respectively. Infra-red frequencies distinguished functional groups in narrow band and fingerprint region of protein in association with out of plane region leading to structural differences among adlay accessions. Comparison of major distinguishing vibrational frequencies among different flours indicated black adlay containing highest functional groups appeared promising for varietal development.
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BACKGROUND: The rate of germination and other physiological characteristics of seeds that are germinating are impacted by deep sowing. Based on the results of earlier studies, conclusions were drawn that deep sowing altered the physio-biochemical and agronomic characteristics of wheat (Triticum aestivum L.). RESULTS: In this study, seeds of wheat were sown at 2 (control) and 6 cm depth and the impact of exogenously applied salicylic acid and tocopherol (Vitamin-E) on its physio-biochemical and agronomic features was assessed. As a result, seeds grown at 2 cm depth witnessed an increase in mean germination time, germination percentage, germination rate index, germination energy, and seed vigor index. In contrast, 6 cm deep sowing resulted in negatively affecting all the aforementioned agronomic characteristics. In addition, deep planting led to a rise in MDA, glutathione reductase, and antioxidants enzymes including APX, POD, and SOD concentration. Moreover, the concentration of chlorophyll a, b, carotenoids, proline, protein, sugar, hydrogen peroxide, and agronomic attributes was boosted significantly with exogenously applied salicylic acid and tocopherol under deep sowing stress. CONCLUSIONS: The results of the study showed that the depth of seed sowing has an impact on agronomic and physio-biochemical characteristics and that the negative effects of deep sowing stress can be reduced by applying salicylic acid and tocopherol to the leaves.
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Germinação , Ácido Salicílico , Tocoferóis , Triticum , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Triticum/efeitos dos fármacos , Ácido Salicílico/farmacologia , Ácido Salicílico/metabolismo , Tocoferóis/metabolismo , Germinação/efeitos dos fármacos , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Antioxidantes/metabolismo , Estresse Fisiológico , Desenvolvimento Sustentável , Clorofila/metabolismoRESUMO
Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.
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Insuficiência Cardíaca , Inibidores de Hidroximetilglutaril-CoA Redutases , MicroRNAs , Animais , Masculino , Camundongos , Células Endoteliais/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , MicroRNAs/metabolismo , RNA Circular/genética , Volume Sistólico/fisiologiaRESUMO
BACKGROUND: In this study, we investigated the protective effects of alizarin (AZ) on endothelial dysfunction (ED). AZ has inhibition of the type 2 diabetes mellitus (T2DM)-induced synthesis of thrombospondin 1 (THBS1). Adenosine 5'-monophosphate- activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. PURPOSE: The aim of this study was to investigate the ameliorative effect of AZ on vascular injury caused by T2DM and to reveal the potential mechanism of AZ in high glucose (HG)-stimulated human umbilical vein endothelial cells (HUVECs) and diabetic model rats. STUDY DESIGN: HUVECs, rats and AMPK-/- transgenic mice were used to investigate the mitigating effects of AZ on vascular endothelial dysfunction caused by T2DM and its in vitro and in vivo molecular mechanisms. METHODS: In type 2 diabetes mellitus rats and HUVECs, the inhibitory effect of alizarin on THBS1 synthesis was verified by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB) so that increase endothelial nitric oxide synthase (eNOS) content in vitro and in vivo. In addition, we verified protein interactions with immunoprecipitation (IP). To probe the mechanism, we also performed AMPKα2 transfection. AMPK's pivotal role in AZ-mediated prevention against T2DM-induced vascular endothelial dysfunction was tested using AMPKα2-/- mice. RESULTS: We first demonstrated that THBS1 and AMPK are targets of AZ. In T2DM, THBS1 was robustly induced by high glucose and inhibited by AZ. Furthermore, AZ activates the AMPK signaling pathway, and recoupled eNOS in stressed endothelial cells which plays a protective role in vascular endothelial dysfunction. CONCLUSIONS: The main finding of this study is that AZ can play a role in different pathways of vascular injury due to T2DM. Mechanistically, alizarin inhibits the increase in THBS1 protein synthesis after high glucose induction and activates AMPKα2, which increases NO release from eNOS, which is essential in the prevention of vascular endothelial dysfunction caused by T2DM.
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Proteínas Quinases Ativadas por AMP , Antraquinonas , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Células Endoteliais da Veia Umbilical Humana , Óxido Nítrico Sintase Tipo III , Transdução de Sinais , Trombospondina 1 , Animais , Humanos , Antraquinonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Trombospondina 1/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Masculino , Ratos , Camundongos , Ratos Sprague-Dawley , Endotélio Vascular/efeitos dos fármacos , Glucose/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Background: The long-term survival of kidney transplants is often influenced by various factors, among which renal allograft rejection is the most notable factor. A noninvasive and reliable imaging biomarker correlating with kidney function and histopathology would facilitate longitudinal long-term follow-up of renal allografts. The aim of the study is to investigate the value of arterial spin labeling (ASL) combined with T1 mapping for assessing kidney function in patients with long-term renal transplant survival, and to establish radiological and histopathologic correlations between the magnetic resonance imaging (MRI) measurements and kidney allograft biopsy findings. Methods: Kidney transplant recipients who were admitted to the Department of Urology in First Affiliated Hospital of Soochow University between January and December 2022 were prospectively consecutively recruited [group A, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; group B, 30≤ eGFR <60 mL/min/1.73 m2; group C, eGFR <30 mL/min/1.73 m2], and part of them underwent biopsies. All patients underwent ASL and T1 mapping. MRI parameters were calculated and analyzed. Results: A total of 63 patients (Group A, 30 cases; Group B, 20 cases; and Group C, 13 cases) were included in this cross-sectional study. Cortical T1 increased, whereas renal blood flow (RBF) and ΔT1 [100% × (cortical T1 - medullary T1)/cortical T1] decreased with the decrease of eGFR. The RBF, cortical T1, and ΔT1 values were moderately correlated with eGFR (r=0.569, -0.573, and 0.672, respectively). The MRI parameters were moderately correlated with Banff scores, which determined renal allograft rejection and chronicity. The area under the curve (AUC) for the discrimination of groups A versus B and groups A versus C were 0.740 [95% confidence interval (CI): 0.597-0.854, P=0.004] and 0.923 (95% CI: 0.800-0.982, P<0.001), respectively, using ASL; 0.873 (95% CI: 0.749-0.950, P<0.001) and 0.926 (95% CI: 0.803-0.983, P<0.001), respectively, using T1 mapping; and 0.892 (95% CI: 0.771-0.962, P<0.001) and 0.956 (95% CI: 0.846-0.995, P<0.001), respectively, using multi-parameter MRI. The AUC for discrimination between groups B and C was 0.729 (95% CI: 0.546-0.868, P=0.02) using ASL. Conclusions: The RBF, cortical T1, and ΔT1 can serve as new imaging biomarkers of kidney function and histopathological microstructure.
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Sphaerophysa salsula (Pall.) DC., also known as Yang Liao Pao, belongs to the Leguminosae family and is the only existing species in the Sphaerophysa genus. S. salsula is tolerance to cold, high salt, and alkaline soil, it is widely cultivated in China as a forage crop, and used as a Chinese folk medicine to treat hypertension (Ma et al., 2002). In 2023, signs and symptoms similar to powdery mildew were found on S. salsula planted in Tumd left (40.515°N, 110.424°E), Baotou City, Inner Mongolia Autonomous Region, China. The white powdery substance covered 90% of the leaf area, and the infected plants showed weak growth and senescence. More than 80% of plants (n=200) had these powdery mildew-like symptoms. Hyphal appressoria are solitary, conidiophores have few branches and septa. Conidia are cylindrical to clavate, 25-32 µm long and 8-15 µm wide (n=30), conidia form single subapical germ tubes, straight to curved-sinuous, with swollen apex or distinctly lobed conidial appressorium. Based on these morphological characteristics, the fungus was tentatively identified as an Erysiphe sp. (Schmidt and Braun 2020). Fungal structures were isolated from diseased leaves, and genomic DNA of the pathogen was extracted using the method described by Zhu et al. (2022). The internal transcribed spacer (ITS) region was amplified by PCR using the primers PMITS1/PMITS2 (Cunnington et al. 2003) and the amplicon sequenced by Invitrogen (Shanghai, China). The powdery mildew strain, named as KMD (GenBank accession no.: PP267067), showed an identity of 100% (645/645bp) with Erysiphe astragali, a powdery mildew reported on Astragalus glycyphyllos in Golestan, Iran (GenBank: OP806834) and identity of 99.6% (643/645bp) with Erysiphe astragali (GenBank: MW142495), a powdery mildew reported on A. scaberrimus in Inner Mongolia, China (Sun et al. 2023). Pathogenicity tests were conducted by brushing the conidia from infected S. salsula leaves onto leaves of four healthy plants, while four control plants were brushed in the same manner. All the treated plants were placed in separate growth chambers maintained at 19°C and 65% humidity, with a 16 h light/8 h dark photoperiod. Nine days after inoculation, the treated plants showed powdery mildew symptoms, while the control plants remained asymptomatic. The same results were obtained for two repeated pathogenicity experiments. The powdery mildew fungus was reisolated and identified as E. astragali based on morphological and molecular analysis, thereby fulfilling Koch's postulates. No report on the occurrence of powdery mildew on S. salsula plants has been found previously. The occurrence of this destructive powdery mildew may adversely affect the cultivation of S. salsula. Identifying the pathogen of powdery mildew will support future efforts to control and manage powdery mildew on S. salsula.
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BACKGROUND: Cardiac involvement in patients with immunoglubin light-chain amyloidosis (AL) is a major determinant of treatment choice and prognosis, and early identification of high-risk patients can initiate intensive treatment strategies to achieve better survival. This study aimed to investigate the prognostic value of native T1 and ECV in patients with AL-cardiac amyloidosis (CA). METHODS: A total of 38 patients (mean age 59 ± 11 years) with AL diagnosed histopathologically from July 2017 to October 2021 were collected consecutively. All patients were performed 3.0-T cardiac magnetic resonance (CMR) including cine, T1 mapping, and late gadolinium enhancement (LGE). Pre- and post-contrast T1 mapping images were transferred to a dedicated research software package (CVI42 v5.11.3) to create parametric T1 and ECV values. In addition, clinical and laboratory data of all patients were collected, and patients or their family members were regularly followed up by telephone every 3 months. The starting point of follow-up was the time of definitive pathological diagnosis, and the main endpoint was all-cause death. Kaplan-Meier analysis and Cox proportional risk model were used to evaluate the association between native T1 and ECV and death in patients with CA. RESULTS: After a median follow-up of 27 (16, 37) months, 12 patients with CA died. Kaplan-Meier analysis showed that elevated native T1 and ECV were closely associated with poor prognosis in patients with CA. The survival rate of patients with ECV > 44% and native T1 > 1389ms were significantly lower than that of patients with ECV ≤ 44% and native T1 ≤ 1389ms (Log-rank P < 0.001), and was not associated with the presence of LGE. After adjusting for clinical risk factors and CMR measurements in a stepwise multivariate Cox regression model, ECV [risk ratio (HR):1.37, 95%CI: 1.09-1.73, P = 0.008] and native T1 (HR:1.01, 95%CI: 1.00-1.02, P = 0.037) remained independent predictors of all-cause mortality in patients with CA. CONCLUSIONS: Both native T1 and ECV were independently prognostic for mortality in patients with CA, and can be used as important indicators for clinical prognosis assessment of AL.
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Amiloidose , Miocárdio , Humanos , Pessoa de Meia-Idade , Idoso , Prognóstico , Miocárdio/patologia , Meios de Contraste , Gadolínio , Amiloidose/patologia , Valor Preditivo dos Testes , Imagem Cinética por Ressonância MagnéticaRESUMO
Objective: Temporal lobe epilepsy (TLE) predominantly originates from the anteromedial basal region of the temporal lobe, and its prognosis is generally favorable following surgical intervention. However, TLE often appears negative in magnetic resonance imaging (MRI), making it difficult to quantitatively diagnose the condition solely based on clinical symptoms. There is a pressing need for a quantitative, automated method for detecting TLE. Methods: This study employed MRI scans and clinical data from 51 retrospective epilepsy cases, dividing them into two groups: 34 patients in TLE group and 17 patients in non-TLE group. The criteria for defining the TLE group were successful surgical removal of the epileptogenic zone in the temporal lobe and a favorable postoperative prognosis. A standard procedure was used for normalization, brain extraction, tissue segmentation, regional brain partitioning, and cortical reconstruction of T1 structural MRI images. Morphometric features such as gray matter volume, cortical thickness, and surface area were extracted from a total of 20 temporal lobe regions in both hemispheres. Support vector machine (SVM), extreme learning machine (ELM), and cmcRVFL+ classifiers were employed for model training and validated using 10-fold cross-validation. Results: The results demonstrated that employing ELM classifiers in conjunction with specific temporal lobe gray matter volume features led to a better identification of TLE. The classification accuracy was 92.79%, with an area under the curve (AUC) value of 0.8019. Conclusion: The method proposed in this study can significantly assist in the preoperative identification of TLE patients. By employing this method, TLE can be included in surgical criteria, which could alleviate patient symptoms and improve prognosis, thereby bearing substantial clinical significance.
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As a special type of branched polymers, comb-like polymers simultaneously possess the structural characteristics of a linear backbone profile and crowded sidechain branches/grafts, and such structural uniqueness leads to reduced interchain entanglement, enhanced molecular orientation, and unique stimulus-response behavior, which greatly expands the potential applications in the fields of super-soft elastomers, molecular sensors, lubricants, photonic crystals, etc. In principle, all these molecular features can be traced back to three structural parameters, i.e., the degree of polymerization of the backbone (Nb), the degree of polymerization of the graft sidechain (Ng), and the grafting density (σ). Consequently, it is of great importance to understand the correlation mechanism between the structural characteristics and physicochemical properties, among which, the conformational properties in dilute solution have received the most attention due to its central position in polymer science. In the past decades, the development of synthetic chemistry and characterization techniques has greatly stimulated the progress of this field, and a number of experiments have been executed to verify the conformational properties; however, due to the complexity of the structural parameters and the diversity of the chemical design, the achieved experimental progress displays significant controversies compared with the theoretical predictions. This review aims to provide a full picture of recent research progress on this topic, specifically, (1) first, a few classical theoretical models regarding the chain conformation are introduced, and the quasi-two-parameter (QTP) theory for the conformation analysis is highlighted; (2) second, the research progress of the static conformation of comb-like polymers in dilute solution is discussed; (3) third, the research progress of the dynamic conformation in dilute solution is further discussed. The key issues, existing controversies and future research directions are also highlighted. We hope that this review can provide insightful information for the understanding of the conformational properties of comb-like polymers, open a new door for the regulation of conformational behavior in related applications, and promote related theoretical and experimental research in the community.
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In recent years, accumulating evidence has demonstrated the role of long noncoding RNAs (lncRNAs) in colon cancer. We aim to investigate the role of MIR143HG, also known as CARMN (Cardiac mesoderm enhancer-associated noncoding RNA) in colon cancer and explore the related mechanisms. An RNAseq data analysis was performed to screen differentially expressed lncRNAs associated with colon cancer. Next, MIR143HG expression was quantified in colon cancer cells. Moreover, the contributory roles of MIR143HG in the progression of colon cancer with the involvement of DNMT1 and HOXB7 (Homeobox B7) were evaluated after restored MIR143HG or depleted HOXB7. Finally, the effects of MIR143HG were investigated in vivo by measuring tumor formation in nude mice. High-throughput transcriptome sequencing was employed to validate the specific mechanisms by which MIR143HG and HOXB7 affect tumor growth in vivo. MIR143HG was found to be poorly expressed, while HOXB7 was highly expressed in colon cancer. MIR143HG could promote HOXB7 methylation by recruiting DNMT1 to reduce HOXB7 expression. Upregulation of MIR143HG or downregulation of HOXB7 inhibited cell proliferation, invasion and migration and facilitated apoptosis in colon cancer cells so as to delay the progression of colon cancer. The same trend was identified in vivo. Our study provides evidence that restoration of MIR143HG suppressed the progression of colon cancer via downregulation of HOXB7 through DNMT1-mediated HOXB7 promoter methylation. Thus, MIR143HG may be a potential candidate for the treatment of colon cancer.
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Neoplasias do Colo , DNA (Citosina-5-)-Metiltransferase 1 , Proteínas de Homeodomínio , RNA Longo não Codificante , Animais , Camundongos , Neoplasias do Colo/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Proteínas de Homeodomínio/genética , Metilação , Metiltransferases , Camundongos Nus , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Fatores de Transcrição , HumanosRESUMO
BACKGROUND: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. PURPOSE: To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. STUDY TYPE: Prospective. POPULATION: Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). FIELD STRENGTH/SEQUENCE: 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm2 ). ASSESSMENT: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. STATISTICAL TESTING: Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant. RESULTS: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408). DATA CONCLUSION: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.
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BACKGROUND: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. PURPOSE: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). STUDY TYPE: Prospective. SUBJECTS: Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). FIELD STRENGTH/SEQUENCE: 1.5 T/T2-weighted imaging and DTI. ASSESSMENT: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. STATISTICAL TEST: One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. RESULTS: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 µmol/L vs. 82.3 ± 20.9 µmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DATA CONCLUSION: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Background: White matter hyperintensity (WMH) is often described in acute lacunar stroke (ALS) patients. However, the specific relationship between regional WMH volume and persistent cognitive impairment remains unclear. Methods: We enrolled patients with ALS who were hospitalized at the First Affiliated Hospital of Soochow University between January 2020 and November 2022. All patients were assessed for global cognitive function using the Montreal Cognitive Assessment (MoCA) scale at 14 ± 2 days and 6 months after the onset of ALS. Manifestations of chronic cerebral small vessel disease (CSVD) were assessed via MRI scan. The distributions of regional WMH were segmented, and their relationship with cognitive impairment was evaluated. Results: A total of 129 patients were enrolled. Baseline frontal WMH volume (OR = 1.18, P = 0.04) was an independent risk factor for long-term cognitive impairment after ALS. Furthermore, the presence of WMH at the genu of the corpus callosum (GCC) at baseline (OR = 3.1, P = 0.033) was strongly associated with persistent cognitive decline. Multivariable logistic regression analysis showed that depression (OR = 6.252, P = 0.029), NIHSS score (OR = 1.24, P = 0.011), and albumin at admission (OR = 0.841, P = 0.032) were also important determinants of long-term cognitive impairment after ALS. Conclusions: Our study found that WMH, especially frontal WMH volume and the presence of WMH at the GCC at baseline, independently contributed to long-term cognitive decline in ALS patients. This study provides new evidence of the clinical relationship between regional WMH volume and cognitive impairment in ALS patients.
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The yield and quality of wheat (Triticum aestivum L.) is seriously affected by soil cadmium (Cd), a hazardous material to plant and human health. Long non-coding RNAs (lncRNAs) of plants are shown actively involved in response to various biotic and abiotic stresses by mediating the gene regulatory networks. However, the functions of lncRNAs in wheat against Cd stress are still obscure. Using deep strand-specific RNA sequencing, 10,044 confident novel lncRNAs in wheat roots response to Cd stress were identified. It was found that 69 lncRNA-target pairs referred to cis-acting regulation and impacted the expressions of their neighboring genes involving in Cd transport and detoxification, photosynthesis, and antioxidant defense. These findings were positively corelated with the physio-biochemical results, i.e. Cd stress affected Cd accumulation, photosynthesis system and ROS in wheat. Overexpression of lncRNA37228 (targeted to a photosystem II protein D1 coding gene), resulted in enhancing Arabidopsis thaliana resistance against Cd stress. By genome-wide identification and characterization, the possible functions of photosystem II protein gene family in wheat under Cd condition were illustrated. Our findings provide novel knowledge into the molecular mechanisms of lncRNAs-regulated wheat tolerance to Cd toxicity and lay foundations for the further studies concerning lncRNAs in food safety production.
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In this work, the adsorption kinetics of the PBAN/AAO system under flushing condition has been investigated, where PBAN and AAO represent poly(benzyl acrylate) and anodic alumina oxide (AAO, average pore radius R0 ≈ 10 nm) nanochannel, respectively. Our specially designed double-pump flushing system is proved to eliminate the overshoot phenomenon and in situ monitor transmembrane pressure (ΔP) as a function of flushing time (t) and flow rate (Q), which gives the effective pore radius (R), cross-sectional coverage factor (χ = [1 - (R/R0)2]), and characteristic ratio (rc) of the increments of χ during each adsorption/desorption cycle at a given bulk solution concentration (Cbulk). Our findings include: (1) by gradient increasing Cbulk from 10 to 200 mg/L at Q = 10 mL/h, the shortest PBA40 displays a saturation adsorption behavior when Cbulk ≥ 80 mg/L and t ≥ 2000 s, which agrees well with the prediction of blob model, whereas for the longer PBAN chains, the chain length (N) and concentration-dependent adsorption tendency get stronger as N increases from 40 to 620 at t ≥ 2000 s, in particular, R/R0 â¼ N-0.20 is observed at Cbulk = 140 mg/L; (2) by focusing on the platform χ in the saturation adsorption regime (χsat), the longer PBAN displays a stronger adsorption trend with partially reversible feature at Q = 5.0 mL/h, namely, as N increases from 40 to 620, χsat increases from 0.15 to 0.83 at Cbulk = 100 mg/L, where rc changes from 0.25 ± 0.10 to 0.80 ± 0.10 as the adsorption/desorption flushing cycle increases from 1 to 8 at Cbulk = 100 mg/L; (3) by further assuming a solvent nonpenetrating and nondraining adsorption layer, χsat determined in the case of curved surface can be comparable to the physical meaning of adsorption thickness (Δad) in the case of flat-surface adsorption, and the fitting result indicates χsat â¼ Δad â¼ N0.58, falling between Δad â¼ N1/2 and Δad â¼ N1.0 predicted by the mean-field and scaling theories for real multichain adsorption, respectively. Overall, the present work not only clarifies some controversies but also provides unambiguous evidence supporting the existence of tightly adsorbed internal and loosely adsorbed external layers.
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Vascular dementia (VD) is one of the most common causes of dementia, taking account for about 20% of all cases. Although studies have found that selenium supplementation can improve the cognitive ability of Alzheimer's patients, there is currently no research on the cognitive impairment caused by VD. This study aimed to investigate the role and mechanism of Amorphous selenium nanodots (A SeNDs) in the prevention of VD. The bilateral common carotid artery occlusion (BCCAO) method was used to establish a VD model. The neuroprotective effect of A SeNDs was evaluated by Morris water maze, Transcranial Doppler TCD, hematoxylin-eosin (HE) staining, Neuron-specific nuclear protein (Neu N) staining and Golgi staining. Detect the expression levels of oxidative stress and Calcium-calmodulin dependent protein kinase II (CaMK II), N-methyl-D-aspartate receptor subunit NR2A, and postsynaptic dense protein 95 (PSD95). Finally, measure the concentration of calcium ions in neuronal cells. The results showed that A SeNDs could significantly improve the learning and memory ability of VD rats, restore the posterior arterial blood flow of the brain, improve the neuronal morphology and dendritic remodeling of pyramidal cells in hippocampal CA1 area, reduce the level of oxidative stress in VD rats, increase the expression of NR2A, PSD95, CaMK II proteins and reduce intracellular calcium ion concentration, but the addition of selective NR2A antagonist NVP-AAMO77 eliminated these benefits. It suggests that A SeNDs may improve cognitive dysfunction in vascular dementia rats by regulating the NMDAR pathway.