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Purpose: This study aimed to compare the risk of vagal reflex during microsurgical subinguinal varicocelectomy (MSV) under general anesthesia (GA) with or without additional local anesthetic (LA) spermatic cord block (SCB). Method: A single-center randomized controlled trial was conducted between January 2022 and June 2023.300 patients with left-sided grade â ¢ varicocele were randomly divided into two groups: SCB group (n = 153) and control group (n = 147)ï¼computer-generated random numbers listï¼. During MSV under GA, the SCB group was given of ropivacaine for SCB before pulling the spermatic cord, while the control group was directly lifted. The primary outcome was the reduction in the lowest heart rate in the SCB group as compared with the control group during spermatic cord traction (SCT). Secondary outcomes included the reduction in the lowest blood pressure in the SCB group as compared with the control group; and the reductions in the lowest heart rate and lowest blood pressure as compared with baseline during SCT. The number of times that surgery and medications were suspended because of symptomatic reflex bradycardia was also recorded. Adverse events were also recorded as secondary outcomes. Result: Five patients in the SCB group and 10 patients in the CG were excluded. The lowest heart rate and systolic blood pressure during SCT in the SCB group and the control group were significantly lower than the baseline values (P < 0.05). However, the decrease in the SCB group (70-73bpm VS 108-115 mmHg) was milder than that of the control groupï¼66-72 bpm VS 105-114 mmHgï¼(P < 0.05). The number of surgeries and medication pauses due to symptomatic reflex bradycardia during surgery was significantly lower in the SCB group (2 VS 1) than in the control group (9 VS 7) (P < 0.05). Conclusion: SCB can effectively reduce the vagal reflex caused by pulling the spermatic cord during MSV, and reduce the risk of anesthesia and surgery.
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Fine-root architecture is critical feature reflecting root explorative and exploitative strategies for soil resources and soil space occupancy. Yet, studies on the variation of fine-root architecture across different species are scare and little work has been done to integrate the potential drivers on these variations along a biogeographical gradient in arid ecosystems. We measured root branching intensity, topological index, and root branching ratios as well as morphological traits (root diameter and length) in dry valley along a 1000 km latitudinal gradient. Influence of phylogeny, environmental factors on fine-root architecture and trade-offs among root traits were evaluated. With increasing latitude, the topological index and second to third root order branching ratio decreased, whereas first-to-second branching ratio increased. Root branching intensity was associated with short and thin fine roots, but has no significant latitudinal pattern. As a whole, soil microbial biomass was the most important driver in the variation of root branching intensity, and soil texture was the strongest predictor of topological index. Additionally, mean annual temperature was an important factor influencing first-to-second branching ratio. Our results suggest variations in fine-root architectures were more dependent on environmental variables than phylogeny, signifying that fine-root architecture is sensitive to environmental variations.
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BACKGROUND: Atrial fibrillation (AF), the most common atrial arrhythmia, presents varied clinical manifestations. Despite the identification of genetic loci associated with AF, particularly in specific populations, research within Asian ethnicities remains limited. This study aimed to develop predictive models for AF using AF-associated single-nucleotide polymorphisms (SNPs) from a Genome-Wide Association Study (GWAS) on a substantial cohort of Taiwanese individuals, evaluating the models' predictive efficacy. METHODS: Involving 75,121 subjects, including 5,694 AF patients and 69,427 normal controls with GWAS data, the study merged polygenic risk scores (PRS) from AF-associated SNPs with Phenome-wide association study (PheWAS)-derived risk factors. Advanced statistical and machine learning techniques were employed to develop and evaluate AF predictive models for discrimination and calibration. RESULTS: The study identified the top 30 significant SNPs associated with AF, predominantly on chromosomes 10 and 16, implicating genes like NEURL1, SH3PXD2A, INA, NT5C2, STN1, and ZFHX3. Notably, INA, NT5C2, and STN1 were newly linked to AF. The GWAS predictive power using PRS-CS analysis for AF exhibited an area under the curve (AUC) of 0.600 (P < 0.001), improving to 0.855 (P < 0.001) after adjusting for age and gender. PheWAS analysis showed the top 10 diseases associated with these genes were circulatory system diseases. CONCLUSIONS: Integrating genetic and phenotypic data enhanced the accuracy and clinical relevance of AF predictive models. The findings suggest promise for refining AF risk assessment, enabling personalized interventions, and reducing AF-related morbidity and mortality burdens.
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Carbon/C3N heteronanotubes (CC3NNTs) have garnered significant interest for their distinctive performance and versatility across various applications. However, the understanding of interfacial heat transport within these heterostructures remains limited. This study aims to enrich the field by constructing models of CC3NNTs through the bonding of CNTs and C3NNTs, and employs nonequilibrium molecular dynamics (NEMD) simulations to predict their heat flux and thermal rectification (TR) effects. Placing the heat source in the CNT region induces a stronger heat flux compared to the C3NNT region, thus demonstrating a pronounced TR effect. This effect can be attributed to the mismatch in phonon spectra, as evidenced by the cumulative correlation factor derived from the phonon density of states (phonon DOS). Using this approach, we predict that the TR ratio for zigzag CC3NNTs (ZCC3NNT) significantly exceeds that of armchair CC3NNTs (ACC3NNT). Notably, in contrast to ACC3NNT, ZCC3NNT exhibits the phenomenon of negative differential thermal resistance in the backward heat flux with a temperature difference of Δ = 120 K. This phenomenon can be attributed to a lower phonon participation ratio at Δ = 120 K compared to other values of Δ. Subsequently, given that ZCC3NNT demonstrates the most pronounced TR ratio at room temperature, we explored how stress-strain, system size, defect density, and interface position impact the TR ratio. These insights are invaluable for guiding the design of thermal rectifiers, smart thermal management systems, and microelectronic processor coolers.
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The efficiency of foam drainage gas recovery is predominantly dictated by the performance of the foaming agent. To better understand their behavior, a novel testing apparatus was developed to simulate the foam drainage gas recovery process within the wellbore. Through the dynamic liquid-carrying performance tests of four foaming agents under uniform conditions, it was discerned that there existed significant disparities in the liquid-carrying performance and action duration. Further interface performance analysis disclosed that the liquid-carrying capacity and the duration were correlated with their adsorption capacity and interface activity at the gas-liquid interface. Notably, foaming agents with lower adsorption capacity and higher interfacial activity demonstrated superior liquid-carrying performance and longer action duration. By analyzing the consumption of foaming agents during the liquid-carrying process, five dynamic liquid-carrying equations were derived based on first-order reaction kinetics, the Malthusian population model, and the logistic function. The outcomes demonstrated that all these five equations could precisely delineate the dynamic liquid-carrying process of the foaming agent. During the research, we found that the consumption of the foaming agent in the foam drainage gas recovery process is related to its adsorption behavior at the gas-liquid interface, and revealed that the dynamic liquid-carrying process of foaming agent is the increasing process of liquid-carrying capacity under the continuous consumption of limited foaming agent resources. This laid a foundation for the further exploration of the functional mechanism of the foaming agent in the foam drainage gas recovery process.
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Macrocyclic conformations play a crucial role in regulating their properties. Our understanding of the determinants to control macrocyclic conformation interconversion is still in its infancy. Here we present a macrocycle, octamethyl cyclo[4](1,3-(4,6)-dimethylbenzene)[4]((4,6-benzene)(1,3-dicarboxylate) (OC-4), that can exist at 298 K as two stable atropisomers with C2v and C4v symmetry denoted as C2v-OC-4 and C4v-OC-4, respectively. Heating induces the efficient stepwise conversion of C2v- to C4v-OC-4 via a Cs-symmetric intermediate (Cs-OC-4). It differs from the typical transition state-mediated processes of simple C-C single bond rotations. Hydrolysis and further esterification with a countercation dependence promote the generation of C2v- and Cs-OC-4 from C4v-OC-4. In contrast to C2v-OC-4, C4v-OC-4 can bind linear guests to form pseudo-rotaxans, or bind C60 or C70 efficiently. The present study highlights the differences in recognition behavior that can result from conformational interconversion, as well as providing insights into the basic parameters that govern coupled molecular rotations.
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Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium-activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type-specific TMEM16F-deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell-expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism.
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Fine roots and absorptive roots play key roles in acquiring resources throughout soil profiles and determining plant functions along environmental gradients. Yet, the geographical pattern of carbon allocation in fine roots, particularly in absorptive roots, and their relations with plant sizes and evironment are less understood. We sampled 243 xerophytic shrubs from 63 species distributed along the latitudinal gradient (23°N to 32°N) in dry valleys of southwest China and synthetically measured biomass fractions of plant organs, especially fine roots and absorptive roots (1st to 3rd root order). We identified latitudinal patterns of biomass allocation fractions of organs and their relationships with plant sizes and environmental factors. The latitudinal patterns of both absorptive root and fine-root fractions followed weak unimodal distributions; stem biomass fraction increased with the latitude, while the leaf biomass fraction decreased. The fraction of fine-root biomass had negative relationships with plant height and root depth. The fractions of root, fine root, and absorptive root biomass were largely explained by soil moisture. Furthermore, fraction of fine-root biomass increased in a relatively humid environment. Overall, soil moisture was the most important factor in driving latitudinal patterns of biomass fraction. Our study highlighted that functional redistribution of root system biomass was the critical adaptive strategy along a latitudinal gradient.
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Cancer remains a major cause of mortality worldwide, and urological cancers are the most common cancers among men. Several therapeutic agents have been used to treat urological cancer, leading to improved survival for patients. However, this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medications. Here, we propose the novel discipline of uro-cardio-oncology, an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological cancer. In this comprehensive review, we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers, including androgen deprivation therapy, vascular endothelial growth factor receptor tyrosine kinase inhibitors, immune checkpoint inhibitors, and chemotherapeutics. In addition, we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance, diagnosis, and effective management of cardiovascular complications. Finally, we provide an analysis of future perspectives in this emerging specialty, identifying areas in need of further research.
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The neuroimaging mechanisms underlying differences in the outcomes of sound therapy for tinnitus patients remain unclear. We hypothesize that abnormal hierarchical architecture is the neuro-biomarker for treatment outcome explanation. We conducted functional connectome gradient analyses on resting-state functional MRI images that acquired before intervention to investigate differences among the patients with effective treatment (ET, n = 27), ineffective treatment (IT, n = 41), and healthy controls (HC, n = 59). General linear models were used to analyze the associations between intergroup differential regions and clinical characteristics. Partial least squares regression was employed to reveal correlations with gene expression. Compared to HC, both ET and IT groups displayed significant differences in the default mode network. Moreover, the ET group exhibited wider gradient range and greater gradient variance. Also, the gradient scores of the differential regions between the ET and HC groups were significantly correlated with Self-rating Anxiety Scale and Self-rating Depression Scale scores, and exhibited positive correlations with the transcriptional profiles of genes related to depression and anxiety. Our results indicated that the abnormalities of ET group, may be more relevant to psychiatric disorders, bringing a higher possible therapeutic potential due to the plasticity of the nervous system. Connectome gradient dysfunction with genetic evidence may serve as an indicator for identifying diverse treatment outcomes of the sound therapy for tinnitus patients before treatment.
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Encéphale , Connectome , Imagerie par résonance magnétique , Acouphène , Humains , Acouphène/physiopathologie , Acouphène/thérapie , Femelle , Mâle , Adulte , Résultat thérapeutique , Adulte d'âge moyen , Encéphale/imagerie diagnostique , Encéphale/physiopathologie , Réseau nerveux/imagerie diagnostique , Réseau nerveux/physiopathologie , Expression des gènesRÉSUMÉ
Nanotechnology has revolutionized the diagnosis, monitoring and treatment of biomedical diseases, in which nanocarriers have greatly improved the targeting and bioavailability of antitumor drugs. The marine natural polysaccharides fucoidan, chitosan, alginate, carrageenan and porphyran have broad-spectrum bioactivities and unique physicochemical properties such as excellent non-toxicity, biocompatibility, biodegradability and reproducibility, which have placed them as a principal focus in the nanocarrier field. Nanocarriers based on different types of marine polysaccharides are distinctive in addressing antitumor therapeutic challenges such as targeting, environmental responsiveness, drug resistance, tissue toxicity, enhancing diagnostic imaging, overcoming the first-pass effect and innovative 3D binding. Additionally, they all share the possibility of relatively easy chemical modification, while their separation into well-defined derivatives provide innovative structure-activity relationship possibilities. Liposomes, nanoparticles and polymer-micelles constructed from them can efficiently deliver drugs such as paclitaxel, gemcitabine, siRNA and others, which are widely used in radiotherapy, chemotherapy, immunotherapy, nucleic acid therapy and photothermal therapy, yet there are still infinite possibilities for innovation and exploration. This article reviews the recent advances and challenges of marine polysaccharide-based delivery systems as oncology drug nanocarriers.
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Antinéoplasiques , Vecteurs de médicaments , Nanoparticules , Polyosides , Polyosides/composition chimique , Polyosides/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Vecteurs de médicaments/composition chimique , Humains , Nanoparticules/composition chimique , Animaux , Organismes aquatiques/composition chimique , Alginates/composition chimique , Chitosane/composition chimique , Tumeurs/traitement médicamenteux , Liposomes/composition chimique , Micelles , Carragénane/composition chimiqueRÉSUMÉ
The weak van der Waals interactions in the out-of-plane direction result in markedly low thermal conductivity in one-dimensional (1D) and two-dimensional (2D) materials, which substantially restricts their applications. Developing three-dimensional (3D) columnar hybrid structures, featuring high thermal conductivity both within and beyond the plane, effectively addresses this challenge. This study investigated a 3D hybrid structure composed of graphene and boron nitride nanotubes (GR-BNNTs) using non-equilibrium molecular dynamics simulations. This approach allowed the examination of the formation mechanisms and key factors influencing thermal rectification (TR) in these materials. Our findings reveal a novel mechanism for independently regulating forward and backward heat fluxes in GR-BNNTs. By manipulating the thermal properties of the BNNTs and the graphene layer, the TR ratio can be controlled flexibly. Additionally, we identify specific strategies for independently adjusting the heat flux, such as altering the intercolumn distance of BNNTs, which impacts the backward flux merely, while applying strain to affect the forward flux merely. This research introduces a novel concept of independent regulation of forward and backward heat fluxes, providing significant insights into phonon thermal transport in 3D hybrid structures.
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Background: Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US. Patients and Methods: This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018-2021). A clinical trial-like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan-Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort. Results: The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6-9.0) months and 16.4 (13.3-21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8-29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age <60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status <3-4 (HR range, 0.13-0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without. Conclusion: These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.
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BACKGROUND: Diabetes damages the seminal vesicle tissues leading to a decrease in seminal fluid secretion, so investigations are ongoing to identify specific therapeutic approaches to address diabetes-induced damage to seminal vesicles. OBJECTIVE: This study investigated the secretory dysfunction of seminal vesicles and how curcumin can ameliorate this dysfunction. MATERIALS AND METHODS: First, 40 diabetic males (DM group) and 40 nondiabetic males (control group) underwent seminal vesicle ultrasound evaluation and ejaculate volume measurements. Then, the effects of curcumin on seminal vesicle function were investigated in a diabetic rat model. Fifty 8-week-old SPF-grade SD rats were categorized into five groups: control, DM (diabetes mellitus), low-dose CUR (curcumin 50 mg/kg/d), medium-dose CUR (curcumin 100 mg/kg/d), and high-dose CUR (curcumin 150 mg/kg/d). After a month-long diet with varying curcumin doses, key parameters such as body weight, blood glucose levels, seminal vesicle volume, and seminal fluid secretion were measured. Transcriptome sequencing was performed to assess differences in gene expression and structural changes in rat seminal vesicle tissues were examined by HE staining. Finally, human seminal vesicle cell lines were cultured and divided into five groups (HG-CON, HG-CUR-5 µM, HG-CUR-10 µM, HG-CUR-20 µM, and HG-CUR-50 µM) to measure the fructose levels in the seminal vesicle cell culture fluids and evaluate the expression of CASP1, GSDMD, and TRPV6. Post TRPV6 interference, variations in the gene expression of CASP1, GSDMD, and TRPV6 were monitored. RESULTS: Diabetic patients exhibited a notable reduction in seminal vesicle volume and ejaculate volume compared with the control group, with a direct correlation between the decrease in ejaculate and seminal vesicle volume. Animal studies demonstrated that curcumin supplementation significantly augmented seminal vesicle volume in diabetic rats and notably improved their seminal vesicle secretory dysfunction, particularly in the high-dose curcumin group. Transcriptome sequencing and experimental verification pinpointed the differential expression of TPRV6 and pyroptosis-associated genes (CASP1, GSDMD), with reduced TRPV6 expression but increased markers of pyroptosis (CASP1 and GSDMD) in diabetic rats. Curcumin treatment reversed these effects with an increase in TRPV6 and a decrease in GSDMD and CASP1. Cell transfection experiments indicated that TRPV6 downregulation increased GSDMD and CASP1 gene expression. CONCLUSION: Curcumin effectively activates TRPV6, thereby diminishing pyroptosis in the seminal vesicle tissues of diabetic rats. This activation not only leads to an increase in the seminal vesicle volume but also significantly ameliorates the seminal vesicle secretory dysfunction in diabetic rats.
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One-dimensional van der Waals (vdWs) heterostructures are celebrated for their exceptional thermal management capabilities, garnering significant research interest. Consequently, our research focused on the one-dimensional vdWs heterojunction comprising carbon nanotube half-wrapped in boron nitride nanotube (BNCNT), specifically their thermal rectification (TR) properties. We employed non-equilibrium molecular dynamics to explore the TR mechanism and assess the impacts of temperature, strain, and coupling strength on heat flux and TR ratio. Our findings reveal that the backward heat flux demonstrates greater atomic vibration instability, as indicated by mean square displacement (MSD), compared to forward heat flux. This instability leads to a higher concentration of localized phonons, thereby diminishing the backward heat flux and enhancing TR. Additionally, we utilized MSD to shed light on the negative differential thermal resistance phenomenon and the influence of stress on forward and backward heat fluxes. Remarkably, TR ratios reached 344% at 3% strain and 400% at -1% strain. Calculations of phonon density of states revealed a competitive mechanism between in-plane and out-of-plane phonons coupling in the inner carbon nanotube and an overlap degree of out-of-plane phonon spectra between the inner carbon nanotube and outer boron nitride nanotube. This accounts for the differing trends in forward and backward heat fluxes as coupling strength χ increases, with TR ratios exceeding 1000% at χ = 7.5. This study provides vital insights for advancing one-dimensional vdWs thermal rectifiers.
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OBJECTIVE: Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. METHODS: Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. RESULTS: Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. CONCLUSION: Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.
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Leucémie aigüe myéloïde , microARN , ARN circulaire , Facteurs de transcription SOX-C , Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Apoptose/génétique , Lignée cellulaire tumorale , Prolifération cellulaire/génétique , Évolution de la maladie , Régulation de l'expression des gènes dans la leucémie , Leucémie aigüe myéloïde/génétique , Leucémie aigüe myéloïde/anatomopathologie , Leucémie aigüe myéloïde/métabolisme , microARN/génétique , Pronostic , ARN circulaire/génétique , Facteurs de transcription SOX-C/génétique , Facteurs de transcription SOX-C/métabolisme , Régulation positive/génétiqueRÉSUMÉ
Skin is the first barrier of body which stands guard for defending aggressive pathogens and environmental pressures all the time. Cutaneous metabolism changes in harmful exposure, following with skin dysfunctions and diseases. Lots of researches have reported that polysaccharides extracted from seaweeds exhibited multidimensional bioactivities in dealing with skin disorder. However, few literature systematically reviews them. The aim of the present paper is to summarize structure, bioactivities and structure-function relationship of algal polysaccharides acting on skin. Algal polysaccharides show antioxidant, immunomodulating, hydration regulating, anti-melanogenesis and extracellular matrix (ECM) regulating abilities via multipath ways in skin. These bioactivities are determined by various parameters, including seaweed species, molecular weight, monosaccharides composition and substitute groups. In addition, potential usages of algae-derived polysaccharides in skin care and therapy are also elaborated. Algal polysaccharides are potential ingredients in formulation that providing anti-aging efficacy for skin.
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Polyosides , Algue marine , Vieillissement de la peau , Polyosides/composition chimique , Polyosides/pharmacologie , Polyosides/usage thérapeutique , Vieillissement de la peau/effets des médicaments et des substances chimiques , Humains , Algue marine/composition chimique , Antioxydants/pharmacologie , Antioxydants/composition chimique , Antioxydants/usage thérapeutique , Animaux , Peau/effets des médicaments et des substances chimiques , Peau/métabolisme , Hygiène de la peau/méthodes , Relation structure-activitéRÉSUMÉ
Keratoconjunctivitis sicca (KCS) is an ocular condition characterized by insufficient tear production and inflammatory irritation, with Sjögren's syndrome (SS) being a major causative factor. This study aimed to extract patient transcriptomic data from the GEO database to identify signature genes associated with the diagnosis and treatment of KCS and the expression of three key genes were experimentally verified. We performed a difference analysis on the SS patient dataset and performed a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the resulting genes. Additionally, a Weighted Gene Co-expression Network Analysis (WGCNA) was constructed. Machine learning techniques were employed to analyze the most strongly correlated gene modules with SS traits. These findings were further validated using KCS immune-correlation microarrays as a validation set. The correlation of the three identified genes with 22 immune cells was assessed through immune infiltration analysis. Subsequently, a rat model of desiccated keratoconjunctivitis was established, and the modeling situation and expression of characteristic genes were analyzed at the morphological, tissue, and molecular levels. Bioinformatic prediction revealed that the expression of JAK1, SKI, ZBTB16 not only differed in the machine learning validation set, but also correlated with some immune cells in the immune infiltration analysis. The results of animal experiments showed that the transcription and expression levels of these three genes were significantly different in rat KCS tissues and normal tissues, and there were also differences in the expression of JAK1 and SKI in rat peripheral blood, as well as significant up-regulation of the expression of related inflammatory factors in KCS tissues. Through bioinformatics prediction and animal experimental validation, this study identified three differentially expressed genes in SS mediated KCS patients, which provide new potential biological targets for the diagnosis and treatment of KCS.
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Marqueurs biologiques , Janus kinase 1 , Kératoconjonctivite sèche , Janus kinase 1/génétique , Janus kinase 1/métabolisme , Animaux , Humains , Rats , Kératoconjonctivite sèche/génétique , Kératoconjonctivite sèche/métabolisme , Marqueurs biologiques/métabolisme , Syndrome de Gougerot-Sjögren/génétique , Protéines proto-oncogènes/génétique , Protéines proto-oncogènes/métabolisme , Réseaux de régulation génique , Inflammation/génétique , Mâle , Analyse de profil d'expression de gènes/méthodes , Femelle , Modèles animaux de maladie humaine , Transcriptome , Apprentissage machine , Biologie informatique/méthodesRÉSUMÉ
BACKGROUND: Preoperative differentiation of the types of mediastinal tumors is essential. Magnetic resonance (MR) elastography potentially provides a noninvasive method to assess the classification of mediastinal tumor subtypes. PURPOSE: To evaluate the use of MR elastography in anterior mediastinal masses and to characterize the mechanical properties of tumors of different subtypes. STUDY TYPE: Prospective. SUBJECTS: 189 patients with anterior mediastinal tumors (AMTs) confirmed by histopathology (62 thymomas, 53 thymic carcinomas, 57 lymphomas, and 17 germ cell tumors). FIELD STRENGTH/SEQUENCE: A gradient echo-based 2D MR elastography sequence and a diffusion-weighted imaging (DWI) sequence at 3.0 T. ASSESSMENT: Stiffness and apparent diffusion coefficients (ADC) were measured in AMTs using MR elastography-derived elastograms and DWI-derived ADC maps, respectively. The aim of this study is to identify whether MR elastography can differentiate between the histological subtypes of ATMs. STATISTICAL TESTS: One-way analysis of variance (ANOVA), two-way ANOVA, Pearson's linear correlation coefficient (r), receiver operating characteristic (ROC) curve analysis; P < 0.05 was considered significant. RESULTS: Lymphomas had significantly lower stiffness than other AMTs (4.0 ± 0.63 kPa vs. 4.8 ± 1.39 kPa). The mean stiffness of thymic carcinomas was significantly higher than that of other AMTs (5.6 ± 1.41 kPa vs. 4.2 ± 0.94 kPa). Using a cutoff value of 5.0 kPa, ROC analysis showed that lymphomas could be differentiated from other AMTs with an accuracy of 59%, sensitivity of 97%, and specificity of 38%. Using a cutoff value of 5.1 kPa, thymic carcinomas could be differentiated from other AMTs with an accuracy of 84%, sensitivity of 67%, and specificity of 90%. However, there was an overlap in the stiffness values of individual thymomas (4.2 ± 0.71; 3.9-4.5), thymic carcinomas (5.6 ± 1.41; 5.0-6.1), lymphomas (4.0 ± 0.63; 3.8-4.2), and germ cell tumors (4.5 ± 1.79; 3.3-5.6). DATA CONCLUSION: MR elastography-derived stiffness may be used to evaluate AMTs of various histologies. TECHNICAL EFFICACY: Stage 2.