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BACKGROUND: Social anxiety symptoms are common and harmful psychological illness in college students. Although some studies have illustrated that physical activity could reduce social anxiety symptoms, the specific mechanism is still unclear. Based on theoretical studies on resilience and sleep, this study constructed a serial mediation model to explore whether they mediate between physical activity and social anxiety symptoms among college students. METHODS: This study surveyed 9,530 college students from three colleges in China to explore the mediating effect of physical activity and sleep problems between physical activity and social anxiety symptoms. Participants were investigated with the International Physical Activity Questionnaire, Connor-Davidson Resilience Scale, Sleep-related problems, and the Social Interaction Anxiety Scale and the Social Phobia Scale. Correlations between variables were analysed using Pearson correlation analysis and mediation analyses were performed using SPSS PROCESS macro 3.3 software. RESULT: The study found that physical activity was negatively associated with social anxiety symptoms and sleep problems, but positively with psychological resilience. After controlling for sociodemographic variables, physical activity can not only indirectly alleviate social anxiety symptoms through the separate mediation of psychological resilience and sleep problems, but also through the serial mediation of psychological resilience and sleep problems. CONCLUSION: These results suggest that improving physical activity levels could reduce social anxiety scores by increasing psychological resilience and sleep quality. This is of great reference significance for the prevention and intervention of college students' mental health.
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Ansiedad , Ejercicio Físico , Resiliencia Psicológica , Trastornos del Sueño-Vigilia , Estudiantes , Humanos , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Masculino , Femenino , China , Adulto Joven , Universidades , Ejercicio Físico/psicología , Ansiedad/psicología , Ansiedad/epidemiología , Trastornos del Sueño-Vigilia/psicología , Adulto , Adolescente , Encuestas y CuestionariosRESUMEN
Given the critical necessity for the development of more potent anti-cancer drugs, a series of novel compounds incorporating trifluoromethyl groups within the privileged 2-anilinoquinoline scaffold was designed, synthesized, and subjected to biological evaluation through a pharmacophore hybridization strategy. Upon evaluating the in vitro anti-cancer characteristics of the target compounds, it became clear that compound 8b, which contains a (4-(piperazin-1-yl)phenyl)amino substitution at the 2-position of the quinoline skeleton, displayed superior efficacy against four cancer cell lines by inducing apoptosis and cell cycle arrest. Following research conducted in a PC3 xenograft mouse model, it was found that compound 8b exhibited significant anti-cancer efficacy while demonstrating minimal toxicity. Additionally, the analysis of a 217-kinase panel pinpointed SGK1 as a potential target for this compound class with anti-cancer capabilities. This finding was further verified through molecular docking analysis and cellular thermal shift assays. To conclude, our results emphasize that compound 8b can be used as a lead compound for the development of anti-cancer drugs that target SGK1.
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As a sirtuin (SIR2) family protein, defense-associated sirtuin2 (DSR2) has been demonstrated to participate in bacterial anti-phage resistance via depleting nicotinamide adenine dinucleotide (NAD+) of infected cells, which can be activated by tail tube protein (TTP) and inhibited by DSR anti-defense 1 (DSAD1) of diverse phages. However, the regulating mechanism remains elusive. Here, we determined the cryo-electron microscopy structure of apo DSR2, as well as the respective complex structures with TTP and DSAD1. Structural analyses and biochemical studies reveal that DSR2 forms a tetramer with a SIR2 central core and two distinct conformations. Monomeric TTP preferentially binds to the closed conformation of DSR2, inducing conformational distortions on SIR2 tetramer assembly to activate its NADase activity. DSAD1 combines with the open conformation of DSR2, directly or allosterically inhibiting TTP activation on DSR2 NAD+ hydrolysis. Our findings decipher the detailed molecule mechanisms for DSR2 NADase activity regulation and lay a foundation for in-depth understanding of the DSR2 anti-phage defense system.
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Bacteriófagos , Microscopía por Crioelectrón , Bacteriófagos/metabolismo , NAD+ Nucleosidasa/metabolismo , NAD+ Nucleosidasa/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Modelos Moleculares , NAD/metabolismo , Unión Proteica , Conformación Proteica , Sirtuina 2/metabolismo , Sirtuina 2/química , Multimerización de ProteínaRESUMEN
OBJECTIVE: Diabetes is considered a significant risk factor for the development of atrial fibrillation/flutter (AF/AFL). However, there is still insufficient evidence to determine the varying effects of different hypoglycemic drugs (HDs) on the incidence of new-onset AF/AFL in diabetic patients. To address this gap, we conducted a network meta-analysis to investigate whether various HDs have different effects on the risk of new-onset AF/AFL compared with insulin. METHOD: We conducted a comprehensive search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify all clinical trials investigating the association between various HDs or insulin and incident AF/AFL up until April 1, 2024. Bayesian random-effects model was used for network meta-analysis, and the results were expressed as relative risk (RR) and 95% confidence interval (CI). RESULT: After searching 2070 articles, a total of 12 studies (2,349,683 patients) were included in the network meta-analysis. The treatment regimen comprised insulin and 8 HDs hypoglycemic drugs, which are sodium-dependent glucose transporters 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonist (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), metformin (Met), sulfonylureas (SU), non-sulfonylureas (nSU), thiazolidinedione (TZD) and α-glycosidase inhibitors (AGI). The use of SGLT2i [RR 0.23, 95%CI (0.11, 0.49)], GLP-1RA [RR 0.28, 95%CI (0.13, 0.57)], and DPP4i [RR 0.34, 95%CI (0.17, 0.67)] demonstrated significant efficacy in reducing the incidence of new-onset AF/AFL when compared to insulin. When HDs were compared in pairs, SGLT2i is more effective than Met [RR 0.35, 95% CI (0.19, 0.62)], SU (RR 0.27, 95% CI (0.14, 0.51)], nSU [RR 0.28, 95% CI (0.08, 0.95)], TZD [RR 0.34, 95% CI (0.17, 0.7)], GLP-1RA is more effective Met [RR 0.42, 95% CI (0.25, 0.71)], SU (RR 0.33, 95% CI (0.18, 0.6)], TZD [RR 0.41, 95% CI (0.21, 0.82)], while Met[RR 1.98, 95% CI (1.23, 3.23)], SU [RR 2.54, 95% CI (1.46, 4.43)], TZD [RR 2.01, 95% CI (1.05, 3.79)] was not as effective as DPP4i. CONCLUSION: SGLT-2i, GLP-1RA, and DPP4i showed a superior efficacy in reducing the risk of new-onset AF/AFL compared to insulin therapy.
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Fibrilación Atrial , Hipoglucemiantes , Insulina , Metaanálisis en Red , Humanos , Hipoglucemiantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Insulina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
Objective: There is limited research on the relationship between the frequency of plant-based food intake and the risk of cardiovascular disease (CVD) among elderly Chinese. This study aims to evaluate the association between plant-based dietary index (PDI) and CVD risks, providing evidence for elderly Chinese to reduce CVD risks by increasing the frequency of plant-based food consumption. Methods: This study analyzed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2011-2018, employing a multivariate modified Poisson regression model, trend tests, and restricted cubic spline (RCS) analysis to assess the linear and non-linear relationship between the PDI and CVD risks. Subgroup analyses and interaction tests were conducted to evaluate the robustness and population-specificity of the results. Results: This study included a total of 1,414 elderly Chinese, and at the end of follow-up, 487 participants had developed CVD. The multivariate modified Poisson regression model revealed a negative association between PDI and CVD risks [RR = 0.983, 95%CI = (0.970, 0.997)]. Similarly, the multivariate trend test (p = 0.031) and RCS analysis (P for nonlinear = 0.600) indicated a linear relationship between PDI and CVD risks. Subgroup analyses showed that the relationship between PDI and CVD risk was not influenced by gender, BMI, smoking, alcohol use, or exercise. Conclusion: The PDI was negatively correlated with CVD risks, indicating that increasing the frequency of plant-based food intake in the diet may reduce CVD risks among elderly Chinese.
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BACKGROUND: SPRR1B, a member of the small proline-rich protein family, is implicated in various epithelial cancers as a potential oncogene linked to tumour growth and poor survival outcomes. However, its role in urothelial bladder carcinoma (UBC) remains to be fully elucidated. METHODS: Transcriptional profiling data from The Cancer Genome Atlas grouped UBC samples in accordance with SPRR1B expression. Bioinformatic analysis was conducted to evaluate whether SPRR1B is a prognostic factor and a survival factor in UBC. Gene set enrichment analysis (GSEA) was performed to study immune cells and pathways. Reverse transcription quantitative real-time polymerase chain reaction detected gene expression. Immunohistochemistry assessed protein expression. Spearman correlation test analysed the correlation between SPRR1B and the protein p53. RESULTS: The bioinformatics results indicated that the expression level of SPRR1B in UBC tissues was significantly increased compared with that in normal bladder tissues, correlating with clinical characteristics. A high expression predicted poor prognosis and survival. Univariate Cox statistics showed that a high expression level of SPRR1B was correlated with UBC patients having poor overall survival (OS) (p < 0.05). In addition, on the basis of the multivariate Cox analysis, SPRR1B expression was independently correlated with OS (p = 0.005). GSEA analysis revealed enrichment in the p53, apoptosis, and cell cycle signalling pathways, and an association with B cells, lymphocytes, and natural killer cells. In addition, SPRR1B was found to be associated with immune infiltration based on the analysis of immune cell infiltration. Performing corresponding verification on a small number of tissues collected from bladder cancer patients revealed that the expression of this protein was negatively correlated with the expression of p53. CONCLUSIONS: SPRR1B overexpression predicts poor UBC outcomes, suggesting its role as a prognostic marker and therapeutic target. Further research is necessary to elucidate its role in UBC progression.
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Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidad , Pronóstico , Masculino , Femenino , Anciano , Proteínas Ricas en Prolina del Estrato Córneo/genética , Proteínas Ricas en Prolina del Estrato Córneo/metabolismo , Persona de Mediana Edad , Tasa de Supervivencia , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Permanent hypoparathyroidism is a significant complication after total thyroidectomy. This study aimed to evaluate the long-term impact of postoperative permanent hypoparathyroidism on kidney outcomes. METHODS: Data of patients undergoing total thyroidectomy from 1999 to 2014 were retrieved. The estimated glomerular filtration rate was determined from serum creatinine results. Permanent hypoparathyroidism was defined as requiring oral calcium and vitamin D supplements postoperatively for at least 6 months. The primary outcome was a sustained decline in the estimated glomerular filtration rate from baseline by ≥50%. Secondary outcomes were end-stage kidney disease (a composite of sustained estimated glomerular filtration rate <15 mL/min/1.73 m2, need for dialysis, and kidney transplantation) and rate of estimated glomerular filtration rate decline. Patients with and without permanent hypoparathyroidism were compared. Multivariable Cox regression analysis was performed to identify independent risk factors for sustained estimated glomerular filtration rate decline by ≥50%. RESULTS: In total, 3,245 patients were eligible for analysis; 418 patients (12.9%) had permanent hypoparathyroidism. Upon median follow-up of 11.6 years, more patients with permanent hypoparathyroidism had a sustained decline in estimated glomerular filtration rate from baseline by ≥50% compared to those without (15.6% vs 6.9%, P < .001). Similar findings were obtained on Kaplan-Meier analysis (P < .001). Permanent hypoparathyroidism was an independent risk factor for sustained estimated glomerular filtration rate decline by ≥50% (adjusted hazard ratio 2.77, P < .001). Other risk factors included age, preoperative estimated glomerular filtration rate <60 mL/min/1.73m2, and diabetes mellitus. Patients with permanent hypoparathyroidism had a more rapid estimated glomerular filtration rate decline (-1.60 vs -0.70 mL/min/1.73 m2/year, difference -0.91 mL/min/1.73m2/year, P < .001). CONCLUSION: Patients with postsurgical permanent hypoparathyroidism were at greater risk of renal impairment. Further research is warranted to improve the identification and preservation of parathyroid glands during thyroidectomy to minimize patient morbidity.
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Tasa de Filtración Glomerular , Hipoparatiroidismo , Complicaciones Posoperatorias , Tiroidectomía , Humanos , Hipoparatiroidismo/etiología , Hipoparatiroidismo/epidemiología , Tiroidectomía/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Factores de Riesgo , Anciano , Estudios de SeguimientoRESUMEN
PURPOSE: This research aims to identify acoustic features which can distinguish patients with Parkinson's disease (PD patients) and healthy speakers. METHODS: Thirty PD patients and 30 healthy speakers were recruited in the experiment, and their speech was collected, including three vowels (/i/, /a/, and /u/) and nine consonants (/p/, /pÊ°/, /t/, /tÊ°/, /k/, /kÊ°/, /l/, /m/, and /n/). Acoustic features like fundamental frequency (F0), Jitter, Shimmer, harmonics-to-noise ratio (HNR), first formant (F1), second formant (F2), third formant (F3), first bandwidth (B1), second bandwidth (B2), third bandwidth (B3), voice onset, voice onset time were analyzed in our experiment. Two-sample independent t test and the nonparametric Mann-Whitney U (MWU) test were carried out alternatively to compare the acoustic measures between the PD patients and healthy speakers. In addition, after figuring out the effective acoustic features for distinguishing PD patients and healthy speakers, we adopted two methods to detect PD patients: (1) Built classifiers based on the effective acoustic features and (2) Trained support vector machine classifiers via the effective acoustic features. RESULTS: Significant differences were found between the male PD group and the male health control in vowel /i/ (Jitter and Shimmer) and /a/ (Shimmer and HNR). Among female subjects, significant differences were observed in F0 standard deviation (F0 SD) of /u/ between the two groups. Additionally, significant differences between PD group and health control were also found in the F3 of /i/ and /n/, whereas other acoustic features showed no significant differences between the two groups. The HNR of vowel /a/ performed the best classification accuracy compared with the other six acoustic features above found to distinguish PD patients and healthy speakers. CONCLUSIONS: PD can cause changes in the articulation and phonation of PD patients, wherein increases or decreases occur in some acoustic features. Therefore, the use of acoustic features to detect PD is expected to be a low-cost and large-scale diagnostic method.
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PURPOSE: Brain aging is a complex and heterogeneous process characterized by both structural and functional decline. This study aimed to establish a novel deep learning (DL) method for predicting brain age by utilizing structural and metabolic imaging data. METHODS: The dataset comprised participants from both the Universal Medical Imaging Diagnostic Center (UMIDC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The former recruited 395 normal control (NC) subjects, while the latter included 438 NC subjects, 51 mild cognitive impairment (MCI) subjects, and 56 Alzheimer's disease (AD) subjects. We developed a novel dual-pathway, 3D simple fully convolutional network (Dual-SFCNeXt) to estimate brain age using [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and structural magnetic resonance imaging (sMRI) images of NC subjects as input. Several prevailing DL models were trained and tested using either MRI or PET data for comparison. Model accuracies were evaluated using mean absolute error (MAE) and Pearson's correlation coefficient (r). Brain age gap (BAG), deviations of brain age from chronologic age, was correlated with cognitive assessments in MCI and AD subjects. RESULTS: Both PET- and MRI-based models achieved high prediction accuracy. The leading model was the SFCNeXt (the single-pathway version) for PET (MAE = 2.92, r = 0.96) and MRI (MAE = 3.23, r = 0.95) on all samples. By integrating both PET and MRI images, the Dual-SFCNeXt demonstrated significantly improved accuracy (MAE = 2.37, r = 0.97) compared to all single-modality models. Significantly higher BAG was observed in both the AD (P < 0.0001) and MCI (P < 0.0001) groups compared to the NC group. BAG correlated significantly with Mini-Mental State Examination (MMSE) scores (r=-0.390 for AD, r=-0.436 for MCI) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores (r = 0.333 for AD, r = 0.372 for MCI). CONCLUSION: The integration of [18F]FDG PET with structural MRI enhances the accuracy of brain age prediction, potentially introducing a new avenue for related multimodal brain age prediction studies.
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Objective: The progression of carotid intima-media thickness (cIMT) can partially predict the occurrence of future cardiovascular events. This network meta-analysis compared the effects of 14 antidiabetic drugs (acarbose, alogliptin, exenatide, glibenclamide, glimepiride, ipragliflozin, metformin, nateglinide, pioglitazone, rosiglitazone, sitagliptin, tofoglifozin, troglitazone, voglibose) on the progression of cIMT. Method: PubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of treatment of cIMT with hypoglycemic agents before March 1, 2024. The differences in the changes in cIMT between the treatment group and control group were evaluated. Result: After screening 8395 citations, 25 studies (6675 patients) were included. The results indicated that exenatide had the best efficacy in slowing down cIMT progress, and exenatide [MD=-0.13,95%CI (-0.25, -0.01)], alogliptin [MD=-0.08,95%CI (-0.13, -0.02)] and metformin [MD=-0.05, 95%CI (-0.09, -0.02)] are more effective than placebo. Conclusion: Long-term treatment of exenatide, alogliptin, and metformin may be more effective than other hypoglycemic drugs in slowing the progression of cIMT. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024519474.
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Grosor Intima-Media Carotídeo , Progresión de la Enfermedad , Hipoglucemiantes , Metaanálisis en Red , Humanos , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológicoRESUMEN
Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.
Diabetic foot ulcers are a serious complication of diabetes and can lead to amputation and death. Therefore, it is crucial to comprehensively elucidate the mechanisms of delayed diabetic wound healing, with emphasis on the role of keratinocyte-derived small extracellular vesicles. In vivo and in vitro experiments showed that keratinocyte-derived small extracellular vesicles suppressed diabetic wound healing, which is partly attributed to the effects of their content (LINC01435) in fibroblasts. This study suggests that LINC01435 could be targeted to regulate diabetic wound healing.
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Electrochemical sensors play a pivotal role in various fields, such as biomedicine and environmental detection, due to their exceptional sensitivity, selectivity, stability, rapid response time, user-friendly operation, and ease of miniaturization and integration. In addition to the research conducted in the application field, significant focus is placed on the selection and optimization of electrode interface materials for electrochemical sensors. The detection performance of these sensors can be significantly enhanced by modifying the interface of either inorganic metal electrodes or printed electrodes. Among numerous available modification materials, conductive polymers (CPs) possess not only excellent conductivity exhibited by inorganic conductors but also unique three-dimensional structural characteristics inherent to polymers. This distinctive combination allows CPs to increase active sites during the detection process while providing channels for rapid ion transmission and facilitating efficient electron transfer during reaction processes. This review article primarily highlights recent research progress concerning CPs as an ideal choice for modifying electrochemical sensors owing to their remarkable features that make them well-suited for biomedical and environmental applications.
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Computer-aided diagnosis (CAD) plays a crucial role in the clinical application of Alzheimer's disease (AD). In particular, convolutional neural network (CNN)-based methods are highly sensitive to subtle changes caused by brain atrophy in medical images (e.g., magnetic resonance imaging, MRI). Due to computational resource constraints, most CAD methods focus on quantitative features in specific regions, neglecting the holistic nature of the images, which poses a challenge for a comprehensive understanding of pathological changes in AD. To address this issue, we propose a lightweight dual multi-level hybrid pyramid convolutional neural network (DMA-HPCNet) to aid clinical diagnosis of AD. Specifically, we introduced ResNet as the backbone network and modularly extended the hybrid pyramid convolution (HPC) block and the dual multi-level attention (DMA) module. Among them, the HPC block is designed to enhance the acquisition of information at different scales, and the DMA module is proposed to sequentially extract different local and global representations from the channel and spatial domains. Our proposed DMA-HPCNet method was evaluated on baseline MRI slices of 443 subjects from the ADNI dataset. Experimental results show that our proposed DMA-HPCNet model performs efficiently in AD-related classification tasks with low computational cost.
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Algoritmos , Enfermedad de Alzheimer , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/diagnóstico , Humanos , Imagen por Resonancia Magnética/métodos , Diagnóstico por Computador/métodos , Atrofia , Encéfalo/diagnóstico por imagen , Anciano , Femenino , Masculino , Aprendizaje Profundo , Bases de Datos FactualesRESUMEN
Misoprostol is a prostaglandin analogue that contracts the uterus, prompting the expulsion of the embryo. No systematic evaluation of the mechanisms of misoprostol has previously been performed. In this study, known targets of misoprostol were obtained from the DrugBank database; potential targets of misoprostol were predicted using data from the SwissTargetPrediction and PharmMapper databases; and the main targets of pregnancy termination were obtained from the GeneCards database. The protein-protein interaction (PPI) network of the shared genes between misoprostol and pregnancy termination was constructed using data from the STRING database, and the "misoprostol-pregnancy termination-pathway" network was constructed and potential targets was verified through molecular docking. We analyzed 37 shared target genes and obtained a network diagram of 134 potential targets, which the core therapeutic targets were HSP90AA1, EGFR, and MAPK1. GO functional and KEGG pathway enrichment analyses showed that misoprostol can modulate the VEGF signaling pathway, calcium signaling pathway, and NF-κB signaling pathway in pregnancy termination and mainly interferes with protein phosphorylation, cell localization, and protein hydrolysis regulation processes. This research illustrates the mechanism underlying the pharmacological effect of misoprostol, namely pregnancy termination. However, further experimental verification is warranted for optimal use of misoprostol during clinical practice.
Le misoprostol est un analogue des prostaglandines qui contracte l'utérus, provoquant l'expulsion de l'embryon. Aucune évaluation systématique des mécanismes du misoprostol n'a été réalisée auparavant. Dans cette étude, les cibles connues du misoprostol ont été obtenues à partir de la base de données DrugBank ; Les cibles potentielles du misoprostol ont été prédites à l'aide des données des bases de données SwissTargetPrediction et PharmMapper ; et les principales cibles de l'interruption de grossesse ont été obtenues à partir de la base de données GeneCards. Le réseau d'interaction protéine-protéine (IPP) des gènes partagés entre le misoprostol et l'interruption de grossesse a été construit à l'aide des données de la base de données STRING, et le réseau « voie d'interruption de grossesse-misoprostol ¼ a été construit et les cibles potentielles ont été vérifiées par amarrage moléculaire. Nous avons analysé 37 gènes cibles partagés et obtenu un diagramme de réseau de 134 cibles potentielles, dont les principales cibles thérapeutiques étaient HSP90AA1, EGFR et MAPK1. Les analyses d'enrichissement des voies fonctionnelles GO et KEGG ont montré que le misoprostol peut moduler la voie de signalisation VEGF, la voie de signalisation du calcium et la voie de signalisation NF-κB lors de l'interruption de grossesse et interfère principalement avec les processus de phosphorylation des protéines, de localisation cellulaire et de régulation de l'hydrolyse des protéines. Cette recherche illustre le mécanisme sous-jacent à l'effet pharmacologique du misoprostol, à savoir l'interruption de grossesse. Cependant, une vérification expérimentale plus approfondie est justifiée pour une utilisation optimale du misoprostol au cours de la pratique clinique.
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Aborto Inducido , Misoprostol , Femenino , Embarazo , Humanos , Misoprostol/farmacología , Simulación del Acoplamiento Molecular , Farmacología en RedRESUMEN
The Qinghai-Tibetan Plateau (QTP) has nurtured a rich diversity of species because of its unique geographical and environmental conditions. Gymnocypris species (subfamily Schizopygopsinae) are primitive fishes that live in the special environment of the plateau, and their evolution and distribution are inseparable from the historical changes of the QTP. Recently, the resources of Gymnocypris species have been decreasing due to habit deterioration and the intensification of human activities. Therefore, the scientific conservation of the genetic resources of Gymnocypris species is urgently required. In this study, we established two models for the priority conservation assessment of germplasm resources of Gymnocypris species on the basis of the genetic diversity and phylogenetic relationships of 674 individuals from eight Gymnocypris species populations. The results show that the Gymnocypris potanini (GPO), Gymnocypris eckloni (GE), and Gymnocypris przewalskii (GPR) populations are the most genetically diverse in terms of combined genetic diversity values and should be prioritized for conservation. In terms of genetic contribution, the GPO, GE, and GPR populations have a positive impact on maintaining the distinctiveness and diversity of the entire Gymnocypris species population and should be prioritized for conservation. However, in terms of different evolutionary clades, the Gymnocypris namensis, Gymnocypris waddellii, Gymnocypris dobula, and GE populations in clade A should be given priority for protection, the GE population in clade B should be given priority, and the GPR population in clade C should be given priority. In conclusion, the two models and assessment of conservation priorities will provide a scientific basis for the conservation of Gymnocypris species.
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OBJECTIVE: In this case report, the auxiliary role of deep learning and 3-dimensional printing technology in the perioperative period was discussed to guide transcatheter aortic valve replacement and coronary stent implantation simultaneously. CASE PRESENTATION: A 68-year-old man had shortness of breath and chest tightness, accompanied by paroxysmal nocturnal dyspnea, 2 weeks before presenting at our hospital. Echocardiography results obtained in the outpatient department showed severe aortic stenosis combined with regurgitation and pleural effusion. The patient was first treated with closed thoracic drainage. After 800 mL of pleural effusion was collected, the patient's symptoms were relieved and he was admitted to the hospital. Preoperative transthoracic echocardiography showed severe bicuspid aortic valve stenosis combined with calcification and aortic regurgitation (mean pressure gradient, 42 mmHg). Preoperative computed tomography results showed a type I bicuspid aortic valve with severe eccentric calcification. The leaflet could be seen from the left coronary artery plane, which indicated an extremely high possibility of coronary obstruction. After preoperative imaging assessment, deep learning and 3-dimensional printing technology were used for evaluation and simulation. Guided transcatheter aortic valve replacement and a coronary stent implant were completed successfully. Postoperative digital subtraction angiography showed that the bioprosthesis and the chimney coronary stent were in ideal positions. Transesophageal echocardiography showed normal morphology without paravalvular regurgitation. CONCLUSION: The perioperative guidance of deep learning and 3-dimensional printing are of great help for surgical strategy formulation in patients with severe bicuspid aortic valve stenosis with calcification and high-risk coronary obstruction.
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Estenosis de la Válvula Aórtica , Aprendizaje Profundo , Impresión Tridimensional , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Masculino , Anciano , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Stents , Válvula Aórtica/cirugía , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/anomalías , Insuficiencia de la Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/diagnóstico por imagenRESUMEN
The inadequate electrical conductivity of metal sulfides, along with their tendency to agglomerate, has hindered their use in energy storage and catalysis. The construction of a heterojunction can ameliorate these deficiencies to some extent. In this paper, MnS-BaS heterojunction catalysts were prepared by a hydrothermal method, which is a simple and inexpensive process. The MnS-BaS heterojunction catalysts exhibited superior performance owing to the strong synergistic interaction between MnS and BaS. Density functional theory (DFT) calculations reveal strong interactions at the heterojunction interface and significant electron transfer between MnS and BaS, which further modulates the electronic structure of Mn. The elevation of the center of the d-band enhances the adsorption of oxygen and oxygen-containing intermediates on the catalyst, thus promoting the oxygen reduction reaction (ORR). The practical application of MnS-BaS catalysts was tested by assembling zinc-air batteries. This study provides a rational strategy for designing transition metal catalysts that are efficient and low cost.
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In the study of TAVR, 3-dimensional (3D) printed aortic root models and pulsatile simulators were used for simulation training and teaching before procedures. The study was carried out in the following three parts: (1) experts were selected and equally divided into the 3D-printed simulation group and the non-3D-printed simulation group to conduct four times of TAVR, respectively; (2) another 10 experts and 10 young proceduralists were selected to accomplish three times of TAVR simulations; (3) overall, all the doctors were organized to complete a specific questionnaire, to evaluate the training and teaching effect of 3D printed simulations. For the 3D-printed simulation group, six proceduralists had a less crossing-valve time (8.3 ± 2.1 min vs 11.8 ± 2.7 min, P < 0.001) and total operation time (102.7 ± 15.3 min vs 137.7 ± 15.4 min, P < 0.001). In addition, the results showed that the median crossing-valve time and the total time required were significantly reduced in both the expert group and the young proceduralist group (all P<0.001). The results of the questionnaire showed that 3D-printed simulation training could enhance the understanding of anatomical structure and improve technical skills. Overall, cardiovascular 3D printing may play an important role in assisting TAVR, which can shorten the operation time and reduce potential complications.
RESUMEN
Garlic is a common vegetable and spice in people's daily diets, in which garlic polysaccharide (GP) is one of the most important active components with a variety of benefits, such as antioxidant, immune-enhancing, anti-inflammatory, liver-protective and bowel-regulating properties. >20 types of GPs, mainly crude polysaccharides, have been identified. However, the exact chemical composition of GPs or the mechanism underlying their pharmacological activity is still not fully understood. The extraction and purification methods of GPs are compared in this review while providing detailed information on their structural features, identification methods, major biological activities, mechanisms of actions, structural modifications, structure-activity relationships as well as potential applications. Finally, the limitations of GP research and future issues that need to be addressed are discussed in this review. GPs are widely recognized as substances with great potential in the pharmaceutical and food industries. Therefore, this review aims to provide a comprehensive summary of the latest research progresses in the field of GPs, together with scientific insights and a theoretical support for the development of GPs in research and industrialization.