RESUMEN
The first asymmetric total synthesis of the hexacyclic veatchine-type C20-diterpenoid alkaloid (-)-garryine is presented. Key steps include a Pd-catalyzed enantioselective Heck reaction, a radical cyclization, and a photoinduced C-H activation/oxazolidine formation sequence. Of note, a highly enantioselective Heck reaction developed in this work provides efficient access to 6/6/6 tricyclic compounds, in particular, containing a C19-functionalitiy, which is useful for diverse transformations.
RESUMEN
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) typically present with a complex anatomical distribution, often accompanied by insidious symptoms. This combination contributes to its high incidence and poor prognosis. It is now understood that the immune features of cellular components within the tumor ecosystem and their complex interactions are critical factors influencing both tumor progression and the effective immune response. METHODS: We obtained single-cell RNA sequencing data of 26,496 cells from three tumor tissues and five normal tissues and performed subsequent analyses. Immunohistochemical staining on tumor sections was used to validate the presence of malignant cells. Additionally, we included bulk RNA sequencing data from 502 HNSCC patients. Kaplan-Meier analysis and the log-rank test were employed to assess predictors of patient outcomes. RESULTS: We identified three epithelial subclusters exhibiting immune-related features. These subclusters promoted the infiltration of T cells, dendritic cells, and monocytes into the tumor microenvironment. Additionally, cancer-associated fibroblasts displayed tumor-promoting and angiogenesis characteristics, contrasting with the predominant antigen-presenting and inflammatory roles observed in fibroblasts from normal tissues. Furthermore, tumor endothelial subsets exhibited a double-sided effect, promoting tumor progression and enhancing the effectiveness of immune response. Finally, follicular helper T cells and T helper 17 cells were found to be significantly correlated with improved outcomes in HNSCC patients. These CD4+ T cell subpopulations could promote the anti-tumor immune response by recruiting and activating B and T cells. CONCLUSION: Our findings provide deeper insights into the immune features of the tumor ecosystem and reveal the prognostic significance of follicular helper T cells and T helper 17 cells. These findings may pave the way for the development of therapeutic approaches.
Asunto(s)
Neoplasias de Cabeza y Cuello , Linfocitos Infiltrantes de Tumor , Análisis de Expresión Génica de una Sola Célula , Carcinoma de Células Escamosas de Cabeza y Cuello , Células Th17 , Microambiente Tumoral , Femenino , Humanos , Masculino , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Linfocitos Infiltrantes de Tumor/inmunología , Pronóstico , RNA-Seq/métodos , Análisis de Expresión Génica de una Sola Célula/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Células T Auxiliares Foliculares/inmunología , Células Th17/inmunología , Microambiente Tumoral/inmunologíaRESUMEN
Stretchable triboelectric nanogenerators (TENGs) are widely applied in wearable and implantable electronics, smart medical devices, and soft robots. However, it is still a challenge to produce stretchable TENGs with both exceptional elasticity and output performance, which limits their application scope. In this work, high-performance stretchable TENGs are developed through a thermo-compression (TC) fabrication process. In particular, a poly(vinylidene fluoride) film is compactly bound to the elastic thermoplastic polyurethane substrate, which inherits excellent stretchability with a strain of up to 815%. Furthermore, owing to the large surface area, tight contact, and effective vertical transport of tribo-induced charges between the coupled fibrous tribo-layer and soft substrate, the TC composite film-based TENGs exhibit a greater output (2-4 times) than unlaminated film-based TENGs. Additionally, the broad universality of this method is proven using various tribo- and substrate materials. The proposed technology provides a novel and effective approach to conjointly boost the output and stretchability of TENGs, showing encouraging application prospects in self-powered wearable and flexible electronics.
RESUMEN
BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a prevalent and aggressive malignancy. Ferroptosis and cuproptosis are recently discovered forms of programmed cell death (PCD) that have attracted much attention. However, their interactions and impacts on MIBC overall survival (OS) and treatment outcomes remain unclear. METHODS: Data from the TCGA-BLCA project (as the training set), cBioPortal database, and GEO datasets (GSE13507 and GSE32894, as the test sets) were utilized to identify hub ferroptosis/cuproptosis-related genes (FRGs and CRGs) and develop a prognostic signature. Differential expression analysis (DEA) was conducted, followed by univariate and multivariate Cox's regression analyses and multiple machine learning (ML) techniques to select genetic features. The performance of the ferroptosis/cuproptosis-related signature was evaluated using Kaplan-Meier (K-M) survival analysis and receiver-operating characteristics (ROC) curves. Mutational and tumour immune microenvironment landscapes were also explored. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) experiments confirmed the expression patterns of the hub genes, and functional assays assessed the effects of SCD knockdown on cell viability, proliferation, and migration. RESULTS: DEA revealed dysregulated FRGs and CRGs in the TCGA MIBC cohort. SCD, DDR2, and MT1A were identified as hub genes. A prognostic signature based on the sum of the weighted expression of these genes demonstrated strong predictive efficacy in the training and test sets. Nomogram incorporating this signature accurately predicted 1-, 3-, and 5-year survival probabilities in the TCGA cohort and GSE13507 dataset. Copy number variation (CNV) and tumour immune microenvironment analysis revealed that high risk score level groups were associated with immunosuppression and lower tumour purity. The associations of risk scores with immunotherapy and chemical drugs were also explored, indicating their potential for guiding treatment for MIBC patients. The dysregulated expression patterns of three hub genes were validated by RT-qPCR experiments. CONCLUSIONS: Targeting hub FRGs and CRGs could be a promising therapeutic approach for MIBC. Our prognostic model offers a new framework for MIBC subtyping and can inform personalized therapeutic strategies.
Asunto(s)
Ferroptosis , Mutación , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Ferroptosis/genética , Pronóstico , Microambiente Tumoral/genética , Biomarcadores de Tumor/genética , Masculino , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica , Femenino , Perfilación de la Expresión Génica , Nomogramas , Estimación de Kaplan-Meier , Línea Celular TumoralRESUMEN
A new asymmetric synthesis of the A/E-ring fragment of C18-diterpenoid alkaloids is described. The crucial contiguous stereogenic centers at C4, C5, and C11 were established through an asymmetric Michael addition/allylation sequence. The unique azabicyclo[3.3.1]nonane motif (A/E rings) was assembled by employing ring-closing metathesis and Mitsunobu reaction as key strategies.
RESUMEN
A streamlined and efficient approach to the key epoxide intermediate for the asymmetric synthesis of triazole antifungal agents is presented. This synthesis highlights a P(NMe2)3-mediated nonylidic olefination of α-keto ester, ensuring the exclusive formation of the requisite (Z)-alkene, followed by a highly enantioselective Jacobsen epoxidation to establish the two vicinal stereocenters in a single step. The versatility of this strategy is exemplified through the efficient synthesis of efinaconazole and ravuconazole.
Asunto(s)
Antifúngicos , Compuestos Epoxi , Antifúngicos/farmacología , Estereoisomerismo , Alquenos , TriazolesRESUMEN
Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.
Asunto(s)
Diseño de Fármacos , Isoquinolinas , Bloqueantes Neuromusculares , Bloqueantes Neuromusculares/farmacología , Bloqueantes Neuromusculares/síntesis química , Bloqueantes Neuromusculares/química , Relación Estructura-Actividad , Animales , Isoquinolinas/química , Isoquinolinas/farmacología , Isoquinolinas/síntesis química , Conejos , Receptores Nicotínicos/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Dosis-Respuesta a Droga , Mivacurio , Atracurio/análogos & derivados , Atracurio/farmacología , Atracurio/síntesis química , Atracurio/químicaRESUMEN
Osteoarthritis (OA) is a major disease that causes disability in middle-aged and elderly people. A comprehensive understanding of its pathogenesis is of great significance in finding new clinical diagnosis and treatment schemes. The role of Semaphorin 3A (Sema3A) in OS has attracted attention recently, and the purpose of this study is to analyze the mechanisms underlying its impact on OS. First, a rat model of OS was established. Hematoxylin-eosin (HE) and TUNEL staining showed that the modeled rats presented typical pathological manifestations of OS, confirming the success of the modeling. Sema3A was significantly underexpressed in OS rats. Subsequently, Sema3A abnormal expression vectors were constructed to intervene in chondrocytes isolated from OS rats. It was found that the proliferation of chondrocytes was decreased, the apoptosis was increased, and the mitochondrial damage and autophagy were intensified after silencing Sema3A expression, while the above pathological processes were reversed when Sema3A expression was increased. In conclusion, Sema3A has an important influence on the pathological progression of OS, and molecular therapies targeting to increase Sema3A expression may become a new treatment for OS in the future.
Asunto(s)
Osteoartritis , Semaforina-3A , Animales , Ratas , Apoptosis/genética , Condrocitos/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Semaforina-3A/genética , Semaforina-3A/metabolismoRESUMEN
BACKGROUND: To evaluate the safety and efficacy of endovascular denervation (EDN) as an adjunct to percutaneous vascular intervention (PVI) for peripheral artery disease (PAD). METHODS: From August 2019 to April 2021, 38 eligible patients with PAD enrolled in this study were randomly and equally assigned into 2 groups: the PVI group and the PVI + EDN group treated with EDN at the iliac and femoral arteries before PVI. The primary endpoint was the improvement in the ankle brachial index at 6 months after the procedure. The secondary endpoints were transcutaneous oxygen pressure (TcPO2), Rutherford category, numerical rating scale score, and safety. RESULTS: The technical success rates of PVI and EDN were 100%, and no device-related or procedure-related major adverse events occurred in either group. Compared with PVI alone, PVI + EDN demonstrated a significant improvement in limb hemodynamics at 6 months (Δ ankle brachial index 0.44 ± 0.31 vs. 0.24 ± 0.15, P = 0.018). Microcirculatory perfusion of PAD was significantly better at 6 months in the PVI + EDN group (ΔTcPO2, 15.68 ± 16.72 vs. 4.95 ± 13.43, P = 0.036). The Rutherford category was significantly improved in the PVI + EDN group in comparison with the PVI group at the 3-month follow-up (100.00% vs. 68.42%, P = 0.02). The decrease in the numerical rating scale score in the PVI + EDN group was greater than that in the PVI group at 1 week following the procedure (3 [2-5] vs. 4 [4-6], P = 0.022). CONCLUSIONS: In this single-center pilot analysis of a heterogeneous cohort of patients with PAD, PVI with EDN demonstrated a significant improvement in limb ischemia at 6 months compared with PVI alone.
Asunto(s)
Procedimientos Endovasculares , Enfermedad Arterial Periférica , Humanos , Microcirculación , Resultado del Tratamiento , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/cirugía , Isquemia/diagnóstico por imagen , Isquemia/cirugía , Desnervación , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Factores de RiesgoRESUMEN
BACKGROUND: Preoperative effective assessment of cervical lymph node metastasis in thyroid cancer plays an important role in formulating the surgical plan. PURPOSE: To investigate the significance of synthetic magnetic resonance imaging (MRI) for quantitatively analyzing cervical lymph node metastasis in thyroid cancer. MATERIAL AND METHODS: A retrospective analysis was conducted on 30 patients with thyroid cancer, consisting of 19 thyroid cancer nodules, 45 metastatic lymph nodes, and 47 non-metastatic lymph nodes. Regions of interest (ROIs) for each type of nodule were manually delineated using a workstation. Quantitative parameters, such as T1, T2, and proton density (PD) values, were automatically extracted from synthetic MRI scans. Statistical tests and regression analysis were performed to assess differences and correlations among the quantitative parameters. RESULTS: There were no significant differences in the quantitative parameter values between the primary tumor and metastatic lymph node tissues (P > 0.05). However, significant differences were observed in the quantitative parameters between the primary tumor and non-metastatic lymph node tissues and between the metastatic and non-metastatic lymph node tissues (P < 0.05). The diagnostic accuracy for cervical lymph node metastasis in thyroid cancer was 94.4% for the T1 and T2 combined index, 91.9% for T2, 86.8% for T1, and 71.7% for PD values. CONCLUSION: The application of quantitative parameters from synthetic MRI can assist clinicians in accurately planning surgical interventions for thyroid cancer patients before surgery.
Asunto(s)
Ganglios Linfáticos , Metástasis Linfática , Imagen por Resonancia Magnética , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Metástasis Linfática/diagnóstico por imagen , Femenino , Masculino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Anciano , Cuello/diagnóstico por imagen , Cuello/patología , Reproducibilidad de los ResultadosRESUMEN
Optic neuropathies are leading causes of irreversible visual impairment and blindness, currently affecting more than 100 million people worldwide. Glaucoma is a group of optic neuropathies attributed to progressive degeneration of retinal ganglion cells (RGCs). We have previously demonstrated an increase in survival of RGCs by the activation of macrophages, whereas the inhibition of macrophages was involved in the alleviation on endotoxin-induced inflammation by antagonist of growth hormone-releasing hormone (GHRH). Herein, we hypothesized that GHRH receptor (GHRH-R) signaling could be involved in the survival of RGCs mediated by inflammation. We found the expression of GHRH-R in RGCs of adult rat retina. After optic nerve crush, subcutaneous application of GHRH agonist MR-409 or antagonist MIA-602 promoted the survival of RGCs. Both the GHRH agonist and antagonist increased the phosphorylation of Akt in the retina, but only agonist MR-409 promoted microglia activation in the retina. The antagonist MIA-602 reduced significantly the expression of inflammation-related genes Il1b, Il6, and Tnf Moreover, agonist MR-409 further enhanced the promotion of RGC survival by lens injury or zymosan-induced macrophage activation, whereas antagonist MIA-602 attenuated the enhancement in RGC survival. Our findings reveal the protective effect of agonistic analogs of GHRH on RGCs in rats after optic nerve injury and its additive effect to macrophage activation, indicating a therapeutic potential of GHRH agonists for the protection of RGCs against optic neuropathies especially in glaucoma.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/agonistas , Macrófagos/patología , Neuroprotección , Traumatismos del Nervio Óptico/patología , Células Ganglionares de la Retina/patología , Animales , Supervivencia Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Hormona del Crecimiento/metabolismo , Hormona Liberadora de Hormona del Crecimiento/antagonistas & inhibidores , Inflamación/genética , Inflamación/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Neuroprotección/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Endogámicas F344 , Receptores de Neuropéptido/metabolismo , Receptores de Hormona Reguladora de Hormona Hipofisaria/metabolismo , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/metabolismo , Factor de Transcripción STAT3/metabolismo , Sermorelina/análogos & derivados , Sermorelina/farmacología , Transducción de Señal/efectos de los fármacos , Cuerpo Vítreo/efectos de los fármacos , Cuerpo Vítreo/metabolismo , Zimosan/farmacologíaRESUMEN
Objective: Given the crucial role of the PI3K/Akt signaling pathway in chondrocyte survival and inflammation in osteoarthritis (OA), this study aimed to investigate the effects of Gu Bi Tang on chondrocyte proliferation, apoptosis, and inflammatory factor expression in a rat model of OA, with a focus on the PI3K/Akt signaling pathway. Methods: Forty-five specific pathogen-free (SPF) C57 mice were randomly divided into three groups: the model group (Group A), the Gu Bi Tang group (Group B), and the Amfenac group (Group C), with 15 rats in each group. All 45 rats underwent anterior cruciate ligament transection (ACLT) surgery to establish an OA model. The ACLT procedure is a well-established method for inducing OA in rodents, as it leads to the destabilization of the knee joint and the development of degenerative changes characteristic of human OA. After 8 weeks of modeling, Group A rats received an equivalent volume of normal saline by gastric lavage, Group B rats were administered 13 mL/kg of Gu Bi Tang, and Group C rats received 19.5 mg/kg of Amfenac solution by gastric lavage. The dosages of Gu Bi Tang and Amfenac were selected based on previous studies examining the therapeutic effects of these interventions in rodent OA models. The gastric lavage frequency for all three groups was maintained at twice daily. The researchers analyzed cartilage morphological changes using toluidine blue staining, chondrocyte proliferation and apoptosis using the TUNEL method, and the expression of PI3K/AKT/mTOR proteins in chondrocytes using Western blotting. Additionally, the expression of inflammatory factors (TNF-α and IL-1ß) in serum was measured using ELISA. Results: Staining: Compared to the model group (Group A), both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) showed significant improvement in cartilage tissue, with deeper toluidine blue staining. Toluidine blue staining is a marker of cartilage integrity and glycosaminoglycan content, indicating improved cartilage structure and composition in the treatment groups. Chondrocyte proliferation and apoptosis: Compared to the model group (Group A), both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) significantly reduced chondrocyte apoptosis (P < .05). This reduction in chondrocyte death contributes to a healthier cartilage environment and helps prevent further cartilage degradation. Protein expression: In comparison to the model group (Group A), the expression of PI3K, AKT, and mTOR proteins in the joint cartilage of the Gu Bi Tang group (Group B) and the Amfenac group (Group C) significantly decreased, with the Amfenac group showing a greater reduction than the Gu Bi Tang group (P < .05). The inhibition of this detrimental PI3K/AKT/mTOR signaling pathway promotes chondrocyte survival and a more favorable cartilage homeostasis. Inflammatory factor expression: Prior to treatment, there was no significant difference in the expression levels of the inflammatory factors TNF-α and IL-1ß in serum among the three groups (P > .05). However, after treatment, both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) showed a significant reduction in the serum expression of TNF-α and IL-1ß compared to the model group (Group A), with the Amfenac group showing a greater reduction than the Gu Bi Tang group (P < .05). This is important, as TNF-α and IL-1ß are key pro-inflammatory cytokines that drive the destructive processes in osteoarthritis. Conclusion: In summary, this study demonstrates that Gu Bi Tang exerts protective effects on chondrocytes in a rat model of osteoarthritis. Specifically, Gu Bi Tang was shown to inhibit chondrocyte apoptosis, reduce the expression of key proteins in the PI3K/AKT/mTOR signaling pathway, and decrease the levels of the pro-inflammatory cytokines TNF-α and IL-1ß. These findings suggest that Gu Bi Tang could offer a novel therapeutic approach for osteoarthritis by modulating key signaling pathways and inflammatory responses. The ability of Gu Bi Tang to preserve chondrocyte viability and maintain a more favorable cartilage homeostasis makes it a promising candidate for further investigation as a potential treatment for osteoarthritis. Future studies should explore the precise mechanisms by which Gu Bi Tang exerts its beneficial effects and evaluate its efficacy in additional animal models and clinical settings.
RESUMEN
OBJECTIVES: We aimed to investigate the influence of preoperative antituberculosis chemotherapy duration on perioperative epididymectomy complications in patients with epididymal tuberculosis (ETB). METHODS: This retrospective study examined patients with ETB between January 1, 2013, and March 31, 2023, who underwent unilateral epididymectomy at our hospital. We selected preoperative antituberculosis chemotherapy duration of 2, 4, and 8 weeks as the cutoffs for this study, to explore whether there are differences in the incidence of intraoperative and 30-day postoperative complications among the patients with different preoperative antituberculosis chemotherapy durations. Intraoperative complications were graded according to the Satava classification, and 30-day postoperative complications were defined according to the Clavien-Dindo classification. The study groups were compared using the unpaired t-test, Wilcoxon rank-sum test, Pearson's chi-square test, or Fisher's exact test, as appropriate. RESULTS: Overall, 155 patients were included. Statistical analysis revealed that there were no significant differences in the incidence of intraoperative and 30-day postoperative complications between patients with shorter preoperative antituberculosis chemotherapy duration and those with longer preoperative antituberculosis chemotherapy duration. CONCLUSIONS: In patients with ETB, preoperative antituberculosis chemotherapy duration did not significantly affect the incidence of perioperative complications after epididymectomy.
Asunto(s)
Antituberculosos , Epidídimo , Complicaciones Posoperatorias , Tuberculosis de los Genitales Masculinos , Humanos , Masculino , Estudios Retrospectivos , Adulto , Epidídimo/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Persona de Mediana Edad , Antituberculosos/administración & dosificación , Antituberculosos/efectos adversos , Tuberculosis de los Genitales Masculinos/diagnóstico , Incidencia , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/etiología , Factores de Tiempo , Cuidados Preoperatorios/métodos , Adulto Joven , Anciano , Epididimitis/epidemiología , Epididimitis/etiología , Epididimitis/diagnósticoRESUMEN
Tauroursodeoxycholic acid (TUDCA) can activate farnesoid X receptor (FXR) to involve in the formation of gallstones. Here, this study aimed to probe the potential mechanism of TUDCA-FXR network in the formation of bile duct stone. The levels of TUDCA, FXR and NCK1 were decreased, while the level of miR-107 was increased in the serum of bile duct stone patients. FXR expression was positively correlated with TUDCA or NCK1 expression in patients, moreover, TUDCA pretreatment in biliary epithelial cells increased the levels of FXR and NCK1, and rescued the decrease of NCK1 caused by FXR knockdown in cells. Then functional analysis showed FXR knockdown caused apoptosis and endoplasmic reticulum stress (ERS) as well as suppressed proliferation in biliary epithelial cells in vitro, which were attenuated by TUDCA pretreatment or NCK1 overexpression Mechanistically, NCK1 was a target of miR-107, which was up-regulated by FXR silencing, and FXR knockdown-induced decrease of NCK1 was rescued by miR-107 inhibition. Additionally, miR-107 expression was negatively correlated with TUDCA expression in bile duct stone patients, and TUDCA pretreatment in biliary epithelial cells decreased miR-107 expression by FXR. Functionally, the pretreatment of TUDCA or FXR agonist suppressed miR-107-evoked apoptosis and ERS in biliary epithelial cells. In conclusion, TUDCA up-regulates FXR expression to activate NCK1 through absorbing miR-107, thus suppressing the apoptosis and ERS in biliary epithelial cells, these results provided a theoretical basis for elucidating the mechanism of bile duct stone formation.
RESUMEN
AIM: This study examined the correlation among turnover intention, emotional intelligence and job burnout in male nurses and determined its influencing factors. BACKGROUND: The number of male nurses has increased in China; however, the turnover rate is very high. Nurses' turnover intention is related to job burnout and emotional intelligence. INTRODUCTION: Recent studies have shown that job burnout and emotional intelligence are related to medical and health institution employees' intention to leave their jobs. It is not clear if the same conclusions can be drawn about male nurses. METHODS: For this cross-sectional study, 627 male nurses were recruited from across China between May and July 2018. Data were collected through an online questionnaire, and Pearson's product-moment correlation coefficient and multiple linear regression were performed to analyse the data. RESULTS: There was a weak negative, moderate positive and moderate negative correlation between turnover intention and emotional intelligence, turnover intention and job burnout, and emotional intelligence and job burnout, respectively. Factors that significantly affected turnover intention among male nurses included job burnout, young age, lack of interest in nursing and working in the emergency department. CONCLUSION: The study revealed the factors that affected male nurses' turnover intention and the relationships between turnover intention, emotional intelligence and job burnout. IMPLICATIONS FOR NURSING MANAGEMENT AND SOCIAL POLICY: Hospital managers should provide necessary help and support to reduce male nurse turnover rates and incorporate emotional intelligence training. The policy should eliminate the unfair college admission practices for students choosing nursing majors, raise the nursing profession's salaries and vigorously develop specialty nursing. In addition, diversified values should be promoted, and stereotypes of male nurses in nursing should be broken.
Asunto(s)
Agotamiento Profesional , Enfermeras y Enfermeros , Personal de Enfermería en Hospital , Humanos , Masculino , Enfermeros , Satisfacción en el Trabajo , Lugar de Trabajo/psicología , Intención , Estudios Transversales , Agotamiento Profesional/psicología , Reorganización del Personal , China , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/psicologíaRESUMEN
Spatiotemporal information on individual trajectories in urban rail transit is important for operational strategy adjustment, personalized recommendation, and emergency command decision-making. However, due to the lack of journey observations, it is difficult to accurately infer unknown information from trajectories based only on AFC and AVL data. To address the problem, this paper proposes a spatiotemporal probabilistic graphical model based on adaptive expectation maximization attention (STPGM-AEMA) to achieve the reconstruction of individual trajectories. The approach consists of three steps: first, the potential train alternative set and the egress time alternative set of individuals are obtained through data mining and combinatorial enumeration. Then, global and local potential variables are introduced to construct a spatiotemporal probabilistic graphical model, provide the inference process for unknown events, and state information about individual trajectories. Further, considering the effect of missing data, an attention mechanism-enhanced expectation-maximization algorithm is proposed to achieve maximum likelihood estimation of individual trajectories. Finally, typical datasets of origin-destination pairs and actual individual trajectory tracking data are used to validate the effectiveness of the proposed method. The results show that the STPGM-AEMA method is more than 95% accurate in recovering missing information in the observed data, which is at least 15% more accurate than the traditional methods (i.e., PTAM-MLE and MPTAM-EM).
RESUMEN
Metal atoms on the support serve as active sites for many heterogeneous catalysts. However, the active metal sites on the support are conventionally described as static, and the intermediates adsorbed on the support far away from the active metal sites cannot be transformed. Herein, we report the first example of operando mobile catalysis to promote catalytic efficiency by enhancing the collision probability between active sites and reactants or reaction intermediates. Specifically, ligand-coordinated Pt single atoms (isolated MeCpPt- species) are bonded on CeO2 and transformed into mobile MeCpPt(H)CO complexes during the reverse water gas shift reaction for operando mobile catalysis. This strategy enables the conversion of inert carbonate intermediates on the CeO2 support. A turnover frequency (TOF) of 6358â molâ CO2 molPt -1 â h-1 and 99 % CO selectivity at 300 °C is obtained for reverse water gas shift reaction, dramatically higher than those of Pt catalysts reported in the literature. Operando mobile catalysis presents a promising strategy for designing high-efficiency heterogeneous catalysts for various chemical reactions and applications.
RESUMEN
The high heterogeneity and mutation rate of cancer cells often lead to the failure of targeted therapy, and therefore, new targets for multitarget therapy of tumors are urgently needed. Aberrantly expressed glycosaminoglycans (GAGs) have been shown to be involved in tumorigenesis and are promising new targets. Recently, the GAG-binding domain rVAR2 of the Plasmodium falciparum VAR2CSA protein was identified as a probe targeting cancer-associated chondroitin sulfate A-like epitopes. In this study, we found that rVAR2 could also bind to heparin (Hep) and chondroitin sulfate E. Therefore, we used rVAR2 as a model to establish a method based on random mutagenesis of the GAG-binding protein and phage display to identify and optimize probes targeting tumor GAGs. We identified a new probe, VAR2HP, which selectively recognized Hep by interacting with unique epitopes consisting of a decasaccharide structure that contains at least three HexA2S(1-4)GlcNS6S disaccharides. Moreover, we found that these Hep-like epitopes were overexpressed in various cancer cells. Most importantly, our in vivo experiments showed that VAR2HP had good biocompatibility and preferentially localizes to tumors, which indicates that VAR2HP has great application potential in tumor diagnosis and targeted therapy. In conclusion, this study provides a strategy for the discovery of novel tumor-associated GAG epitopes and their specific probes.
Asunto(s)
Heparina , Neoplasias , Humanos , Heparina/metabolismo , Epítopos/química , Glicosaminoglicanos/metabolismo , Sulfatos de Condroitina/genética , Sulfatos de Condroitina/metabolismo , Neoplasias/genéticaRESUMEN
Vilmoraconitine belongs to one of the most complex skeleton types in the C19-diterpenoid alkaloids, which architecturally features an unprecedented heptacyclic core possessing a rigid cyclopropane unit. Here, we report the first total synthesis of vilmoraconitine relying on strategic use of efficient ring-forming reactions. Key steps include an oxidative dearomatization-induced Diels-Alder cycloaddition, a hydrodealkenylative fragmentation/Mannich sequence, and an intramolecular Diels-Alder cycloaddition.
RESUMEN
A new strategy focusing on the last-stage asymmetric assembly of the ring D, which inherently possesses the densest part of stereogenic centers and functional groups in the A/B/C/D ring system of (-)-cephalotaxine, has been developed, in which a novel Rh-catalyzed asymmetric (2 + 3) annulation of tertiary enamides with enoldiazoacetates is designed and explored for enantioselective construction of the crucial cyclopentane ring D bearing a unique spirocyclic aza-quaternary stereocenter. Based on the expeditious access of chiral functionalized building block with the tetracyclic A/B/C/D ring system, a concise enantioselective total synthesis of (-)-cephalotaxine starting from readily available homopiperonyl alcohol has been achieved in nine steps with only two column chromatography purifications. Following the tactical introduction of the Meinwald rearrangement, enantioselective divergent syntheses of (-)-cephalotine B with an additional C3-O-C11 oxo-bridged bond (14 steps), (-)-fortuneicyclidin B with an unprecedented C3-C10 bond (14 steps), and its 2-epimer (-)-fortuneicyclidin A (16 steps) have been also accomplished for the first time.