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Water electrolysis has become an attractive hydrogen production method. Oxygen evolution reaction (OER) is a bottleneck of water splitting as its four-electron transfer procedure presents sluggish reaction kinetics. Designing composite catalysts with high performance for efficient OER still remains a huge challenge. Here, the P-doped cobalt oxide/NiFe layered double hydroxides (P-CoOX/NiFe LDHs) composite catalysts with amorphous/crystalline interfaces are successfully prepared for OER by hydrothermal-electrodeposition combined method. The results of electrochemical characterizations, operando Raman spectra, and DFT theoretical calculations have demonstrated the electrons in the P-CoOX/NiFe LDHs heterointerfaces are easily transferred from Ni2+ to Co3+ because that the amorphous configuration of P-CoOX can well induce Ni-O-Co orbital coupling. The electron transfer of Ni2+ to the surrounding Fe3+ and Co3+ will lead to the unoccupied eg orbitals of Ni3+ that can promote water dissociation and accelerate *OOH migration to improve OER catalytic performance. The optimized P-CoOX/NiFe LDHs exhibit superior catalytic performance for OER with a very low overpotential of 265 mV at 300 mA cm-2 and excellent long-term stability of 500 h with almost no attenuation at 100 mA cm-2. This work will provide a new method to design high-performance NiFe LDHs-based catalysts for OER.
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The development of efficient urea oxidation reaction (UOR) catalysts helps UOR replace the oxygen evolution reaction (OER) in hydrogen production from water electrolysis. Here, we prepared Fe-doped Ni2P/NiSe2 composite catalyst (Fe-Ni2P/NiSe2-12) by using phosphating-selenizating and acid etching to increase the intrinsic activity and active areas. Spectral characterization and theoretical calculations demonstrated that electrons flowed through the Ni-P-Fe-interface-Ni-Se-Fe, thus conferring high UOR activity to Fe-Ni2P/NiSe2-12, which only needed 1.39 V vs RHE to produce the current density of 100 mA cm-2. Remarkably, this potential was 164 mV lower than that required for the OER under the same conditions. Furthermore, EIS demonstrated that UOR driven by the Fe-Ni2P/NiSe2-12 exhibited faster interfacial reactions, charge transfer, and current response compared to OER. Consequently, the Fe-Ni2P/NiSe2-12 catalyst can effectively prevent competition with OER and NSOR, making it suitable for efficient hydrogen production in UOR-assisted water electrolysis. Notably, when water electrolysis is operated at a current density of 40 mA cm-2, this UOR-assisted system can achieve a decrease of 140 mV in the potential compared to traditional water electrolysis. This study presents a novel strategy for UOR-assisted water splitting for energy-saving hydrogen production.
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A long-term goal of rechargeable zinc-air batteries (ZABs) has always been to design bifunctional electrocatalysts that are robust, effective, and affordable for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). It has become a feasible method to construct metal/metal oxide interfaces to achieve superior electrocatalytic performance for ORR and OER by enhanced charge transfer. In this study, Co/Co3O4 heterojunctions were successfully prepared and encased in porous N-doped mesoporous carbon (Co/Co3O4@NC) via a simple condensation-carbonization-etching method. The extensive specific surface area of Co/Co3O4@NC facilitates effective interaction between the electrolyte and the catalyst, thereby enabling sufficient exposure of active sites for the ORR and the OER, consequently enhancing the rate of transport of active species. The well-designed Co/Co3O4@NC delivers superior ORR catalytic activity with a half-wave potential of 0.82 V (vs RHE) and a low overpotential of 347 mV at 10 mA cm-2 for OER in alkaline solution. The power density of Co/Co3O4@NC-based alkaline aqueous ZAB (156.5 mW cm-2) is superior to the commercial Pt/C + IrO2-based alkaline aqueous ZAB, and the cycling stability of ZAB is up to 220 h. In addition, Co/Co3O4@NC-based ZAB shows a high power density (50.1 mW cm-2). The construction of metal/metal oxide heterojunction encased in N-doped mesoporous carbon provides a novel route for the design of bifunctional electrocatalysts for high-performance ZABs.
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A precursor-directed biosynthesis approach led to the accumulation of seven new neoantimycin derivatives (1-7) from Streptomyces conglobatus RJ2. Structure elucidation was conducted using NMR and HRESIMS analysis, and the absolute configuration was determined by advanced Marfey's method, Mosher's analysis, and ECD analysis. The obtained compounds revealed selective and significant cytotoxicity, specifically against colorectal cancer cells bearing the K-ras mutation, with IC50 values ranging from 40 nM to 3.5 µM.
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Streptomyces , Streptomyces/química , Streptomyces/metabolismo , Humanos , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Ensayos de Selección de Medicamentos Antitumorales , Mutación , Resonancia Magnética Nuclear Biomolecular , Compuestos OrgánicosRESUMEN
Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood-brain barrier architecture, and intriguingly, the regulation of emotions and behaviors. Microglia have a profound impact on neuronal survival, brain wiring and synaptic plasticity. As professional phagocytic cells in the brain, they remove dead cell debris and neurotoxic agents via an elaborate mechanism. The functional profile of microglia varies considerately depending on age, gender, disease context and other internal or external environmental factors. Numerous studies have demonstrated a pivotal involvement of microglia in neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain and other symptoms associated with major depression disorder, anxiety disorder, autism spectrum disorder and schizophrenia. In this review, we summarized the latest discoveries regarding microglial ontogeny, cell subtypes or state spectrum, biological functions and mechanistic underpinnings of emotional and behavioral disorders. Furthermore, we highlight the potential of microglia-targeted therapies of neuropsychiatric disorders, and propose outstanding questions to be addressed in future research of human microglia.
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Trastorno del Espectro Autista , Microglía , Humanos , Sistema Nervioso Central , Encéfalo/fisiología , Plasticidad NeuronalRESUMEN
BACKGROUND: The inflammation and immune response contribute to ischemic stroke pathology. Damaged brain cells release inflammatory substances to activate the immune system in the acute phase of stroke, including altering the interferon signaling pathway. However, the involvement of histone deacetylation in stroke remains unclear. METHODS: To investigate whether histone deacetylation modulation could regulate the interferon signaling pathway and mediate the pathogenic changes after stroke, the middle cerebral artery occlusion (MCAO) mouse model was treated with histone deacetylase 3 (HDAC3) inhibitor and RGFP966. Additionally, a series of approaches, including middle cerebral artery occlusion (MCAO), real-time polymerase chain reaction (PCR), western blot, 2,3,5-triphenyltetrazolium chloride (TTC) staining, behavioral experiments, and confocal imaging were utilized. RESULTS: It is observed that RGFP966 pretreatment could lead to better outcomes in the MCAO mouse model, including the decrease of infarction volumes, the amelioration of post-stroke anxiety-like behavior, and the relief of inflammatory responses. Furthermore, we found that RGFP966 could counteract the hyperactivation of the interferon signaling pathway and the excessive expression of Z-DNA Binding Protein 1 (ZBP1) in microglia. CONCLUSIONS: We demonstrated a novel mechanism that HDAC3 inhibition could ameliorate the pathological injury after ischemic stroke by downregulating the ZBP1/phosphorylated Interferon Regulatory Factor 3 (p-IRF3) pathway. Thus, these data provide a new promising target for therapies for ischemic stroke.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratones , Animales , Infarto de la Arteria Cerebral Media , Interferones , Histonas , Modelos Animales de EnfermedadRESUMEN
With the common use of poly ADP-ribose polymerase inhibitors (PARPi) for the man-agement of epithelial ovarian cancer (EOC) across the treatment life cycle, there is a critical need for the development of functional tests, as a complementary to genomic assays, in the study of PARPi sensitivity and resistance. Patient-derived organoids (PDOs) are found feasible for rapid functional testing and predicting drug response. Here, we established a series of PDOs from EOC and tested the sensitivity of seven cases to various agents including PARPi. PDOs recapitulated patient clinical response to platinum chemotherapy and displayed drug response heterogeneity to targeted agents including PARPi. Of three PDOs harboring mutational signature of homologous recombination repair (HRR) deficiency, two were PARPi sensitive while one was inherent resistant. Another PDO derived from a patient who relapsed during olaparib maintenance therapy was found acquired resistant to PARPi. Subsequent functional analysis revealed the potential resistant mechanisms related to replication fork protection and HRR functional restoration, and combination strategies targeting the mechanisms could reverse the resistance. Our research demonstrated the capacity of EOC PDOs for evaluating the sensitivity to PARPi under different settings, exploring mechanisms of resistance, and identifying effective combined strategies, which has implications for the clinical application of PARPi.
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Antineoplásicos , Neoplasias Ováricas , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/genética , Resistencia a Antineoplásicos , Femenino , Humanos , Organoides , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéuticoRESUMEN
Quantitative detection of different types of reactive oxygen species (ROS) is vital for understanding the crucial roles of them in biological processes. However, few researches achieved the detection of multiple types of ROS with one probe until now. Given this, we designed and prepared fluorescent gold nanoclusters capped by dual ligand bovine serum albumin and lysozyme (BSA-LYS-AuNCs), which could detect 3 specific types of ROS based on its different fluorescent responses to H2O2, â¢OH and ClO-, respectively. The limit of detection (LOD) of H2O2, â¢OH, and ClO- was as low as 0.82 µM, 0.45 µM, and 0.62 µM. Moreover, as an important ROS type, ClO- was detected with high sensitivity and low LOD by BSA-LYS-AuNCs. It was also proved that the crosslinking of protein mainly contributed to the unique fluorescent characteristics of the probe exposing to ClO-. Furthermore, the fluorescent probe achieved the smart detection of hROS (including â¢OH and ClO-) and wROS (the form of H2O2) in the real sample, which could also been applied specifically to the detection of antioxidants, e.g. ascorbic acid. The gold nanoclusters developed have high potential for the smart detection of multiple ROS in the body fluid of organisms.
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Oro , Peróxido de Hidrógeno , Ligandos , Especies Reactivas de OxígenoRESUMEN
Tumour necrosis factor-α (TNF-α), a crucial cytokine, has various homeostatic and pathogenic bioactivities. The aim of this study was to assess the neuroprotective effect of ketamine against TNF-α-induced motor dysfunction and neuronal necroptosis in male C57BL/6J mice in vivo and HT-22 cell lines in vitro. The behavioural testing results of the present study indicate that ketamine ameliorated TNF-α-induced neurological dysfunction. Moreover, immunohistochemical staining results showed that TNF-α-induced brain dysfunction was caused by necroptosis and microglial activation, which could be attenuated by ketamine pre-treatment inhibiting reactive oxygen species production and mixed lineage kinase domain-like phosphorylation in hippocampal neurons. Therefore, we concluded that ketamine may have neuroprotective effects as a potent inhibitor of necroptosis, which provides a new theoretical and experimental basis for the application of ketamine in TNF-α-induced necroptosis-associated diseases.
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Hipocampo/efectos de los fármacos , Ketamina/farmacología , Trastornos Motores/tratamiento farmacológico , Necrosis/tratamiento farmacológico , Neuronas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Línea Celular , Supervivencia Celular , Hipocampo/patología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/metabolismo , Modelos Animales , Trastornos Motores/inducido químicamente , Necrosis/inducido químicamente , Necrosis/patología , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológicoRESUMEN
Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B-E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B-E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS-PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.
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Antibióticos Antineoplásicos/biosíntesis , Proteínas Bacterianas/metabolismo , Depsipéptidos/biosíntesis , Hidroxibenzoatos/química , Sintasas Poliquetidas/metabolismo , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/toxicidad , Línea Celular Tumoral , Supervivencia Celular , Depsipéptidos/química , Depsipéptidos/toxicidad , Humanos , Compuestos Orgánicos/química , Compuestos Orgánicos/metabolismo , Compuestos Orgánicos/toxicidad , Streptomyces/enzimología , Streptomyces/metabolismoRESUMEN
Asperfloketals A (1) and B (2), two 1(10 â 6)-abeo-14,15-secosteroids featuring a novel trioxahexaheterocyclic ring system, were isolated from the sponge-associated fungus Aspergillus flocculosus 16D-1. Their structures were elucidated by extensive spectroscopic analysis and NMR chemical shifts calculations, supported by DP4+ probability analysis, and their absolute configurations were determined by ECD calculations and the modified Mosher's method. Asperfloketals A and B showed strong anti-inflammatory activity in the CuSO4-induced transgenic fluorescent zebrafish but displayed no cytotoxicity against HeLa, HepG2, and SW480 cell lines.
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Aspergillus , Pez Cebra , Animales , Ergosterol/análogos & derivados , Estructura MolecularRESUMEN
The aim of this study was to evaluate the effects of butyrolactone-I (A6) on type 2 diabetes (T2D) in db/db mice because A6 was found to inhibit α-glucosidase activities and TNF-α release, which were associated with improving T2D. Male db/db mice were divided into 6 groups and given an equivalent volume of olive oil, acarbose, or different doses of A6 for 4 wk (n = 8/group). In this study, 11 butenolide derivatives were screened for their α-glucosidase and TNF-α suppressive activity in vitro. A6, an efficient α-glucosidase inhibitor, exerts hypoglycemic and multiple activities in reducing weight, improving glucose tolerance and insulin resistance, increasing short-chain fatty acid (SCFA) levels, activating SCFA-induced increases in glucagon-like peptide 1 and peroxisome proliferator-activated receptor-γ expression, enhancing intestinal mucosal barrier function and mitigating endoxemia in db/db mice. These effects may result from mediation of gut microbiota by A6. Meanwhile, A6, with potent TNF-α-lowering properties, was demonstrated to have multiple salutary effects with excellent structural stability and long-term safety in vivo. A6, an effective α-glucosidase inhibitor with high security and stability, exerted potent antidiabetic effects in vivo. Furthermore, the modulation of gut microbiota of A6 was demonstrated to be one of the mechanisms contributing to anti-inflammation properties and improving endoxemia. Our work confirms that the compound A6 is a prospective drug candidate for T2D.-Wu, W., Liu, L., Zhu, H., Sun, Y., Wu, Y., Liao, H., Gui, Y., Li, L., Liu, L., Sun, F., Lin, H. Butyrolactone-I, an efficient α-glucosidase inhibitor, improves type 2 diabetes with potent TNF-α-lowering properties through modulating gut microbiota in db/db mice.
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4-Butirolactona/análogos & derivados , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , 4-Butirolactona/farmacología , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiología , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/patología , Ácidos Grasos Volátiles/metabolismo , Masculino , RatonesRESUMEN
PURPOSE: To identify a lncRNA signature to predict survival of breast cancer (BRCA) patients. METHODS: A total of 1222 BRCA case and control datasets were downloaded from the TCGA database. The weighted gene co-expression network analysis of differentially expressed mRNAs was performed to generate the modules associated with BRCA overall survival status and further construct a hub on competing endogenous RNA (ceRNA) network. LncRNA signatures for predicting survival of BRCA patients were generated using univariate survival analyses and a multivariate Cox hazard model analysis and validated and characterized for prognostic performance measured using receiver operating characteristic (ROC) curves. RESULTS: A prognostic score model of eight lncRNAs signature was identified as Prognostic score = (0.121 × EXPAC007731.1) + (0.108 × EXPAL513123.1) + (0.105 × EXPC10orf126) + (0.065 × EXPWT1-AS) + (- 0.126 × EXPADAMTS9-AS1) + (- 0.130 × EXPSRGAP3-AS2) + (0.116 × EXPTLR8-AS1) + (0.060 × EXPHOTAIR) with median score 1.088. Higher scores predicted higher risk. The lncRNAs signature was an independent prognostic factor associated with overall survival. The area under the ROC curves (AUC) of the signature was 0.979, 0.844, 0.99 and 0.997 by logistic regression, support vector machine, decision tree and random forest models, respectively, and the AUCs in predicting 1- to 10-year survival were between 0.656 and 0.748 in the test dataset from TCGA database. CONCLUSIONS: The eight-lncRNA signature could serve as an independent biomarker for prediction of overall survival of BRCA. The lncRNA-miRNA-mRNA ceRNA network is a good tool to identify lncRNAs that is correlated with overall survival of BRCA.
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Biomarcadores de Tumor , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , ARN Largo no Codificante/genética , Anciano , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , MicroARNs/genética , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas , Interferencia de ARN , ARN Mensajero/genética , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
A novel marine actinomycete, designated LHW63014T, isolated from a marine sponge, Craniella species, collected in the South China Sea, was examined using a polyphasic approach. The 16S rRNA gene sequence of strain LHW63014T showed highest similarities to Jishengella endophytica 202201T (98.9â%), Micromonospora olivasterospora DSM 43868T (98.7â%), Micromonospora maris AB-18-032T (98.6â%) and Micromonospora gifhornensis DSM 44337T (98.6â%). Phylogenetic analyses of the family Micromonosporaceae based on the 16S rRNA and gyrB gene sequences indicated that strain LHW63014T and J. endophytica 202201T located within the genus Micromonospora. Morphological and chemotaxonomic characteristics confirmed their affiliation to the genus Micromonospora. Based on phenotypic characteristics, phylogenetic data and digital DNA-DNA hybridization results, strain LHW63014T could be distinguished from its closest taxa, representing a novel species of the genus Micromonospora, for which the name Micromonospora craniellae sp. nov., is proposed, with the type strain LHW63014T (=DSM 106193T=CCTCC AA 2018012T). It is also proposed that J. endophytica be transferred to genus Micromonospora as Micromonospora endophytica comb. nov. (type strain 202201T =CGMCC 4.5597T=DSM 45430T).
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Micromonospora/clasificación , Filogenia , Poríferos/microbiología , Animales , Técnicas de Tipificación Bacteriana , China , ADN Bacteriano/genética , Genes Bacterianos , Micromonospora/aislamiento & purificación , Micromonosporaceae/clasificación , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
Four new cycloheptapeptides, fuscasins A-D (1-4), were isolated from the marine sponge Phakellia fusca collected from the South China Sea. Their planar structures were fully characterized by spectroscopic methods, and the absolute configurations of amino acid residues were determined using the advanced Marfey's method. Structurally, 1 is a unique cycloheptapeptide with a backbone bearing a pyrrolidine-2,5-dione unit. Among the isolated compounds, 1 exhibited potent growth-inhibitory activity against HepG2 cells with an IC50 value of 4.6 µM, whereas it did not show apparent inhibitory effects against the other five human cancer cell lines, MCF-7, HeLa, NCI-H460, PC9, and SW480. Encouragingly, 1 exhibited no cytotoxicity against nonmalignant cells even with a concentration up to 100 µM. These findings suggest that 1 may display a selective inhibitory effect on the growth of HepG2 cells.
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Péptidos Cíclicos/aislamiento & purificación , Poríferos/química , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Biología MarinaRESUMEN
Background: Emergence agitation (EA) is one of the most common complications in clinical general anesthesia during recovery in adults. Remifentanil and propofol can reduce the incidence of EA, but with no randomized controlled trial to evaluate their effectiveness for treating EA. This study aims to compare the effectiveness of remifentanil and propofol for treating EA following general anesthesia. Patients and methods: Among 152 randomized patients with a mean of 49.5 years, and 99 (65.1%) of them being male, 149 were divided into two groups for subsequent analysis. The remifentanil group (Group R, n = 74) received a 0.5µg kg-1 remifentanil infusion followed by a 0.05µg kg-1 min-1 infusion until 15 minutes, after the onset of agitation. The propofol group (Group P, n = 75) received a 1mg kg-1 propofol infusion once agitation occurred. Emergence agitation was assessed using the Riker Sedation Agitation Score, with a score of ≥5 defining emergence agitation. During the post-anesthesia care unit (PACU), the recurrence of emergence agitation, time to extubation, and discharge from PACU were evaluated. Results: The incidence of reoccurring emergence agitation was lower in Group R (29.7%) compared with Group P (49.3%), with an odds ratio of 0.44 (95% CI 0.22-0.85; P=0.014). The time to extubation was shorter in Group R (mean 12min, range 8-15 min) compared with Group P (mean 17min, range 13-21 min) (P<0.001), as was the time discharge from the PACU (mean 30.5 min, range 25-40 min) vs Group P (mean 37.5 min, range 31-50 min) (P=0.001). Conclusion: Treatment of emergence agitation in adults with remifentanil infusion is more effective than propofol, with a shorter time to extubation and discharge from PACU.
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Delirio del Despertar , Propofol , Adulto , Humanos , Masculino , Femenino , Propofol/efectos adversos , Remifentanilo/uso terapéutico , Delirio del Despertar/tratamiento farmacológico , Anestesia General/efectos adversos , Incidencia , Periodo de Recuperación de la Anestesia , Anestésicos Intravenosos/efectos adversosRESUMEN
Introduction: The rapid increasing prevalence of ASD has become a significant global health issue. Caregivers of children with ASD are experiencing higher level of psychological stress and mental disorders. However, interventions to improve the psychological health of caregivers of children with ASD have largely been neglected. Methods: Based on the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model, we initially did in-depth interviews with 8 caregivers, and conducted field observation in two rehabilitation centers to analyze the daily lives, the empowered components, the emotional moments of the children with autism and their caregivers. Then we designed the outline of the picture book, and developed it by a multi-disciplinary team by 4 rounds. After that, this picture book was sent out to 54 caregivers of children with ASD for family-child reading in one month. A quantitative questionnaire was administered before and after their reading to evaluate the efficacy of reducing their stress and affiliate stigma, and improving self-efficacy, resilience, empowerment capacity; and exit interviews were conducted after their initial reading to assess the acceptability, content appropriateness, perceived benefits and generalizability of this picture book. Quantitative data were analyzed by descriptive analysis and paired t-tests using IBM SPSS 26.0. Qualitative data were analyzed using template analysis. Results: In total, 54 caregivers read the picture book with their child, with the total of 149 (an average of 2.76 per family) times reading in one month. Among them, 39 caregivers returned the following-up questionnaires. Although most of the outcome measures did not showed significant changes except the stress level decreased statistically significant (13.38 ± 3.864 to 11.79 ± 3.238, P=0.001), caregivers reported that the picture book echoed their daily lives and gave them a sense of warmth, inspiration, and hope, as well as some insight on family relationships and attitudes towards the disorder. They also expressed a willingness to disseminate the book to other families with children suffering ASD and the public. Conclusion: This specially designed picture book has been proven to be an acceptable, content-appropriate, and effective family-centered psychological intervention, which could be easily scaled up.
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Phase separation, also known as biomolecule condensate, participates in physiological processes such as transcriptional regulation, signal transduction, gene expression, and DNA damage repair by creating a membrane-free compartment. Phase separation is primarily caused by the interaction of multivalent non-covalent bonds between proteins and/or nucleic acids. The strength of molecular multivalent interaction can be modified by component concentration, the potential of hydrogen, posttranslational modification, and other factors. Notably, phase separation occurs frequently in the cytoplasm of mitochondria, the nucleus, and synapses. Phase separation in vivo is dynamic or stable in the normal physiological state, while abnormal phase separation will lead to the formation of biomolecule condensates, speeding up the disease progression. To provide candidate suggestions for the clinical treatment of nervous system diseases, this review, based on existing studies, carefully and systematically represents the physiological roles of phase separation in the central nervous system and its pathological mechanism in neurodegenerative diseases.
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Sistema Nervioso Central , Enfermedades Neurodegenerativas , Humanos , Sistema Nervioso Central/metabolismo , Animales , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Condensados Biomoleculares/metabolismo , Condensados Biomoleculares/química , Mitocondrias/metabolismo , Separación de FasesRESUMEN
BACKGROUND: Interprofessional education (IPE) has been advocated for all healthcare students, and readiness for interprofessional learning significantly influences its effectiveness. It is essential to explore the antecedent factors of readiness for interprofessional learning among nursing students to promote IPE. While a proactive personality might impact readiness for interprofessional learning, its specific role has remained unspecified. OBJECTIVE: To examine the mediation effects of perceived social support and professional identity on the association between proactive personality and readiness for interprofessional learning among nursing students. DESIGN: The study utilised a cross-sectional design. SETTINGS: Research was conducted at two universities and two vocational schools in Hainan Province, China. PARTICIPANTS: On-campus nursing students were invited to participate between March and May 2023. METHODS: A flyer was distributed to the participants with a QR code to scan to voluntarily complete the online survey, including the Readiness for Interprofessional Learning Scale (RIPLS), Proactive Personality Scale, Perceived Social Support Scale and Professional Identity Status Questionnaire Scale 5d. Descriptive analysis, Pearson associations and mediation analysis were conducted using SPSS software version 26.0 and PROCESS version 4.2 for SPSS. RESULTS: The participants' average RIPLS score was 66.93 ± 9.28. Proactive personality (r = 0.633, p < 0.01), perceived social support (r = 0.605, p < 0.01) and professional identity (r = 0.549, p < 0.01) were all positively related to readiness for interprofessional learning. Meanwhile, the relationship between proactive personality and readiness for interprofessional learning was partly mediated by perceived social support (25.15 %), professional identity (13.35 %) and the chain effects (9.48 %) of perceived social support and professional identity. CONCLUSIONS: The nursing students in Hainan, China demonstrated a medium level of readiness for interprofessional learning. Compound strategies that foster proactive personality, provide social support and boost positive professional identity are warranted to improve nursing students' readiness for interprofessional learning.
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Relaciones Interprofesionales , Personalidad , Identificación Social , Apoyo Social , Estudiantes de Enfermería , Humanos , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Estudios Transversales , Femenino , Masculino , China , Encuestas y Cuestionarios , Adulto , Adulto Joven , Educación Interprofesional/métodos , Aprendizaje , Bachillerato en Enfermería/métodos , Actitud del Personal de SaludRESUMEN
Intravenous injectable metformin-Cu(II)-EGCG infinite coordination polymer nanoparticles (metformin-Cu(II)-EGCG ICP NPs) have been synthesized, and an efficient strategy for synergistic tumor therapy by utilizing these nanoparticles in conjunction with micro-electrothermal needles (MENs) was proposed. These nanoparticles display exceptional uniformity with a diameter of 117.5 ± 53.3 nm, exhibit an extraordinary drug loading capacity of 90% and allow for precise control over the drug ratio within the range of 1 : 1 to 1 : 20 while maintaining excellent thermal stability. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction were employed to determine their chemical structure and coordination state. The combination index (CI) value of the metformin-Cu(II)-EGCG ICP NPs was calculated to be 0.19, surpassing that of the two individual drugs and metformin mixed with EGCG (0.98). Importantly, upon intravenous injection, metformin in nanoparticles demonstrated exceptional stability in the bloodstream, while both drugs were rapidly released within the acidic tumor microenvironment. Animal experiments showcased an impressive tumor inhibition rate of 100% within a mere 20-day time frame after the synergistic therapy with a lower dosage (5.0 mg kg-1 of nanoparticles), coupled with a minimal tumor recurrence rate of only 18.75% over a 60-day observation period. These findings indicate the promising prospects of these nanoparticles in tumor treatment.