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Lasers play a significant role in optical communication, medical, and scientific research, owing to their high brightness and high coherence. However, the high spatial coherence will lead to specific challenges, such as speckle noise in imaging and wavefront distortion during propagation through scattering media. Here, a continuous-wave (cw) degenerate cavity laser (DCL) with low spatial coherence is demonstrated with efficient suppression of the thermal lensing effect from the gain crystal. Experimentally, a cw degenerate laser output with about 2000 transverse modes corresponding to a speckle contrast of about 0.0224 is achieved. This laser can be used for speckle reduction and is robust against atmospheric turbulence, which may find applications in the field of laser imaging technology and illumination.
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Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg-1·d-1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1-10 µM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.
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The acidic electrocatalytic conversion of CO2 to multi-carbon (C2+) oxygenates is of great importance in view of enhancing carbon utilization efficiency and generating products with high energy densities, but suffering from low selectivity and activity. Herein, we synthesized Ag-Cu alloy catalyst with highly rough surface, by which the selectivity to C2+ oxygenates can be greatly improved. In a strongly acidic condition (pH=0.75), the maximum C2+ products Faradaic efficiency (FE) and C2+ oxygenates FE reach 80.4% and 56.5% at -1.9 V versus reversible hydrogen electrode, respectively, with a ratio of FEC2+ oxygenates to FEethylene up to 2.36. At this condition, the C2+ oxygenates partial current density is as high as 480 mA cm-2. The in situ Raman measurements and control experiments indicate that the high generation of C2+ oxygenates over the catalyst originates from its large surface roughness and Ag alloying.
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Benzotriazoles are a class of ultraviolet absorbents which absorb UV ranging from 280 to 400 nm and are widely used in personal care products and industrial production. Their residues in environmental matrices have received great concern in recent years, but most studies have focused on pollution in water and few have examined BUVs in marine sediments. In this study, we investigated the occurrence, potential sources, and ecological risk of 15 types of BUVs in the sediments of Bohai Sea in China for the first time. The total concentrations of the 15 BUVs ranged from 0.139 to 4.125 ng/g dw with a median concentration of 0.340 ng/g. UV-327 and UV-360 were predominant among the BUV congeners, accounting for 22.6% and 17.7% of the total concentration of Σ15BUVs, respectively. The detection frequencies of the BUV congeners generally exceeded 95%, reflecting the wide use and persistence of these chemicals. The concentrations of the BUV congeners in this study were one order of magnitude lower than those in other areas. Moreover, the distributions of BUVs presented a decreasing gradient from nearshore to offshore, indicating that coastal input was the main influencing factor. Two potential primary sources, plastic manufacturing and domestic wastewater, were identified via principle component analysis. The ecological risks of BUVs to aquatic organisms in the sediments were evaluated using the risk quotient (RQ) method. Generally, the risk to aquatic organisms from exposure to BUVs in Bohai Sea could be considered low at the measured concentrations. While our study provides important new insight into the ecological risks of BUVs in the estuary, further research on the pollution levels and toxicity risks of BUVs in Bohai Sea should be conducted to better understand the ecological effect of these pollutants.
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Coupling by metal-carbene transfer enables the formation of several different bonds at the carbenoid site, enabling prochiral Csp3 centers that are fundamental three-dimensional substructures for medicines to be forged with increased efficiency. However, strategies using bulk chemicals are rare because of the challenge of breaking two unactivated geminal bonds. Herein, we report the reactivity of ethers to form metal-carbene intermediate by cleavage of α-Csp3-H/Csp3-O bonds, which achieve selective coupling with arylmagnesium bromides and chlorosilanes. These couplings are catalysed by cyclic (alkyl)(amino)carbene-chromium complex and enable the one-step formation of 1,n-arylsilyl alcohols and α-arylated silanes. Mechanistic studies indicate that the in-situ formed low-valent Cr might react with iodobenzene to form phenyl radical species, which abstracts the α-H atom of ether in giving α-oxy radical. The latter combines with Cr by breaking α-Csp3-O bond to afford metal-carbene intermediate, which couples with aryl Grignard and chlorosilane to form two σ-bonds.
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Sinensetin is a product isolated from Orthosiphon aristatus, and its antitumor activities have been well established. This study focused on the role and mechanism of sinensetin in lung adenocarcinoma (LUAD). LUAD cells were treated with various concentrations of sinensetin. The proliferation, migration, invasion, and angiogenesis of LUAD cells were detected using colony formation, transwell, and tube formation assays, respectively. The protein levels of VEGF-A, VEGFR-2, and phosphorylated AKT (ser473) were measured by western blotting. The targeted relationship between VEGF-A and miR-374c-5p was verified by luciferase reporter assay. BALB/c nude mice inoculated with A549 cells were treated with sinensetin (40 mg/kg/day) by gavage for 21 days to investigate the effect of sinensetin on tumor growth and angiogenesis in vivo. We found that sinensetin reduced proliferation, migration, invasion, angiogenesis, and cancer stem characteristics of LUAD cells. Sinensetin also suppressed LUAD tumor growth and angiogenesis in vivo. Sinensetin downregulated VEGF-A expression in LUAD cells by enhancing miR-374c-5p expression. MiR-374c-5p inhibited the VEGF-A/VEGFR-2/AKT pathway in LUAD cells. The antitumor effect of sinensetin was reversed by overexpression of VEGF-A or inhibition of miR-374c-5p. Overall, sinensetin upregulates miR-374c-5p to inhibit the VEGF-A/VEGFR-2/AKT pathway, thereby exerting antitumor effect on LUAD.
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Renewing metal-poisoned NH3-SCR catalysts holds great potential for mitigating environmental pollution and utilizing hazardous wastes simultaneously. Ionic compounds containing heavy metals often exhibit limited solubility due to their high polarizability, making traditional washing techniques ineffective in removing heavy metal poisons. This study presents a gas-based method for regenerating heavy-metal-poisoned V2O5-WO3/TiO2 catalysts employed in NH3-SCR techniques. The regeneration is achieved by employing a masking and reconstruction strategy, which involves the in situ formation of NO2 to mediate the production of SO3. This enables the effective bonding of Pb and triggers the reconstruction of active VOx sites. In situ spectroscopy confirms that the sulfation of PbO restores acidity, while the occupied effect resulting from the sulfation of TiO2 promotes the formation of more polymeric VOx species. Consequently, the regenerated catalyst exhibits enhanced activity and superior resistance to metal poisons compared with the fresh catalyst. The innovative method offers a promising solution for extending the lifespan of poisoned catalysts, reducing waste generation, and enhancing the efficiency of NH3-SCR systems.
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PURPOSE: Cutaneous metastasis (CM) accounts for 5-30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM. MATERIALS: We retrospectively reviewed a total of 13 patients with histological or cytological diagnosis of breast cancer and CM. Clinical information was extracted from the medical records. The mutational landscape of matched primary tumors with their lymph nodes or CM tissues were analyzed using next-generation sequencing (NGS) of 425 cancer-relevant genes. All tissues were also analyzed by immunohistochemistry (IHC). The association of prognosis with various clinical and molecular factors was also evaluated. RESULTS: More than half of the patients were Ki67 low (< 50%, 53.7%). Most patients (12, 92.3%) had other metastasis sites other than skin. The median time from diagnosis to the presentation of CM (T1) was 15 months (range: 0-94 months) and the median time from CM to death (T2) was 13 months (range 1-78). The most frequently altered genes across the three types of tissues were TP53 (69.6%, 16/23), PIK3CA (34.8%, 8/23), and MYC (26.1%). The number of alterations in CM tends to be higher than in primary tumors (median 8 vs. 6, P = 0.077). Copy number loss in STK11, copy number gain in FGFR4, TERT, AR, FLT4 and VEGFA and mutations in ATRX, SRC, AMER1 and RAD51C were significantly enriched in CM (all P < 0.05). Ki67 high group (> 50%) showed significantly shorter T1 than the Ki67 low group (≤ 50%) (median 12.5 vs. 50.0 months, P = 0.036). TP53, PIK3CA mutations, and TERT amplification group were associated with inferior T2 (median 11 vs. 36 months, P = 0.065; 8 vs. 36 months, P = 0.013, 7 vs. 36 months, P = 0.003, respectively). All p values were not adjusted. CONCLUSION: We compared the genomic features of primary breast cancer tissues with their corresponding CM tissues and discussed potential genes and pathways that may contribute to the skin metastasis of advanced breast cancers patients. TP53, PIK3CA mutant, and TERT amplification may serve as biomarkers for poor prognosis for CM patients.
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Biomarcadores Tumorais , Neoplasias da Mama , Mutação , Neoplasias Cutâneas , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Prognóstico , Biomarcadores Tumorais/genética , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Idoso de 80 Anos ou mais , Imuno-HistoquímicaRESUMO
Reverse electrodialysis (RED) systems employing charged nanochannels have gained prominence for harvesting salinity gradient energy. Nevertheless, fabricating nanochannel membranes with optimal ion selectivity and high energy conversion efficiency remains a significant challenge. In this study, we develop oppositely charged bacterial cellulose (BC)/polymer composite nano-channel membranes with precisely designed nanochannel architectures by integrating chemical modification with composite material technology. Initially, BC undergoes chemical modifications, including 2,2,6,6-Tetramethylpiperidine 1-oxy radical (TEMPO) oxidation and quaternisation. Subsequently, a polymer network is integrated into the modified BC network through a polymer synthesis technique. This approach successfully yields negatively charged BC/poly(sodium p-styrene sulfonate) (NBC/PSS) composite double-networked nanochannel membranes and positively charged BC/poly(dopamine) (PBC/PDA) composite double-networked nanochannel membranes. Notably, these membranes exhibit significantly enhanced ionic conductivities, with values of 0.0008 and 0.0014 S cm-1 for the NBC/PSS and PBC/PDA composites, respectively, while also demonstrating superior ion selectivity with cation transfer numbers of 0.9 and 0.1 respectively. Furthermore, a series connection of 30 BCE/charged polymer-based RED devices successfully powers an electronic calculator. This work offers novel insights into the design of BC-based RED devices by integrating chemical modification and polymeric composite strategies for efficient salinity gradient energy generation.
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Celulose , Membranas Artificiais , Polímeros , Salinidade , Celulose/química , Polímeros/química , Bactérias , Óxidos N-Cíclicos/química , Nanoestruturas/químicaRESUMO
Shift work is a recognized work pattern for nurses worldwide. The disruption of shift workers' biological clocks usually leads to sleep disorders and affects their awareness at work. Eveningness and occupational stress might be effective in causing burnout syndrome. Therefore, this study aimed to evaluate the chronotype, job burnout and perceived stress among Chinese tertiary hospital nurses, and understand the predictors of circadian rhythm in this group. Between July and September 2020, 23 hospitals were randomly selected from 113 tertiary hospitals in Hunan Province. Twenty-five percent of the nurses working in each hospital were targeted for selection. 28.1% and 17.6% of nurses reported eveningness type and morningness type, respectively. The scores for emotional exhaustion, depersonalization, and perceived stress of eveningness nurses were higher than those of morningness counterparts. Eveningness nurses also reported a lower sense of personal accomplishment. Risk factors of eveningness included being under 30 years old, never exercising, having the stressors of late-night shifts and career development, higher levels of emotional exhaustion, sleep latency, sleep duration, and hypnotic use. Shifts may be unavoidable for nurses, nevertheless, understanding the predictors and related factors of chronotype for nurses is necessary for nursing educators and managers to develop a reasonable shift system and appropriate measures to assist nurses in adjusting their work.
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Esgotamento Profissional , Cronotipo , Enfermeiras e Enfermeiros , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Estudos Transversais , População do Leste Asiático , Recursos Humanos de Enfermagem Hospitalar/psicologia , Estresse Ocupacional , Fatores de Risco , Jornada de Trabalho em Turnos , Sono/fisiologia , Inquéritos e Questionários , Centros de Atenção Terciária , Tolerância ao Trabalho ProgramadoRESUMO
Passively mode-locked fiber lasers based on nonlinear polarization rotation (NPR) have been widely used due to their ability to produce short pulses with high peak power. Nevertheless, environmental perturbations can influence the mode-locked state, making it a challenge for the practical implementation. Therefore, researchers are searching for assessment criteria to quickly assist and maintain mode-locking of NPR fiber lasers. Speckle patterns containing spectral information can be generated when the laser transmits through a scattering medium, which can serve as indicators of the mode-locked state. The mode-locked regions are confined to the area close to the minimum texture contrast of speckle patterns. Based on these characteristics, we manually simulate the automatic mode-locking (AML). In addition, we utilize convolutional neural networks (CNNs) to recognize speckle patterns of wavelength tunable lasers and determine the center wavelength.
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Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.
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Acetilcisteína , Biofilmes , Candida parapsilosis , Candidemia , Infecções Relacionadas a Cateter , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Acetilcisteína/farmacologia , Humanos , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/genética , Candida parapsilosis/fisiologia , Infecções Relacionadas a Cateter/microbiologia , Candidemia/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Antifúngicos/farmacologiaRESUMO
Benzotriazole ultraviolet absorbents (BUAs) of emerging concern were recently monitored in seawater and sediments from the Bohai Sea (BS) and North Yellow Sea (NYS), which are impacted by human activities, to elucidate their regional occurrence patterns, phase distributions, and contamination profiles. Although environmental variables such as sedimentary organic carbon, particle size, and salinity, as well as hydrological conditions, affected the environmental occurrence of BUAs in the BS and NYS, the source dependence of BUA distributions associated with urban impacts and riverine inputs was highlighted. Substantial spatial variability in the composition patterns and contamination profiles of BUAs identified through correlation and principal component analyses were likely caused by region-specific sources and characteristics. The distribution of target BUAs between the sediment and seawater phases showed no dependence on the octanol-water partition coefficient (KOW) but exhibited marked spatial variations. The diversity of BUA sorption behaviors was further explained by the total organic carbon (TOC)-normalized distribution coefficient (KTOC). Classic logKTOC-logKOW linear relationships accurately predicted the phase distributions of UV-326, UV-328, and UV-234, but deviations were found for lighter and heavier BUAs, possibly due to the influences of physical disturbance and microparticle binding.
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INTRODUCTION: Depression is a major global health problem, with high prevalence rates of depressive symptoms observed among the elderly population in China, particularly exacerbating in rural areas. Due to a lack of professional mental health training and inadequate psychotherapy capacity within primary medical staff, rural elderly individuals grappling with depressive symptoms often encounter challenges in receiving timely diagnosis and treatment. In this landscape, the modified behavioural activation treatment (MBAT) emerges as a promising approach due to its practicality, ease of therapist training and application, patient acceptability, and broad applicability. However, existing evidence for MBAT mainly hails from developed countries, leaving a gap in its adaptation and implementation within rural China. This study aims to develop an MBAT training programme for primary medical staff to manage depressive symptoms among rural elderly and evaluate its effectiveness. METHODS AND ANALYSIS: A cluster randomised controlled trial will be conducted in 10 randomly selected township hospitals in Lengshuijiang and Lianyuan, Hunan Province. We aim to recruit 150 participants, with 5 township hospitals selected for each group, each consisting of 15 participants. The intervention group will implement the MBAT training programme, while the control group will receive usual care training programme. Depressive symptoms, psychosocial functioning, quality of life and satisfaction will be measured at baseline, immediately post-intervention, and at 3 and 6 months post-intervention. Effectiveness will be assessed using linear or generalised linear mixed models. ETHICS AND DISSEMINATION: This study has obtained approval from the Institutional Review Board of the Third Xiangya Hospital, Centre South University (No.: 2022-S261). Results will be disseminated through publication in international peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300074544.
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Depressão , População Rural , Humanos , China , Depressão/terapia , Idoso , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Masculino , Qualidade de Vida , Pessoal de Saúde/educação , Pessoal de Saúde/psicologia , Terapia Comportamental/métodos , Atenção Primária à SaúdeRESUMO
n-propanol is an important pharmaceutical and pesticide intermediate. To produce n-propanol by electrochemical reduction of CO2 is a promising way, but is largely restricted by the very low selectivity and activity. How to promote the coupling of *C1 and *C2 intermediates to form the *C3 intermediate for n-propanol formation is challenging. Here, we propose the construction of bicontinuous structure of Cu2O/Cu electrocatalyst, which consists of ultra-small Cu2O nanodomains, Cu nanodomains and large amounts of grain boundaries between Cu2O and Cu nanodomains. The n-propanol current density is as high as 101.6â mA cm-2 at the applied potential of -1.1â V vs. reversible hydrogen electrode in flow cell, with the Faradaic efficiency up to 12.1 %. Moreover, the catalyst keeps relatively stable during electrochemical CO2 reduction process. Experimental studies and theoretical calculations reveal that the bicontinuous structure of Cu2O/Cu can facilitate the *CO formation, *CO-*CO coupling and *CO-*OCCO coupling for the final generation of n-propanol.
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Vascular aging exacerbates diabetes-associated vascular damage, a major cause of microvascular and macrovascular complications. This study aimed to elucidate key genes and pathways underlying vascular aging in diabetes using integrated bioinformatics and machine learning approaches. Gene expression datasets related to vascular smooth muscle cell (VSMC) senescence and diabetic vascular aging were analyzed. Differential expression analysis identified 428 genes associated with VSMC senescence. Functional enrichment revealed their involvement in cellular senescence, ECM-receptor interaction, PI3K-Akt and AGE-RAGE signaling pathways. Further analysis of diabetic vascular aging datasets revealed 52 differentially expressed genes, enriched in AMPK signaling, AGE-RAGE signaling, cellular senescence, and VEGF signaling pathways. Machine learning algorithms, including LASSO regression and SVM-RFE, pinpointed six key genes: TFB1M, FOXRED2, LY75, DALRD3, PI4K2B, and NDOR1. Immune cell infiltration analysis demonstrated correlations between diabetic vascular aging, the identified key genes, and infiltration levels of plasma cells, M1 macrophages, CD8+ T cells, eosinophils, and regulatory T cells. In conclusion, this study identified six pivotal genes (TFB1M, FOXRED2, LY75, DALRD3, PI4K2B, and NDOR1) closely associated with diabetic vascular aging through integrative bioinformatics and machine learning approaches. These genes are linked to alterations in the immune microenvironment during diabetic vascular aging. This study provides a reference and basis for molecular mechanism research, biomarker mining, and diagnosis and treatment evaluation of diabetes-related vascular aging.
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Envelhecimento , Biologia Computacional , Aprendizado de Máquina , Humanos , Envelhecimento/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Transdução de Sinais/genética , Diabetes Mellitus/genética , Senescência Celular/genéticaRESUMO
AIMS: Ischaemia/reperfusion (I/R) injury is an important complication of reperfusion therapy for acute myocardial infarction, extremely compromising the cardiac benefits of revascularization; however, specific and efficient treatment for cardiac I/R injury is still lacking. Isthmin-1 (ISM1) is a novel adipokine and plays indispensable roles in regulating glycolipid metabolism and cell survival. The present study aims to investigate the potential role and molecular mechanism of ISM1 in cardiac I/R injury using gain- and loss-of-function approaches. METHODS AND RESULTS: Cardiac-specific ISM1 overexpression and silence were achieved using an adeno-associated virus serotype 9 system, and then these mice were subjected to I/R surgery, followed by biochemical test, echocardiography and histopathologic examinations, etc. Meanwhile, neonatal rat cardiomyocytes (NRCMs) with ISM1 silence or overexpression also received simulated I/R (sI/R) injury to further verify its role in vitro. The potential downstream pathways and molecular targets of ISM1 were screened by RNA sequencing. We also treated injured mice and NRCMs with recombinant ISM1 (rISM1) to explore whether supplementation with ISM1 was sufficient to protect against I/R injury. Furthermore, acute myocardial infarction patients with percutaneous coronary intervention (PCI) and paired healthy controls were included to reveal the clinical relevance of circulating ISM1. Cardiac-specific ISM1 silencing aggravated while ISM1 overexpression alleviated I/R-induced acute cardiac injury and cardiac remodelling and dysfunction. Mechanistically, ISM1 targeted αvß5 integrin to facilitate the nuclear accumulation of nuclear transcription factor Y subunit alpha, transcriptionally increased soluble guanylyl cyclase beta subunit expression, and eventually enhanced cGMP generation. Besides, we confirmed that treatment with rISM1 before or after reperfusion could confer cardioprotective effects in mice. Clinically, lower ISM1 levels post-PCI was associated with worse outcome in patients. CONCLUSION: ISM1 can protect against cardiac I/R injury through cGMP-PKG signalling pathway, and it is a promising therapeutic and predictive target of cardiac I/R injury.
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GMP Cíclico , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Transdução de Sinais , Animais , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Humanos , Masculino , GMP Cíclico/metabolismo , Células Cultivadas , Adipocinas/metabolismo , Adipocinas/genética , Função Ventricular Esquerda , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/genética , Estudos de Casos e Controles , Remodelação Ventricular , Ratos , Ratos Sprague-Dawley , Sistemas do Segundo Mensageiro , Camundongos , Proteínas de MembranaRESUMO
BACKGROUND: Psychological stress and anxiety have seriously affected the ability of new clinicians to adapt and coordinate their clinical work. Traditional pre-job training is often not very good at assisting new recruits to regulate their emotional problems. METHODS: This study is a randomized controlled study. A total of 435 newly recruited clinicians participated in the study. 428 clinicians were randomized into a control group (n = 214) and an intervention group (n = 214). The control group conducted regular pre-job training. Doctors of the intervention group attend a themed course every two weeks on the basis of regular induction training. Their physiological status was evaluated by Perceived Stress Scale (PPS-10), Generalized Anxiety Scale (GAD-7) and Psychological Resilience Scale (CD-RISC-10) 3 months later. Participants in the intervention group received a training satisfaction questionnaire. RESULTS: After entering the clinic for 3 months, the PSS-10 and GAD-7 scores of the intervention group were significantly lower than that of the control group. Consistently, the CD-RISC-10 score of new clinicians who received proof-of-concept pre-job training was significantly higher than that of new doctors in the control group. CONCLUSION: New doctors received the proof-of-concept group experienced alleviation in stress and anxiety.