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The development of electrocatalysts with low cost, high efficiency, and long-term durability is crucial for advancing green hydrogen production. Transition metal phosphides (TMPs) have been proved to be efficient electrocatalyst, while the improvement in the performance and durability of the TMPs remains a big challenge. Employing atmospheric pressure chemical vapor deposition (APCVD) and phosphorization, FeP/Ti electrodes are fabricated featuring controllable oxygen ingredients (O-FeP/Ti). This manipulation of oxygen content fine-tunes the electronic structure of the catalyst, resulting in improved surface reaction kinetics and catalytic activity. The optimized O-FeP-400/Ti exhibits outstanding HER activity with overpotentials of 142 and 159 mV at -10 mA cm-2 in 0.5 M H2SO4 and 1 M KOH, respectively. Notably, the obtained O-FeP/Ti cathode also displays remarkable durability of up to 200 h in acidic electrolyte with surface topography remaining intact. For the first time, the low-valence titanium oxide (Ti3O) interlayer is identified in the composite electrode and ascribed for the superior connection between Ti substrate and the surface O-FeP catalyst, as supported by experimental results and density functional theory (DFT) analysis. This work has expanded the potential applications of transition metal phosphides (TMPs) as a cost-effective, highly efficient and durable catalyst for water splitting.
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The large mid-infrared (MIR) spectral region, ranging from 2.5 µm to 25 µm, has remained under-exploited in the electromagnetic spectrum, primarily due to the absence of viable transceiver technologies. Notably, the 8-14 µm long-wave infrared (LWIR) atmospheric transmission window is particularly suitable for free-space optical (FSO) communication, owing to its combination of low atmospheric propagation loss and relatively high resilience to turbulence and other atmospheric disturbances. Here, we demonstrate a direct modulation and direct detection LWIR FSO communication system at 9.1 µm wavelength based on unipolar quantum optoelectronic devices with a unprecedented net bitrate exceeding 55 Gbit s-1. A directly modulated distributed feedback quantum cascade laser (DFB-QCL) with high modulation efficiency and improved RF-design was used as a transmitter while two high speed detectors utilizing meta-materials to enhance their responsivity are employed as receivers; a quantum cascade detector (QCD) and a quantum-well infrared photodetector (QWIP). We investigate system tradeoffs and constraints, and indicate pathways forward for this technology beyond 100 Gbit s-1 communication.
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Previous theories have established the mental model activation of processing different types of conditionals, stating that counterfactual conditionals expressing events that contradict known facts (e.g., "If it had rained, then they would not go to the park.") are considered to trigger two mental models: (1) a hypothetical but factually wrong model (e.g., "rain" and "did not go to the park") and (2) a corresponding real-world model (e.g., "did not rain" and "went to the park"). This study aimed to investigate whether pragmatic factors differentially influence readers' comprehension and distinction between counterfactual and hypothetical conditional sentences in Mandarin Chinese. Participants were required to read and judge the comprehensibility of Chinese hypothetical and counterfactual conditionals, which were different in temporal indicators (past vs. future temporal indicators) in the antecedent. Different polarities (with vs. without negators) and different moving directions (different directional verbs: lai2 [come] vs. qu4 [go]) in the consequent were also manipulated. Linear mixed-effects models (LMEM) revealed that hypothetical conditionals (with future temporal indicators) were more comprehensible than counterfactual conditionals (with past temporal indicators). The semantic similarities within the subordinate clause revealed future temporal indicators had higher lexical-semantic co-occurrence than past indicators, suggesting that temporal indicators impact comprehension partly through lexical semantics in the premise, and hypothetical conditionals are more easily processed. However, the semantic similarity analysis of the main and the subordinate clauses showed no effect of temporal indicators, suggesting that lexical-semantic co-occurrence across clauses may not substantially contribute to the distinction between hypothetical conditionals and counterfactual conditionals. In conclusion, this study offers insights into the comprehension of Chinese conditional sentences by shedding light on the pragmatic factors influencing the activation of different mental models.
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BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune disease that is often more severe than adult-onset SLE and is challenging to diagnose due to its variable presentation and lack of specific diagnostic tests. OBJECTIVES: This study aimed to identify potential diagnostic biomarkers for cSLE by analyzing differentially expressed genes (DEGs) using machine learning algorithms. METHODS: In this study, we utilized the Gene Expression Omnibus database to investigate the DEGs between cSLE and normal samples, conducting a functional enrichment analysis on DEGs. Subsequently, we employed machine learning algorithms, including Least Absolute Shrinkage and Selection Operator regression and Support Vector Machine-Recursive Feature Elimination, to identify hub DEGs, which serve as crucial biomarkers. We delved into the role of these hub DEGs in the pathogenesis of the disease and the correlation between these hub DEGs and immune infiltration by comprehensive immune infiltration analysis using the CIBERSORT algorithm. RESULTS: We identified 110 DEGs in cSLE, including 95 upregulated and 15 downregulated genes. Functional annotation revealed that these DEGs were involved in immune response processes, viral defense mechanisms, and regulation of interferon responses. Machine learning algorithms identified CCR1 and SAMD9L as hub DEGs, which were validated in multiple datasets and demonstrated high diagnostic value for cSLE. Mechanistic exploration suggested that CCR1 and SAMD9L are involved in immune response modulation, particularly in interferon signaling and the innate immune system. Assessment of immune cell infiltration revealed significant differences in immune cell composition between cSLE patients and healthy controls, with cSLE patients exhibiting a higher proportion of neutrophils. Moreover, CCR1 and SAMD9L expression levels showed positive correlations with neutrophil infiltration and other immune cell types. CONCLUSION: CCR1 and SAMD9L were identified as potential diagnostic biomarkers for cSLE using machine learning and were validated in multiple datasets. These findings provide novel insights into the biological underpinnings of cSLE.
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Biomarcadores , Lúpus Eritematoso Sistêmico , Aprendizado de Máquina , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Biomarcadores/metabolismo , Biomarcadores/análise , Criança , Algoritmos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Máquina de Vetores de SuporteRESUMO
BACKGROUND: Limited data are available regarding the risk factors for fistula-in-ano (FIA) in infants and toddlers, potentially affecting their daily lives. OBJECTIVES: The purpose of this study was to identify potential risk factors for FIA in infants and toddlers, in order to implement early preventive interventions, avoid disease progression, and develop therapeutic strategies. DESIGN AND SETTINGS: A retrospective case-control study was conducted, comparing 41 infants and toddlers diagnosed with FIA with 41 healthy controls, between August 2020 and December 2021. INDEPENDENT VARIABLES: (a) maternal characteristics during pregnancy and delivery, (b) perinatal characteristics, dietary behaviors, and defecation-related behaviors in infants and toddlers, (c) family dietary behaviors. RESULTS: Mothers of infants and toddlers with FIA had given birth more times in the past, while the infants and toddlers themselves had less mealtime, a higher rate of exclusive breastfeeding, frequent loose stools, and a larger proportion of used wipes, experiencing perianal skin anomalies. The logistic regression analysis revealed that there are four significant risk factors associated with the development of FIA in infants and toddlers, including the number of previous deliveries by the mother (OR 6.327), defecation frequency score (OR 5.351), stool consistency score (OR 5.017), and cleaning with wipes after defecation (OR 8.089). CONCLUSION: Based on our data, it appeared that FIA in infants and toddlers could be attributed to several factors. These included an increased number of previous deliveries by mothers, frequent loose stools, and repeated wipe use. To prevent the occurrence and worsening of the disease, it is important to improve the frequency and consistency of stooling and provide proper care. Further research is required to verify these findings in other clinical settings.
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Fístula Retal , Humanos , Lactente , Fatores de Risco , Estudos de Casos e Controles , Feminino , Estudos Retrospectivos , Masculino , Pré-Escolar , Fístula Retal/etiologia , Defecação , Aleitamento Materno , Gravidez , Recém-NascidoRESUMO
Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of ortho-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound 7a exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, Ki = 3.9 nM, MOR/KOR = 270, DOR/KOR = 1075; [35S]GTPγS binding, EC50 = 3.4 nM). Additionally, this compound exhibited robust and persistent antinociceptive effects in rodent models with different animal strains (hot plate test, ED50 = 0.20-0.30 mg/kg, i.p.; abdominal constriction test, ED50 = 0.20-0.60 mg/kg, i.p.), with its KOR-mediated mechanism for antinociception firmly established. Notably, compound 7a, unlike conventional KOR agonists, displayed minimal sedation and aversion at the antinociceptive ED50 dose. This feature addresses a crucial limitation in existing KOR agonists, positioning compound 7a as a promising novel therapeutic agent.
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Receptores Opioides kappa , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/metabolismo , Animais , Camundongos , Relação Estrutura-Atividade , Masculino , Humanos , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/síntese química , Hipnóticos e Sedativos/química , Ratos , Analgésicos/farmacologia , Analgésicos/síntese química , Analgésicos/química , Descoberta de Drogas , Ratos Sprague-Dawley , CricetulusRESUMO
As an iron dependent regulatory cell death process driven by excessive lipid peroxides (LPO), ferroptosis is recognized as a powerful weapon for pancreatic cancer (PC) therapy. However, the tumor microenvironment (TME) with hypoxia and elevated glutathione (GSH) expression not only inhibits LPO production, but also induces glutathione peroxidase 4 (GPX4) mediated LPO clearance, which greatly compromise the therapeutic outcomes of ferroptosis. To address these issues, herein, a novel triple-enhanced ferroptosis amplifier (denoted as Zal@HM-PTBC) is rationally designed. After intravenous injection, the overexpressed H2O2/GSH in TME induces the collapse of Zal@HM-PTBC and triggers the production of oxygen and reactive oxygen species (ROS), which synergistically amplify the degree of lipid peroxidation (broaden sources). Concurrently, GSH consumption because of the degradation of the hollow manganese dioxide (HM) significantly weakens the activity of GPX4, resulting in a decrease in LPO clearance (reduce expenditure). Moreover, the loading and site-directed release of zalcitabine further promotes autophagy-dependent LPO accumulation (enhance effectiveness). Both in vitro and in vivo results validated that the ferroptosis amplifier demonstrated superior specificity and favorable therapeutic responses. Overall, this triple-enhanced LPO accumulation strategy demonstrates the ability to facilitate the efficacy of ferroptosis, injecting vigorous vitality into the treatment of PC.
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Ferroptose , Glutationa , Peróxidos Lipídicos , Neoplasias Pancreáticas , Ferroptose/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Animais , Peróxidos Lipídicos/metabolismo , Humanos , Linhagem Celular Tumoral , Glutationa/metabolismo , Camundongos , Compostos de Manganês/química , Óxidos/química , Espécies Reativas de Oxigênio/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Camundongos Nus , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Iatrogenic aortic dissection (IAD) is a rare but highly lethal complication that may occur following coronary artery bypass grafting (CABG) surgery. Aortic dissection (AD) is often asymptomatic, making early detection difficult. We aimed to optimize preoperative evaluation strategies of CABG surgery for minimizing the incidence of IAD and assess early recognition and management of IAD for improving outcomes. METHODS: Electronic databases were searched to identify all case reports of patients undergoing CABG surgery who developed IAD. Clinical characteristics, operative information, perioperative management, and patient outcomes were compiled and analyzed. RESULTS: Nineteen case reports involving 27 patients aged 50 to 81 were included. Patients were from Europe (nâ =â 23) and Asia (nâ =â 4), mostly men (nâ =â 25). The aorta was described as normal, abnormal, and unmentioned (nâ =â 8, 5, and 14, respectively). Sixteen patients had a bypass with more than 3 grafts. Most patients (nâ =â 25) experienced type A dissection. There were intraoperative (nâ =â 12) and postoperative (nâ =â 15) cases. Surgery (nâ =â 19) was the most common treatment, with 9 patients selecting deep hypothermic circulatory arrest. Eighteen patients were restored to health, while 9 patients died (3 died before treatment). CONCLUSIONS: Our study focused on patients with IAD and developed a recommended management protocol for patients undergoing CABG surgery.
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Dissecção Aórtica , Ponte de Artéria Coronária , Doença Iatrogênica , Complicações Pós-Operatórias , Humanos , Ponte de Artéria Coronária/efeitos adversos , Dissecção Aórtica/cirurgia , Doença Iatrogênica/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Pessoa de Meia-Idade , Masculino , Idoso de 80 Anos ou maisRESUMO
Although the antidepressant-like effect of magnolol has been revealed in previous reports, the mechanism remains unclear. In this study, the antidepressant-like effect of magnolol on corticosterone-induced (CORT-induced) mice was investigated in vivo. After 21 days of CORT induction, the mice showed marked depressive-like behaviors, with a decrease in sucrose preference score and an increase in immobility time in the tail suspension test (TST) and forced swimming test (FST). Pretreatment with either magnolol (50 mg/kg, i.p.) or the kappa opioid receptor (KOR) antagonist nor-BNI (10 mg/kg, i.p.) prevented CORT-induced depression-like behavior and reduced CORT-induced dynorphin (DYN A) elevation in the hippocampal ventral DG. However, no depression-like behavior was observed in mice with KOR downregulation in the ventral DG. We further found that upregulation of DYN A in the DG caused depression-like behavior, which was blocked by intraperitoneal injection of nor-BNI and modulated by magnolol. The present study demonstrated that magnolol could ameliorate CORT-induced depression-like behaviors, by modulating the DYN A/KOR system in the ventral DG of the hippocampus.
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Antidepressivos , Depressão , Animais , Camundongos , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , CorticosteronaRESUMO
BACKGROUND: The objective of this study is to conduct a systematic review and meta-analysis examining the relationship between the vasoactive-inotropic score (VIS) and patient outcomes in surgical settings. METHODS: Two independent reviewers searched PubMed, Web of Science, EMBASE, Scopus, Cochrane Library, Google Scholar, and CNKI databases from November 2010, when the VIS was first published, to December 2022. Additional studies were identified through hand-searching the reference lists of included studies. Eligible studies were those published in English that evaluated the association between the VIS and short- or long-term patient outcomes in both pediatric and adult surgical patients. Meta-analysis was performed using RevMan Manager version 5.3, and quality assessment followed the Joanna Briggs Institute (JBI) Critical Appraisal Checklists. RESULTS: A total of 58 studies comprising 29,920 patients were included in the systematic review, 34 of which were eligible for meta-analysis. Early postoperative VIS was found to be associated with prolonged mechanical ventilation (OR 5.20, 95% CI 3.78-7.16), mortality (OR 1.08, 95% CI 1.05-1.12), acute kidney injury (AKI) (OR 1.26, 95% CI 1.13-1.41), poor outcomes (OR 1.02, 95% CI 1.01-1.04), and length of stay (LOS) in the ICU (OR 3.50, 95% CI 2.25-5.44). The optimal cutoff value for the VIS as an outcome predictor varied between studies, ranging from 10 to 30. CONCLUSION: Elevated early postoperative VIS is associated with various adverse outcomes, including acute kidney injury (AKI), mechanical ventilation duration, mortality, poor outcomes, and length of stay (LOS) in the ICU. Monitoring the VIS upon return to the Intensive Care Unit (ICU) could assist medical teams in risk stratification, targeted interventions, and parent counseling. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022359100.
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Cirurgia Geral , Avaliação de Resultados da Assistência ao Paciente , Adulto , Criança , Humanos , Injúria Renal Aguda , Lista de Checagem , Bases de Dados Factuais , Unidades de Terapia Intensiva , Tempo de InternaçãoRESUMO
BACKGROUND: Sepsis-induced cardiomyopathy (SIC) is a cardiac dysfunction caused by sepsis, with mitochondrial dysfunction being a critical contributor. Pyruvate dehydrogenase kinase 4 (PDK4) is a kinase of pyruvate dehydrogenase with multifaceted actions in mitochondrial metabolism. However, its role in SIC remains unknown. METHODS: Serum PDK4 levels were measured and analyzed in 27 children with SIC, 30 children with sepsis, and 29 healthy children. In addition, for mice exhibiting SIC, the effects of PDK4 knockdown or inhibition on the function and structure of the myocardium and mitochondria were assessed. RESULTS: The findings from the analysis of children with SIC revealed that PDK4 was significantly elevated and correlated with disease severity and organ injury. Nonsurvivors displayed higher serum PDK4 levels than survivors. Furthermore, mice with SIC benefited from PDK4 knockdown or inhibition, showing improved myocardial contractile function, reduced myocardial injury, and decreased mitochondrial structural injury and dysfunction. In addition, inhibition of PDK4 decreased the inhibitory phosphorylation of PDHE1α (pyruvate dehydrogenase complex E1 subunit α) and improved abnormal pyruvate metabolism and mitochondrial dysfunction. CONCLUSIONS: PDK4 is a potential biomarker for the diagnosis and prognosis of SIC. In experimental SIC, PDK4 promoted mitochondrial dysfunction with increased phosphorylation of PDHE1α and abnormal pyruvate metabolism.
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Cardiomiopatias , Doenças Mitocondriais , Proteínas Quinases , Sepse , Animais , Criança , Humanos , Camundongos , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Miocárdio/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Piruvatos/metabolismo , Sepse/complicações , Sepse/metabolismoRESUMO
Despite the proliferation of research on anesthesiology training at all stages of medical education, there is relatively little published literature surveying the perspectives and concerns of anesthesiologists regarding cardiovascular anesthesia training. Therefore, we conducted a survey to investigate the attitudes, barriers, expectations, stress experiences, satisfaction, and future aspirations of anesthesiologists trained at a tertiary cardiovascular specialty hospital in China. A questionnaire survey was conducted among 260 anesthesiologists who received cardiovascular anesthesia training at departments of anesthesiology in a tertiary cardiovascular specialty hospital in China. After the study protocol was approved, electronic questionnaires were distributed to the target group through the online survey software "Wen Juan Xing." Respondents were asked to complete an anonymous questionnaire on their smartphones through WeChat, with the restriction of one response per device enabled. Of the 260 trainees, 240 (98%) completed the questionnaire. The majority of the trainees were 31 years of age or above. A large majority had approximately 10 years of clinical anesthesia practice, and nearly one-third had never undertaken cardiovascular specialty anesthesia practice before. The most common reasons for attending the refresher training were the need to learn basic specialty theory and improve clinical skills. The barriers were mainly time constraints or staff shortages in the department. Sixty-one (93.8%) trainees described the experience as "stressful or highly stressful" and identified poor teacher interaction as the highest-ranking stressor. Anesthesiologists were most dissatisfied with job rewards, with a satisfaction rate of only 15%. Anesthesiologists are highly stressed during the refresher training. Poor teacher interaction and low job rewards were identified as the highest-ranking stressors during cardiovascular anesthesia training. Training providers need to pay more attention to these stressors to enhance the quality of cardiovascular anesthesia training.
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Anestesia em Procedimentos Cardíacos , Anestesia , Anestesiologia , Humanos , Anestesiologia/educação , Anestesiologistas , Inquéritos e QuestionáriosRESUMO
Urine-derived stem cells (USCs) are autologous stem cells with self-renewal ability and multi-lineage differentiation potential. Our previous studies have shown that hypoxia preconditioning can improve self-renewal and migration abilities of USCs by up-regulating autophagy. The purpose of this study was to investigate the specific mechanism by which hypoxia treatment promotes the biological function of USCs. We found that hypoxia treatment upregulated the expression of phosphralated ERK protein without affecting the expression of total ERK protein. Inhibiting ERK signaling with the PD98059 inhibitor decreased cell proliferation, migration and colony formation during hypoxia treatment. Hypoxia increased ATP production, mitochondrial membrane potential and mt-DNA copy number, which were reversed by inhibiting the ERK signal. Additionally, the number of autophagosomes and autophagic lysosomes was significantly lower in PD98059 group than in the hypoxia group. PD98059 treatment inhibited the up-regulation of autophagy related proteins induced by hypoxia. Therefore, this study suggests that hypoxia improves the self-renewal and migration abilities of USCs by upregulating autophagy and mitochondrial function through ERK signaling pathway. This finding may provide a new therapeutic mechanism for hypoxia pretreated USCs as a source of stem cell transplantation.
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Transdução de Sinais , Células-Tronco , Humanos , Hipóxia/metabolismo , Autofagia , MitocôndriasRESUMO
Thoracic endovascular aortic repair (TEVAR) is a new alternative surgical treatment for aortic pathologies, which is more minimally invasive. The aim of current study was to summarize the single-center experience of general anesthesia for patients undergoing TEVAR. In adult patients undergoing surgery for congenital heart disease, the strategy of "fast-track" anesthesia with early extubation in theater is associated with a shorter intensive care unit (ICU) stay, and lower health-care-related costs. Fast-track anesthesia has not been assessed in patients under TEVAR. Adult patients who received general anesthesia for TEVAR in our center from January 2020 to December 2020 were included. Baseline characteristics, airway management, anesthetic techniques and major complications were collected. A total of 204 (171 male, mean age 58.1 ± 11.5 years) patients met inclusion criteria for this study. The distribution of pathologies included 29 descending thoracic aneurysms, 87 type B dissections, and 88 intramural hematoma/perforating aortic ulcer. Etomidate was the induction agent in 190 (93.1%) patients, compared with propofol in 16 (7.8%). Cisatracurium was the muscle relaxant in 201 (98.5%), compared with rocuronium in 3 (1.5%). Midazolam (benzodiazepines) was given to 124 (60.8%) patients during anesthesia induction. General anesthesia was maintained with sevoflurane in 85.3% (174) patients, dexmedetomidine in 201 (98.5%) and propofol in 204 (100%). Postoperative length of stay (LOS) in the hospital was 6.0 (5.0-7.8) days. LOS in the ICU was 23.0 (20.0-27.8) hours. Overall neurologic event rate was 2.0% (n = 4) (spinal cord ischemia 1.5% [n = 3]; stroke 0.5% [n = 1]). After matching, patients who received "fast-track" anesthesia had a shorter LOS in ICUs (21.0 [18.0-24.0] vs 24.0 [20.0-44.0] hours; P = .005), and a shorter postoperative LOS in hospital (5.0 [4.0-7.0] vs 6.0 [5.0-8.0] days; P = .001). There were no in-hospital deaths. Fast-track anesthesia is feasible and safe in patients underwent TEVAR. This management strategy is associated with shorter LOS of ICU and total postoperative hospital stays. An early extubation strategy should be implemented for hemodynamically stable patients.
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Aneurisma da Aorta Torácica , Doenças da Aorta , Implante de Prótese Vascular , Procedimentos Endovasculares , Propofol , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Correção Endovascular de Aneurisma , Implante de Prótese Vascular/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações , Doenças da Aorta/complicações , Anestesia Geral/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Aorta Torácica/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/etiologiaRESUMO
To strengthen the antitumor efficacy and avoid toxicity to normal cells of cisplatin and triptolide, herein, an acid and glutathione (GSH) dual-controlled nanoplatform for enhanced cancer treatment through the synergy of both "1+1" apoptosis and "1+1" ferroptosis is designed. Remarkably, ZIF8 in response to tumor microenvironment enhances drug targeting and protects drugs from premature degradation. Meanwhile, the PtIV center can be easily reduced to cisplatin because of the large amount of GSH, thus liberating the triptolide as the coordinated ligand. The released cisplatin and hemin in turn boost the tumor cell "1+1" apoptosis through chemotherapy and photodynamic therapy, respectively. Furthermore, GSH reduction through PtIV weakens the activation of glutathione peroxidase 4 (GPX4) effectively. The released triptolide can inhibit the expressions of GSH by regulating nuclear factor E2 related factor 2 (Nrf2), further promoting membrane lipid peroxidation, thus "1+1" ferroptosis can be achieved. Both in vitro and in vivo results demonstrate that the nanosystem can not only perform superior specificity and therapeutic outcomes but also reduce the toxicity to normal cells/tissues of cisplatin and triptolide effectively. Overall, the prodrug-based smart system provides an efficient therapeutic strategy for cancer treatment by virtue of the effect of enhanced "1+1" apoptosis and "1+1" ferroptosis therapies.
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Neoplasias da Mama , Diterpenos , Pró-Fármacos , Humanos , Feminino , Cisplatino/farmacologia , Neoplasias da Mama/tratamento farmacológico , Pró-Fármacos/farmacologia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have attracted attention in the field of regenerative medicine due to their potential ability to repair damaged hearts. However, the immature phenotype of these cells limits their clinical application. Cardiomyocyte maturation is accompanied by changes in mitochondrial quality. PTEN-induced putative kinase 1 (PINK1) has been linked to mitochondrial quality control. However, whether the changes in mitochondrial quality in hiPSC-CMs are associated with PINK1, and the impact of PINK1 on hiPSC-CMs development are not clear. In this study, we found that knockdown of PINK1 in hiPSC-CMs resulted in mitochondrial fragmentation and impaired mitochondrial functions such as mitophagy and mitochondrial biogenesis. PINK1 deletion also inhibited the maturation of hiPSC-CMs, reverting them to a naive structural and functional state. We found that restoring the mitochondrial structure did not completely rescue the mitochondrial dysfunction caused by PINK1 deletion, while activation of PINK1 kinase activity using kinetin promoted mitochondrial fusion, increased the mitochondrial membrane potential and ATP production, and maintained the development and maturation of hiPSC-CMs. In conclusion, PINK1 regulates the mitochondrial structure and function of hiPSC-CMs, and is essential for the maturation of hiPSC-CMs.
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The present experiment was carried out to analyze the longitudinal changes in milk microorganisms. For this purpose, milk samples were collected from 12 healthy cows (n = 96; six primiparous cows and six multiparous cows) at eight different time points. The characteristics and variations in microbial composition were analyzed by 16S rRNA gene high-throughput sequencing. In the primiparous group, higher and more stable alpha diversity was observed in transitional and mature milk compared with the colostrum, with no significant difference in alpha diversity at each time point in the multiparous group. Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota were the most dominant phyla, and Pseudomonas, UCG-005, Acinetobacter, Vibrio, Lactobacillus, Bacteroides, Serratia, Staphylococcus, and Glutamicibacter were the most dominant genera in both primiparous and multiparous cow milk. Some typically gut-associated microbes, such as Bacteroides, UCG-005, and Rikenellaceae_RC9_gut_group, etc., were enriched in the two groups. Biomarker taxa with the day in time (DIM) were identified by a random forest algorithm, with Staphylococcus showing the highest degree of interpretation, and the difference in milk microbiota between the two groups was mainly reflected in 0 d-15 d. Additionally, network analysis suggested that there were bacteria associated with the total protein content in milk. Collectively, our results disclosed the longitudinal changes in the milk microbiota of primiparous and multiparous cows, providing further evidence in dairy microbiology.
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Hemorrhagic fever with renal syndrome (HFRS), a natural epidemic disease caused by hantavirus (HV), is one of the viral diseases that pose a major threat to our health. Considering the increasing number of atypical-onset cases reported in some countries, it is important to be familiar with the symptoms of HFRS and the signs of HV infection. This report describes the case of a 55-year-old man with complaints of fever, vomiting, and diarrhea. His symptoms showed no significant improvement after routine anti-infective, antipyretic, and other symptomatic supportive treatments administered at a local clinic. During these treatments, the patient had progressive oliguria; after 3 days, he also developed multiple organ failures, such as the liver and kidney, and was examined for positive serum IgM antibodies to hemorrhagic fever during treatment at our hospital. The patient was finally diagnosed with HFRS followed by multiple organ failure. After antiviral therapy, including ribavirin, piperacillin, and tazobactam, continuous renal replacement therapy, fluid metabolism adjustment, and related supportive therapy were administered, which improved his liver and kidney function. He was discharged on the 25th day after hospitalization. It is difficult to manage patients who develop multiple organ failure after HFRS. Moreover, this condition is rare in clinical settings, with fever being the initial indication. For diseases with unknown origin such as refractory fever and diarrhea, it is crucial to differentiate them from common pathogenic infection and HV infections to provide timely treatment that improves the prognosis of patients.
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Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Masculino , Humanos , Pessoa de Meia-Idade , Febre Hemorrágica com Síndrome Renal/complicações , Febre Hemorrágica com Síndrome Renal/diagnóstico , Febre Hemorrágica com Síndrome Renal/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Rim , Febre/complicações , Diarreia/complicaçõesRESUMO
This systematic review and meta-analysis of nonrandomized studies (NRSs) aimed to evaluate the clinical efficacy and safety of two types of surgical interventions (respectively drainage alone and drainage with primary fistula treatment) for perianal abscesses (PAs) in children. Studies from 1992 to July 2022 were searched in 10 electronic databases. All relevant NRSs with available data which compared surgical drainage with or without primary fistula treatment were included. Patients with underlying diseases which led to abscess formation were excluded. The Newcastle-Ottawa Scale was used to assess the risk of bias and quality of the included studies. The outcomes were the healing rate, fistula formation rate, fecal incontinence, and wound healing duration. A total of 16 articles with 1,262 patients were considered suitable for the final meta-analysis. Primary fistula treatment was associated with a significantly higher healing rate when compared with incision and drainage alone (odds ratio [OR]: 5.76, 95% confidence interval [CI]: 4.04-8.22). This aggressive procedure for PA resulted in an 86% reduction in the fistula formation rate (OR: 0.14, 95% CI: 0.06-0.32). Limited data showed patients who underwent primary fistula treatment have a minor effect on postoperative fecal incontinence. Primary fistula treatment demonstrates a better clinical efficacy in promoting the healing rate and decreasing the formation of fistulas in PAs in children. The available evidence for a minor impact on anal function after this intervention is less strong.
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High bitrate mid-infrared links using simple (NRZ) and multi-level (PAM-4) data coding schemes have been realized in the 8 µm to 14 µm atmospheric transparency window. The free space optics system is composed of unipolar quantum optoelectronic devices, namely a continuous wave quantum cascade laser, an external Stark-effect modulator and a quantum cascade detector, all operating at room-temperature. Pre- and post-processing are implemented to get enhanced bitrates, especially for PAM-4 where inter-symbol interference and noise are particularly detrimental to symbol demodulation. By exploiting these equalization procedures, our system, with a full frequency cutoff of 2 GHz, has reached transmission bitrates of 12 Gbit/s NRZ and 11 Gbit/s PAM-4 fulfilling the 6.25 % overhead hard-decision forward error correction threshold, limited only by the low signal-to-noise ratio of our detector.