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Mangroves grow in tropical/subtropical intertidal habitats with extremely high salt tolerance. Trehalose and trehalose-6-phosphate (T6P) have an alleviating function against abiotic stress. However, the roles of trehalose in the salt tolerance of salt-secreting mangrove Avicennia marina is not documented. Here, we found that trehalose was significantly accumulated in A. marina under salt treatment. Furthermore, exogenous trehalose can enhance salt tolerance by promoting the Na+ efflux from leaf salt gland and root to reduce the Na+ content in root and leaf. Subsequently, eighteen trehalose-6-phosphate synthase (AmTPS) and 11 trehalose-6-phosphate phosphatase (AmTPP) genes were identified from A. marina genome. Abscisic acid (ABA) responsive elements were predicted in AmTPS and AmTPP promoters by cis-acting elements analysis. We further identified AmTPS9A, as an important positive regulator, that increased the salt tolerance of AmTPS9A-overexpressing Arabidopsis thaliana by altering the expressions of ion transport genes and mediating Na+ efflux from the roots of transgenic A. thaliana under NaCl treatments. In addition, we also found that ABA could promote the accumulation of trehalose, and the application of exogenous trehalose significantly promoted the biosynthesis of ABA in both roots and leaves of A. marina. Ultimately, we confirmed that AmABF2 directly binds to the AmTPS9A promoter in vitro and in vivo. Taken together, we speculated that there was a positive feedback loop between trehalose and ABA in regulating the salt tolerance of A. marina. These findings provide new understanding to the salt tolerance of A. marina in adapting to high saline environment at trehalose and ABA aspects.
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Ácido Abscísico , Avicennia , Regulação da Expressão Gênica de Plantas , Tolerância ao Sal , Sódio , Trealose , Trealose/metabolismo , Tolerância ao Sal/genética , Ácido Abscísico/metabolismo , Avicennia/fisiologia , Avicennia/genética , Sódio/metabolismo , Plantas Geneticamente Modificadas , Arabidopsis/genética , Arabidopsis/fisiologia , Arabidopsis/metabolismo , Glucosiltransferases/metabolismo , Glucosiltransferases/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Raízes de Plantas/fisiologia , Folhas de Planta/metabolismo , Folhas de Planta/genética , Folhas de Planta/fisiologiaRESUMO
Salicylic acid (SA) is known to enhance salt tolerance in plants. However, the mechanism of SA-mediated response to high salinity in halophyte remains unclear. Using electrophysiological and molecular biological methods, we investigated the role of SA in response to high salinity in mangrove species, Kandelia obovata, a typical halophyte. Exposure of K. obovata roots to high salinity resulted in a rapid increase in endogenous SA produced by phenylalanine ammonia lyase pathway. The application of exogenous SA improved the salt tolerance of K. obovata, which depended on the NADPH oxidase-mediated H2O2. Exogenous SA and H2O2 increased Na+ efflux and reduced K+ loss by regulating the transcription levels of Na+ and K+ transport-related genes, thus reducing the Na+/K+ ratio in the salt-treated K. obovata roots. In addition, exogenous SA-enhanced antioxidant enzyme activity and its transcripts, and the expressions of four genes related to AsA-GSH cycle as well, then alleviated oxidative damages in the salt-treated K. obovata roots. However, the above effects of SA could be reversed by diphenyleneiodonium chloride (the NADPH oxidase inhibitor) and paclobutrazol (a SA biosynthesis inhibitor). Collectively, our results demonstrated that SA-induced salt tolerance of K. obovata depends on NADPH oxidase-generated H2O2 that affects Na+/K+ and redox homeostasis in response to high salinity.
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Homeostase , Peróxido de Hidrogênio , NADPH Oxidases , Oxirredução , Raízes de Plantas , Potássio , Ácido Salicílico , Tolerância ao Sal , Sódio , Peróxido de Hidrogênio/metabolismo , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia , Potássio/metabolismo , Tolerância ao Sal/genética , Sódio/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Raízes de Plantas/metabolismo , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/metabolismo , Plantas Tolerantes a Sal/fisiologia , Regulação da Expressão Gênica de Plantas , Rhizophoraceae/fisiologia , Rhizophoraceae/genética , Rhizophoraceae/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody for the treatment of instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors in adults, including those with advanced colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The aim of this investigation was to examine the pharmacokinetic and exposure-response (E-R) profile of envafolimab in patients with solid tumors to support the approval of fixed and alternative dose regimens. METHODS: In this study, a population pharmacokinetic (PopPK) modeling approach will be employed to quantitatively evaluate intrinsic and extrinsic covariates. Additionally, PopPK-estimated exposure parameters were used to evaluate E-R relationship for safety and efficacy to provide a theoretical basis for recommending optimal treatment regimens. Simulations were performed on the dosing regimens of body weight-based regimen of 2.50 mg/kg QW, fixed dose 150 mg QW, and 300 mg Q2W for the selection of alternative dosing regimens. Data from 4 clinical studies (NCT02827968, NCT03101488, NCT03248843, and NCT03667170) were utilized. RESULTS: The PopPK dataset comprised 182 patients with 1810 evaluable envafolimab concentration records. Finally, a one-compartment model incorporating first-order absorption, first-order linear elimination, and time-dependent elimination according to an Emax function was found to accurately describe the concentration-time data of envafolimab in patients with advanced solid tumors. Creatinine clearance and country were identified as statistically significant factors affecting clearance, but had limited clinical significance. A relative flat exposure-response relationship was observed between early measures of safety and efficacy to verify that no dose adjustment is required. Simulation results indicated that 2.50 mg/kg QW, 150 mg QW, and 300 mg Q2W regimen yield similar steady-state exposure. CONCLUSIONS: No statistically significant difference was observed between weight-based and fixed dose regimens. Model-based simulation supports the adoption of a 150 mg weekly or 300 mg biweekly dosing regimen of envafolimab in the solid tumor population, as these schedules effectively balance survival benefits and safety risks.
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PURPOSE: Whether long-term aspirin usage is associated with colorectal cancer (CRC) risk needs more evidence. The study evaluated the association between long-term aspirin use and prevalence of CRC in a large, nationally representative database. METHODS: Hospitalized patients aged ≥ 50 years during 2018 were identified in the United States (US) National Inpatient Sample (NIS). Patients without complete information of age, sex, race, income, and insurance status were excluded, as well as those with inflammatory bowel disease (IBD) or malignancies other than CRC. Propensity score matching (PSM) was applied to balance the characteristics between patients with and without long-term aspirin use. Logistic regressions were performed to determine the relationship between long-term aspirin use and the presence of CRC. CRC and aspirin use were identified through the administrative International Classification of Diseases (ICD) codes. RESULTS: Data from 3,490,226 patients were included, in which 688,018 (19.7%) had a record of long-term aspirin use. After 1:1 PSM, there remained 1,376,006 patients, representing 6,880,029 individuals in the US after weighting. After adjusting for confounders, long-term aspirin use was significantly associated with lower CRC odds (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] 0.62, 0.67). This association was not changed when stratified by age, sex, race, body mass index (BMI), and smoking. CONCLUSIONS: From a national inpatient dataset, US adults ≥ 50 years on long-term aspirin are less likely to have CRC, regardless of age, sex, race, BMI, and smoking status.
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Aspirina , Neoplasias Colorretais , Adulto , Humanos , Estados Unidos/epidemiologia , Pacientes Internados , Prevalência , Neoplasias Colorretais/epidemiologiaRESUMO
Brassinosteroid (BR) has been shown to modulate plant tolerance to various stresses. S-nitrosoglutathione reductase (GSNOR) is involved in the plant response to environment stress by fine-turning the level of nitric oxide (NO). However, whether GSNOR is involved in BR-regulated Na+ /K+ homeostasis to improve the salt tolerance in halophyte is unknown. Here, we firstly reported that high salinity increases the expression of BR-biosynthesis genes and the endogenous levels of BR in mangrove Kandelia obovata. Then, salt-induced BR triggers the activities and gene expressions of GSNOR and antioxidant enzymes, thereafter decrease the levels of malondialdehyde, hydrogen peroxide. Subsequently, BR-mediated GSNOR negatively regulates NO contributions to the reduction of reactive oxygen species generation and induction of the gene expression related to Na+ and K+ transport, leading to the decrease of Na+ /K+ ratio in the roots of K. obovata. Finally, the applications of exogenous BR, NO scavenger, BR biosynthetic inhibitor and GSNOR inhibitor further confirm the function of BR. Taken together, our result provides insight into the mechanism of BR in the response of mangrove K. obovata to high salinity via GSNOR and NO signaling pathway by reducing oxidative damage and modulating Na+ /K+ homeostasis.
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Óxido Nítrico , Rhizophoraceae , Óxido Nítrico/metabolismo , Oxirredutases/metabolismo , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Rhizophoraceae/genética , Rhizophoraceae/metabolismo , Tolerância ao Sal , Transdução de SinaisRESUMO
Pentatricopeptide repeat (PPR) gene family constitutes one of the largest gene families in plants, which mainly participate in RNA editing and RNA splicing of organellar RNAs, thereby affecting the organellar development. Recently, some evidence elucidated the important roles of PPR proteins in the albino process of plant leaves. However, the functions of PPR genes in the woody mangrove species have not been investigated. In this study, using a typical true mangrove Kandelia obovata, we systematically identified 298 PPR genes and characterized their general features and physicochemical properties, including evolutionary relationships, the subcellular localization, PPR motif type, the number of introns and PPR motifs, and isoelectric point, and so forth. Furthermore, we combined genome-wide association studies (GWAS) and transcriptome analysis to identify the genetic architecture and potential PPR genes associated with propagule leaves colour variations of K. obovata. As a result, we prioritized 16 PPR genes related to the albino phenotype using different strategies, including differentially expressed genes analysis and genetic diversity analysis. Further analysis discovered two genes of interest, namely Maker00002998 (PLS-type) and Maker00003187 (P-type), which were differentially expressed genes and causal genes detected by GWAS analysis. Moreover, we successfully predicted downstream target chloroplast genes (rps14, rpoC1 and rpoC2) bound by Maker00002998 PPR proteins. The experimental verification of RNA editing sites of rps14, rpoC1, and rpoC2 in our previous study and the verification of interaction between Maker00002998 and rps14 transcript using in vitro RNA pull-down assays revealed that Maker00002998 PPR protein might be involved in the post-transcriptional process of chloroplast genes. Our result provides new insights into the roles of PPR genes in the albinism mechanism of K. obovata propagule leaves.
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In plants, C-to-U RNA editing mainly occurs in plastid and mitochondrial transcripts, which contributes to a complex transcriptional regulatory network. More evidence reveals that RNA editing plays critical roles in plant growth and development. However, accurate detection of RNA editing sites using transcriptome sequencing data alone is still challenging. In the present study, we develop PlantC2U, which is a convolutional neural network, to predict plastid C-to-U RNA editing based on the genomic sequence. PlantC2U achieves >95% sensitivity and 99% specificity, which outperforms the PREPACT tool, random forests, and support vector machines. PlantC2U not only further checks RNA editing sites from transcriptome data to reduce possible false positives, but also assesses the effect of different mutations on C-to-U RNA editing based on the flanking sequences. Moreover, we found the patterns of tissue-specific RNA editing in the mangrove plant Kandelia obovata, and observed reduced C-to-U RNA editing rates in the cold stress response of K. obovata, suggesting their potential regulatory roles in plant stress adaptation. In addition, we present RNAeditDB, available online at https://jasonxu.shinyapps.io/RNAeditDB/. Together, PlantC2U and RNAeditDB will help researchers explore the RNA editing events in plants and thus will be of broad utility for the plant research community.
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Aprendizado Profundo , Edição de RNA , Edição de RNA/genética , Plantas/metabolismo , Plastídeos/genética , Plastídeos/metabolismo , Transcriptoma , RNA de Plantas/genética , RNA de Plantas/metabolismoRESUMO
BACKGROUND: Robot-assisted surgery has been increasingly adopted in colorectal cancer resection. OBJECTIVE: The study aimed to compare the inpatient outcomes of robot-assisted versus conventional laparoscopic colorectal cancer resection in patients aged 75 years and older. DESIGN: A retrospective, population-based study. SETTINGS: This study analyzed data from the United States Nationwide Inpatient Sample from 2005 to 2018. PATIENTS: Patients with colorectal cancer aged 75 years and older and who underwent robot-assisted or conventional laparoscopic resection. MAIN OUTCOME MEASURES: Postoperative complications, prolonged length of stay, and total hospital costs were assessed. RESULTS: Data from 14,108 patients were analyzed. After adjustment, any postoperative complications (adjusted OR = 0.87; 95% CI, 0.77-0.99; p = 0.030) and prolonged length of stay (adjusted OR = 0.78; 95% CI, 0.67-0.91; p = 0.001) were significantly less in the robotic than the laparoscopic group. In addition, robotic surgery was associated with significantly higher total hospital costs (26.06 USD greater cost; 95% CI, 21.35-30.77 USD; p < 0.001). LIMITATIONS: The analysis was limited by its retrospective and observational nature, potential coding errors, and the lack of intraoperative factors, such as operative time, laboratory measures, and information on surgeons' experience. CONCLUSIONS: In the United States, in patients with colorectal cancer aged 75 years and older who were undergoing tumor resections, compared to conventional laparoscopic surgery, robotic surgery is associated with better inpatient outcomes in terms of complication rate and risk of prolonged length of stay. This finding is especially true among patients with colon cancer. However, robotic surgery is associated with higher total hospital costs. See Video Abstract . RESULTADOS DE LA CIRUGA ASISTIDA POR ROBOT FRENTE A LA CIRUGA LAPAROSCPICA PARA EL CNCER COLORRECTAL EN ADULTOS AOS DE EDAD UN ANLISIS EMPAREJADO POR PUNTUACIN DE PROPENSIN DE LA MUESTRA NACIONAL DE PACIENTES HOSPITALIZADOS DE ESTADOS UNIDOS: ANTECEDENTES:La cirugía asistida por robot se ha adoptado cada vez más en la resección del cáncer colorrectal.OBJETIVO:El estudio tuvo como objetivo comparar los resultados hospitalarios de la resección del cáncer colorrectal asistida por robot versus la laparoscópica convencional en pacientes ≥ 75 años.DISEÑO:Estudio retrospectivo de base poblacional.AJUSTES:Este estudio analizó datos de la Muestra Nacional de Pacientes Hospitalizados de Estados Unidos de 2005 a 2018.PACIENTES:Pacientes con cáncer colorrectal ≥ 75 años y sometidos a resección laparoscópica convencional o asistida por robot.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron las complicaciones posoperatorias, la duración prolongada de la estancia hospitalaria y los costos hospitalarios totales.RESULTADOS:Se analizaron datos de 14.108 pacientes. Después del ajuste, cualquier complicación posoperatoria (aOR = 0,87; IC del 95 %: 0,77-0,99, p = 0,030) y duración prolongada de la estancia hospitalaria (aOR = 0,78; IC del 95 %: 0,67-0,91, p = 0,001) fueron significativamente menores en el grupo robótico que el grupo laparoscópico. Además, la cirugía robótica se asoció con costos hospitalarios totales significativamente mayores ($26,06 USD mayor costo; IC 95%: 21,35-30,77 USD, p < 0,001).LIMITACIONES:El análisis estuvo limitado por su naturaleza retrospectiva y observacional, posibles errores de codificación y la falta de factores intraoperatorios como el tiempo operatorio, medidas de laboratorio e información sobre la experiencia de los cirujanos.CONCLUSIONES:En Estados Unidos, los pacientes con cáncer colorrectal ≥ 75 años que se sometieron a resecciones tumorales, en comparación con la cirugía laparoscópica convencional, la cirugía robótica se asocia con mejores resultados hospitalarios en términos de tasa de complicaciones y riesgo de estadía prolongada, especialmente entre pacientes con cáncer de colon. Sin embargo, la cirugía robótica se asocia a costes hospitalarios totales más elevados. (Traducción-Yesenia Rojas-Khalil ).
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Neoplasias Colorretais , Laparoscopia , Tempo de Internação , Complicações Pós-Operatórias , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Humanos , Idoso , Masculino , Feminino , Laparoscopia/métodos , Laparoscopia/economia , Laparoscopia/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Neoplasias Colorretais/cirurgia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Idoso de 80 Anos ou mais , Tempo de Internação/estatística & dados numéricos , Custos Hospitalares/estatística & dados numéricos , Colectomia/métodos , Colectomia/economia , Resultado do TratamentoRESUMO
BACKGROUND: Both atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. If the two exist together, the risk of stroke, hospitalization for HF and all-cause death is increased. Currently, research on left atrial appendage closure (LAAC) in patients with AF and HF is limited and controversial. This study was designed to investigate the safety and effectiveness of LAAC in AF patients with different types of HF. METHODS: Patients with non-valvular atrial fibrillation (NVAF) and HF who underwent LAAC in the First Affiliated Hospital of Army Medical University from August 2014 to July 2021 were enrolled. According to left ventricular ejection fraction (LVEF), the study divided into HF with reduced ejection fraction (LVEF < 50%, HFrEF) group and HF with preserved ejection fraction (LVEF ≥ 50%, HFpEF) group. The data we collected from patients included: gender, age, comorbid diseases, CHA2DS2-VASc score, HAS-BLED score, NT-proBNP level, residual shunt, cardiac catheterization results, occluder size, postoperative medication regimen, transthoracic echocardiography (TTE) results and transesophageal echocardiography (TEE) results, etc. Patients were followed up for stroke, bleeding, device related thrombus (DRT), pericardial tamponade, hospitalization for HF, and all-cause death within 2 years after surgery. Statistical methods were used to compare the differences in clinical outcome of LAAC in AF patients with different types of HF. RESULTS: Overall, 288 NVAF patients with HF were enrolled in this study, including 142 males and 146 females. There were 74 patients in the HFrEF group and 214 patients in the HFpEF group. All patients successfully underwent LAAC. The CHA2DS2-VASc score and HAS-BLED score of HFrEF group were lower than those of HFpEF group. A total of 288 LAAC devices were implanted. The average diameter of the occluders was 27.2 ± 3.5 mm in the HFrEF group and 26.8 ± 3.3 mm in the HFpEF group, and there was no statistical difference between the two groups (P = 0.470). Also, there was no statistically significant difference in the occurrence of residual shunts between the two groups as detected by TEE after surgery (P = 0.341). LVEF was significantly higher in HFrEF group at 3 days, 3 months and 1 year after operation than before (P < 0.001). At 45-60 days after surgery, we found DRT in 9 patients and there were 4 patients (5.4%) in HFrEF group and 5 patients (2.3%) in HFpEF group, with no significant difference between the two groups (P = 0.357). One patient with DRT had stroke. The incidence of stroke was 11.1% in patients with DRT and 0.7% in patients without DRT (P = 0.670). There was one case of postoperative pericardial tamponade, which was improved by pericardiocentesis at 24 h after surgery in the HFpEF group, and there was no significant difference between the two groups (P = 1.000). During a mean follow-up period of 49.7 ± 22.4 months, there were no significant differences in the incidence of stroke, bleeding, DRT and HF exacerbation between the two groups. We found a statistical difference in the improvement of HF between HFrEF group and HFpEF group (P < 0.05). CONCLUSIONS: LAAC is safe and effective in AF patients with different types of HF. The improvement of cardiac function after LAAC is more pronounced in HFrEF group than in HFpEF group.
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Fibrilação Atrial , Função do Átrio Esquerdo , Insuficiência Cardíaca , Oclusão do Apêndice Atrial Esquerdo , Acidente Vascular Cerebral , Função Ventricular Esquerda , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/fisiopatologia , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Oclusão do Apêndice Atrial Esquerdo/efeitos adversos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Volume Sistólico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: With its minimally invasive approach, laparoscopic surgery has transformed the medical landscape. As the demand for these procedures escalates, there is a pressing need for adept surgeons trained in laparoscopic techniques. However, current training often falls short of catering to medical school education. This study evaluates the impact of a custom-designed laparoscopic training workshop on medical students' surgical skills and career aspirations. METHODS: This prospective experimental study was conducted at the E-Da hospital in Kaohsiung City, Taiwan. Medical students from Taiwanese medical schools undergoing Clerk 5, Clerk 6, and Postgraduate Year 1 and 2 were invited to participate. Medical students (n = 44) underwent an endoscopic skill training workshop consisting of lectures, box training, and live tissue training. The trainees performed multiple tasks before and after training using our objective evaluation system. The primary outcome was assessed before and after training through a questionnaire assessing the influence of training on students' interest in surgery as a career. The secondary outcome measured improvement in skill acquisition, comparing the task completion time pre- and post-workshop. For the primary outcome, descriptive statistics were used to summarize the questionnaire responses, and paired t-tests were performed to determine significant changes in interest levels post-workshop. For the secondary outcome, paired t-tests were used to compare the time recorded pre- and post-training. RESULTS: Post-training, participants exhibited significant proficiency gains, with task completion times reducing notably: 97 s (p = 0.0015) for Precision Beads Placement, 88.5 s (p < 0.0001) for Beads Transfer Exercise, 95 s (p < 0.0001) for Precision Balloon Cutting, and 137.8 s (p < 0.0001) for Intracorporeal Suture. The primary outcome showcased an increased mean score from 8.15 pre-workshop to 9.3 post-workshop, indicating a bolstered interest in surgery as a career. Additionally, post-training sentiment analysis underscored a predominant inclination toward surgery among 88% of participants. CONCLUSION: The custom-designed laparoscopic workshop significantly improved technical skills and positively influenced students' career aspirations toward surgery. Such hands-on training workshops can play a crucial role in medical education, bridging the gap between theoretical knowledge and practical skills and potentially shaping the future of budding medical professionals.
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Escolha da Profissão , Competência Clínica , Laparoscopia , Estudantes de Medicina , Humanos , Laparoscopia/educação , Estudos Prospectivos , Feminino , Taiwan , Masculino , Educação de Graduação em Medicina/métodos , Adulto Jovem , AdultoRESUMO
Hydrogen sulfide (H2 S) is considered to mediate plant growth and development. However, whether H2 S regulates the adaptation of mangrove plant to intertidal flooding habitats is not well understood. In this study, sodium hydrosulfide (NaHS) was used as an H2 S donor to investigate the effect of H2 S on the responses of mangrove plant Avicennia marina to waterlogging. The results showed that 24-h waterlogging increased reactive oxygen species (ROS) and cell death in roots. Excessive mitochondrial ROS accumulation is highly oxidative and leads to mitochondrial structural and functional damage. However, the application of NaHS counteracted the oxidative damage caused by waterlogging. The mitochondrial ROS production was reduced by H2 S through increasing the expressions of the alternative oxidase genes and increasing the proportion of alternative respiratory pathway in the total mitochondrial respiration. Secondly, H2 S enhanced the capacity of the antioxidant system. Meanwhile, H2 S induced Ca2+ influx and activated the expression of intracellular Ca2+ -sensing-related genes. In addition, the alleviating effect of H2 S on waterlogging can be reversed by Ca2+ chelator and Ca2+ channel blockers. In conclusion, this study provides the first evidence to explain the role of H2 S in waterlogging adaptation in mangrove plants from the mitochondrial aspect.
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Avicennia , Sulfeto de Hidrogênio , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Cálcio/metabolismo , Avicennia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse OxidativoRESUMO
BACKGROUND: To compare OCs(oral contraceptives) + metformin and OCs alone for metabolic effects in nonobese polycystic ovary syndrome (PCOS) patients. METHODS: The search was performed in PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for all published studies up to 30 April 2022 and was limited to English-language articles. All randomized controlled trials (RCTs) comparing OCs + metformin and OCs alone for reproductive-age women with PCOS were included. Data were processed using Revman 5.3 software. RESULTS: Of 396 studies identified, 14 RCTs were included for analysis comprising 707 women. OCs+metformin significantly modified fasting glucose (MD = -0.21 [95% confidence interval (CI) = -0.31, -0.12], p < .00001) and fasting insulin (MD = -2.54 [95%CI = -4.04, -1.04], p = .0009) at study completion compared with OCs alone in nonobese PCOS subjects. There was no statistic difference in the homoeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol or triglycerides at study end between the two groups. CONCLUSIONS: Metformin, via its positive effects on insulin clearance, in combination with OCs, improved glucose metabolism and offered a good treatment alternative in nonobese women with PCOS.
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Metformina , Síndrome do Ovário Policístico , Feminino , Humanos , Anticoncepcionais Orais , Hipoglicemiantes/uso terapêutico , Insulina , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Coordination polymers (CPs) have recently emerged as promising candidates for heterogeneous photocatalysis due to their structural designability and tunable properties. Herein, we developed two novel Ag(I)-calix[4]arene coordination polymers with the formula {[Ag2(µ-NO3)L1]}n (CP 1) and {[AgL1]·PF6}n (CP 2) (L1 = 2-mercapto-5-methyl-1,3,4-thiadiazole resorcinol calix[4]arene). Crystallography revealed that anion coordination and self-inclusion behavior induced the cavitand and silver ions to self-assemble into well-defined CPs 1 and 2 with different topological coordination frameworks, respectively. Furthermore, CPs 1 and 2 display high photocatalytic activity for the photodegradation of rhodamine B (RhB) and methyl orange (MO) in an aqueous solution under mild conditions (WLED and UV irradiation). The comparison results demonstrate that CP 1 exhibited better photocatalytic performance than CP 2, which correlated well with the differences in their molecular structure and HOMO-LUMO energy gaps. The photocatalysis products and possible intermediates were successfully monitored and determined using mass spectrum, gas chromatography, and electron paramagnetic resonance measurements. The rational photocatalysis mechanism was further investigated and proposed.
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BACKGROUND AND AIM: Morbid obesity is associated with poorer postoperative outcomes in colorectal cancer (CRC) patients. We aimed to evaluate short-term outcomes after robotic versus conventional laparoscopic CRC resection in morbidly obese patients. METHODS: This population-based, retrospective study extracted data from the US Nationwide Inpatient Sample during 2005-2018. Adults ≥ 20 years old, with morbid obesity and CRC, and undergoing robotic or laparoscopic resections were identified. Propensity score matching (PSM) was applied to minimize the confounding. Univariate and multivariable regression was conducted to evaluate the associations between outcomes and study variables. RESULTS: After PSM, 1296 patients remained. The risks of any postoperative complication (adjusted odds ratio [aOR] = 0.99, 95% confidence interval [CI]: 0.80, 1.22), prolonged length of stay (LOS) (aOR = 0.80, 95% CI: 0.63, 1.01), death (aOR = 0.57, 95% CI: 0.11, 3.10), or pneumonia (aOR = 1.13, 95% CI: 0.73, 1.77) were not significantly different between the two procedures after adjustment. Robotic surgery was significantly associated with greater hospital cost (aBeta = 26.26, 95% CI: 16.08, 36.45) than laparoscopic surgery. Stratified analyses revealed that, in patients with tumor located at the colon, robotic surgery was associated with lower risk of prolonged LOS (aOR = 0.72, 95% CI: 0.54, 0.95). CONCLUSIONS: In patients with morbid obesity, risks of postoperative complication, death, or pneumonia are not significantly different between robotic and laparoscopic CRC resection. Among patients with tumor located at the colon, robotic surgery is associated with lower risk of prolonged LOS. These findings fill the knowledge gap and provide useful information for clinicians on risk stratification and treatment choice.
Assuntos
Neoplasias Colorretais , Laparoscopia , Obesidade Mórbida , Procedimentos Cirúrgicos Robóticos , Robótica , Adulto , Humanos , Adulto Jovem , Estudos Retrospectivos , Pacientes Internados , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Resultado do TratamentoRESUMO
Soil nitrous oxide (N2O) is produced by abiotic and biotic processes, but it is solely consumed by denitrifying microbes-encoded by nosZ genes. The nosZ gene includes two groups i.e. Clade I and Clade II, which are highly sensitive to pH. Managing pH of acidic soils can substantially influence soil N2O production or consumption through nosZ gene abundance. Nevertheless, the response of nosZ (Clade I and Clade II) to pH management needs elucidation in acidic soils. To clarify this research question, a pot experiment growing rice crop was conducted with three treatments: control (only soil), low dose of dolomite (LDD), and high dose of dolomite (HDD). The soil pH increased from 5.41 to 6.23 in the control, 6.5 in LDD and 6.8 in HDD treatment under flooded condition. The NH4+ and NO3- contents increased and reached the maximum at 30.4 and 21.5 mg kg-1, respectively, in HDD treatment under flooding condition. The contents of dissolved organic carbon and microbial biomass carbon showed a swift rise at midseason aeration and reached maximum at 30.7 and 101 mg kg-1 in the HDD treatment. Clade I, Clade II and 16S rRNA genes abundance increased with the onset of flooding, and occurred maximum in the HDD treatment. A peak in N2O emissions (5.96 µg kg-1 h-1) occurred at midseason events in the control when no dolomite was added. Dolomite application significantly (p ≤ 0.001) suppressed N2O emissions, and HDD treatment was more effective in reducing emissions. Pearson correlation, linear regressions and principal component analysis displayed that increased soil pH and Clade I and Clade II were the main controlling factors for N2O emission mitigation in acidic soil. This research demonstrates that ameliorating soil acidity with dolomite application is a potential option for the mitigation of N2O emissions.
Assuntos
Oryza , Solo , Solo/química , Oryza/genética , RNA Ribossômico 16S , Carbono , Óxido Nitroso , Concentração de Íons de Hidrogênio , Microbiologia do SoloRESUMO
BACKGROUND: Although numerous studies have examined the effect of prenatal per- and polyfluoroalkyl substances (PFAS) exposure on neurodevelopment in children, findings have been inconsistent. OBJECTIVE: To better understand the effects of PFAS exposure during pregnancy on offspring neurodevelopment, we conducted a systematic review of prenatal exposure to different types of PFAS and neurodevelopment in children. METHODS: A comprehensive search was conducted in the PubMed, Web of Science, and EMBASE electronic databases up to March 2023. Only birth cohort studies that report a specific association between PFAS exposure during pregnancy and neurodevelopment were included in this review. RESULTS: 31 birth cohort studies that met the inclusion criteria were qualitatively integrated. Among these, 14 studies investigated the impact of PFAS exposure during pregnancy on cognition, 13 on neurobehavior, and 4 on both cognition and neurobehavior. Additionally, 4 studies explored the influence of PFAS on children's comprehensive development. CONCLUSION: Prenatal PFAS exposure was associated with poor neurodevelopment in children, including psychomotor development, externalizing behavior, and comprehensive development. However, conclusive evidence regarding its effects on other neurological outcomes remains limited. In addition, sex-specific effects on social behavior and sleep problems were identified.
RESUMO
KEY MESSAGE: This study provided important insights into the genetic architecture of variations in A. thaliana leaf ionome in a cell-type-specific manner. The functional interpretation of traits associated variants by expression quantitative trait loci (eQTL) analysis is usually performed in bulk tissue samples. While the regulation of gene expression is context-dependent, such as cell-type-specific manner. In this study, we estimated cell-type abundances from 728 bulk tissue samples using single-cell RNA-sequencing dataset, and performed cis-eQTL mapping to identify cell-type-interaction eQTL (cis-eQTLs(ci)) in A. thaliana. Also, we performed Genome-wide association studies (GWAS) analyses for 999 accessions to identify the genetic basis of variations in A. thaliana leaf ionome. As a result, a total of 5,664 unique eQTL genes and 15,038 unique cis-eQTLs(ci) were significant. The majority (62.83%) of cis-eQTLs(ci) were cell-type-specific eQTLs. Using colocalization, we uncovered one interested gene AT2G25590 in Phloem cell, encoding a kind of plant Tudor-like protein with possible chromatin-associated functions, which colocalized with the most significant cis-eQTL(ci) of a Mo-related locus (Chr2:10,908,806:A:C; P = 3.27 × 10-27). Furthermore, we prioritized eight target genes associated with AT2G25590, which were previously reported in regulating the concentration of Mo element in A. thaliana. This study revealed the genetic regulation of ionomic variations and provided a foundation for further studies on molecular mechanisms of genetic variants controlling the A. thaliana ionome.
Assuntos
Arabidopsis , Locos de Características Quantitativas , Arabidopsis/genética , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genéticaRESUMO
HSK7653 is a novel super long-acting dipeptidyl peptidase-4 inhibitor, which is promising for the treatment of type 2 diabetes mellitus with the twice-monthly dosing regimen. In this article, a robust and sensitive HPLC coupled with tandem mass spectrometry method for determining the concentration of HSK7653 in human plasma and urine was developed and validated for the first time. Plasma and urine samples were prepared by protein precipitation. After that, the extracts were analyzed using an LC-20A HPLC system coupled with API 4000 tandem MS equipped with an electrospray ionization source in positive mode. Separation was obtained using an XBridge Phenyl column (2.1 × 50 mm, 3.5 µm) with a gradient elution of acetonitrile and water containing 0.1% formic acid and 5% acetonitrile at room temperature. This bioanalysis method has been fully validated and the results showed good sensitivity and specificity. In brief, the standard curves were linear over the concentration range of 2.00-2000 ng/ml for plasma and 20.0-20,000 ng/ml for urine, respectively. In addition, the precisions of inter- and intra-run of HSK7653 were less than 12.7% and the accuracies were -3.3% to 6.3% for both plasma and urine. Finally, this method was successfully applied to explore the pharmacokinetic characteristics of HSK7653 in Chinese healthy volunteers in a first-in-human study.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Reprodutibilidade dos Testes , Hipoglicemiantes , Dipeptidil Peptidases e Tripeptidil PeptidasesRESUMO
Due to the heterogeneity of ultrasound (US) images and the indeterminate US texture of liver fibrosis (LF), automatic evaluation of LF based on US images is still challenging. Thus, this study aimed to propose a hierarchical Siamese network that combines the information from liver and spleen US images to improve the accuracy of LF grading. There were two stages in the proposed method. In stage one, a dual-channel Siamese network was trained to extract features from paired liver and spleen patches that were cropped from US images to avoid vascular interferences. Subsequently, the L1 distance was used to quantify the liver-spleen differences (LSDs). In stage two, the pretrained weights from stage one were transferred into the Siamese feature extractor of the LF staging model, and a classifier was trained using the fusion of the liver and LSD features for LF staging. This study was retrospectively conducted on US images of 286 patients with histologically proven liver fibrosis stages. Our method achieved a precision and sensitivity of 93.92% and 91.65%, respectively, for cirrhosis (S4) diagnosis, which is about 8% higher than that of the baseline model. The accuracy of the advanced fibrosis (≥S3) diagnosis and the multi-staging of fibrosis (≤S2 vs. S3 vs. S4) both improved about 5% to reach 90.40% and 83.93%, respectively. This study proposed a novel method that combined hepatic and splenic US images and improved the accuracy of LF staging, which indicates the great potential of liver-spleen texture comparison in noninvasive assessment of LF based on US images.
Assuntos
Fígado , Baço , Humanos , Baço/diagnóstico por imagem , Baço/patologia , Estudos Retrospectivos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , FibroseRESUMO
This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 â for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.