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Precise manipulation of individual DNA molecules entering and leaving the channel ports, as well as their smooth passage across the channel, is essential for the detection and screening of DNA molecules using nano-/micro-fluidic technologies. In this paper, by combining single-molecule fluorescence imaging and numerical simulations, the motion states of DNA molecules translocating through a microfluidic channel under the action of the applied electric field are monitored and analyzed in detail. It is found that, under certain conditions of the applied electric field DNA molecules exhibit various motion states, including translation crossing, deflection outflow, reverse outflow, reciprocal movement, and elliptical movement. Simulations indicate that, under the action of Saffman force, DNA molecules can only undergo deflective motion when they experience a velocity gradient in the microchannel flow field; and they can only undergo elliptical motion when their deflective motion is accompanied by a spin motion. In this case, the Magnus force also plays an important role. The detailed study and elucidation of the movement states, dynamic characteristics and mechanisms of DNA molecules such as the deflective and elliptical motions under the actions of Saffman and Magnus forces have helpful implications for the development of related DNA/gene nano-/microfluidic chips, and for the separation, screening and detection of DNA molecules.
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ADN , ADN/química , Movimiento (Física) , Técnicas Analíticas Microfluídicas/instrumentaciónRESUMEN
Primary malignant melanoma (MM) arising from the cervix is an exceedingly rare occurrence, and patients diagnosed with this condition often face a dismal clinical prognosis. Here, we present a case study of a postmenopausal woman presenting with vaginal bleeding and a conspicuous 5-centimeter black mass on the cervix. Based on the staging criteria established by the International Federation of Gynecology and Obstetrics, she was diagnosed with stage IIB primary cervical MM. The patient underwent neoadjuvant therapy prior to a radical hysterectomy and a bilateral salpingo-oophorectomy. Subsequently, she completed 18 cycles of pembrolizumab therapy, achieving clinical complete remission. Notably, at the 31-month follow-up, there were no signs of recurrence. This successful treatment outcome serves as a valuable clinical reference for the management of primary cervical MM.
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BACKGROUND: Recently, the application of deep learning (DL) has made great progress in various fields, especially in cancer research. However, to date, the bibliometric analysis of the application of DL in cancer is scarce. Therefore, this study aimed to explore the research status and hotspots of the application of DL in cancer. METHODS: We retrieved all articles on the application of DL in cancer from the Web of Science database Core Collection database. Biblioshiny, VOSviewer and CiteSpace were used to perform the bibliometric analysis through analyzing the numbers, citations, countries, institutions, authors, journals, references, and keywords. RESULTS: We found 6,016 original articles on the application of DL in cancer. The number of annual publications and total citations were uptrend in general. China published the greatest number of articles, USA had the highest total citations, and Saudi Arabia had the highest centrality. Chinese Academy of Sciences was the most productive institution. Tian, Jie published the greatest number of articles, while He Kaiming was the most co-cited author. IEEE Access was the most popular journal. The analysis of references and keywords showed that DL was mainly used for the prediction, detection, classification and diagnosis of breast cancer, lung cancer, and skin cancer. CONCLUSIONS: Overall, the number of articles on the application of DL in cancer is gradually increasing. In the future, further expanding and improving the application scope and accuracy of DL applications, and integrating DL with protein prediction, genomics and cancer research may be the research trends.
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Bibliometría , Aprendizaje Profundo , Neoplasias , HumanosRESUMEN
OBJECTIVE: To overcome the limitation of the supraclavicular artery island flap (SCAIF), we describe a modified SCAIF which incorporates a portion of the upper trapezius and the superficial branch of the transverse cervical artery (TCA) for the reconstruction of oral and maxillofacial defects. STUDY DESIGN: The modified SCAIF was used on 20 patients at our hospital between April 2013 and August 2022. All patients underwent resection of the primary lesion site and immediate reconstruction with the modified SCAIF. Demographic data and flap details were recorded. Complications were assessed for at least a 6-month follow-up period. RESULTS: This study included 20 patients. The mean flap harvest time was 50 minutes. The mean flap length was 6.0 cm, and the mean flap width was 5.0 cm. All flaps of 20 cases survived with good appearance, and no shoulder morbidity was found during a follow-up period of at least 6 months. CONCLUSION: The modified SCAIF is a versatile and reliable local flap option for moderate to large reconstruction in this special region after resection of the primary lesions. We found this simple flap design has overcome the limitations of the traditional one with a reliable blood supply and adequate tissue for larger defects.
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The development of growth factor-free biomaterials for bone tissue regeneration with anti-infection and anti-inflammatory activities remains challenging. Black phosphorus nanosheets (BPNs), with distinctive attributes, including photothermal conversion and calcium ion chelation, offer potential for use in bone tissue engineering and infection prevention. However, BPNs are prone to oxidation and degradation in aqueous environments, and methods to stabilize BPNs for long-term bone repair remain insufficient. Herein, zeolitic imidazolate framework-8 (ZIF-8) was used to stabilize BPNs via in situ crystallization onto the surface of BPNs (BP@ZIF-8 nanocomposite). A novel injectable dual-component hydrogel comprising gelatin methacryloyl (GelMA) and methacrylate-modified hyaluronic acid (HAMA) was used as a BP@ZIF-8 nanocomposite carrier (GelMA/HAMA/BP@ZIF-8). The BP@ZIF-8 nanocomposite could effectively protect internal BPNs from oxidation and enhance the long-term photothermal performance of the hydrogel in both in vitro and in vivo settings. The GelMA/HAMA/BP@ZIF-8 hydrogel was injectable and exhibited outstanding performance for photothermal conversion, mechanical strength, and biodegradability, as well as excellent photothermal antibacterial activity against Staphylococcus aureus and Escherichia coli in vitro and in an in vivo rat model. The GelMA/HAMA/BP@ZIF-8 hydrogel also provided a microenvironment conducive to osteogenic differentiation, promoting the transformation of M2 macrophages and inhibiting inflammatory responses. Furthermore, the hydrogel promoted bone regeneration and had a synergistic effect with near-infrared irradiation in a rat skull-defect model. Transcriptome sequencing analysis revealed that the PI3K-AKT- and calcium-signaling pathways may be involved in promoting osteogenic differentiation induced by the GH-BZ hydrogel. This study presents an innovative, multifaceted solution to the challenges of bone tissue regeneration with antibacterial and anti-inflammatory effects, providing insights into the design of smart biomaterials with dual therapeutic capabilities.
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Antibacterianos , Escherichia coli , Hidrogeles , Osteogénesis , Fósforo , Staphylococcus aureus , Zeolitas , Antibacterianos/química , Antibacterianos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Animales , Osteogénesis/efectos de los fármacos , Fósforo/química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Ratas , Zeolitas/química , Zeolitas/farmacología , Gelatina/química , Gelatina/farmacología , Ratones , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Ratas Sprague-Dawley , Metacrilatos/química , Metacrilatos/farmacología , Pruebas de Sensibilidad Microbiana , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Nanocompuestos/química , Células RAW 264.7 , Regeneración Ósea/efectos de los fármacos , Nanoestructuras/químicaRESUMEN
Infection is known to occur in a substantial proportion of patients following spinal surgery and predictive modeling may provide a useful means for identifying those at higher risk of complications and poor prognosis, which could help optimize pre- and postoperative management strategies. The outcome measure of the present study was to investigate the occurrence of all-cause infection during hospitalization following scoliosis surgery. To meet this aim, the present study retrospectively analyzed 370 patients who underwent surgery at the Second Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2016 and October 2022, and patients who either experienced or did not experience all-cause infection while in hospital were compared in terms of their clinicodemographic characteristics, surgical variables and laboratory test results. Logistic regression was subsequently applied to data from a subset of patients in order to build a model to predict infection, which was validated using another subset of patients. All-cause, in-hospital postoperative infections were found to have occurred in 66/370 patients (17.8%). The following variables were included in a predictive model: Sex, American Society of Anesthesiologists (ASA) classification, body mass index (BMI), diabetes mellitus, hypertension, preoperative levels of white blood cells and preoperative C-reactive protein (CRP) and duration of surgery. The model exhibited an area under the curve of 0.776 against the internal validation set. In conclusion, dynamic nomograms based on sex, ASA classification, BMI, diabetes mellitus, hypertension, preoperative levels of white blood cells and CRP and duration of surgery may have the potential to be a clinically useful predictor of all-cause infection following scoliosis. The predictive model constructed in the present study may potentially facilitate the real-time visualization of risk factors associated with all-cause infection following surgical procedures.
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Background: The description of long-term trends in the cancer burden among children aged zero to nine years from 1990 to 2019 reveals significant changes in children's health. It helps in resource allocation and health policy planning. We analysed data on the incidence, mortality, and disability-adjusted life years (DALYs) by sex and age group in children aged zero to nine. Methods: Estimates of DALYs for children aged zero to nine years, appeared as part of the Global Burden of Diseases, Injuries, and Risk Factor Study 2019, by age, sex, and location for 1990-2019. We also provided estimations by the sociodemographic index (SDI) quintile, a systematic measure to indicate educational attainment, income per capita, and total fertility rate for those younger than 25 years. We used age-period-cohort models to investigate paediatric cancers prevalence, incidence, mortality, and DALYs rates and auto-regressive integrated moving average models to predict cancer in children of different age groups in males and females. Results: A total of 6 224 010 DALY numbers for cancer cases occurred globally in 2019 among children aged zero to nine years. Additionally, the incidence of paediatric cancers in 2019 in the middle SDI countries was the highest, including 60 662 cases, and the highest mortality and DALYs cases of paediatric cancers were in the low SDI countries (25 502 and 2 199 790). The joinpoint regression analysis revealed that the trend of total cancer burden in age-standardised mortality rates and age-standardised DALYs rates showed a significant decrease with an average annual percentage change of -2.10 and -2.03 from 1990 to 2019. Furthermore, the paediatric cancer spectrum was changing. Other malignant neoplasms and other leukaemia were the major components of cancer in all age groups of children. Conclusions: The disease burden in children aged zero to nine years decreased significantly globally from 1990 to 2019. However, the overall prediction of childhood cancer increased slightly from 2020 to 2040. Our findings may help guide investments and inform policies. This highlights the necessity to improve current treatment measures and establish effective prevention strategies to reduce the cancer burden among children aged zero to nine years.
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Años de Vida Ajustados por Discapacidad , Carga Global de Enfermedades , Salud Global , Neoplasias , Humanos , Neoplasias/epidemiología , Neoplasias/mortalidad , Femenino , Masculino , Preescolar , Lactante , Niño , Salud Global/estadística & datos numéricos , Años de Vida Ajustados por Discapacidad/tendencias , Recién Nacido , Carga Global de Enfermedades/tendencias , IncidenciaRESUMEN
The blood-brain barrier (BBB) protects the central nervous system from infections or harmful substances1; its impairment can lead to or exacerbate various diseases of the central nervous system2-4. However, the mechanisms of BBB disruption during infection and inflammatory conditions5,6 remain poorly defined. Here we find that activation of the pore-forming protein GSDMD by the cytosolic lipopolysaccharide (LPS) sensor caspase-11 (refs. 7-9), but not by TLR4-induced cytokines, mediates BBB breakdown in response to circulating LPS or during LPS-induced sepsis. Mice deficient in the LBP-CD14 LPS transfer and internalization pathway10-12 resist BBB disruption. Single-cell RNA-sequencing analysis reveals that brain endothelial cells (bECs), which express high levels of GSDMD, have a prominent response to circulating LPS. LPS acting on bECs primes Casp11 and Cd14 expression and induces GSDMD-mediated plasma membrane permeabilization and pyroptosis in vitro and in mice. Electron microscopy shows that this features ultrastructural changes in the disrupted BBB, including pyroptotic endothelia, abnormal appearance of tight junctions and vasculature detachment from the basement membrane. Comprehensive mouse genetic analyses, combined with a bEC-targeting adeno-associated virus system, establish that GSDMD activation in bECs underlies BBB disruption by LPS. Delivery of active GSDMD into bECs bypasses LPS stimulation and opens the BBB. In CASP4-humanized mice, Gram-negative Klebsiella pneumoniae infection disrupts the BBB; this is blocked by expression of a GSDMD-neutralizing nanobody in bECs. Our findings outline a mechanism for inflammatory BBB breakdown, and suggest potential therapies for diseases of the central nervous system associated with BBB impairment.
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Barrera Hematoencefálica , Encéfalo , Células Endoteliales , Gasderminas , Inflamación , Animales , Femenino , Humanos , Masculino , Ratones , Membrana Basal/metabolismo , Membrana Basal/ultraestructura , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Barrera Hematoencefálica/ultraestructura , Barrera Hematoencefálica/virología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/ultraestructura , Caspasas Iniciadoras/metabolismo , Dependovirus , Células Endoteliales/metabolismo , Células Endoteliales/ultraestructura , Gasderminas/antagonistas & inhibidores , Gasderminas/metabolismo , Inflamación/patología , Inflamación/metabolismo , Klebsiella pneumoniae/fisiología , Receptores de Lipopolisacáridos/metabolismo , Lipopolisacáridos/sangre , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Piroptosis , Sepsis/metabolismo , Sepsis/patología , Sepsis/microbiología , Análisis de la Célula Individual , Uniones Estrechas/metabolismo , Uniones Estrechas/ultraestructuraRESUMEN
ABSTRACT: Sepsis-induced myocardial dysfunction commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. This study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. In addition, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NOD-like receptor protein-3 (NLRP3) upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for sepsis-induced myocardial dysfunction therapy.
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Antiinflamatorios , Modelos Animales de Enfermedad , Lipopolisacáridos , Ratones Endogámicos C57BL , Miocitos Cardíacos , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Sepsis , Transducción de Señal , Espirostanos , Animales , Lipopolisacáridos/toxicidad , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Espirostanos/farmacología , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Piroptosis/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Línea Celular , Antiinflamatorios/farmacología , Ratones , Cardiomiopatías/prevención & control , Cardiomiopatías/patología , Cardiomiopatías/metabolismo , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/inducido químicamente , Mediadores de Inflamación/metabolismoRESUMEN
Background: The lung ultrasound score was developed for rapidly assessing the extent of lung ventilation, and it can predict failure to wean various types of patients off mechanical ventilation. Whether it is also effective for COVID-19 patients is unclear. Methods: This single-center, prospective, observational study was conducted to assess the ability of the 12-region lung ultrasound score to predict failure to wean COVID-19 patients off ventilation. In parallel, we assessed whether right hemidiaphragmatic excursion or previously published predictors of weaning failure can apply to these patients. Predictive ability was assessed in terms of the area under the receiver operating characteristic curve (AUC). Results: The mean age of the 35 patients in the study was (75 ± 9) years and 12 patients (37%) could not be weaned off mechanical ventilation. The lung ultrasound score predicted these failures with an AUC of 0.885 (95% CI 0.770-0.999, p < 0.001), and a threshold score of 10 provided specificity of 72.7% and sensitivity of 92.3%. AUCs were lower for previously published predictors of weaning failure, and right hemidiaphragmatic excursion did not differ significantly between the two groups. Conclusion: The lung ultrasound score can accurately predict failure to wean critically ill COVID-19 patients off mechanical ventilation, whereas assessment of right hemidiaphragmatic excursion does not appear helpful in this regard. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05706441.
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COVID-19 , Respiración Artificial , Humanos , Anciano , Anciano de 80 o más Años , Desconexión del Ventilador , Estudios Prospectivos , Valor Predictivo de las Pruebas , Pulmón/diagnóstico por imagenRESUMEN
Background: The etiopathogenesis of periodontitis is closely associated with environmental conditions. However, the relationship between ethylene oxide exposure and periodontitis risk remains unclear. Methods: We selected qualified participants from National Health and Nutrition Examination Survey (NHANES) 2013-2014. Periodontitis was identified according to the criteria of the Community Periodontal Index (CPI), Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) definition. Ethylene oxide exposure was quantified by hemoglobin adducts of ethylene oxide (HbEO) levels. Log2-transformation was used to normalize HbEO levels. We designed three logistic regression models to explore potential relationship between HbEO and periodontitis. Restricted cubic spline (RCS) and subgroup analysis were also conducted with all covariates adjusted. We performed multivariable linear regression to appraise the association between the risk of periodontitis and different indicators of inflammation, including white blood cells, neutrophils, lymphocytes, and monocytes. Mediation analysis was subsequently performed to examine whether ethylene oxide exposure contributed to periodontitis development through systemic body inflammation. Results: A total of 1,065 participants aged more than 30 were incorporated in this study. We identified that participants with higher HbEO levels showed increased risk of periodontitis after adjusting for all covariates (OR = 1.49, 95% CI: 1.14, 1.95, p = 0.0014). The results of subgroup analysis remained stable. The restricted cubic spline (RCS) curve also revealed a non-linear correlation between log2-transformed HbEO levels with the risk of periodontitis (p for nonlinear < 0.001). Mediation analysis indicated that HbEO level was significantly associated with four inflammatory mediators, with the mediated proportions of 14.44% (p < 0.001) for white blood cell, 9.62% (p < 0.001) for neutrophil, 6.17% (p = 0.006) for lymphocyte, and 6.72% (p < 0.001) for monocyte. Conclusion: Participants with higher ethylene oxide exposure showed higher risk of periodontitis, which was partially mediated by systemic body inflammation. More well-designed longitudinal studies should be carried out to validate this relationship.
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Óxido de Etileno , Periodontitis , Humanos , Encuestas Nutricionales , Periodontitis/epidemiología , Periodontitis/complicaciones , Inflamación/complicaciones , HemoglobinasRESUMEN
The molecular details of an electrocatalytic interface play an essential role in the production of sustainable fuels and value-added chemicals. Many electrochemical reactions exhibit strong cation-dependent activities, but how cations affect reaction kinetics is still elusive. We report the effect of cations (K+, Li+, and Ba2+) on the interfacial water structure using second-harmonic generation (SHG) and classical molecular dynamics (MD) simulation. The second- (χH2O(2)) and third-order (χH2O(3)) optical susceptibilities of water on Pt are smaller in the presence of Ba2+ compared to those of K+, suggesting that cations can affect the interfacial water orientation. MD simulation reproduces experimental SHG observations and further shows that the competition between cation hydration and interfacial water alignment governs the net water orientation. The impact of cations on interfacial water supports a cation hydration-mediated mechanism for hydrogen electrocatalysis; i.e., the reaction occurs via water dissociation followed by cation-assisted hydroxide/water exchange on Pt. Our study highlights the role of interfacial water in electrocatalysis and how innocent additives (such as cations) can affect the local electrochemical environment.
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Even though nucleation is ubiquitous in different science and engineering problems, investigating nucleation is extremely difficult due to the complicated ranges of time and length scales involved. In this work, we simulate NaCl nucleation in both molten and aqueous environments using enhanced sampling of all-atom molecular dynamics with deep-learning-based estimation of reaction coordinates. By incorporating various structural order parameters and learning the reaction coordinate as a function thereof, we achieve significantly improved sampling relative to traditional ad hoc descriptions of what drives nucleation, particularly in an aqueous medium. Our results reveal a one-step nucleation mechanism in both environments, with reaction coordinate analysis highlighting the importance of local ion density in distinguishing solid and liquid states. However, although fluctuations in the local ion density are necessary to drive nucleation, they are not sufficient. Our analysis shows that near the transition states, descriptors such as enthalpy and local structure become crucial. Our protocol proposed here enables robust nucleation analysis and phase sampling and could offer insights into nucleation mechanisms for generic small molecules in different environments.
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Background: Mitochondria are dynamic organelles, and mitochondrial dynamics are important for the maintenance of mitochondrial inheritance and function. Recently, an increasing number of studies have shown that mitochondrial dynamics play an important role in the occurrence and development of hepatocellular carcinoma (HCC). However, bibliometric analyses of mitochondrial dynamics in HCC are scarce. Therefore, we conducted a bibliometric analysis to explore the current global research status and trends in mitochondrial dynamics and HCC. Methods: Global publications on mitochondrial dynamics and HCC published between 2007 and May 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using Bibliometrix, VOSviewer, and CiteSpace to analyze the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results: A total of 518 publications were retrieved fromthe WoSCC database. China and The Fourth Military Medical University were the most productive countries and institutions. Zorzano, A published the most literature whereas Chen, HC was the author with the highest number of co-citations. Plos One was the most popular journal, whereas the Journal of Biological Chemistry had the highest number of co-citations. The most frequently used keyword was "mitochondria". Further analysis of the references and keywords showed that the molecular mechanisms linking them to drug therapy targets should be the focus of future studies. Conclusions: Research on mitochondrial dynamics in HCC has received much attention, and many studies have been published. However, research on mitochondrial dynamics and HCC has been limited by insufficient regional development imbalances and global cooperation. Nevertheless, future research on mitochondrial dynamics and HCC is promising, especially regarding the molecular mechanisms of mitochondrial fission and fusion and how to link the currently known molecular mechanisms with drug therapy targets for HCC.
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Purpose: Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI. Methods: The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRTâPCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the AKT agonist SC79 were used to confirm the protective effect of the TRPV1/AKT axis against ALI. The autophagy agonist rapamycin (Rapa) and the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPS-induced autophagy. Results: Our findings demonstrated that CAP effectively suppressed inflammation and autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/AKT signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression. Conclusion: Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/AKT signaling pathway, presenting a novel strategy for ALI therapy.
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This study investigated the removal performance of ofloxacin (OFL) by a novel electro-Fenton enhanced microfiltration membrane. The membranes used in this study consisted of metal-organic framework derived porous carbon, carbon nanotubes and Fe2+, which were able to produce hydroxyl radicals (â¢OH) in-situ via reducing O2 to hydrogen peroxide. Herein, membrane filtration with bias not only concentrated the pollutants to the level that could be efficiently treated by electro-Fenton but also confined/retained the toxic intermediates within the membrane to ensure a prolonged contact time with the oxidants. After validated by experiments, the applied bias of -1.0 V, pH of 3 and electrolyte concentration of 0.1 M were the relatively optimum conditions for OFL degradation. Under these conditions, the average OFL removal rate could be reach 75% with merely 5% membrane flux loss after 4 cycles operation by filtrating 1 mg/L OFL. Via decarboxylation reaction, piperazinyl ring opening, dealkylation and ipso substitution reaction, etc., OFL could be gradually and efficiently degraded to intermediate products and even to CO2 by â¢OH. Moreover, the oxidation reaction was preferred to following first-order reaction kinetics. This research verified a possibility for antibiotic removal by electro-enhanced microfiltration membrane.
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Nanotubos de Carbono , Contaminantes Químicos del Agua , Ofloxacino , Porosidad , Antibacterianos , Oxidantes , Peróxido de Hidrógeno , Oxidación-ReducciónRESUMEN
The pituitary represents an essential hub in the hypothalamus-pituitary-adrenal (HPA) axis. Pituitary hormone-producing cells (HPCs) release several hormones to regulate fundamental bodily functions under normal and stressful conditions. It is well established that the pituitary endocrine gland modulates the immune system by releasing adrenocorticotropic hormone (ACTH) in response to neuronal activation in the hypothalamus. However, it remains unclear how systemic inflammation regulates the transcriptomic profiles of pituitary HPCs. Here, we performed single-cell RNA-sequencing (scRNA-seq) of the mouse pituitary and revealed that upon inflammation, all major pituitary HPCs respond robustly in a cell type-specific manner, with corticotropes displaying the strongest reaction. Systemic inflammation also led to the production and release of noncanonical bioactive molecules, including Nptx2 by corticotropes, to modulate immune homeostasis. Meanwhile, HPCs up-regulated the gene expression of chemokines that facilitated the communication between the HPCs and immune cells. Together, our study reveals extensive interactions between the pituitary and immune system, suggesting multifaceted roles of the pituitary in mediating the effects of inflammation on many aspects of body physiology.
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Hormona Liberadora de Corticotropina , Hipófisis , Ratones , Animales , Hormona Liberadora de Corticotropina/genética , Hipófisis/metabolismo , Hormona Adrenocorticotrópica/genética , Hormona Adrenocorticotrópica/metabolismo , Hormona Adrenocorticotrópica/farmacología , Inflamación/genética , Perfilación de la Expresión GénicaRESUMEN
Hemostatic disturbances after cardiac surgery can lead to excessive postoperative bleeding. Thromboelastography (TEG) was employed to evaluate perioperative coagulative alterations in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), investigating the correlation between factors concomitant with cardiac surgery and modifications in coagulation. Coagulation index as determined by TEG correlated significantly with postoperative bleeding at 24-72â h after cardiac surgery (P < .001). Among patients with a normal preoperative coagulation index, those with postoperative hypocoagulability showed significantly lower nadir temperature (P = .003), larger infused fluid volume (P = .003), and longer CPB duration (P = .033) than those with normal coagulation index. Multivariate logistic regression showed that nadir intraoperative temperature was an independent predictor of postoperative hypocoagulability (adjusted OR: 0.772, 95% CI: 0.624-0.954, P = .017). Multivariate linear regression demonstrated linear associations of nadir intraoperative temperature (P = .017) and infused fluid volume (P = .005) with change in coagulation index as a result of cardiac surgery. Patients are susceptible to hypocoagulability after cardiac surgery, which can lead to increased postoperative bleeding. Ensuring appropriate temperature and fluid volume during cardiac surgery involving CPB may reduce risk of postoperative hypocoagulability and bleeding.
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Coagulación Sanguínea , Procedimientos Quirúrgicos Cardíacos , Humanos , Estudios Retrospectivos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Tromboelastografía , Hemorragia Posoperatoria/etiología , Factores de Riesgo , Puente Cardiopulmonar/efectos adversosRESUMEN
STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To explore the association of early postoperative nadir hemoglobin with risk of a composite outcome of anemia-related and other adverse events. METHODS: We retrospectively analyzed data from spinal tumor patients who received intraoperative blood transfusion between September 1, 2013 and December 31, 2020. Uni- and multivariate logistic regression was used to explore relationships of clinicodemographic and surgical factors with risk of composite in-hospital adverse events, including death. Subgroup analysis explored the relationship between early postoperative nadir hemoglobin and composite adverse events. RESULTS: Among the 345 patients, 331 (95.9%) experienced early postoperative anemia and 69 (20%) experienced postoperative composite adverse events. Multivariate logistic regression analysis showed that postoperative nadir Hb (OR = .818, 95% CI: .672-.995, P = .044), ASA ≥3 (OR = 2.007, 95% CI: 1.086-3.707, P = .026), intraoperative RBC infusion volume (OR = 1.133, 95% CI: 1.009-1.272, P = .035), abnormal hypertension (OR = 2.199, 95% CI: 1.085-4.457, P = .029) were correlated with composite adverse events. The lumbar spinal tumor was associated with composite adverse events with a decreased odds compared to thoracic spinal tumors (OR = .444, 95% CI: .226-.876, P = .019). Compared to patients with postoperative nadir hemoglobin ≥11.0 g/dL, those with nadir <9.0 g/dL were at significantly higher risk of postoperative composite adverse events (OR = 2.709, 95% CI: 1.087-6.754, P = .032). CONCLUSION: Nadir hemoglobin <9.0 g/dL after spinal tumor surgery is associated with greater risk of postoperative composite adverse events in patients who receive intraoperative blood transfusion.
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OBJETIVES: To investigate the positional changes in the temporomandibular joint (TMJ) disc-condyle-fossa complex of patients with anterior disc displacement without reduction (ADDWoR) and to evaluate the effect of disc repositioning (DR) surgery. MATERIAL AND METHODS: Fifteen patients with unilateral ADDWoR (30 joints) were included. MRI of the TMJ was performed at T0 (1 week before surgery), T1 (1 month after surgery), and T2 (9-12 months after surgery). The glenoid fossa, disc, and condyle were reconstructed and analyzed using Mimics software. RESULTS: In the patients with unilateral ADDWoR, the disc on the ADD side showed a tendency to downward shift in the coronal direction and forward shift in the sagittal direction; the condyle of ADD side showed a tendency to backward shift in the sagittal direction and upward shift in the coronal direction. When comparing the same ADDwoR TMJ at T0, T1, and T2, the disc was found to move upward and backward after DR surgery at T1 and T2, and the condyle was found to move upward and backward after DR surgery at T1 but returned to the original position at T2. CONCLUSIONS: ADDWoR leads to forward and downward displacement of the disc relative to the condyle and upward displacement of the condyle relative to the tuberosity. DR surgery improved upon the structural abnormalities of the TMJ complex, for which stability was maintained as determined in the 9 to 12 month postoperative follow-up. CLINIC RELEVANCE: DR surgery effectively and constantly improves the positional abnormalities of the TMJ complex.