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SignificanceATP8B1 is a P4 ATPase that maintains membrane asymmetry by transporting phospholipids across the cell membrane. Disturbance of lipid asymmetry will lead to the imbalance of the cell membrane and eventually, cell death. Thus, defects in ATP8B1 are usually associated with severe human diseases, such as intrahepatic cholestasis. The present structures of ATP8B1 complexed with its auxiliary noncatalytic partners CDC50A and CDC50B reveal an autoinhibited state of ATP8B1 that could be released upon substrate binding. Moreover, release of this autoinhibition could be facilitated by the bile acids, which are key factors that alter the membrane asymmetry of hepatocytes. This enabled us to figure out a feedback loop of bile acids and lipids across the cell membrane.
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Adenosina Trifosfatases , Colestase Intra-Hepática , Adenosina Trifosfatases/metabolismo , Ácidos e Sais Biliares/metabolismo , Membrana Celular/metabolismo , Colestase Intra-Hepática/metabolismo , Humanos , Proteínas de Transferência de Fosfolipídeos/metabolismo , Fosfolipídeos/metabolismoRESUMO
Myocardial ischemia-reperfusion injury (MIRI) represents a critical pathology in acute myocardial infarction (AMI), which is characterized by high mortality and morbidity. Cardiac microvascular dysfunction contributes to MIRI, potentially culminating in heart failure (HF). Pigment epithelium-derived factor (PEDF), which belongs to the non-inhibitory serpin family, exhibits several physiological effects, including anti-angiogenesis, anti-inflammatory and antioxidant properties. Our study aims to explore the impact of PEDF and its functional peptide 34-mer on both cardiac microvascular perfusion in MIRI rats and human cardiac microvascular endothelial cells (HCMECs) injury under hypoxia reoxygenation (HR). It has been shown that MIRI is accompanied by ferroptosis in HCMECs. Furthermore, we investigated the effect of PEDF and its 34-mer, particularly regarding the Nrf2/HO-1 signalling pathway. Our results demonstrated that PEDF 34-mer significantly ameliorated cardiac microvascular dysfunction following MIRI. Additionally, they exhibited a notable suppression of ferroptosis in HCMECs, and these effects were mediated through activation of Nrf2/HO-1 signalling. These findings highlight the therapeutic potential of PEDF and 34-mer in alleviating microvascular dysfunction and MIRI. By enhancing cardiac microvascular perfusion and mitigating endothelial ferroptosis, PEDF and its derivative peptide represent promising candidates for the treatment of AMI.
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Células Endoteliais , Proteínas do Olho , Ferroptose , Traumatismo por Reperfusão Miocárdica , Fator 2 Relacionado a NF-E2 , Fatores de Crescimento Neural , Serpinas , Transdução de Sinais , Serpinas/farmacologia , Serpinas/metabolismo , Fatores de Crescimento Neural/farmacologia , Fatores de Crescimento Neural/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Ferroptose/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Proteínas do Olho/metabolismo , Proteínas do Olho/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ratos , Heme Oxigenase-1/metabolismo , Masculino , Ratos Sprague-Dawley , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Microvasos/patologia , Peptídeos/farmacologiaRESUMO
BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury causes cardiac dysfunction to myocardial cell loss and fibrosis. Prevention of cell death is important to protect cardiac function after I/R injury. The process of reperfusion can lead to multiple types of cardiomyocyte death, including necrosis, apoptosis, autophagy, and ferroptosis. However, the time point at which the various modes of cell death occur after reperfusion injury and the mechanisms underlying ferroptosis regulation in cardiomyocytes are still unclear. METHODS: Using a left anterior descending coronary artery ligation mouse model, we sought to investigate the time point at which the various modes of cell death occur after reperfusion injury. To discover the key molecules involved in cardiomyocyte ferroptosis, we performed a metabolomics study. Loss/gain-of-function approaches were used to understand the role of 15-lipoxygenase (Alox15) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α) in myocardial I/R injury. RESULTS: We found that apoptosis and necrosis occurred in the early phase of I/R injury, and that ferroptosis was the predominant form of cell death during the prolonged reperfusion. Metabolomic profiling of eicosanoids revealed that Alox15 metabolites accumulated in ferroptotic cardiomyocytes. We demonstrated that Alox15 expression was specifically increased in the injured area of the left ventricle below the suture and colocalized with cardiomyocytes. Furthermore, myocardial-specific knockout of Alox15 in mice alleviated I/R injury and restored cardiac function. 15-Hydroperoxyeicosatetraenoic acid (15-HpETE), an intermediate metabolite derived from arachidonic acid by Alox15, was identified as a trigger for cardiomyocyte ferroptosis. We explored the mechanism underlying its effects and found that 15-HpETE promoted the binding of Pgc1α to the ubiquitin ligase ring finger protein 34, leading to its ubiquitin-dependent degradation. Consequently, attenuated mitochondrial biogenesis and abnormal mitochondrial morphology were observed. ML351, a specific inhibitor of Alox15, increased the protein level of Pgc1α, inhibited cardiomyocyte ferroptosis, protected the injured myocardium, and caused cardiac function recovery. CONCLUSIONS: Together, our results established that Alox15/15-HpETE-mediated cardiomyocyte ferroptosis plays an important role in prolonged I/R injury.
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Araquidonato 15-Lipoxigenase , Ferroptose , Traumatismo por Reperfusão Miocárdica , Animais , Camundongos , Apoptose , Araquidonato 12-Lipoxigenase/metabolismo , Araquidonato 12-Lipoxigenase/farmacologia , Araquidonato 15-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/farmacologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Necrose/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ubiquitinas/metabolismo , Ubiquitinas/farmacologiaRESUMO
Fringe projection profilometry (FPP) faces significant challenges regarding calibration difficulty and stitching error accumulation when operating across scenes ranging from tens to hundreds of meters. This Letter presents a calibration-free 3D measurement method by integrating a binocular vision of a FPP scanner with a wide field-of-view (FoV) vision that constructs global benchmarks to unify local 3D scanning and global 3D stitching, which is adaptable to arbitrarily large-scale scenes. A posterior global optimization model is then established to determine the reconstruction parameters and stitching poses simultaneously at each scanning node with adaptively distributed benchmarks. Consequently, the integrated vision measurement system not only eliminates the large-scale pre-calibration and stitching error accumulation but also overcomes system structural instability during moving measurement. With the proposed method, we achieved 3D measurements with an accuracy of 0.25 mm and a density of 0.5 mm for over 50-m-long scenes.
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OBJECTIVE: The purpose of this study was to develop an individual survival prediction model based on multiple machine learning (ML) algorithms to predict survival probability for remnant gastric cancer (RGC). METHODS: Clinicopathologic data of 286 patients with RGC undergoing operation (radical resection and palliative resection) from a multi-institution database were enrolled and analyzed retrospectively. These individuals were split into training (80%) and test cohort (20%) by using random allocation. Nine commonly used ML methods were employed to construct survival prediction models. Algorithm performance was estimated by analyzing accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), confusion matrices, five-fold cross-validation, decision curve analysis (DCA), and calibration curve. The best model was selected through appropriate verification and validation and was suitably explained by the SHapley Additive exPlanations (SHAP) approach. RESULTS: Compared with the traditional methods, the RGC survival prediction models employing ML exhibited good performance. Except for the decision tree model, all other models performed well, with a mean ROC AUC above 0.7. The DCA findings suggest that the developed models have the potential to enhance clinical decision-making processes, thereby improving patient outcomes. The calibration curve reveals that all models except the decision tree model displayed commendable predictive performance. Through CatBoost-based modeling and SHAP analysis, the five-year survival probability is significantly influenced by several factors: the lymph node ratio (LNR), T stage, tumor size, resection margins, perineural invasion, and distant metastasis. CONCLUSIONS: This study established predictive models for survival probability at five years in RGC patients based on ML algorithms which showed high accuracy and applicative value.
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Aprendizado de Máquina , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Idoso , Gastrectomia , Coto Gástrico/patologia , Curva ROC , Medição de Risco/métodos , AlgoritmosRESUMO
Although Qixue Shuangbu Prescription (QSP) is a classic Chinese medicine prescription for treating chronic heart failure. Low bioavailability due to the insolubility and poor biofilm permeability of the main bioactive ingredients of QSP is still a key factor limiting its efficacy. In this study, a novel self-microemulsifying drug delivery system was proposed to effectively improve the bioavailability of QSP. The qualified ultra-high-performance liquid chromatography-tandem mass spectrometry methodology was established to investigate the pharmacokinetics characteristics of the QSP self-microemulsifying drug delivery system. Our results showed that 11 components in the self-microemulsifying drug delivery system group had prolonged T1/2 and MRT0-t values compared with QSP extract. The Cmax of calycosin-7-glucoside (CG), vanillic acid and paeoniflorin increased 2.5 times, 2.4 times and 2.3 times, respectively. The relative bioavailability values of CG, paeoniflorin and ononin were most significantly affected, increasing by 383.2%, 336.5% and 307.1%, respectively. This study promoted the development of new dosage forms of QSP and provided a useful reference for improving dosage forms to solve the problem of low bioavailability of traditional Chinese medicine.
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Medicamentos de Ervas Chinesas , Glucosídeos , Monoterpenos , Espectrometria de Massas em Tandem , Animais , Ratos , Administração Oral , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Prescrições , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodosRESUMO
Objective: The clinical effect of tonsillectomy with the preservation of tonsillar capsule and stent tissue and punctuated suture of tonsillar capsule and stent tissue was analyzed retrospectively. Methods: From January 2013 to January 2022, a total of 960 patients underwent tonsillectomy, consisting of 530 males and 430 females with ages ranging from 4 to 60 years (median age: 11 years). The capsule and scaffold tissues were preserved in all patients during the operation, and the surrounding mucosa, capsule, and scaffold tissues were sutured without tension. Indexes such as operation time, intraoperative blood loss, tonsillar white membrane, incidence of postoperative bleeding, postoperative pain score, and incidence of tonsillar remnant were recorded, and the school attendance of children (≤12 years old) was recorded. Results: The mucosal covering of tonsillar fossa healed well in all patients, and the sutures were completely removed at 4 weeks after reexamination. All patients were followed up for 1-8 years, and there was no residual hyperplasia or residual inflammation. Children under 12 years old could return to school 4 days after surgery without any postoperative complications. Conclusion: Tonsillectomy, preserving the tonsillar capsule and scaffold tissue followed by punctate suturing, offered several advantages: it resulted in less intraoperative blood loss and postoperative pain. Patients could resume a normal diet 6 hours after the surgery without an increased risk of complications. Moreover, it significantly reduced the risk of postoperative bleeding.
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BACKGROUND: To investigate the knowledge, attitude, and practice (KAP) of healthcare professionals regarding cognitive dysfunction and cognitive rehabilitation in Parkinson's disease (PD). METHODS: This multicenter, cross-sectional survey enrolled physicians and nurses in 10 hospitals between October 2022 and November 2022. A self-administered questionnaire was developed to collect the demographic information of the participants and their knowledge, attitude, and practice toward cognitive dysfunction in PD and cognitive rehabilitation. RESULTS: This study enrolled 224 physicians and 229 nurses. The knowledge, attitude, and practice scores were 12.57 ± 3.76 (total score: 22), 29.10 ± 3.71 (total score: 32), and 21.07 ± 8.03 (total score: 28) among physicians, and 9.97 ± 4.70 (total score: 22), 25.27 ± 8.96 (total score: 32), and 25.27 ± 8.96 (total score: 28) among nurses. Among physicians, the knowledge scores (OR = 4.23, 95%CI: 2.36-7.58, P < 0.001) and attitude scores (OR = 3.00, 95%CI: 1.67-5.37, P < 0.001) were independently associated with good practice. Among nurses, the knowledge scores (OR = 4.31, 95%CI: 2.31-8.05, P < 0.001), attitude scores (OR = 5.18, 95%CI: 2.82-9.53, P < 0.001), working department (Ref: rehabilitation; neurology: OR = 2.26, 95%CI: 1.01-5.08, P = 0.048; public health service/chronic disease follow-up center: OR = 2.98, 95%CI: 1.12-7.92, P = 0.028) were independently associated with good practice. CONCLUSIONS: Physicians and nurses have insufficient knowledge, favorable attitudes, and active practice regarding cognitive dysfunction and cognitive rehabilitation in PD. This study identified gaps in KAP and suggested education activities to improve the KAP toward cognitive dysfunction in PD.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Treino Cognitivo , Disfunção Cognitiva/etiologiaRESUMO
Flight parameters are crucial criteria for UAV control, playing a significant role in ensuring the safe and efficient completion of missions. Launch force and airspeed information are key parameters in the early and middle stages of flight, serving as important data for monitoring the UAV's flight status. In response to challenges such as weak launch force, low identification rates, small airspeed, and low recognition accuracy in UAVs, a method for identifying UAV flight parameters based on launch force and airspeed is proposed. From the aspect of launch force identification, a recognition method based on a low-g value accelerometer information source is proposed, utilizing a 'multi-level time window + threshold' approach. For airspeed identification, an optimization method for airspeed measurement under the Kalman filter architecture is introduced. A device for airspeed measurement based on pressure sensors is designed, and the recommended installation position is determined through simulation. Furthermore, the feasibility and robustness of the proposed launch force identification and airspeed measurement optimization methods are validated through simulation. Finally, the effectiveness of the design is verified through centrifuge and wind tunnel experiments. This research provides technical support for the identification of the launch force and airspeed measurement in UAVs.
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Rhodamines have emerged as a useful class of dye for bioimaging. However, intrinsic issues such as short emission wavelengths and small Stokes shifts limit their widespread applications in living systems. By taking advantage of the homoadamantane-fused tetrahydroquinoxaline (HFT) moiety as an electron donor, we developed a new class of asymmetric NIR rhodamine dyes, NNR1-7. These new dyes retained ideal photophysical properties from the classical rhodamine scaffold and showed large Stokes shifts (>80 nm) with improved chemo/photostability. We found that NNR1-7 specifically target cellular mitochondria with superior photobleaching resistance and improved tolerance for cell fixation compared to commercial mitochondria trackers. Based on NNR4, a novel NIR pH sensor (NNR4M) was also constructed and successfully applied for real-time monitoring of variations in lysosomal pH. We envision this design strategy would find broad applications in the development of highly stable NIR dyes with a large Stokes shift.
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Elétrons , Corantes Fluorescentes , Rodaminas/química , Corantes Fluorescentes/química , LisossomosRESUMO
CRISPR-based directed evolution is an effective breeding biotechnology to improve agronomic traits in plants. However, its gene diversification is still limited using individual single guide RNA. We described here a multiplexed orthogonal base editor (MoBE), and a randomly multiplexed sgRNAs assembly strategy to maximize gene diversification. MoBE could induce efficiently orthogonal ABE (<36.6%), CBE (<36.0%), and A&CBE (<37.6%) on different targets, while the sgRNA assembling strategy randomized base editing events on various targets. With respective 130 and 84 targets from each strand of the 34th exon of rice acetyl-coenzyme A carboxylase (OsACC), we observed the target-scaffold combination types up to 27 294 in randomly dual and randomly triple sgRNA libraries. We further performed directed evolution of OsACC using MoBE and randomly dual sgRNA libraries in rice, and obtained single or linked mutations of stronger herbicide resistance. These strategies are useful for in situ directed evolution of functional genes and may accelerate trait improvement in rice.
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Edição de Genes , Oryza , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas , Oryza/genética , Melhoramento VegetalRESUMO
OBJECTIVE: Patients with postdissection thoracoabdominal aortic aneurysms (TAAAs) have been more likely to develop endoleaks than those with degenerative TAAAs after fenestrated or branched endovascular aortic repair (F/BEVAR). In the present study, we aimed to determine the risk factors for target vessel (TV)-related endoleaks after visceral segment F/BEVAR for postdissection TAAAs. METHODS: We performed a retrospective analysis of all patients with degenerative and postdissection TAAAs treated with F/BEVAR between 2017 and 2021. All the patients had undergone computed tomography angiography before and 3 months, 6 months, and annually after discharge. Two experienced vascular surgeons had used data from computed tomography angiography and vascular angiography to judge the presence of endoleaks. The study end points were mortality, aneurysm rupture, and the emergence of and reintervention for TV-related endoleaks. RESULTS: A total of 195 patients (mean age, 66 ± 10 years; 69% men) had undergone F/BEVAR for 99 postdissection TAAAs and 96 degenerative TAAAs. During a mean follow-up of 16 ± 12 months, we found that the patients with postdissection TAAAs were younger (age, 64 ± 10 years vs 69 ± 9 years; P = .001), had required more prior aortic repairs (58% vs 40%; P = .012), and had had a higher body mass index (26.1 ± 3.4 kg/m2 vs 24.8 ± 3 kg/m2; P = .008), a larger visceral segment aortic diameter (47.1 ± 7.5 mm vs 44.5 ± 7.5 mm; P = .016), and more TV-related endoleaks (18% vs 7%; P = .023) compared with those with degenerative TAAAs. Of the 99 patients with postdissection TAAAs, 327 renal-mesenteric arteries were revascularized using 12 scallops, 141 fenestrations, and 174 inner or outer branch stents. A total of 25 TV-related endoleaks were identified among 18 patients during follow-up, including 6 type Ic (retrograde from the distal end of the branch), 3 type IIIb (bridging stent fabric tear), and 16 type IIIc endoleaks (detachment or loose connection of the bridging stent). The patients with an endoleak had had a larger visceral aortic diameter (52.7 ± 6.4 mm vs 45.8 ± 7.2 mm; P < .001) and had undergone revascularization of more TVs (3.7 ± 0.7 vs 3.2 ± 0.9; P = .032). In contrast, true lumen compression did not seem to affect the occurrence of TV endoleaks (39% vs 27%; P = .323). The use of presewn branch stents in the fenestration position was associated with a lower risk of TV-related endoleaks (5% vs 11%; P = .025). In addition, TVs derived entirely or partially from the false lumen were more prone to the development of endoleaks after reconstruction (19% vs 4% [P < .001]; and 15% vs 4% [P = .047], respectively). CONCLUSIONS: We found that patients with postdissection TAAAs were more likely to have TV-related endoleaks after F/BEVAR in the visceral region than those with degenerative TAAAs. Additionally, patients with a larger aortic diameter and a greater number of fenestrations in the visceral region were more likely to have experienced TV-related endoleaks. Branch vessels deriving from the false lumen were also more likely to develop endoleaks after reconstruction, and prefabricated branch stents were related to a lower possibility of TV-related endoleaks.
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Aneurisma da Aorta Abdominal , Aneurisma da Aorta Torácica , Aneurisma da Aorta Toracoabdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Médicos , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Endoleak/etiologia , Prótese Vascular/efeitos adversos , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Correção Endovascular de Aneurisma , Implante de Prótese Vascular/efeitos adversos , Estudos Retrospectivos , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Fatores de RiscoRESUMO
We present a new, to the best of our knowledge, simulation method for laser-induced breakdown spectroscopy during the plasma expansion phase in nonlocal thermodynamic equilibrium. Our method uses the particle-in-cell/Monte Carlo collision model to calculate dynamic processes and line intensity of nonequilibrium laser-induced plasma (LIP) in the afterglow phase. The effects of ambient gas pressure and type on LIP evolution are investigated. This simulation provides an added way to understand the nonequilibrium processes in more detail than the current fluid and collision radiation models. Our simulation results are compared with experimental and SimulatedLIBS package results and show good agreement.
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Lasers , Luz , Simulação por Computador , Termodinâmica , Análise EspectralRESUMO
Lithium-sulfur (Li-S) batteries are a promising energy storage technology due to their tempting high theoretical capacity and energy density. Nevertheless, the wastage of active materials that originates from the shuttling effect of polysulfides still hinders advancement of Li-S batteries. The effective design of cathode materials is extremely pivotal to solve this thorny problem. Herein, surface engineering in covalent organic polymers (COPs) has been performed to investigate the influence of pore wall polarity on the performance of COP-based cathodes used for Li-S batteries. With the assistance of experimental investigation and theoretical calculations, performance improvement by increasing pore surface polarity and a synergy effect of the polarized functionalities, along with nano-confinement effect of the COPs, are disclosed, to which the improved performance of Li-S batteries including outstanding Coulombic efficiency (99.0 %) and extremely low capacity decay (0.08 % over 425 cycles at 1.0â C) is attributed. This work not only enlightens the designable synthesis and applications of covalent polymers as polar sulfur hosts with high utilization of active materials, but also provides a feasible guide for the design of effective cathode materials for future advanced Li-S batteries.
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[Figure: see text].
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Leucotrieno B4/metabolismo , Macrófagos/metabolismo , Infarto do Miocárdio/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinase 3/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL4/genética , Quimiocina CCL4/metabolismo , Quimiocina CXCL2/metabolismo , Feminino , Lipoxigenase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Proteínas Serina-Treonina Quinases/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores do Leucotrieno B4/antagonistas & inibidores , Receptores do Leucotrieno B4/metabolismo , Serina-Treonina Quinase 3/genéticaRESUMO
Cancer development is a long-lasting process during which macrophages play a pivotal role. However, how macrophages maintain their cellular identity, persistence, expanding and pro-tumor property during malignant progression remains elusive. Inspired by the recent report of the activation of stem cell-like self-renewal mechanism in mature macrophages, we postulate that intra-tumoral macrophages might be trained to assume stem-like properties and memory-like activity favoring cancer development. Herein we demonstrated that tumor infiltrating macrophages rapidly converted into the CD11b+F4/80+Ly6C-Bcl6+ phenotype, and adopted stem cell-like properties involving expression of stemness-related genes, long-term persistence and self-renewing. Importantly, Bcl6+ macrophages stably maintained cell identity, gene signature, metabolic profile, and pro-tumor property even after long-term culture in tumor-free medium, which were hence termed stem cell-like memory macrophages (SMMs). Mechanistically, we showed that transcriptional factor Bcl6 co-opted the demethylase Tet2 and the deacetylase SIRT1 to confer the epigenetic imprinting and mitochondrial metabolic traits to SMMs, bolstering the stability and longevity of trained immunity in tumor-associated macrophages (TAMs). Furthermore, tumor-derived redHMGB1 was identified as the priming signal, which, through TLR4 and mTOR/AKT pathway, induced Bcl6-driven program underpinning SMMs generation. Collectively, our study uncovers a distinct macrophage population with a hybrid of stem cell and memory cell properties, and unveils a regulatory mechanism that integrates transcriptional, epigenetic and metabolic pathways to promote long-lasting pro-tumor immunity.
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Macrófagos , Neoplasias , Humanos , Macrófagos/metabolismo , Diferenciação Celular/genética , Neoplasias/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismoRESUMO
Aconitum carmichaelii is widely used to treat chronic and intractable diseases due to its remarkable curative effect, but it is also a highly toxic herb with severe cardiac and neurotoxicity. It has been combined with honey for thousands of years to reduce toxicity and enhance efficacy, but there has been no study on the chemical constituent changes in the honey-processing so far. In this study, the chemical constituents of A. carmichaelii before and after honey-processing were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The results showed that a total of 118 compounds were identified, of which six compounds disappeared and five compounds were newly produced after honey-processing, and the cleavage pathway of main components was elucidated. At the same time, 25 compounds were found to have significant effects on different products, among which four compounds with the biggest difference were selected for quantitative analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study not only explained the chemical differences between the different products, but also helped to control the quality of the honey-processed products more effectively, and laid a foundation for further elucidating the mechanism of chemical constituent change during the honey-processing of A. carmichaelii.
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Aconitum , Medicamentos de Ervas Chinesas , Mel , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Aconitum/química , Mel/análise , Medicamentos de Ervas Chinesas/análiseRESUMO
Uniform temperature distribution during quenching thermal treatment is crucial for achieving exceptional mechanical and physical properties of alloy materials. Accurate and rapid prediction of the 3D transient temperature field model of large-scale aluminum alloy workpieces is key to realizing effective thermal treatment. This paper establishes a 3D transient temperature field model of large aluminum alloy workpieces and proposes a multi-loss consistency optimization-based physics-informed neural network (MCO-PINN) to realize soft sensing of the 3D temperature field model. The method is based on a MLP structure and adopts Gaussian activation functions. A surrogate model of the partial differential equation (PDE) is first constructed, and the residuals of the PDE, initial and boundary conditions, and observed data are encoded into the loss functions of the network. By establishing a Gaussian probability distribution model of each loss function and combining it with maximum likelihood estimation, the weight consistency optimization method of each loss function is then proposed to further improve the approximation ability of the model. To optimize the training speed of the network, an adaptive initial-value-eigenvector coding clustering (AIV-ECC) algorithm is finally proposed, which quickly determines the parameters of the Gaussian activation function, reduces the dependence on the initial value and improves the generalization performance of the network. Simulation and industrial experiments demonstrate that the proposed MCO-PINN can solve the 3D transient temperature field model with high precision and high time efficiency based on sparse measurements.
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The coexistence of nanoplastics and antibiotics in the aquatic environment has raised a complicated risk for ecosystems and human health. How the environmental factors e.g., light, regulate the interaction between nanoplastics and antibiotics and the resulting combined toxicity is poorly understood. Here, we investigated the individual and combined toxicity of polystyrene nanoplastics (nPS, 100 mg L1) and sulfamethoxazole (SMX, 2.5 and 10 mg L-1) toward the microalgae Chlamydomonas reinhardtii under low (LL, 16 µmol m-2·s-1), normal (NL, 40 µmol m-2·s-1), and high light (HL, 150 µmol m-2·s-1) in terms of cellular responses. Results indicated that the joint toxicity of nPS and SMX commonly exhibited a strong antagonistic/mitigative effect under LL/NL at 24 h, and under NL at 72 h. nPS could adsorb more SMX under LL/NL at 24 h (1.90/1.33 mg g-1) and under NL at 72 h (1.01 mg g-1), thereby alleviating SMX toxicity to C. reinhardtii. However, the self-toxicity of nPS had a negative influence on the degree of antagonism between nPS and SMX. The experimental results coupled with computational chemistry further revealed that the adsorption capacity of SMX on nPS was stimulated by low pH under LL/NL at 24 h (â¼7.5), while by less co-existing saline ions (0.83 ppt) and algae-derived dissolved organic matter (9.04 mg L-1) under NL at 72 h. nPS toxicity that was responsible for the toxic action modes was mainly attributed to the shading effect induced by hetero-aggregation and hindrance of light transmittance (>60%), as well as being regulated by additives leaching (0.49-1.07 mg L-1) and oxidative stress. Overall, these findings provided a critical basis for the risk assessment and management of multiple pollutants in the complex natural environment.
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Chlamydomonas reinhardtii , Microalgas , Nanopartículas , Poluentes Químicos da Água , Humanos , Poliestirenos/toxicidade , Microplásticos/toxicidade , Sulfametoxazol/toxicidade , Ecossistema , Poluentes Químicos da Água/análise , Antibacterianos/farmacologiaRESUMO
The present study aimed to optimize the process for extracting cellulose nanocrystals (CNCs) from sugarcane bagasse through ultrasonic-assisted sulfuric acid hydrolysis and its subsequent modification with L-malic acid and silane coupling agent KH-550. The effects of the different modification methods and the order of modification on the structures and properties of bagasse CNCs were explored. The results indicated that the optimal process conditions were achieved at an acid-digestion temperature of 50 °C, a reaction time of 70 min, an ultrasonic power of 250 W, and a volume fraction of 55%. The modified CNCs were analyzed using infrared spectral, X-ray diffraction, and thermogravimetric techniques, which revealed that L-malic acid was attached to the hydroxyl group on the CNCs via ester bond formations, and the silane coupling agent KH-550 was adsorbed effectively on the CNCs' surfaces. Moreover, it was observed that the modification of the CNCs by L-malic acid and the KH-550 silane coupling agent occurred only on the surface, and the esterification-crosslinking modification method provided the best thermal stability. The performance of self-made CNC was found to be superior to that of purchased CNC based on the transmission electron microscopy analysis. Furthermore, the modified esterified-crosslinked CNCs exhibited the best structure and performance, thereby offering a potential avenue for the high-value utilization of sugarcane bagasse, a byproduct of sugarcane sugar production, and the expansion of the comprehensive utilization of sugarcane bagasse.