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In artificial intelligence, it is crucial for pattern recognition systems to process data with uncertain information, necessitating uncertainty reasoning approaches such as evidence theory. As an orderable extension of evidence theory, random permutation set (RPS) theory has received increasing attention. However, RPS theory lacks a suitable generation method for the element order of permutation mass function (PMF) and an efficient determination method for the fusion order of permutation orthogonal sum (POS). To solve these two issues, this paper proposes a reasoning model for RPS theory, called random permutation set reasoning (RPSR). RPSR consists of three techniques, including RPS generation method (RPSGM), RPSR rule of combination, and ordered probability transformation (OPT). Specifically, RPSGM can construct RPS based on Gaussian discriminant model and weight analysis; RPSR rule incorporates POS with reliability vector, which can combine RPS sources with reliability in fusion order; OPT is used to convert RPS into a probability distribution for the final decision. Besides, numerical examples are provided to illustrate the proposed RPSR. Moreover, the proposed RPSR is applied to classification problems. An RPSR-based classification algorithm (RPSRCA) and its hyperparameter tuning method are presented. The results demonstrate the efficiency and stability of RPSRCA compared to existing classifiers.
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BACKGROUND: Global longitudinal strain (GLS) and atrial voltage are acknowledged markers for worse rhythm outcome after ablation of persistent atrial fibrillation (PeAF). The majority of research efforts have been directed towards the left atrium (LA), with relatively fewer studies focusing on the right atrium (RA). The aim of this study was to investigate the effect of the biatrial substrate on the outcome following radiofrequency catheter ablation (RFCA). METHODS: All patients underwent two-dimensional speckle tracking echocardiography (2D-STE) and high-density mapping (HDM) on LA and RA in preoperative and postoperative stages of RFCA. Atrial substrate was assessed by GLS, average voltage, and low voltage zone (LVZ). RESULTS: This retrospective study enrolled 48 patients. With a follow-up of 385.98 ± 161.78 days, 22.92% (11/48) of all patients had AF recurrence and 63.64% in low strain group. Left atrial-low voltage zone (LA-LVZ) prior to RFCA was 67.52 ± 15.27% and 54.21 ± 20.07%, respectively, in the recurrence group and non-recurrence group. Multivariate regression analysis showed that preoperative LA-GLS (OR 0.047, 95%CI 0.002-0.941, p = .046) was independent predictors of AF recurrence. Biatrial average voltage in preoperative and postoperative stages were positively correlated (preoperative: r = 0.563 p < .001; postoperative: r = 0.464 p = .002). There was no significant difference in the proportion of RA in the recurrence group except the septum in preoperative and postoperative stages. CONCLUSIONS: Low LA-GLS and high LA-LVZ may be predictors of RFCA recurrence in PeAF patients. Biatrial average voltage were positively correlated in preoperative and postoperative stages.
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Inspired by tug-of-war, a game-changing bone-tendon fixation paradigm was developed. Specifically, injectable citrate-based bioactive self-expansive and planar-fixing screw (iCSP-Scr) consisting of reactive isocyanate (NCO) terminalized citrate-based polyurethane, proanthocyanidin modified hydroxyapatite (HAp) and water (with/without porogen) was developed and administrated in the bone-tendon gap. Instead of the "point to point" tendon fixation by traditional interface screws, along with the moisture-induced crosslinking and expansion of iCSP-Scr within the confined space of the irregularly shaped bone-tendon gap, the tendon graft was evenly squeezed into the bone tunnel in a "surface to surface" manner to realize strong and stable bone-tendon fixation via physical expansion, mechanical interlocking and chemical bonding (between -NCO and the -NH2, -SH groups on bone matrix). The optimized iCSP-Scr exhibited rapid crosslinking, moderate expansion rate, high porosity after crosslinking, as well as tunable elasticity and toughness. The iCSP-Scr possessed favorable biodegradability, biocompatibility, and osteoinductivity derived from citrate, PC and HAp, it was able to promote osteogenesis and new bone growth inward of bone tunnel thus further enhanced the bone/iCSP-Scr mechanical interlock, ultimately leading to stronger tendon fixation (pull-out force 106.15 ± 23.15 N) comparing to titanium screws (93.76 ± 17.89 N) after 14 weeks' ACL reconstruction in a rabbit model. The iCSP-Scr not only can be used as a self-expansive screw facilitating bone-tendon healing, but also can be expanded into other osteogenic application scenarios.
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BACKGROUND: Impaired hospitalizations for heart failure (HHF) and mortality are associated with tricuspid regurgitation (TR). OBJECTIVES: The objective of this study was to investigate the benefit of transcatheter tricuspid valve replacement (TTVR) over guideline-directed medical therapy (GDMT) in patients with symptomatic severe TR. METHODS: Between May 2020 and April 2023, 88 patients with symptomatic severe TR were treated in our center. Of these, 57 patients received GDMT alone, and 31 patients underwent combined TTVR and GDMT. We collected and analyzed baseline data, and follow-up information for both groups. The primary endpoints were all-cause mortality and the combined endpoint (including all-cause mortality and HHF). RESULTS: At a median follow-up of 20 (IQR 10-29) months, significant improvements were shown in TR severity, right ventricular function, and dimensions in TTVR group (all P < 0.001). It also resulted in superior survival rates (75.8% vs. 48.4%, P = 0.019), improved freedom from combined endpoint (61.5% vs. 45.9%, P = 0.007) and fewer major adverse events. After stratification by TRI-SCORE, the subgroup with < 6 points in the TTVR group exhibited a significant difference in the combined endpoint compared to the other subgroups (all P < 0.05), while no significant differences were observed in the GDMT subgroups (P = 0.680). CONCLUSIONS: The utilization of LuX-Valve in TTVR effectively improves TR and is associated with lower rates of major adverse events, HHF and all-cause mortality. The TRI-SCORE may help identify higher-benefit patients with TR from TTVR. Clinical trial registration ClinicalTrials.gov Protocol Registration System (NCT02917980).
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Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Tricúspide , Humanos , Insuficiencia de la Válvula Tricúspide/cirugía , Masculino , Femenino , Estudios Retrospectivos , Anciano , Implantación de Prótesis de Válvulas Cardíacas/métodos , Válvula Tricúspide/cirugía , Persona de Mediana Edad , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Cateterismo Cardíaco/métodosRESUMEN
A heat-driven catch-and-release strategy for CoCl2 capture is described. It is based on the use of an immobilized neutral dicyclohexylacetamide-based receptor L supported on polystyrene (PS-L). An X-ray diffraction analysis of a single crystal of L·CoCl2 revealed an ion-pair complex comprising a hexacoordinated cobalt cation [L·Co]2+ and a tetrachlorocobaltate anion [CoCl4]2-. Temperature dependent binding was seen, as inferred from UV-vis spectroscopic studies. Fits to the van't Hoff equation yielded values of ΔH° = 12.4 kJ/mol and ΔS° = 56.0 J/K·mol for L + CoCl2, and ΔH° = 16.5 kJ/mol and ΔS° = 85.0 J/K·mol for PS-L + CoCl2 in 95% ethanol. Consequently, cobalt capture and release are mediated by heating and cooling, respectively. The material PS-L exhibits a preference for binding cobalt over manganese and nickel as inferred from Langmuir-Freundlich isotherm analyses that revealed binding constants of KLF = 88.5 M-1 for CoCl2, 52.7 M-1 for MnCl2, and 49.7 M-1 for NiCl2. In a simulated ion mixture containing equimolar CoCl2, MnCl2, and NiCl2, ICP-MS analyses served to confirm that cobalt was selectively enriched to 52 mol % (from an initial level of ca. 32 mol %) after one catch-and-release cycle and 76.6% after three cycles. Our experimental results were validated by density functional theory calculations, which also show stronger binding of Co over Mn and Ni to L.
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Microglia play a major role in the immune defense system of the central nervous system and are activated in many neurological diseases. The immunomodulatory cytokine interleukin (IL)-15 is known to be involved in microglia response and inflammatory factors release. Neoprzewaquinone A (NEO) is an active compound isolated from Salvia miltiorrhiza Bunge. Our previous study has shown that NEO significantly inhibit the proliferation of IL-15-treated Mo7e cells. However, the role of NEO in the structure and function of IL-15-treated human microglial cells (HMC3) remains unclear. Thus, our study aimed to quantitatively analyze the beneficial effects of NEO on HMC3 cells following IL-15 treatment. The cell viability, phagocytosis, migration and energy metabolism were evaluated by Cell Counting Kit-8 (CCK8), scratch assay, pHrodo™ Red Zymosan BioParticles™ Conjugate, and Agilent Seahorse XF Cell Mito Test. Cephalothin (CEP) was selected as a positive drug because it has obvious inhibitory effect on IL-15 and IL-15RÉ. Our results showed that IL-15 stimulated the proliferation, migration and phagocytosis of HMC3 cells in a time-dependent manner. Interestingly, NEO exhibited significant suppressive effects on these IL-15-induced changes, which were even superior to those observed with the CEP. Moreover, IL-15 treatment did not significantly alter energy metabolism, including glycolysis and mitochondrial respiration. NEO and CEP alone effectively reduced glycolysis, non-mitochondrial respiration, basal respiration, ATP turnover, respiration capacity, and H+ leak in HMC3 cells. Furthermore, NEO displayed a partial regulatory effect on mitochondrial function in IL-15-treated HMC3 cells. Our study confirms the effectively inhibition of NEO on IL-15-induced microglial activation and provides valuable insights into the therapeutic prospects of NEO in neuropsychiatric disorders associated with IL-15 and microglia.
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Aqueous zinc-ion batteries (AZIBs) are widely regarded as desirable energy storage devices due to their inherent safety and low cost. Hydrogel polymer electrolytes (HPEs) are cross-linked polymers filled with water and zinc salts. They are not only widely used in flexible batteries but also represent an ideal electrolyte candidate for addressing the issues associated with the Zn anode, including dendrite formation and side reactions. In HPEs, an abundance of hydrophilic groups can form strong hydrogen bonds with water molecules, reducing water activity and inhibiting water decomposition. At the same time, special Zn2+ transport channels can be constructed in HPEs to homogenize the Zn2+ flux and promote uniform Zn deposition. However, HPEs still face issues in practical applications, including poor ionic conductivity, low mechanical strength, poor interface stability, and narrow electrochemical stability windows. This Review discusses the issues associated with HPEs for advanced AZIBs, and the recent progresses are summarized. Finally, the Review outlines the opportunities and challenges for achieving high performance HPEs, facilitating the utilization of HPEs in AZIBs.
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The first wide-view image of multiple structural and phase transformations for MOFs from crystal state transformations further to the extreme limit approaching liquid/glass phase, was presented based on a square-layer framework of [Co2(pybz)2(CH3COO)2]·DMF (Co2). The process involves i) an initial crystalline transformation brings to a 3-fold interpenetrated and ordered vacancies contained framework [Co(pybz)2(CH3OH)2]·2CH3OH (CoM) due to in-situ disassemble-reassemble, ii) thermal induced departure of a pair of cis-form coordinated methanol in CoM leads to amorphous framework (a-dCoM), iii) glass transition (Tg = 566 K) to super-cooled liquid (scl-dCoM, spanning 38 K), iv) obtaining MOF glass g-dCoM upon quenching the super-cooled liquid, and v) re-crystallization of super-cooled liquid to six-fold interpenetrated dia-net framework [Co(pybz)2]6n (rec-dCoM) under heating above 604 K. The access to glass from CoM, provides a new self-perturbation strategy to create more MOF glasses without melting. The wider pore size distribution in amorphous/glassy MOFs than crystalline precursor realized the first time selective hydrocarbon gas separation by breakthrough experiments, which bring efficient separation of 1:99 C2H2/C2H4 by either a-dCoM or g-dCoM and produce polymer grade C2H4 with purity ≥ 99.5% after a single adsorption process. Furthermore, the mixture of 50:50 C3H6/C3H8 can be separated by a-dCoM.
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The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders.
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BACKGROUND: Despite improvement in treatment strategies for atrial fibrillation (AF), a significant proportion of patients still experience recurrence after ablation. This study aims to propose a novel algorithm based on Transformer using surface electrocardiogram (ECG) signals and clinical features can predict AF recurrence. METHODS: Between October 2018 to December 2021, patients who underwent index radiofrequency ablation for AF with at least one standard 10-second surface ECG during sinus rhythm were enrolled. An end-to-end deep learning framework based on Transformer and a fusion module was used to predict AF recurrence using ECG and clinical features. Model performance was evaluated using areas under the receiver operating characteristic curve (AUROC), sensitivity, specificity, accuracy and F1-score. RESULTS: A total of 920 patients (median age 61 [IQR 14] years, 66.3% male) were included. After a median follow-up of 24 months, 253 patients (27.5%) experienced AF recurrence. A single deep learning enabled ECG signals identified AF recurrence with an AUROC of 0.769, sensitivity of 75.5%, specificity of 61.1%, F1 score of 55.6% and overall accuracy of 65.2%. Combining ECG signals and clinical features increased the AUROC to 0.899, sensitivity to 81.1%, specificity to 81.7%, F1 score to 71.7%, and overall accuracy to 81.5%. CONCLUSIONS: The Transformer algorithm demonstrated excellent performance in predicting AF recurrence. Integrating ECG and clinical features enhanced the models' performance and may help identify patients at low risk for AF recurrence after index ablation.
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Fibrilación Atrial , Ablación por Catéter , Aprendizaje Profundo , Electrocardiografía , Recurrencia , Humanos , Fibrilación Atrial/cirugía , Masculino , Femenino , Persona de Mediana Edad , AncianoRESUMEN
The development of noninvasive approaches to precisely control neural activity in mammals is highly desirable. Here, we used the ion channel transient receptor potential ankyrin-repeat 1 (TRPA1) as a proof of principle, demonstrating remote near-infrared (NIR) activation of endogenous neuronal channels in mice through an engineered nanoagonist. This achievement enables specific neurostimulation in nongenetically modified mice. Initially, target-based screening identified flavins as photopharmacological agonists, allowing for the photoactivation of TRPA1 in sensory neurons upon ultraviolet A/blue light illumination. Subsequently, upconversion nanoparticles (UCNPs) were customized with an emission spectrum aligned to flavin absorption and conjugated with flavin adenine dinucleotide, creating a nanoagonist capable of NIR activation of TRPA1. Following the intrathecal injection of the nanoagonist, noninvasive NIR stimulation allows precise bidirectional control of nociception in mice through remote activation of spinal TRPA1. This study demonstrates a noninvasive NIR neurostimulation method with the potential for adaptation to various endogenous ion channels and neural processes by combining photochemical toolboxes with customized UCNPs.
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Rayos Infrarrojos , Nanopartículas , Canal Catiónico TRPA1 , Animales , Canal Catiónico TRPA1/metabolismo , Canal Catiónico TRPA1/agonistas , Ratones , Nanopartículas/química , Células Receptoras Sensoriales/metabolismo , Células Receptoras Sensoriales/fisiología , Células Receptoras Sensoriales/efectos de los fármacos , Canales Iónicos/metabolismo , Nocicepción/efectos de los fármacosRESUMEN
BACKGROUND: The mechanisms by which SLC2A1 enhances chemo-resistance of taxanes to non-small cell lung cancer (NSCLC) remains enigmatic. METHODS: An investigation into the SLC2A1 expression pattern and prognosis across diverse datasets, as well as our internally collected samples, was undertaken. Additionally, the biological function of SLC2A1 was further delved into through in vitro experiments. The study also examined the chemo-resistance of NSCLC to taxanes using CCK-8, Annexin-V, and caspase-3 assays. Furthermore, the impact of taxanes on SLC2A1 expression was determined via western blot analysis. The effects of SLC2A1 on the formation of CSCs was examined via flow cytometry and metabolomics techniques. Finally, the impact of SLC2A1 on the tumor microenvironment was analyzed using single-cell sequencing and cellchat. RESULTS: In the present investigation, it was observed that there was an elevated expression of SLC2A1 in NSCLC tumor tissues, which exhibited a significant association with a poorer prognosis. SLC2A1 overexpression in vitro promoted NSCLC cell proliferation, invasion, migration, chemo-resistance, and the formation of CD90+ and EpCAM+ CSCs. NSCLC cells were categorized based on SLC2A1 and EpCAM expression. SLC2A1highEpCAM+ CSCs were more chemo-resistance to taxanes. NSCLC patients with high SLC2A1 and EpCAM expression had poorer prognosis. Mechanically, SLC2A1 promoted the formation of CD90+ and EpCAM+ CSCs via activating glycolysis. Finally, SLC2A1low tumor cells promoted CD8+T cell function via HLA-A, B, C, and suppressed NK cell function via HLA-E. CONCLUSION: Together, SLC2A1 plays an important role in enhancing chemo-resistance of taxanes to NSCLC.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune-inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single-cell level. METHODS: We performed single-cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co-culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single-cell analyses. RESULTS: LSCC with COPD showed increased proportions of tumour-associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-programmed cell death-1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. CONCLUSIONS: Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. HIGHLIGHT: Our results demonstrated higher proportions of tumour-associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-PD-L1 signalling pathway, facilitating immune evasion.
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Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Análisis de Expresión Génica de una Sola Célula , Humanos , Antígenos de Diferenciación de Linfocitos B/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Evasión Inmune/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Análisis de Expresión Génica de una Sola Célula/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Lungs can undergo facultative regeneration, but handicapped regeneration often leads to fibrosis. How microenvironmental cues coordinate lung regeneration via modulating cell death remains unknown. Here, we reveal that the neurotransmitter dopamine modifies the endothelial niche to suppress ferroptosis, promoting lung regeneration over fibrosis. A chemoproteomic approach shows that dopamine blocks ferroptosis in endothelial cells (ECs) via dopaminylating triosephosphate isomerase 1 (TPI1). Suppressing TPI1 dopaminylation in ECs triggers ferroptotic angiocrine signaling to aberrantly activate fibroblasts, leading to a transition from lung regeneration to fibrosis. Mechanistically, dopaminylation of glutamine (Q) 65 residue in TPI1 directionally enhances TPI1's activity to convert dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (GAP), directing ether phospholipid synthesis to glucose metabolism in regenerating lung ECs. This metabolic shift attenuates lipid peroxidation and blocks ferroptosis. Restoring TPI1 Q65 dopaminylation in an injured endothelial niche overturns ferroptosis to normalize pro-regenerative angiocrine function and alleviate lung fibrosis. Overall, dopaminylation of TPI1 balances lipid/glucose metabolism and suppresses pro-fibrotic ferroptosis in regenerating lungs.
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Células Endoteliales , Ferroptosis , Pulmón , Animales , Ratones , Pulmón/metabolismo , Pulmón/patología , Humanos , Células Endoteliales/metabolismo , Regeneración , Triosa-Fosfato Isomerasa/metabolismo , Ratones Endogámicos C57BL , Transducción de Señal , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , MasculinoRESUMEN
BACKGROUND: Intrahepatic cholangiocarcinoma (ICCA) with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma with worse outcomes.1,2 Surgical resection with negative margins is the only effective treatment for ICCA.3,4 Neoadjuvant therapy is considered to improve the possibility of surgery for patients;5,6 however, laparoscopic radical resection after neoadjuvant therapy for ICCA with hepatic hilus involvement remains at the exploratory stage due to technical challenges.7 METHODS: A 19-year-old man presented with an ICCA on the left side of the liver invading the blood vessels and bile ducts in the hepatic hilum. Five courses of neoadjuvant therapy were administered after a multidisciplinary team determined that the tumor was extremely difficult and risky to operate on. A laparoscopic left hepatectomy plus caudal lobectomy was performed to complete the resection of the negative margins. Three-dimensional visualization enabled precise preoperative planning and intraoperative guidance, including visualization of the tumor location, simulation of bile duct and vessel dissection steps, as well as determining the extent of liver resection. Vascular skeletonization, lymphadenectomy and biliary reconstruction were performed during operation. RESULTS: The operation time was 415 min with a blood loss of 100 mL. Postoperative pathohistology confirmed cholangiocarcinoma with low to intermediate differentiation. The resection margin was negative (R0) and lymph node pathology was tumor-negative (0/10). The patient was discharged on postoperative day 10 without complications. CONCLUSION: Laparoscopic radical resection after neoadjuvant therapy for ICCA with hepatic hilus involvement is safe and feasible in a large-throughput hepatic surgery center.
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Surface functionalization of Cu-based catalysts has demonstrated promising potential for enhancing the electrochemical CO2 reduction reaction (CO2RR) toward multi-carbon (C2+) products, primarily by suppressing the parasitic hydrogen evolution reaction and facilitating a localized CO2/CO concentration at the electrode. Building upon this approach, we developed surface-functionalized catalysts with exceptional activity and selectivity for electrocatalytic CO2RR to C2+ in a neutral electrolyte. Employing CuO nanoparticles coated with hexaethynylbenzene organic molecules (HEB-CuO NPs), a remarkable C2+ Faradaic efficiency of nearly 90% was achieved at an unprecedented current density of 300 mA cm-2, and a high FE (> 80%) was maintained at a wide range of current densities (100-600 mA cm-2) in neutral environments using a flow cell. Furthermore, in a membrane electrode assembly (MEA) electrolyzer, 86.14% FEC2+ was achieved at a partial current density of 387.6 mA cm-2 while maintaining continuous operation for over 50 h at a current density of 200 mA cm-2. In-situ spectroscopy studies and molecular dynamics simulations reveal that reducing the coverage of coordinated Kâ H2O water increased the probability of intermediate reactants (CO) interacting with the surface, thereby promoting efficient C-C coupling and enhancing the yield of C2+ products. This advancement offers significant potential for optimizing local micro-environments for sustainable and highly efficient C2+ production.
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BACKGROUND: The regions of the liver with cholestasis caused by biliary tumors or thrombosis can be distinctly identified using indocyanine green (ICG) fluorescence imaging.1 The authors' team reported the application of bile-duct obstructed area imaging (BOAI) to assist open hepatectomy for intrahepatic cholangiocarcinoma (ICC) combined with intrahepatic bile duct obstruction previously.2 This video is the first report of real-time BOAI-guided three-dimensional (3D) laparoscopic hepatectomy using a 3D-4K fluorescence imaging system. METHODS: A 65-year-old man was admitted to the authors' institution with clonorchiasis. Preoperative computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed an obstruction and diffuse dilation of the right hepatic duct. A 15-min retention of ICG (ICG R15) was performed 5 days before the operation, with a 3.3% result. Preoperative planning involved performing laparoscopic right hemi-hepatectomy with regional lymph node dissection assisted by visualization technology.3 During the procedure, significant fluorescence accumulation in the right liver was shown by fluorescence imaging. With the guidance of real-time BOAI (Fig. 1), the regions of biliary obstruction were precisely resected, and the middle hepatic vein (MHV) was passively and adequately exposed on the cutting plane. Fig. 1 Administration steps for real-time bile duct-obstructed area imaging. A ICG is injected intravenously 3-5 days before operation at a dose of 0.5 mg/kg. B ICG is accumulated in the whole liver within a few minutes after injection. C ICG is selectively absorbed by the liver and excreted into the intestines, whereby it is retained in areas of biliary obstruction RESULTS: The histopathologic diagnosis indicated high-grade intraepithelial neoplasia of the right bile duct tumor without lymph node metastases and clonorchiasis. The duration of the operation was 300 min, with an intraoperative blood loss of 50 ml. No postoperative complications occurred, and the patient was discharged after 7 days. CONCLUSION: Laparoscopic right hemi-hepatectomy for the bile-duct obstructed area with the guidance of real-time BOAI is feasible and effective.
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With its annually increasing prevalence, non-alcoholic fatty liver disease (NAFLD) has become a serious threat to people's life and health. After a preliminary research, we found that Lactucopicrin has pharmacological effects, such as lowering blood lipids and protecting the liver. Further research showed its significant activation for fatty acid ß-oxidase hydroxyacyl-coenzyme A (CoA) dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), so we hypothesized that Lactucopicrin could ameliorate lipid accumulation in hepatocytes by promoting fatty acid ß-oxidation. In this study, free fatty acid (FFA)-induced human hepatoblastoma cancer cells (HepG2) were used to establish an in vitro NAFLD model to investigate the molecular basis of Lactucopicrin in regulating lipid metabolism. Staining with Oil red O and measurements of triglyceride (TG) content, fatty acid ß-oxidase (FaßO) activity, reactive oxygen species (ROS) content, mitochondrial membrane potential, and adenosine triphosphate (ATP) content were used to assess the extent to which Lactucopicrin ameliorates lipid accumulation and promotes fatty acid ß-oxidation. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods were used to explore the regulatory effects of Lactucopicrin on factors related to fatty acid ß-oxidation. Results showed that Lactucopicrin downregulated phosphorylated mammalian target of rapamycin (P-mTOR) by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway and upregulated the messenger RNA (mRNA) and protein expression levels of coactivators (peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)), transcription factors (peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor γ (PPARγ)), and oxidative factors (carnitine palmitoyltransferase 1A (CPT1A) and HADHA). This phenomenon resulted in a significant increase in FaßO activity, ATP content, and JC-1 and a significant decrease in ROS level, TG content, and intracellular lipid droplets. With the addition of Dorsomorphin, all the effects of Lactucopicrin intervention were suppressed. In summary, Lactucopicrin promotes fatty acid ß-oxidation by activating the AMPK pathway, thereby ameliorating FFA-induced intracellular lipid accumulation in HepG2 cells.