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1.
Nature ; 593(7857): 67-73, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953412

RESUMO

Transition metal (oxy)hydroxides are promising electrocatalysts for the oxygen evolution reaction1-3. The properties of these materials evolve dynamically and heterogeneously4 with applied voltage through ion insertion redox reactions, converting materials that are inactive under open circuit conditions into active electrocatalysts during operation5. The catalytic state is thus inherently far from equilibrium, which complicates its direct observation. Here, using a suite of correlative operando scanning probe and X-ray microscopy techniques, we establish a link between the oxygen evolution activity and the local operational chemical, physical and electronic nanoscale structure of single-crystalline ß-Co(OH)2 platelet particles. At pre-catalytic voltages, the particles swell to form an α-CoO2H1.5·0.5H2O-like structure-produced through hydroxide intercalation-in which the oxidation state of cobalt is +2.5. Upon increasing the voltage to drive oxygen evolution, interlayer water and protons de-intercalate to form contracted ß-CoOOH particles that contain Co3+ species. Although these transformations manifest heterogeneously through the bulk of the particles, the electrochemical current is primarily restricted to their edge facets. The observed Tafel behaviour is correlated with the local concentration of Co3+ at these reactive edge sites, demonstrating the link between bulk ion-insertion and surface catalytic activity.

2.
Small ; 20(22): e2307346, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38213011

RESUMO

α-In2Se3 semiconductor crystals realize artificial synapses by tuning in-plane and out-of-plane ferroelectricity with diverse avenues of electrical and optical pulses. While the electrically induced ferroelectricity of α-In2Se3 shows synaptic memory operation, the optically assisted synaptic plasticity in α-In2Se3 has also been preferred for polarization flipping enhancement. Here, the synaptic memory behavior of α-In2Se3 is demonstrated by applying electrical gate voltages under white light. As a result, the induced internal electric field is identified at a polarization flipped conductance channel in α-In2Se3/hexagonal boron nitride (hBN) heterostructure ferroelectric field effect transistors (FeFETs) under white light and discuss the contribution of this built-in electric field on synapse characterization. The biased dipoles in α-In2Se3 toward potentiation polarization direction by an enhanced internal built-in electric field under illumination of white light lead to improvement of linearity for long-term depression curves with proper electric spikes. Consequently, upon applying appropriate electric spikes to α-In2Se3/hBN FeFETs with illuminating white light, the recognition accuracy values significantly through the artificial learning simulation is elevated for discriminating hand-written digit number images.

3.
Nucleic Acids Res ; 50(13): 7298-7309, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35801910

RESUMO

Autophagy, a catabolic process to remove unnecessary or dysfunctional organelles, is triggered by various signals including nutrient starvation. Depending on the types of the nutrient deficiency, diverse sensing mechanisms and signaling pathways orchestrate for transcriptional and epigenetic regulation of autophagy. However, our knowledge about nutrient type-specific transcriptional regulation during autophagy is limited. To understand nutrient type-dependent transcriptional mechanisms during autophagy, we performed single cell RNA sequencing (scRNAseq) in the mouse embryonic fibroblasts (MEFs) with or without glucose starvation (GS) as well as amino acid starvation (AAS). Trajectory analysis using scRNAseq identified sequential induction of potential transcriptional regulators for each condition. Gene regulatory rules inferred using TENET newly identified CCAAT/enhancer binding protein γ (C/EBPγ) as a regulator of autophagy in AAS, but not GS, condition, and knockdown experiment confirmed the TENET result. Cell biological and biochemical studies validated that activating transcription factor 4 (ATF4) is responsible for conferring specificity to C/EBPγ for the activation of autophagy genes under AAS, but not under GS condition. Together, our data identified C/EBPγ as a previously unidentified key regulator under AAS-induced autophagy.


Assuntos
Aminoácidos , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Transcriptoma , Fator 4 Ativador da Transcrição/metabolismo , Aminoácidos/genética , Aminoácidos/metabolismo , Animais , Autofagia/genética , Epigênese Genética , Fibroblastos/metabolismo , Camundongos , Análise de Célula Única
4.
Proc Natl Acad Sci U S A ; 118(3)2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33436411

RESUMO

Biominerals such as seashells, coral skeletons, bone, and tooth enamel are optically anisotropic crystalline materials with unique nanoscale and microscale organization that translates into exceptional macroscopic mechanical properties, providing inspiration for engineering new and superior biomimetic structures. Using Seriatopora aculeata coral skeleton as a model, here, we experimentally demonstrate X-ray linear dichroic ptychography and map the c-axis orientations of the aragonite (CaCO3) crystals. Linear dichroic phase imaging at the oxygen K-edge energy shows strong polarization-dependent contrast and reveals the presence of both narrow (<35°) and wide (>35°) c-axis angular spread in the coral samples. These X-ray ptychography results are corroborated by four-dimensional (4D) scanning transmission electron microscopy (STEM) on the same samples. Evidence of co-oriented, but disconnected, corallite subdomains indicates jagged crystal boundaries consistent with formation by amorphous nanoparticle attachment. We expect that the combination of X-ray linear dichroic ptychography and 4D STEM could be an important multimodal tool to study nano-crystallites, interfaces, nucleation, and mineral growth of optically anisotropic materials at multiple length scales.


Assuntos
Antozoários/química , Biomimética , Biomineralização , Cristalinas/química , Animais , Anisotropia , Antozoários/ultraestrutura , Carbonato de Cálcio/química , Cristalinas/ultraestrutura , Microscopia Eletrônica de Transmissão e Varredura , Minerais/química , Radiografia , Engenharia Tecidual , Raios X
5.
Int J Mol Sci ; 25(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39000009

RESUMO

Yohimbine (YHB) has been reported to possess anti-inflammatory, anticancer, and cardiac function-enhancing properties. Additionally, it has been reported to inhibit the proliferation, migration, and neointimal formation of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor (PDGF) stimulation by suppressing the phospholipase C-gamma 1 pathway. However, the transcriptional regulatory mechanism of YHB controlling the behavior of VSMCs is not fully understood. In this study, YHB downregulated the expression of cell cycle regulatory proteins, such as proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinase 4 (CDK4), and cyclin E, by modulating the transcription factor FOXO3a in VSMCs induced by PDGF. Furthermore, YHB decreased p-38 and mTOR phosphorylation in a dose-dependent manner. Notably, YHB significantly reduced the phosphorylation at Y397 and Y925 sites of focal adhesion kinase (FAK), and this effect was greater at the Y925 site than Y397. In addition, the expression of paxillin, a FAK-associated protein known to bind to the Y925 site of FAK, was significantly reduced by YHB treatment in a dose-dependent manner. A pronounced reduction in the migration and proliferation of VSMCs was observed following co-treatment of YHB with mTOR or p38 inhibitors. In conclusion, this study shows that YHB inhibits the PDGF-induced proliferation and migration of VSMCs by regulating the transcription factor FOXO3a and the mTOR/p38/FAK signaling pathway. Therefore, YHB may be a potential therapeutic candidate for preventing and treating cardiovascular diseases such as atherosclerosis and vascular restenosis.


Assuntos
Movimento Celular , Proliferação de Células , Proteína Forkhead Box O3 , Músculo Liso Vascular , Miócitos de Músculo Liso , Fator de Crescimento Derivado de Plaquetas , Ioimbina , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Proteína Forkhead Box O3/metabolismo , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Animais , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ioimbina/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Células Cultivadas , Paxilina/metabolismo , Ratos Sprague-Dawley , Masculino
6.
Molecules ; 29(2)2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38276606

RESUMO

Astaxanthin (AST)-encapsulated nanoparticles were fabricated using glycol chitosan (Chito) through electrostatic interaction (abbreviated as ChitoAST) to solve the aqueous solubility of astaxanthin and improve its biological activity. AST was dissolved in organic solvents and then mixed with chitosan solution, followed by a dialysis procedure. All formulations of ChitoAST nanoparticles showed small diameters (less than 400 nm) with monomodal distributions. Analysis with Fourier transform infrared (FT-IR) spectroscopy confirmed the specific peaks of AST and Chito. Furthermore, ChitoAST nanoparticles were formed through electrostatic interactions between Chito and AST. In addition, ChitoAST nanoparticles showed superior antioxidant activity, as good as AST itself; the half maximal radical scavenging concentrations (RC50) of AST and ChitoAST nanoparticles were 11.8 and 29.3 µg/mL, respectively. In vitro, AST and ChitoAST nanoparticles at 10 and 20 µg/mL properly inhibited the production of intracellular reactive oxygen species (ROSs), nitric oxide (NO), and inducible nitric oxide synthase (iNOS). ChitoAST nanoparticles had no significant cytotoxicity against RAW264.7 cells or B16F10 melanoma cells, whereas AST and ChitoAST nanoparticles inhibited the growth of cancer cells. Furthermore, AST itself and ChitoAST nanoparticles (20 µg/mL) efficiently inhibited the migration of cancer cells in a wound healing assay. An in vivo study using mice and a pulmonary metastasis model showed that ChitoAST nanoparticles were efficiently delivered to a lung with B16F10 cell metastasis; i.e., fluorescence intensity in the lung was significantly higher than in other organs. We suggest that ChitoAST nanoparticles are promising candidates for antioxidative and anticancer therapies of B16F10 cells.


Assuntos
Quitosana , Nanopartículas , Camundongos , Animais , Quitosana/química , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Antioxidantes/farmacologia , Antioxidantes/química , Xantofilas
7.
J Minim Access Surg ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38958005

RESUMO

INTRODUCTION: Minimally invasive liver resection (MILR) is performed for other gastrointestinal applications. At our centre, all liver resections are systematically performed using a minimally invasive approach. This study aimed to describe our experience in minimising open surgery and emphasised the importance of minimally invasive surgery. PATIENTS AND METHODS: We retrospectively reviewed 260 patients who underwent liver surgery and compared the surgical outcomes between the open and MILR groups. RESULTS: A total of 154 patients (68%) underwent MILR. The proportion of patients who underwent prior abdominal surgery and resection was higher in the open surgery group. However, the proportion of patients with liver cirrhosis was similar between the two groups. The MILR group was superior in terms of operative time, blood loss, Pringle manoeuvre rate and mean hospital stay. In addition, major complication and bile leak rates were lower in the MILR group. No significant differences in the tumour size, number of lesions or underlying liver pathology were observed between the two groups. CONCLUSION: Acceptable outcomes can be achieved even when the minimally invasive approach is considered the primary option for all patients who require liver resection. Minimally invasive tools are necessary for the modern practice of liver surgery; therefore, laparoscopic or robotic surgery should be included in the armamentarium of liver surgeons.

8.
Nat Mater ; 21(5): 547-554, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35177785

RESUMO

Constitutive laws underlie most physical processes in nature. However, learning such equations in heterogeneous solids (for example, due to phase separation) is challenging. One such relationship is between composition and eigenstrain, which governs the chemo-mechanical expansion in solids. Here we developed a generalizable, physically constrained image-learning framework to algorithmically learn the chemo-mechanical constitutive law at the nanoscale from correlative four-dimensional scanning transmission electron microscopy and X-ray spectro-ptychography images. We demonstrated this approach on LiXFePO4, a technologically relevant battery positive electrode material. We uncovered the functional form of the composition-eigenstrain relation in this two-phase binary solid across the entire composition range (0 ≤ X ≤ 1), including inside the thermodynamically unstable miscibility gap. The learned relation directly validates Vegard's law of linear response at the nanoscale. Our physics-constrained data-driven approach directly visualizes the residual strain field (by removing the compositional and coherency strain), which is otherwise impossible to quantify. Heterogeneities in the residual strain arise from misfit dislocations and were independently verified by X-ray diffraction line profile analysis. Our work provides the means to simultaneously quantify chemical expansion, coherency strain and dislocations in battery electrodes, which has implications on rate capabilities and lifetime. Broadly, this work also highlights the potential of integrating correlative microscopy and image learning for extracting material properties and physics.

9.
Brain ; 145(1): 305-323, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35022692

RESUMO

Mitochondrial defects are a hallmark of early pathophysiology in Alzheimer's disease, with pathologically phosphorylated tau reported to induce mitochondrial toxicity. Mitophagy constitutes a key pathway in mitochondrial quality control by which damaged mitochondria are targeted for autophagy. However, few details are known regarding the intersection of mitophagy and pathologies in tauopathy. Here, by applying biochemical and cell biological approaches including time-lapse confocal imaging in live tauopathy neurons, combined with gene rescue experiments via stereotactic injections of adeno-associated virus particles into tauopathy mouse brains, electrophysiological recordings and behavioural tests, we demonstrate for the first time that mitochondrial distribution deficits at presynaptic terminals are an early pathological feature in tauopathy brains. Furthermore, Parkin-mediated mitophagy is extensively activated in tauopathy neurons, which accelerates mitochondrial Rho GTPase 1 (Miro1) turnover and consequently halts Miro1-mediated mitochondrial anterograde movement towards synaptic terminals. As a result, mitochondrial supply at tauopathy synapses is disrupted, impairing synaptic function. Strikingly, increasing Miro1 levels restores the synaptic mitochondrial population by enhancing mitochondrial anterograde movement and thus reverses tauopathy-associated synaptic failure. In tauopathy mouse brains, overexpression of Miro1 markedly elevates synaptic distribution of mitochondria and protects against synaptic damage and neurodegeneration, thereby counteracting impairments in learning and memory as well as synaptic plasticity. Taken together, our study reveals that activation of the Parkin pathway triggers an unexpected effect-depletion of mitochondria from synaptic terminals, a characteristic feature of early tauopathy. We further provide new mechanistic insights into how parkin activation-enhanced Miro1 degradation and impaired mitochondrial anterograde transport drive tauopathy-linked synaptic pathogenesis and establish a foundation for future investigations into new therapeutic strategies to prevent synaptic deterioration in Alzheimer's disease and other tauopathies.


Assuntos
Doença de Alzheimer , Mitofagia , Doença de Alzheimer/metabolismo , Animais , Humanos , Camundongos , Mitocôndrias/metabolismo , Mitofagia/genética , Neurônios/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
10.
J Environ Manage ; 342: 118237, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37267764

RESUMO

This review describes the applicability of biofloc technology (BFT) to future aquaculture technologies. BFT is considered an innovative alternative for solving the problems of traditional aquaculture (for example, environmental pollution, high maintenance costs, and low productivity). Extensive research is being conducted to apply BFT to breed and raise many aquatic animal species. In BFT, maintaining an appropriate C:N ratio by adding a carbon source promotes the growth of microorganisms in water and maintains the aquaculture water quality through microbial processes such as nitrification. For the efficient use and sustainability of BFT, various factors such as total suspended solids, water turbidity, temperature, dissolved oxygen, pH, and salinity, stocking density, and light should be considered. The application of the transformative fourth industrial revolution technologies, Information and Communications Technology (ICT) and Internet of Things (IoT), to aquaculture can reduce the risk factors and manual interventions in aquaculture through automation and intelligence. The combination of ICT/IoT with BFT can enable real-time monitoring of the necessary elements of BFT farming using various sensors, which is expected to increase productivity by ensuring the growth and health of the organisms being reared.


Assuntos
Aquicultura , Nitrificação , Animais , Tecnologia , Qualidade da Água , Fatores de Risco
11.
Molecules ; 28(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37959678

RESUMO

Peanut shells, rich in antioxidants, remain underutilized due to limited research. The present study investigated the changes in the functional compound content and skin aging-related enzyme inhibitory activities of peanut shells by electron-beam treatment with different sample states and irradiation doses. In addition, phenolic compounds in the peanut shells were identified and quantified using ultra-performance liquid chromatography with ion mobility mass spectrometry-quadrupole time-of-flight and high-performance liquid chromatography with a photodiode array detector, respectively. Total phenolic compound content in solid treatment gradually increased from 110.31 to 189.03 mg gallic acid equivalent/g as the irradiation dose increased. Additionally, electron-beam irradiation significantly increased 5,7-dihydroxychrome, eriodictyol, and luteolin content in the solid treatment compared to the control. However, liquid treatment was less effective in terms of functional compound content compared to the solid treatment. The enhanced functional compound content in the solid treatment clearly augmented the antioxidant activity of the peanut shells irradiated with an electron-beam. Similarly, electron-beam irradiation substantially increased collagenase and elastase inhibitory activities in the solid treatment. Mutagenicity assay confirmed the stability of toxicity associated with the electron-beam irradiation. In conclusion, electron-beam-irradiated peanut shells could serve as an important by-product with potential applications in functional cosmetic materials.


Assuntos
Arachis , Elétrons , Arachis/química , Fenóis/análise , Antioxidantes/química , Cromatografia Líquida de Alta Pressão
12.
Acta Chir Belg ; 123(2): 156-162, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34365897

RESUMO

PURPOSE: Many studies have shown extra-hepatic surgery in patients with chronic liver disease (CLD) with or without portal hypertension can result in complications. The aim of this study was to analyze the results of major pancreatectomy in patients with CLD including cirrhosis and to evaluate their efficacy and safety. METHODS: We retrospectively reviewed 319 patients undergoing open pancreatoduodenectomy (PD) or distal pancreatectomy (DP) in our center. Those who received PD and DP in patients without CLD were classified into groups A and D, and those with CLD into groups B and C, respectively. Group B and C were subdivided into groups 1 and 2 according to the presence of portal hypertension. RESULTS: Forty-three patients (13.5%) had CLD. Of the 221 patients who received PD, 25 had CLD. Of the 98 patients who received DP, 18 (Group C) had CLD. In the PD group, patients with portal hypertension (group B1) had longer operative time. However, the transfusion rate and complication rate were not significantly different from other groups. There was no mortality in patients with CLD without portal hypertension (group B2) and the complication and mortality rate was comparable to patients with normal liver function (group A). In the DP group, the transfusion rate, complication rate and mortality rate were significantly higher in patients with portal hypertension (group C1). CONCLUSIONS: Acceptable outcomes were obtainable following pancreatic surgery in cirrhotic, non-portal hypertensive patients with surgical outcomes equivalent to non-cirrhotic patients.AbbreviationsCLDchronic liver diseasePDpancreaticoduodenectomyDPdistal pancreatectomy.


Assuntos
Hipertensão Portal , Neoplasias Pancreáticas , Humanos , Pancreatectomia/métodos , Estudos Retrospectivos , Pancreaticoduodenectomia/efeitos adversos , Hipertensão Portal/complicações , Hipertensão Portal/cirurgia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/etiologia
13.
Nat Mater ; 20(7): 991-999, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33686277

RESUMO

Layered oxides widely used as lithium-ion battery electrodes are designed to be cycled under conditions that avoid phase transitions. Although the desired single-phase composition ranges are well established near equilibrium, operando diffraction studies on many-particle porous electrodes have suggested phase separation during delithiation. Notably, the separation is not always observed, and never during lithiation. These anomalies have been attributed to irreversible processes during the first delithiation or reversible concentration-dependent diffusion. However, these explanations are not consistent with all experimental observations such as rate and path dependencies and particle-by-particle lithium concentration changes. Here, we show that the apparent phase separation is a dynamical artefact occurring in a many-particle system driven by autocatalytic electrochemical reactions, that is, an interfacial exchange current that increases with the extent of delithiation. We experimentally validate this population-dynamics model using the single-phase material Lix(Ni1/3Mn1/3Co1/3)O2 (0.5 < x < 1) and demonstrate generality with other transition-metal compositions. Operando diffraction and nanoscale oxidation-state mapping unambiguously prove that this fictitious phase separation is a repeatable non-equilibrium effect. We quantitatively confirm the theory with multiple-datastream-driven model extraction. More generally, our study experimentally demonstrates the control of ensemble stability by electro-autocatalysis, highlighting the importance of population dynamics in battery electrodes (even non-phase-separating ones).

14.
Nat Mater ; 20(3): 353-361, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33432141

RESUMO

Sodium ion batteries, because of their sustainability attributes, could be an attractive alternative to Li-ion technology for specific applications. However, it remains challenging to design high energy density and moisture stable Na-based positive electrodes. Here, we report an O3-type NaLi1/3Mn2/3O2 phase showing anionic redox activity, obtained through a ceramic process by carefully adjusting synthesis conditions and stoichiometry. This phase shows a sustained reversible capacity of 190 mAh g-1 that is rooted in cumulative oxygen and manganese redox processes as deduced by combined spectroscopy techniques. Unlike many other anionic redox layered oxides so far reported, O3-NaLi1/3Mn2/3O2 electrodes do not show discernible voltage fade on cycling. This finding, rationalized by density functional theory, sheds light on the role of inter- versus intralayer 3d cationic migration in ruling voltage fade in anionic redox electrodes. Another practical asset of this material stems from its moisture stability, hence facilitating its handling and electrode processing. Overall, this work offers future directions towards designing highly performing sodium electrodes for advanced Na-ion batteries.

15.
Microb Pathog ; 166: 105545, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35452787

RESUMO

Shrimp aquaculture industry has steadily increased with demand and development of aquaculture technology. In recent years, frequent diseases have become a major risk factor for shrimp aquaculture, such as a drastically reduced the production of shrimp and causing national economic loss. Among them, shrimp bacterial diseases such as hepatopancreatic necrosis disease (AHPND) and necrotizing hepatopancreatitis (NHP-B) and parasitic disease such as Aphanomyces astaci (crayfish plague) are emerging and evolving into new types. OIE (World Organization for Animal Health) regularly updates information on diseases in the Aquatic Code and Aquatic Manual, but in-depth information on the shrimp diseases are lacking. Therefore, the purpose of this review is to provide information necessary for the response and prevention of shrimp diseases by understanding the characteristics and diagnosis of shrimp diseases designated by OIE.


Assuntos
Doenças Parasitárias , Penaeidae , Animais , Aquicultura , Necrose , Penaeidae/microbiologia , Alimentos Marinhos
16.
EMBO Rep ; 21(9): e49801, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32627320

RESUMO

Synaptic mitochondria are particularly vulnerable to physiological insults, and defects in synaptic mitochondria are linked to early pathophysiology of Alzheimer's disease (AD). Mitophagy, a cargo-specific autophagy for elimination of dysfunctional mitochondria, constitutes a key quality control mechanism. However, how mitophagy ensures synaptic mitochondrial integrity remains largely unknown. Here, we reveal Rheb and Snapin as key players regulating mitochondrial homeostasis at synapses. Rheb initiates mitophagy to target damaged mitochondria for autophagy, whereas dynein-Snapin-mediated retrograde transport promotes clearance of mitophagosomes from synaptic terminals. We demonstrate that synaptic accumulation of mitophagosomes is a feature in AD-related mutant hAPP mouse brains, which is attributed to increased mitophagy initiation coupled with impaired removal of mitophagosomes from AD synapses due to defective retrograde transport. Furthermore, while deficiency in dynein-Snapin-mediated retrograde transport recapitulates synaptic mitophagy stress and induces synaptic degeneration, elevated Snapin expression attenuates mitochondrial defects and ameliorates synapse loss in AD mouse brains. Taken together, our study provides new insights into mitophagy regulation of synaptic mitochondrial integrity, establishing a foundation for mitigating AD-associated mitochondria deficits and synaptic damage through mitophagy enhancement.


Assuntos
Doença de Alzheimer , Mitofagia , Doença de Alzheimer/genética , Animais , Autofagia , Camundongos , Mitocôndrias/genética , Sinapses , Proteínas de Transporte Vesicular
17.
Langenbecks Arch Surg ; 407(3): 1271-1276, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35284953

RESUMO

PURPOSE: Single-incision laparoscopic distal pancreatectomy has not been widely applied due to technical challenges and increased operative risks. The newly released da Vinci SP system has been introduced to overcome these limitations and offer improvements for established robotic single-site procedures. We report our experience of robotic single port plus one port distal pancreatectomy using the da Vinci SP system. METHODS: We performed robotic distal pancreatectomy in three patients using the da Vinci SP surgical system with one additional port used for applying the energy device and stapling. Technical and clinical feasibility were examined. RESULTS: The mean age and body mass index were 70.7 years and 27.8 kg/m2, respectively. The mean operation time was 215 min. The estimated blood loss was less than 500 mL. All patients underwent combined splenectomy. The postoperative course of all patients was uneventful. CONCLUSION: Robotic distal pancreatectomy using the da Vinci SP system is safe and feasible, with acceptable perioperative outcomes.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Laparoscopia/métodos , Duração da Cirurgia , Pancreatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos
18.
Langenbecks Arch Surg ; 407(7): 2873-2880, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35739405

RESUMO

PURPOSE: Before performing anterior sectionectomy (AS) or central bisectionectomy (CBS), the anatomy of the right posterior bile duct (RPBD) must be cautiously assessed owing to the many variations of the RPBD and its variations could be related to bile duct injury. METHODS: Clinical data of patients who underwent AS or CBS from 2009 to 2018 were reviewed. The bile duct anatomy according to Okubo's criteria and the right bile duct (RBD) length were evaluated using MRI, and we performed a risk factor analysis of the RPBD stricture (RPBDS). RESULTS: A total of 68 patients were included. Type A bile ducts were the most common (n = 36, 52.9%). Five (7.2%) patients had RPBDS requiring intervention. RPBDS only occurred in patients with a type A bile duct and a type A portal vein undergoing surgery using the Glissonian sheath approach. Moreover, when the RBD length was > 12 mm, the sensitivity and specificity were 0.8 and 0.889, respectively. In multivariate analysis, RBD length of > 12 mm was significant. CONCLUSION: A careful review of RPBD anatomy especially in patient with long RBD and caution when using the anterior Glissonian sheath approach might be helpful to prevent RPBDS during AS or CBS.


Assuntos
Hepatectomia , Veia Porta , Humanos , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/cirurgia , Fatores de Risco
19.
Proc Natl Acad Sci U S A ; 116(42): 21140-21149, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31570593

RESUMO

Retinoic acid-related orphan receptor α (RORα) functions as a transcription factor for various biological processes, including circadian rhythm, cancer, and metabolism. Here, we generate intestinal epithelial cell (IEC)-specific RORα-deficient (RORαΔIEC) mice and find that RORα is crucial for maintaining intestinal homeostasis by attenuating nuclear factor κB (NF-κB) transcriptional activity. RORαΔIEC mice exhibit excessive intestinal inflammation and highly activated inflammatory responses in the dextran sulfate sodium (DSS) mouse colitis model. Transcriptome analysis reveals that deletion of RORα leads to up-regulation of NF-κB target genes in IECs. Chromatin immunoprecipitation analysis reveals corecruitment of RORα and histone deacetylase 3 (HDAC3) on NF-κB target promoters and subsequent dismissal of CREB binding protein (CBP) and bromodomain-containing protein 4 (BRD4) for transcriptional repression. Together, we demonstrate that RORα/HDAC3-mediated attenuation of NF-κB signaling controls the balance of inflammatory responses, and therapeutic strategies targeting this epigenetic regulation could be beneficial to the treatment of chronic inflammatory diseases, including inflammatory bowel disease (IBD).


Assuntos
Homeostase/fisiologia , Inflamação/metabolismo , Intestinos/fisiologia , Receptores Nucleares Órfãos/metabolismo , Animais , Epigênese Genética/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica/fisiologia , Transcriptoma/fisiologia
20.
HPB (Oxford) ; 24(10): 1804-1812, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35871134

RESUMO

BACKGROUND: Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database. METHODS: A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP). RESULTS: ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion. CONCLUSION: LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP.


Assuntos
Carcinoma Ductal Pancreático , Laparoscopia , Neoplasias Pancreáticas , Humanos , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Viés de Seleção , Estudos Retrospectivos , Neoplasias Pancreáticas/patologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Neoplasias Pancreáticas
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