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Coordination polymers can take advantage of both transition metal redox and organic ligand redox, thus serving as promising cathodes with multiple redox centers toward higher-performance lithium-ion batteries (LIBs). Here, we selected the high-capacity carbonyl compound of chloranilic acid (CA) as organic ligand to coordinate with the high-voltage Cu2+ as transition metal node and successfully synthesized copper(II) chloranilate (CuCA) with π-d conjugation, layered structure and monocrystalline nature. The resulting CuCA presents inorganic and organic redox centers, high electronic conductivity and fast Li+ diffusion kinetics, leading to high discharge capacity (297.0â mAh g-1 at 50â mA g-1 ), excellent rate capability (160.6â mAh g-1 at 1000â mA g-1 ) and good cycling stability (165.5â mAh g-1 at 500â mA g-1 after 50â cycles) with quasi-solid-state electrolyte. This work will provide insightful understanding of the materials design strategies to develop more efficient coordination polymer cathodes for LIBs.
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BACKGROUND: There is uncertainty in the literature about preserving the left colic artery (LCA) during low anterior resection for rectal cancer. We analyzed the effect of preserving the LCA on long-term oncological outcomes. METHODS: We retrospectively collected clinicopathological and follow-up details of patients who underwent low anterior resection for rectal cancer in the General Surgery Department of Guangdong Provincial People's Hospital, from January 2014 to December 2015. Cases were divided into low ligation (LL), LCA preserved, or high ligation (HL), LCA not preserved, of the inferior mesenteric artery. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared between the two groups. RESULTS: Altogether, there were 221 and 295 cases in the LL group and HL groups, respectively. Operating time in the LL group was significantly longer than in the HL group (224.7 vs. 211.7 min, p = 0.039). Postoperative 30-day mortality, early complications including anastomotic leakage showed no significant differences between the LL and HL groups (postoperative 30-day mortality, 0.9% LL, 1.4% HL, p = 0.884; early complications, 41.2% LL, 38.3% HL, p = 0.509; anastomotic leakage 8.6% LL, 13.2% HL, p = 0.100). The median follow-up periods were 51.4 (7-61) months in the LL group and 51.2 (8-61) months in the HL group. During follow-up, the percentages of patients who died, had local recurrence, or had metastases were 39.8, 7.7, and 38.5%, respectively, in the LL group and 39, 8.5, and 40%, respectively, in the HL group; these differences were not significant (all p > 0.05). The 5-year OS and DFS were 69.6 and 59.6% in the LL group, respectively, and 69.1 and 56.2% in the HL group, respectively; these differences were not significant (all p > 0.05). After stratification by tumor-node-metastasis stage, the difference between the 5-year OS and DFS for stages I, II, and III cancer were not significant (all p > 0.05). CONCLUSIONS: The long-term oncological outcomes of LL group are comparable with HL group. LL cannot be supported due to the absence of lower complication rates and the longer operating times.
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Laparoscopia/mortalidade , Artéria Mesentérica Inferior/cirurgia , Protectomia/mortalidade , Neoplasias Retais/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Artéria Mesentérica Inferior/patologia , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Potassium-ion batteries (KIBs) are plagued by a lack of materials for reversible accommodation of the large-sized K+ ion. Herein we present, the Bi anode in combination with the dimethoxyethane-(DME) based electrolyte to deliver a remarkable capacity of ca. 400â mAh g-1 and long cycle stability with three distinct two-phase reactions of Biâ KBi2 âK3 Bi2 âK3 Bi. These are ascribed to the gradually developed three-dimensional (3D) porous networks of Bi, which realizes fast kinetics and tolerance of its volume change during potassiation and depotassiation. The porosity is linked to the unprecedented movement of the surface Bi atoms interacting with DME molecules, as suggested by DFT calculations. A full KIB of Bi//DME-based electrolyte//Prussian blue of K0.72 Fe[Fe(CN)6 ] is demonstrated to present large energy density of 108.1â Wh kg-1 with average discharge voltage of 2.8â V and capacity retention of 86.5 % after 350â cycles.
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High fat diet-induced obesity is associated with insulin resistance (IR) and other chronic, diet related illnesses, including dementia. Alzheimer disease is the most common form of dementia, and is characterized by the presence of amyloid plaques and neurofibrillary tangles in brain. This study was designed to determine whether diet-induced changes in peripheral insulin sensitivity could contribute to alterations in brain insulin signaling and cognitive functions. Six week old, male C57BL/6NHsd mice were randomly assigned a high fat diet (40% energy from fat) with 42g/L liquid sugar (HFS) added to the drinking water or a normal chow diet (12% energy from fat) for 14weeks. Metabolic phenotypes were characterized for energy expenditure, physical activity, and food intake, and glucose and insulin tolerance tests. In addition, we examined the changes in protein expression related to brain insulin signaling and cognitive function. Mice fed HFS exhibited a statistically significant increase in obesity, and lower glucose and insulin tolerance as compared to animals fed the normal chow diet. In brain, HFS elicited IR as evidenced by a significant decrease in tyrosine phosphorylation of insulin receptor and an increase serine phosphorylation of IRS-1. These changes were accompanied by inflammatory (NFκB, JNK) and stress responses (p38 MAPK, CHOP) in whole brain lysate. In addition, HFS mouse brain exhibited biochemical changes related to increased amyloid beta deposition and neurofibrillary tangle formation, and decreased synaptic plasticity. These results suggested changes in insulin sensitivity might contribute to cognitive impairment associated with the HFS diet in mice.
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Doença de Alzheimer/etiologia , Encéfalo/patologia , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Obesidade/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Metabolismo Energético , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/patologia , Transdução de SinaisRESUMO
nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFß gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression.
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Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica , Dieta Ocidental , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Obesidade/genética , Adipócitos Brancos/patologia , Alanina Transaminase/metabolismo , Animais , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Sacarose Alimentar , Modelos Animais de Doenças , Fibrose , Frutose , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Hiperfagia , Immunoblotting , Resistência à Insulina , Fígado/patologia , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Tamanho do Órgão , Fenótipo , Proteínas Proto-Oncogênicas c-akt , Transcriptoma , Fator de Crescimento Transformador beta/genética , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Plectasin might serve as a substitute for traditional antibiotics, but its yields and antimicrobial activities warrant further investigation. OBJECTIVE: To identify the influence of inducible versus constitutive expression of plectasin on yields and antimicrobial activities. METHODS: Through SOE-PCR, a recombinant plectasin gene was generated and inserted into inducible (pPICZαA) and constitutive (pGAPZαA) vectors in order to create Pichia pastoris GS115 strains. After 120 h of fermentation, supernatants were purified by an AKTA purifier using nickel columns. Minimal inhibitory concentration (MIC) and inhibition zone assays were performed after Tricine-SDS-PAGE. RESULTS: After 120 h of fermentation, the yield of constitutive plectasin (370 µg/ml) was much lower than that from inducible vector (880 µg/ml) (P < 0.05). However, constitutive strain reached its plateau phase faster and keep more consistent yield (P < 0.05). The MICs of inducible plectasin against Methicillin-resistant Staphylococcus aureus (MRSA) 15471118, vancomycin-resistant Enterococcus feces (VREF), and penicillin-resistant Streptococcus pneumonia (PRSP) 31355 were 64, 32, and 64 µg/ml, respectively, while those of constitutive plectasin were 4, 4, and 16 µg/ml. No significant differences were observed in antimicrobial activities between inducible and constitutive plectasin for MRSA 15471118, VREF and PRSP 31355 (all P ï¼ 0.05). However, constitutive plectasin had a larger inhibition zone than inducible plectasin with the same mass. CONCLUSIONS: Although P. pastoris GS115 (pGAPZαA-Plectasin-GS115) had lower expression than P. pastoris GS115 (pPICZαA-plectasin-GS115), it reached the plateau phase faster, had steadier yields and showed superiority in antimicrobial activities. Therefore, pGAPZαA might be more suitable for expression of plectasin in GS115 compared with pPICZαA.
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Antibacterianos/biossíntese , Peptídeos/genética , Peptídeos/metabolismo , Pichia/genética , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Humanos , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia , Pichia/classificação , Pichia/metabolismoRESUMO
OBJECTIVE: The aim of this report is to describe a case with Aspergillus vertebral osteomyelitis complicating pulmonary granuloma in an immunocompetent adult. CLINICAL PRESENTATION AND INTERVENTION: A 53-year-old male patient was found to have lesions on lumbar vertebra 5 months after thoracoscopic resection of pulmonary granuloma that lacked a definite etiology. Three operations on the lumbar lesions were performed successively; however, an Aspergillus infection was not confirmed until hyphae were clearly detected at the last surgery. The patient was treated with voriconazole and recovered well. CONCLUSION: This case shows that simultaneous occurrence of granulomatous nodules in the lung and vertebral lesions should raise suspicion of aspergillosis, even in immunocompetent patients.
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Aspergilose/complicações , Granuloma/complicações , Vértebras Lombares/patologia , Pneumopatias/complicações , Osteomielite/complicações , Antifúngicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/microbiologiaRESUMO
PURPOSE: A number of different clinical characteristics have been reported to singly correlate with therapeutic activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced non-small-cell lung cancer (NSCLC). This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. PATIENTS AND METHODS: EGFR gene typing in 33 advanced NSCLC patients received gefitinib (250 mg/day) were analyzed with mutant-enriched PCR assay. Gefitinib response was evaluated with potential predictive factors retrospectively. RESULTS: The overall objective response rate (ORR) and median progression-free survival (PFS) in the 33 patients treated by gefitinib were 45.5% and 3.0 (2.0-4.0) months. The ORR and median PFS in EGFR gene mutation patients were significantly higher/longer than those in EGFR gene wild-type patients (P<0.01). Similarly, the ORR and median PFS in non-smoker patients were significantly higher/longer than those in smoker patients (P<0.05, P<0.01, respectively). However, no difference for ORR and median PFS occurred between male and female patients. Logistic multivariate analysis showed that only EGFR mutated gene was significantly associated with the ORR (P<0.01). Both EGFR mutated gene and non-smoker were the major factors that contributed to PFS (P<0.05). CONCLUSIONS: EGFR mutated gene and non-smoker status are potential predictors for gefitinib response in NSCLC patients.
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Vitrification of reproductive cells is definitely essential and integral in animal breeding, as well as in assisted reproduction. However, issues accompanied with this technology such as decreased oocyte competency and relatively low embryo survival rates appear to be a tough conundrum that has long perplexed us. As significant organelles in cell metabolism, mitochondria play pivotal roles in numerous pathways. Nonetheless, extensive evidence has demonstrated that vitrification can seriously impair mitochondrial function in mammalian oocytes. Thus, in this article, we summarize the current progress in oocyte vitrification and particularly outline the common mitochondrial abnormalities alongside subsequent injury cascades seen in mammalian oocytes following vitrification. Based on existing literature, we tentatively come up with the potential mechanisms related to mitochondrial dysfunction and generalize efficacious ways which have been recommended to restore mitochondrial function.
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Plasma membrane damage in vitrified oocytes is closely linked to mitochondrial dysfunction. However, the mechanism underlying mitochondria-regulated membrane stability is not elucidated. A growing body of evidence indicates that mitochondrial activity plays a pivotal role in cell adaptation. Since mitochondria work at a higher temperature than the constant external temperature of the cell, we hypothesize that suppressing mitochondrial activity would protect oocytes from extreme stimuli during vitrification. Here we show that metformin suppresses mitochondrial activity by reducing mitochondrial temperature. In addition, metformin affects the developmental potential of oocytes and improves the survival rate after vitrification. Transmission electron microscopy results show that mitochondrial abnormalities are markedly reduced in vitrified oocytes pretreated with metformin. Moreover, we find that metformin transiently inhibits mitochondrial activity. Interestingly, metformin pretreatment decreases cell membrane fluidity after vitrification. Furthermore, transcriptome results demonstrate that metformin pretreatment modulates the expression levels of genes involved in fatty acid elongation process, which is further verified by the increased long-chain saturated fatty acid contents in metformin-pretreated vitrified oocytes by lipidomic profile analysis. In summary, our study indicates that metformin alleviates cryoinjuries by reducing membrane fluidity via mitochondrial activity regulation.
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Fluidez de Membrana , Metformina , Mitocôndrias , Oócitos , Metformina/farmacologia , Animais , Fluidez de Membrana/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Suínos , Feminino , Criopreservação , Vitrificação/efeitos dos fármacosRESUMO
Metabolic balance is essential for oocyte maturation and acquisition of developmental capacity. Suboptimal conditions of in vitro cultures would lead to lipid accumulation and finally result in disrupted oocyte metabolism. However, the effect and mechanism underlying lipid catabolism in oocyte development remain elusive currently. In the present study, we observed enhanced developmental capacity in Procyanidin B2 (PCB2) treated oocytes during in vitro maturation. Meanwhile, reduced oxidative stress and declined apoptosis were found in oocytes after PCB2 treatment. Further studies confirmed that oocytes treated with PCB2 preferred to lipids catabolism, leading to a notable decrease in lipid accumulation. Subsequent analyses revealed that mitochondrial uncoupling was involved in lipid catabolism, and suppression of uncoupling protein 1 (UCP1) would abrogate the elevated lipid consumption mediated by PCB2. Notably, we identified peroxisome proliferator-activated receptor gamma (PPARγ) as a potential target of PCB2 by docking analysis. Subsequent mechanistic studies revealed that PCB2 improved oocyte development capacity and attenuated oxidative stress by activating PPARγ mediated mitochondrial uncoupling. Our findings identify that PCB2 intricately improves oocyte development capacity through targeted activation of the PPARγ/UCP1 pathway, fostering uncoupling lipid catabolism while concurrently mitigating oxidative stress.
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Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn+ and Grem1+ SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+ SSC subpopulation, which was potent at suppressing macrophage inflammation. The microgel carriers promoted the YAP nuclear translocation, and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2 in microgels-delivered SSC, which further suppressed the expression of TNF-É, IL-1ß and promoted the expression of IL-10 in macrophages. SSC delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without microgels. Chemically blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic macrophages. Moreover, microgel carriers significantly prolonged SSC retention time in vivo without increasing SSC implanting into osteoarthritic joints. Together, our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into nucleus. The study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level, but also provide new insight for microgel carriers in stem cell-based therapy.
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Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.
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The ammonium and nitrate removal performance and metabolic pathways of a biocontrol strain, Pseudomonas fluorescens 2P24, were investigated. Strain 2P24 could completely remove 100 mg/L ammonium and nitrate, with removal rates of 8.27 mg/L/h and 4.29 mg/L/h, respectively. During these processes, most of the ammonium and nitrate were converted to biological nitrogen via assimilation, and only small amounts of nitrous oxide escaped. The inhibitor allylthiourea had no impact on ammonium transformation, and diethyl dithiocarbamate and sodium tungstate did not inhibit nitrate removal. Intracellular nitrate and ammonium were detectable during the nitrate and ammonium transformation process, respectively. Moreover, the nitrogen metabolism functional genes (glnK, nasA, narG, nirBD, nxrAB, nirS, nirK, and norB) were identified in the strain. All results highlighted that P. fluorescens 2P24 is capable of assimilatory and dissimilatory nitrate reduction, ammonium assimilation and oxidation, and denitrification.
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Compostos de Amônio , Pseudomonas fluorescens , Nitratos/metabolismo , Compostos de Amônio/metabolismo , Pseudomonas fluorescens/metabolismo , Desnitrificação , Nitrogênio , Redes e Vias MetabólicasRESUMO
Surgical scene segmentation provides critical information for guidance in micro-neurosurgery. Segmentation of instruments and critical tissues contributes further to robot assisted surgery and surgical evaluation. However, due to the lack of relevant scene segmentation dataset, scale variation and local similarity, micro-neurosurgical segmentation faces many challenges. To address these issues, a high correlative non-local network (HCNNet), is proposed to aggregate multi-scale feature by optimized non-local mechanism. HCNNet adopts two-branch design to generate features of different scale efficiently, while the two branches share common weights in shallow layers. Several short-term dense concatenate (STDC) modules are combined as the backbone to capture both semantic and spatial information. Besides, a high correlative non-local module (HCNM) is designed to guide the upsampling process of the high-level feature by modeling global context generated from the low-level feature. It filters out confused pixels of different classes in the non-local correlation map. Meanwhile, a large segmentation dataset named NeuroSeg is constructed, which contains 15 types of instruments and 3 types of tissues that appear in meningioma resection surgery. The proposed HCNNet achieves the state-of-the-art performance on NeuroSeg, it reaches an inference speed of 54.85 FPS with the highest accuracy of 59.62% mIoU, 74.7% Dice, 70.55% mAcc and 87.12% aAcc.
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Procedimentos Cirúrgicos Robóticos , Processamento de Imagem Assistida por Computador , SemânticaRESUMO
It is acknowledged that excessive reactive oxygen species (ROS) level attributes greatly to the compromised developmental potential of oocytes matured in vitro. Although agents were applied to alleviate ROS levels, results were varied because of the distinct antioxidative activity and cell toxicity. Leonurine (LEO), extracted from the natural Chinese herb motherwort, is considered to be a potent free radical scavenger. Yet, it is undetermined whether LEO is benefit for oocyte development during in vitro maturation (IVM). In the present study, the effect of LEO on the quality of bovine oocyte as well as the underlying mechanism was investigated. We found that maturation rate (P < 0.01), subsequent blastocyst formation rate (P < 0.05), and the total blastocyst cell number (P < 0.05) after parthenogenetic activation were significantly increased in the group treated with 20 µM LEO. Moreover, a dramatic decline in ROS (P < 0.01), decreased lipid content (P < 0.01), elevated MMP level (P < 0.05), increased ATP content (P < 0.05), and reduced mitochondrial temperature (P < 0.01) were observed in oocytes treated with LEO. Furthermore, the expression level of anti-apoptotic protein BCL2 was significantly higher in LEO treated oocytes (P < 0.01), and the ratio of BAX/BCL2 was obvious decreased (P < 0.01). Finally, we found that LC3B intensity was significantly reduced (P < 0.05) while the rate of EdU positive nuclei was markedly increased (P < 0.05) in embryos derived from LEO-treated oocytes. Our results demonstrate that LEO exhibits a potent protective role in the acquisition of oocyte development capacity against oxidative stress during IVM, and provides a new solution for optimizing the in vitro culture system of bovine embryos.
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Desenvolvimento Embrionário , Técnicas de Maturação in Vitro de Oócitos , Gravidez , Feminino , Animais , Bovinos , Espécies Reativas de Oxigênio/metabolismo , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Estresse Oxidativo , Oócitos/fisiologia , Mitocôndrias , Blastocisto/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
Nonalcoholic fatty liver disease (NAFLD), which ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), is the most common chronic liver disease. Yet, the molecular mechanisms for the progression of steatosis to NASH remain largely undiscovered. Thus, there is a need for identifying specific gene and pathway changes that drive the progression of NAFLD. This study uses high-fat Western diet (HFWD) together with liquid sugar [fructose and sucrose (F/S)] feeding for 12 weeks in mice to induce obesity and examine hepatic transcriptomic changes that occur in NAFLD progression. The combination of a HFWD+F/S in the drinking water exacerbated HFWD-induced obesity, hyperinsulinemia, hyperglycemia, hepatic steatosis, inflammation, and human and murine fibrosis gene set enrichment that is consistent with progression to NASH. RNAseq analysis revealed differentially expressed genes (DEGs) associated with HFWD and HFWD+F/S dietary treatments compared to Chow-fed mice. However, liquid sugar consumption resulted in a unique set of hepatic DEGs in HFWD+F/S-fed mice, which were enriched in the complement and coagulation cascades using network and biological analysis. Cluster analysis identified Orosomucoid (ORM) as a HFWD+F/S upregulated complement and coagulation cascades gene that was also upregulated in hepatocytes treated with TNFα or free fatty acids in combination with hypoxia. ORM expression was found to correlate with NAFLD parameters in obese mice. Taken together, this study examined key genes, biological processes, and pathway changes in the liver of HFWD+F/S mice in an effort to provide insight into the molecular basis for which the addition of liquid sugar promotes the progression of NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transcriptoma , Frutose/efeitos adversos , Frutose/metabolismo , Sacarose/efeitos adversos , Sacarose/metabolismo , Dieta Ocidental/efeitos adversos , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
In recent intelligent-robot-assisted surgery studies, an urgent issue is how to detect the motion of instruments and soft tissue accurately from intra-operative images. Although optical flow technology from computer vision is a powerful solution to the motion-tracking problem, it has difficulty obtaining the pixel-wise optical flow ground truth of real surgery videos for supervised learning. Thus, unsupervised learning methods are critical. However, current unsupervised methods face the challenge of heavy occlusion in the surgical scene. This paper proposes a novel unsupervised learning framework to estimate the motion from surgical images under occlusion. The framework consists of a Motion Decoupling Network to estimate the tissue and the instrument motion with different constraints. Notably, the network integrates a segmentation subnet that estimates the segmentation map of instruments in an unsupervised manner to obtain the occlusion region and improve the dual motion estimation. Additionally, a hybrid self-supervised strategy with occlusion completion is introduced to recover realistic vision clues. Extensive experiments on two surgical datasets show that the proposed method achieves accurate motion estimation for intra-operative scenes and outperforms other unsupervised methods, with a margin of 15% in accuracy. The average estimation error for tissue is less than 2.2 pixels on average for both surgical datasets.
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Procedimentos Cirúrgicos Robóticos , Cirurgia Assistida por Computador , Algoritmos , Movimento (Física) , Cirurgia Assistida por Computador/métodosRESUMO
Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.
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Neoplasias Ósseas , Osteossarcoma , Adolescente , Criança , Humanos , Carboxipeptidase H/genética , Prognóstico , Osteossarcoma/genética , Neoplasias Ósseas/genética , BiomarcadoresRESUMO
Background: Enhanced recovery after surgery is used in gastrointestinal surgery. This study aimed to access the effects of early liquid drinking (ELD) on gastrointestinal function recovery in patients with gastric cancer (GC) who underwent radical gastrectomy, as high-quality evidence on the outcomes of ELD after gastrectomy is currently lacking. Methods: Clinicopathological data of patients with GC from 11 centers were retrospectively analysed. Clinical outcomes were investigated in 555 patients, including 225 who started drinking liquid within 48 h (ELD group) of surgery and 330 who started drinking liquid after flatus resumption (traditional liquid drinking [TLD] group). Propensity score matching (PSM) analysis was performed using a match ratio of 1:1 and 201 patients were selected from each group for the analysis. Primary outcome was time to first passage of flatus. Secondary outcomes included time to first defecation, post-operative hospitalization days, occurrence of short-term post-operative complications, and hospitalization costs. Results: After PSM, baseline characteristics were not significantly different between the two groups. The time to first flatus (2.72 ± 1.08 vs 3.36 ± 1.39 days), first defecation (4.34 ± 1.85 vs 4.77 ± 1.61 days), and post-operative hospital stay (8.27 ± 4.02 vs 12.94 ± 4.43 days) were shorter in the ELD group than in the TLD group (all P < 0.05). The ELD group had lower hospitalization costs than the TLD group ([7.83 ± 2.44 vs 8.78 ± 3.41] × 104 RMB, P = 0.041). No significant differences were observed in the incidence of post-operative complications. Conclusions: Compared with TLD, post-operative ELD could promote rapid recovery of gastrointestinal function and reduce hospitalization costs; moreover, ELD does not increase the risk of post-operative complications.