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Structural degradation of oxide electrodes during the electrocatalytic oxygen evolution reaction (OER) is a major challenge in water electrolysis. Although the OER is known to induce changes in the surface layer, little is known about its effect on the bulk of the electrocatalyst and its overall phase stability. Here, we show that under OER conditions, a highly active SrCoO3-x electrocatalyst develops bulk lattice instability, which results in the formation of molecular O2 dimers inside the bulk and nanoscale amorphization induced via chemo-mechanical coupling. Using high-resolution resonant inelastic X-ray scattering and first-principles calculations, we unveil the potential-dependent evolution of lattice oxygen inside the perovskite and demonstrate that O2 dimers are stable in a densely packed crystal lattice, thus challenging the assumption that O2 dimers require sufficient interatomic spacing. We also show that the energy cost of local atomic rearrangements in SrCoO3-x becomes very low under the OER conditions, leading to an unusual amorphization under intercalation-induced stress. As a result, we propose that the amorphization energy can be calculated from the first principles and can be used to assess the stability of electrocatalysts. Our study demonstrates that extreme oxidation of electrocatalysts under OER can intrinsically destabilize the lattice and result in bulk anion redox and disorder, suggesting why some oxide materials are unstable and develop a thick amorphous layer under water electrolysis conditions.
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Obesity and its related metabolic complications represent a significant global health challenge. Central to this is the dysregulation of glucolipid metabolism, with a predominant focus on glucose metabolic dysfunction in the current research, whereas adipose metabolism impairment garners less attention. Exosomes (EXs), small extracellular vesicles (EVs) secreted by various cells, have emerged as important mediators of intercellular communication and have the potential to be biomarkers, targets, and therapeutic tools for diverse diseases. In particular, EXs have been found to play a role in adipose metabolism by transporting cargoes such as noncoding RNAs (ncRNA), proteins, and other factors. This review article summarizes the current understanding of the role of EXs in mediating adipose metabolism disorders in obesity. It highlights their roles in adipogenesis (encompassing adipogenic differentiation and lipid synthesis), lipid catabolism, lipid transport, and white adipose browning. The insights provided by this review offer new avenues for developing exosome-based therapies to treat obesity and its associated comorbidities.
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Adipogenia , Tecido Adiposo , Exossomos , Metabolismo dos Lipídeos , Obesidade , Exossomos/metabolismo , Humanos , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Animais , Adipogenia/fisiologia , Metabolismo dos Lipídeos/fisiologiaRESUMO
AIMS: Carbohydrate antigen 199 (CA199) is a standard tumor marker, and recent studies have found elevated in CA199 levels in patients with diabetes. However, there is no systematic measurement and comparison of serum CA199 levels in patients with diabetes and cancer. Here, a detailed description of the changes in serum CA199 levels in patients with type 2 diabetes and various cancers was explored. METHODS: A total of 5,641 participants were screened for clinical laboratory test results of serum CA199 levels over the past three years (2020-2023). This study included 2,464 healthy controls, 688 patients with type 2 diabetes, and 2,489 patients with 16 different types of cancer. Each type of cancer had more than 30 independent serum CA199 level test results. The serum CA199 levels were compared between cancer groups, type 2 diabetes patients, and healthy controls. Additionally, the CA199 levels of cancer patients were compared with those of patients with type 2 diabetes. RESULTS: The serum CA199 levels of esophagus cancer, lung cancer, pancreatic cancer, ovarian cancer, breast cancer, rectum cancer, prostate cancer, bladder cancer, liver cancer, gastric cancer, cervical cancer, colon cancer, lymphoma, thyroid cancer, intracranial tumors, and nasopharyngeal laryngeal cancer were found to be elevated compared to healthy controls (P < 0.01). In addition, the serum CA199 levels of patients with type 2 diabetes were also significantly elevated compared to healthy controls (P < 0.01). Moreover, the degree of elevation in serum CA199 levels in patients with type 2 diabetes was not significantly different from that observed in some types of cancer, such as esophagus cancer (P = 0.163), breast cancer (P = 0.927), prostate cancer (P = 1.000), bladder cancer (P = 0.406), Lymphoma (P = 0.975), thyroid cancer (P = 1.000), intracranial tumors (P = 0.161), nasopharyngeal and laryngeal cancer (P = 1.000). CONCLUSIONS: Serum CA199 levels also increase in type 2 diabetes, and the magnitude of the increase is similar to that seen in some cancers.
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Neoplasias Encefálicas , Diabetes Mellitus Tipo 2 , Neoplasias Esofágicas , Neoplasias Laríngeas , Linfoma , Neoplasias da Glândula Tireoide , Neoplasias da Bexiga Urinária , Masculino , Humanos , Antígenos Glicosídicos Associados a Tumores , Biomarcadores TumoraisRESUMO
Neuroblastoma is the most common extracranial solid tumor in children. The purpose of the present study is to detect the prognostic role and potential therapeutic efficacy of the T lymphoma invasion and metastasis 1 (Tiam1) in neuroblastoma. The overexpression of Tiam1 protein is frequently observed in neuroblastoma. Tiam1 expression is closely associated with adverse prognosis of neuroblastoma and risk group classification. Knockdown of TIAM1 by lentivirus expressing short hairpin RNA against TIAM1 (sh-TIAM1) inhibited the proliferation, invasion and cell-cycle progression, and promoted apoptosis of the neuroblastoma cell lines SH-SY5Y and SK-N-AS. Additionally, downregulation of the differentiation-related protein expression and decreased Rac1 expression was observed in the sh-TIAM1-transfected SH-SY5Y cells. In vivo, nude mice bearing TIAM1 knockdown SH-SY5Y cells showed improved overall survival and tumor growth suppression. The results demonstrate that inhibition of Tiam1 expression is a potential strategy for targeted therapy in neuroblastoma.
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Linfoma , Neuroblastoma , Animais , Camundongos , Criança , Humanos , Neuroblastoma/genética , Camundongos Nus , Transdução de Sinais , Proliferação de Células/genética , Linhagem Celular TumoralRESUMO
Background: Colorectal cancer (CRC) is the third most prevalent malignancy globally, ranking as the second leading cause of cancer-related mortality. Emerging evidence highlights RAB10's involvement in the progression of various malignant tumors; however, its specific role in CRC remains unclear. Objective: To explore the oncogenic role of RAB10 in colorectal cancer progression by investigating its impact on NF-κB activation, aiming to identify a novel genetic biomarker for enhanced diagnosis and treatment of CRC. Methods: This study collected CRC tissue samples and utilized The Cancer Genome Atlas (TCGA) database for RAB10 expression verification through Western blot (WB). Cellular phenotype experiments were conducted on CRC cell lines, including quantitative real-time-polymerase chain reaction (qRT-PCR), CCK-8, transwell assay, and wound healing assay (HCT116 and SW480). Additionally, the impact of RAB10 on NF-κB signaling was assessed through qRT-PCR and WB. Results: RAB10 exhibited upregulation in CRC tissue samples compared to normal counterparts. Furthermore, RAB10 promoted the proliferation, migration, and invasion of HCT116 and SW480 cells. Notably, RAB10 induced NF-κB activation in CRC in vitro. Conclusion: This study revealed the oncogenic function of RAB10, explaining its role in activating NF-κB in CRC. The findings present RAB10 as a potential genetic biomarker for CRC diagnosis and treatment.
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Anthocyanins are ubiquitous pigments derived from the phenylpropanoid compound conferring red, purple and blue pigmentations to various organs of horticultural crops. The metabolism of flavonoids in the cytoplasm leads to the biosynthesis of anthocyanin, which is then conveyed to the vacuoles for storage by plant glutathione S-transferases (GST). Although GST is important for transporting anthocyanin in plants, its identification and characterization in eggplant (Solanum melongena L.) remains obscure. In this study, a total of 40 GST genes were obtained in the eggplant genome and classified into seven distinct chief groups based on the evolutionary relationship with Arabidopsis thaliana GST genes. The seven subgroups of eggplant GST genes (SmGST) comprise: dehydroascorbate reductase (DHAR), elongation factor 1Bγ (EF1Bγ), Zeta (Z), Theta(T), Phi(F), Tau(U) and tetra-chlorohydroquinone dehalogenase TCHQD. The 40 GST genes were unevenly distributed throughout the 10 eggplant chromosomes and were predominantly located in the cytoplasm. Structural gene analysis showed similarity in exons and introns within a GST subgroup. Six pairs of both tandem and segmental duplications have been identified, making them the primary factors contributing to the evolution of the SmGST. Light-related cis-regulatory elements were dominant, followed by stress-related and hormone-responsive elements. The syntenic analysis of orthologous genes indicated that eggplant, Arabidopsis and tomato (Solanum lycopersicum L.) counterpart genes seemed to be derived from a common ancestry. RNA-seq data analyses showed high expression of 13 SmGST genes with SmGSTF1 being glaringly upregulated on the peel of purple eggplant but showed no or low expression on eggplant varieties with green or white peel. Subsequently, SmGSTF1 had a strong positive correlation with anthocyanin content and with anthocyanin structural genes like SmUFGT (r = 0.9), SmANS (r = 0.85), SmF3H (r = 0.82) and SmCHI2 (r = 0.7). The suppression of SmGSTF1 through virus-induced gene silencing (VIGs) resulted in a decrease in anthocyanin on the infiltrated fruit surface. In a nutshell, results from this study established that SmGSTF1 has the potential of anthocyanin accumulation in eggplant peel and offers viable candidate genes for the improvement of purple eggplant. The comprehensive studies of the SmGST family genes provide the foundation for deciphering molecular investigations into the functional analysis of SmGST genes in eggplant.
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Antocianinas , Regulação da Expressão Gênica de Plantas , Glutationa Transferase , Solanum melongena , Antocianinas/metabolismo , Antocianinas/biossíntese , Arabidopsis/genética , Arabidopsis/metabolismo , Cromossomos de Plantas/genética , Frutas/genética , Frutas/metabolismo , Genoma de Planta , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Solanum melongena/enzimologia , Solanum melongena/genética , Solanum melongena/metabolismoRESUMO
Semiconductor alloy materials are highly versatile due to their adjustable properties; however, exploring their structural space is a challenging task that affects the control of their properties. Traditional methods rely on ad hoc design based on the understanding of known chemistry and crystallography, which have limitations in computational efficiency and search space. In this work, we present ChecMatE (Chemical Material Explorer), a software package that automatically generates machine learning potentials (MLPs) and uses global search algorithms to screen semiconductor alloy materials. Taking advantage of MLPs, ChecMatE enables a more efficient and cost-effective exploration of the structural space of materials and predicts their energy and relative stability with ab initio accuracy. We demonstrate the efficacy of ChecMatE through a case study of the InxGa1-xN system, where it accelerates structural exploration at reduced costs. Our automatic framework offers a promising solution to the challenging task of exploring the structural space of semiconductor alloy materials.
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A common theme among previously proposed models for network epidemics is the assumption that the propagating object (e.g., a pathogen [in the context of infectious disease propagation] or a piece of information [in the context of information propagation]) is transferred across network nodes without going through any modification or evolutionary adaptations. However, in real-life spreading processes, pathogens often evolve in response to changing environments and medical interventions, and information is often modified by individuals before being forwarded. In this article, we investigate the effects of evolutionary adaptations on spreading processes in complex networks with the aim of 1) revealing the role of evolutionary adaptations on the threshold, probability, and final size of epidemics and 2) exploring the interplay between the structural properties of the network and the evolutionary adaptations of the spreading process.
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Segurança Computacional/estatística & dados numéricos , Epidemias/estatística & dados numéricos , Retroalimentação , Internet/estatística & dados numéricos , Modelos Teóricos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/transmissão , Evolução Molecular , Humanos , Internet/normasRESUMO
BACKGROUND: Skin aging involves genetic, environmental and hormonal factors. Facial wrinkles also depend on muscular activity. Gene expression investigation may be useful for new anti-aging products. METHODS AND RESULTS: To evaluate structure and gene expression differences among exposed and unexposed skin in menopausal women. Cross-sectional study, including 15 menopausal women, 55-65 years, phototype III; photo-exposed, periorbital wrinkles (A1), preauricular, not wrinkled (A2), and unexposed gluteal (A3) areas were described and compared by non-invasive measures, histology, immunohistochemistry and gene expression (RNASeq); participants mean age was 61yo, presenting moderate periorbital wrinkles and light facial photodamage. Higher roughness, wrinkles number and echogenicity were observed in A1 and A2 versus A3. Decreased epidermal thickness and dermal collagen IV were demonstrated in A1 versus A2 and A3. Exposed areas impacted different pathways compared to unexposed. Exposed wrinkled skin (A1) showed impact on cell movement with decreased inflammatory activation state. Pathways related to lipid and aminoacids metabolism were modulated in non-wrinkled exposed (A2) compared to unexposed (A3) skin. CONCLUSIONS: Expected histological findings and gene expression differences among areas were observed. Photoaging in menopausal women may modulate lipid and aminoacids metabolism and decrease inflammatory and keratinization pathways, cellular homeostasis, immune response, fibrogenesis and filament formation. These findings may help development of new therapies for skin health and aging control.
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Envelhecimento da Pele , Envelhecimento/patologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Pele/patologia , Envelhecimento da Pele/genética , TranscriptomaRESUMO
BACKGROUND: Research suggests that fibrinogen (Fib) is related to mild cognitive impairment (MCI) and diabetic peripheral neuropathy (DPN) and the risk of MCI in patients with DPN is greatly increased, although no studies have evaluated the predictive value of Fib for the risk of MCI in patients with DPN. METHODS: This prospective observational clinical study enrolled 207 type 2 diabetes mellitus (T2DM) patients, who were divided into diabetes with no neuropathy (102 cases) and diabetes with neuropathy (105 cases) groups. Meanwhile, 90 healthy unrelated subjects were recruited as controls. The incidence of MCI in the DPN patients was followed up for 2 years. Divide patients in the DPN group into subgroups according to whether MCI occur, use multivariate logistic regression to analyze independent factors of MCIs in DPN patients within 2 years, and use ROC curve to analyze the predictive value of Fib for MCI in DPN patients. RESULTS: Fib levels were significantly higher in diabetic subjects with neuropathy compared with those without (P < 0.001). In further subgroup analysis of DPN patients who were divided according to the occurrence of MCI, baseline data of the MCI subgroup showed Fib levels were higher than that in the non-MCI group while education levels declined (P < 0.001). The education level and increased Fib levels were independent factors for the occurrence of MCI within 2 years after the onset of DPN (OR = 0.769, 95% CI: 0.605 ~ 0.968, P = 0.037; OR = 2.674, 95% CI: 1.094 ~ 3.168, P = 0.002). The ROC curve indicated that the predictive value of Fib was (AUC = 0.764, 95% CI: 0.671 ~ 0.842, P < 0.001). CONCLUSIONS: Fib may function as a predictor for assessing the risk of MCI in DPN patients.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Humanos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Fibrinogênio , Fatores de RiscoRESUMO
Aqueous rutile TiO2(110) is the most widely studied water-oxide interface, and yet questions about water dissociation are still controversial. Theoretical studies have systematically investigated the influence of the slab thickness on water dissociation energy (Ediss) at 1 monolayer coverage using static density functional theory calculation and found that Ediss exhibits odd-even oscillation with respect to the TiO2 slab thickness. However, less studies have accounted for the full solvation of an aqueous phase using ab initio molecular dynamics due to high computational costs in which only three, four, and five trilayer models of rutile(110)-water interfaces have been simulated. Here, we report Machine Learning accelerated Molecular Dynamics (MLMD) simulations of defect-free rutile(110)-water interfaces, which allows for a systematic study of the slab thickness ranging from 3 to 17 trilayers with much lower costs while keeping ab initio accuracy. Our MLMD simulations show that the dissociation degree of surface water (α) oscillates with the slab thickness and converges to â¼2% as the TiO2 slab becomes thicker. Converting α into dissociation free energy (ΔAdiss) and comparing with dissociation total energy Ediss calculated with a single monolayer of water, we find that the full solvation of the interfaces suppresses surface water from dissociating. It is interesting to note that the machine learning potential trained from the dataset containing exclusively the five trilayer TiO2 model exhibits excellent transferability to other slab thicknesses and further captures the oscillating behavior of surface water dissociation. Detailed analyses indicate that the central plane in odd trilayer slabs modulates the interaction between double trilayers and, thus, the bonding strength between terminal Ti and water, which affects pKa of surface water and water dissociation degree.
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The color of fruit peel is an economically important character of eggplant, and black-purple eggplant has received much attention for being rich in anthocyanin. However, the reason why different fruit peel colors form in eggplant is not well understood. In the present study, an integrative analysis of the metabolome and transcriptome profiles was performed in five eggplant varieties with different fruit colors. A total of 260 flavonoids were identified, and most of them showed significantly higher abundance in black-purple varieties than in other varieties. The transcriptome analysis indicated the activation of early phenylpropanoid biosynthesis genes (SmPAL, SmC4H, and Sm4CL) was more responsible for anthocyanin accumulation, while SmF3'5'H was the key factor for the formation of a purple color. Furthermore, two transcription factors, SmGL2 and SmGATA26, were identified as new hub genes associated with anthocyanin accumulation. The silencing of SmGL2 and SmGATA26 reduced anthocyanin accumulation in eggplant fruit peels, suggesting the possible involvement of SmGL2 and SmGATA26 in regulating anthocyanin biosynthesis. In addition, the pathway of plant hormone signal transduction was significantly enriched, indicating that phytohormones may cooperatively interact to modulate flavonoid biosynthesis. This study provides comprehensive information of flavonoid metabolites and new insights into the regulatory network of fruit coloration, which might be useful for the molecular breeding of eggplant.
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Solanum melongena , Solanum melongena/genética , Solanum melongena/metabolismo , Frutas/genética , Frutas/metabolismo , Antocianinas/metabolismo , Regulação da Expressão Gênica de Plantas , Pigmentação/genética , Perfilação da Expressão Gênica , Transcriptoma , Metaboloma , Flavonoides/metabolismoRESUMO
Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, is required for many physiological reactions and processes. However, it remains largely unknown how NAD affects plant response to salt stress. We isolated a salt-sensitive mutant named hypersensitive to salt stress (hss) from an ethyl methanesulfonate-induced mutation population. A point mutation was identified by MutMap in the encoding region of Quinolinate Synthase (QS) gene required for the de novo synthesis of NAD. This point mutation caused a substitution of amino acid in the highly-conserved NadA domain of QS, resulting in an impairment of NAD biosynthesis in the mutant. Molecular and chemical complementation have restored the response of the hss mutant to salt stress, indicating that the decreased NAD contents in the mutant were responsible for its hypersensitivity to salt stress. Furthermore, the endogenous levels of abscisic acid (ABA) and proline were also reduced in stress-treated hss mutant. The application of ABA or proline could alleviate stress-induced oxidative damage of the mutant and partially rescue its hypersensitivity to salt stress, but not affect NAD concentration. Taken together, our results demonstrated that the NadA domain of QS is important for NAD biosynthesis, and NAD participates in plant response to salt stress by affecting stress-induced accumulation of ABA and proline.
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Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Complexos Multienzimáticos/genética , NAD/metabolismo , Prolina/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Complexos Multienzimáticos/metabolismo , Complexos Multienzimáticos/fisiologia , Mutação , Estresse Salino , Alinhamento de SequênciaRESUMO
BACKGROUND: Exercise therapy is a key intervention in the management of knee osteoarthritis (KOA) and recommended in international guidelines on KOA management. An effective home-exercise programme for frail older adults with KOA was successful in achieving high adherence. This randomised controlled trial was to compare the adherence to the exercise and lasting effects of follow-up 3 months. METHODS: Sixty-eight participants in the original Wuqinxi (WQX) exercise study were community dwelling older adults (age = 70.95 ± 9.85 years) with KOA were categorised into 34 controls group, 34 WQX group adherers. The Western Ontario and Mc Master Universities Osteoarthritis Index questionnaire score (WOMAC) pain and Berg Balance Scale, Timed Up and Go Test, 6-min Walk Test, 30-s chair stand test, isokinetic muscle strength testing of knee flexion and extension measured at pre-test and post-test of the intervention period and follow-up for two groups. RESULTS: The WQX group maintained or improved in all nine measures from post-test to follow-up, whereas the control group significantly declined in WOMAC pain, Knee extensor strength and Knee flexor strength. CONCLUSION: The WQX programme was an effective home-exercise programme that achieves high adherence in older adults with KOA who lived in these communities.
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Osteoartrite do Joelho , Idoso , Terapia por Exercício , Seguimentos , Humanos , Pessoa de Meia-Idade , Ontário , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/terapia , Dor , Manejo da Dor , Equilíbrio Postural , Estudos de Tempo e MovimentoRESUMO
BACKGROUND: Understanding the vascular anatomy is critical for performing central vascular ligation (CVL) in right hemicolectomy with complete mesocolic excision (CME). This study aimed to investigate the predictive value of multi-slice spiral computed tomography (MSCT) with coronal reconstruction in right hemicolectomy with CME. METHODS: This is a retrospective descriptive study. Eighty patients with right colon cancer who underwent right hemicolectomy from December 2015 to January 2020 were included. The intraoperative reports (including imaging data) and MSCT images with coronal reconstruction were analysed and compared. The detection rates of the ileocolic vein (ICV) and ileocolic artery (ICA) roots and the accuracy in predicting their anatomical relationship were analysed. The detection rate and accuracy in predicting the location of the gastrocolic trunk of Henle (GTH), middle colic artery (MCA) and middle colic vein (MCV) were analysed. The distance from the ICV root to the GTH root (ICV-GTH distance) was measured and analysed. The maximum distance from the left side of the superior mesenteric artery (SMA) to the right side of the superior mesenteric vein (SMV), named the 'lsSMA-rsSMV distance', was also measured and analysed. RESULTS: In seventy-four (92.5%) patients, both the ICV and ICA roots were located; their anatomical relationship was determined by MSCT, and the accuracy of the prediction was 97.2% (72/74). The GTH was located by MSCT in 75 (93.7%) patients, and the accuracy of the prediction was 97.33% (73/75). The MCA was located by MSCT in 47 (58.75%) patients, and the accuracy was 78.72% (37/47). The MCV was located by MSCT in 51 (63.75%) patients, and the accuracy of the prediction was 84.31% (43/51). The ICV-GTH distance was measured in 73 (91.2%) patients, and the mean distance was 4.28 ± 2.5 cm. The lsSMA-rsSMV distance was measured in 76 (95%) patients, and the mean distance was 2.21 ± 0.6 cm. CONCLUSIONS: With its satisfactory accuracy in predicting and visualising the information of key anatomical sites, MSCT with coronary reconstruction has some predictive value in CME with CVL in right hemicolectomy.
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Neoplasias do Colo , Laparoscopia , Mesocolo , Colectomia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/cirurgia , Humanos , Mesocolo/cirurgia , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Although the survival rate has increased dramatically over the last decades, patients struggle with the adverse side effects of treatment. Treatment for ALL includes chemotherapy and irradiation - both of which are linked to cognitive impairments and alterations in central nervous system (CNS) structure and function detected by neuroimaging and in neurocognitive studies. The present article is a meta-analysis of the existing evidence for the mechanisms underlying changes in the CNS and neurocognitive function in ALL survivors after treatment. We found that compared with controls, ALL survivors develop: (i) cognitive sequelae in intelligence, academics, attention, memory, processing speed and executive function domains; (ii) decreased grey and white matter volume in cortical and several subcortical brain regions, with functional changes particularly in frontal regions and the hippocampus; (iii) neurocognitive impairments related to CNS changes; and (iv) reduction, but not resolution, of late neurocognitive sequelae in patients in whom prophylactic irradiation was replaced by systemic/intrathecal chemotherapy. Continued work with advanced functional magnetic resonance imaging techniques will hopefully allow the detection of early CNS changes as biomarkers to help guide early diagnosis and intervention for neurocognitive defects in patients with childhood ALL.
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Sistema Nervoso Central/anatomia & histologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Análise de SobrevidaRESUMO
Tendon derived stem cells (TDSCs) were vital in tendon homeostasis. Nevertheless, the regulation of TDSCs differentiation in tendinopathy is unclear. Matrix stiffness modulated stem cells differentiation, and matrix stiffness of tendinopathic tissues decreased significantly. In order to clarify the role of matrix stiffness in TDSCs differentiation, they were cultured on the gelatin hydrogels with the stiffness from 2.34⯱â¯1.48â¯kPa to 24.09⯱â¯14.03â¯kPa. The effect of matrix stiffness on TDSCs proliferation and differentiation were investigated with CCK8 assay, immunofluorescences, real time PCR and western blot. It was found the proliferation of TDSCs increased and more stress fibers formed with increasing matrix stiffness. The differentiation of TDSCs into tenogenic, chondrogenic, and osteogenic lineages were inhibited on stiff hydrogel evidenced by reduced expression of tenocyte markers THBS4, TNMD, SCX, chondrocyte marker COL2, and osteocyte markers Runx2, Osterix, and ALP. Furthermore, the phosphorylation of FAK and ERK1/2 were enhanced when TDSCs grew on stiff hydrogel. After FAK or ERK1/2 was inhibited, the effect of matrix stiffness on differentiation of TDSCs was inhibited as well. The above results indicated matrix stiffness modulated the proliferation and differentiation of TDSCs, and the regulation effect could correlate to the activation of FAK or ERK1/2.
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Diferenciação Celular , Quinase 1 de Adesão Focal/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Células-Tronco/enzimologia , Tendões/citologia , Citoesqueleto de Actina/ultraestrutura , Animais , Proliferação de Células , Sobrevivência Celular , Ativação Enzimática , Gelatina , Hidrogéis , Sistema de Sinalização das MAP Quinases , Ratos Sprague-Dawley , Células-Tronco/citologiaRESUMO
BACKGROUND The uncoupling protein 1 (UCP1) gene has a role in mitochondrial energy expenditure in brown adipose tissue. This study aimed to investigate the effects of berberine, a benzylisoquinoline alkaloid used in traditional Chinese medicine, on energy expenditure, expression of the UCP1 gene, the cell stress protein inositol-requiring enzyme 1α (IRE1α), apoptosis genes, and macrophage phenotype (M1 and M2) in white and brown adipose tissue in an obese mouse model fed a high-fat diet. MATERIAL AND METHODS Four-week-old C57BL/6J male mice (n=20) were divided into a high-fat diet group, a normal diet group, a group treated with berberine at 100 mg/kg/d in 0.9% normal saline, and a non-treated group. Whole-body fat mass, blood glucose, insulin resistance, and oxygen expenditure during physical activity were measured. After 16 weeks, the mice were euthanized for examination of liver and adipose tissue. The expression of pro-inflammatory cytokines, apoptosis genes, thermogenic genes (including UCP1), and IRE1α, were investigated using immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR), in white and brown adipose tissue. Magnetic cell sorting harvested M1 and M2 macrophages in adipose tissue. Clodronate liposomes were used to inhibit macrophage recruitment. RESULTS Berberine treatment in mice fed a high-fat diet increased energy metabolism, glucose tolerance, and expression of UCP1, and reduced expression of pro-inflammatory cytokines, macrophage recruitment, and resulted in M2 macrophage polarization in white adipose tissue. Polarized M2 macrophages showed reduced expression of apoptotic genes and IRE1α. CONCLUSIONS Berberine improved metabolic function in a mouse model fed a high-fat diet.
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Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Berberina/farmacologia , Tecido Adiposo/efeitos dos fármacos , Animais , China , Dieta Hiperlipídica , Endorribonucleases/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Inflamação/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteína Desacopladora 1/efeitos dos fármacosRESUMO
BACKGROUND: Male sterility (MS) is an effective tool for hybrid production. Although MS has been widely reported in other plants, such as Arabidopsis and rice, the molecular mechanism of MS in eggplant is largely unknown. To understand the mechanism, the comparative transcriptomic file of MS line and its maintainer line was analyzed with the RNA-seq technology. RESULTS: A total of 11,7695 unigenes were assembled and 19,652 differentially expressed genes (DEGs) were obtained. The results showed that 1,716 DEGs were shared in the three stages. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these DEGs were mainly involved in oxidation-reduction, carbohydrate and amino acid metabolism. Moreover, transcriptional regulation was also the impact effector for MS and anther development. Weighted correlation network analysis (WGCNA) showed two modules might be responsible for MS, which was similar to hierarchical cluster analysis. CONCLUSIONS: A number of genes and pathways associated with MS were found in this study. This study threw light on the molecular mechanism of MS and identified several key genes related to MS in eggplant.