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Titanium (Ti) is generally considered as an ideal bipolar plate (BPP) material because of its excellent corrosion resistance, good machinability and lightweight nature. However, the easy-passivation property, which leads to increased interfacial contact resistance (ICR) and subsequently decreased cell performance, limits its large-scale commercial application in proton exchange membrane fuel cells (PEMFCs). In this paper, we proposed a NiTi alloy prepared by suction casting as a promising bipolar plate for PEMFCs. This NiTi alloy exhibits significantly decreased ICR values (16.8 mΩ cm2 at 1.4 MPa) compared with pure Ti (88.6 mΩ cm2 at 1.4 MPa), along with enhanced corrosion resistance compared with pure nickel (Ni). The superior corrosion resistance of NiTi alloy is accredited to the nobler open circuit potential and corrosion potential, coupled with low corrosion current densities and passive current densities. The improved ICR can be interpreted by the existence of high-proportioned metallic Ni in the passive film, which contributes to the reduced capacitance characteristic of the passive film (compared with Ti) and enhances charge conduction. This work provides a feasible option to ameliorate BPP material that may have desirable corrosion resistance and ICR.
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Nanofeatured polyaniline (PANI) electrodes have demonstrated impressive sensing performance due to the enhanced electrolyte diffusion and ion transport. However, the retaining of these nanostructures on substrates via electrophoretic deposition (EPD) faces an insurmountable challenge from the involved dedoping process. Here, camphorsulfonic acid is utilized with high steric effects to dope PANI (PANI-CSA) that can be directly used EPD without involving a dedoping process. Five different nanofeatures (sea cucumber-like, nanofiber, amorphous, nanotube, and nanorod) are synthesized, and they have been all successfully transferred onto indium tin oxide substrate in a formic acid/acetonitrile system, namely a morphology memory effect. The mechanism of retaining these nanofeatures is revealed, which is realized via the processes of dissolution of PANI-CSA, codoping and solvation, and reassembly of basic units into the original nanofeature. The enhanced protonation level by the codoping of formic acid and solvation of acetonitrile plays the key role in retaining these nanofeatures. This method is also applicable to transfer PANI/gold nanorod composites (PANI-CSA/AuNRs). The PANI-CSA/AuNRs electrode as an ascorbic acid sensor has shown an excellent sensing performance with a sensitivity up to 872.7 µA mm-1 cm-2 and a detection limit of as low as 0.18 × 10-6 m.
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OBJECTIVES: Malignancy is related to idiopathic inflammatory myopathies (IIM) and leads to a poor prognosis. Early prediction of malignancy is thought to improve the prognosis. However, predictive models have rarely been reported in IIM. Herein, we aimed to establish and use a machine learning (ML) algorithm to predict the possible risk factors for malignancy in IIM patients. METHODS: We retrospectively reviewed the medical records of 168 patients diagnosed with IIM in Shantou Central hospital, from 2013 to 2021. We randomly divided patients into two groups, the training sets (70%) for construction of the prediction model, and the validation sets (30%) for evaluation of model performance. We constructed six types of ML algorithms models and the AUC of ROC curves were used to describe the efficacy of the model. Finally, we set up a web version using the best prediction model to make it more generally available. RESULTS: According to the multi-variable regression analysis, three predictors were found to be the risk factors to establish the prediction model, including age, ALT<80U/L, and anti-TIF1-γ, and ILD was found to be a protective factor. Compared with five other ML algorithms models, the traditional algorithm logistic regression (LR) model was as good or better than the other models to predict malignancy in IIM. The AUC of the ROC using LR was 0.900 in the training set and 0.784 in the validation set. We selected the LR model as the final prediction model. Accordingly, a nomogram was constructed using the above four factors. A web version was built and can be visited on the website or acquired by scanning the QR code. CONCLUSIONS: The LR algorithm appears to be a good predictor of malignancy and may help clinicians screen, evaluate and follow up high-risk patients with IIM.
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Miosite , Neoplasias , Humanos , Modelos Logísticos , Estudos Retrospectivos , Neoplasias/diagnóstico , Neoplasias/terapia , Aprendizado de Máquina , Miosite/diagnósticoRESUMO
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with obscure origin and multidirectional differentiation. Application of RNA-Seq in the detection of COL1A1-PDGFB is still at early stages. OBJECTIVE: We aim to test the efficacy of fusion gene detection using bulk RNA-Seq in DFSPs, explore altered molecular pathways and biological processes for evidences of tumor origin and cell identity shift. MATERIALS AND METHODS: Dermatofibrosarcoma protuberans and normal dermis samples were acquired for RNA-Seq. Fusion gene detection was performed using STAR-Fusion. RNA-Seq 2G yielded differentially expressed genes. Altered pathways, key gene ontology terms, and similar cell/tissue types were identified with gene set enrichment analysis. xCell was used for cell types enrichment analysis. RESULTS: 28/30 CD34(+) cases were positive for COL1A1-PDGFB. 406 upregulated and 543 downregulated genes were determined. Among the top 10 upregulated genes, 6 had neural distribution, function, or disease correlation. The upregulated genes were related to synapse, trans-synaptic signaling, neural development, and extracellular matrix. Similarities between DFSP and nervous system components were highlighted, with fibroblast cellular abundancy increased during xCell analysis. CONCLUSION: Bulk RNA-Seq provided with high detection rate of COL1A1-PDGFB. Dermatofibrosarcoma protuberans showed fibroblastic activity and neural features, which validated DFSP's fibroblast origin and tendency of neural differentiation.
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Dermatofibrossarcoma , Neoplasias Cutâneas , Humanos , Proteínas Proto-Oncogênicas c-sis/genética , Proteínas Proto-Oncogênicas c-sis/metabolismo , Transcriptoma , RNA-Seq , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/genética , Dermatofibrossarcoma/patologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Extracellular matrix communicates with surrounding cells to maintain skin homeostasis and modulate multiple cellular processes including wound healing. OBJECTIVE: To elucidate the dynamic composition and potential roles of extracellular matrix in normal skin, wound healing process, and abnormal skin scarring. MATERIALS AND METHODS: Literature review was performed to identify relevant publications pertaining to the extracellular matrix deposition in normal skin and wound healing process, as well as in abnormal scars. RESULTS: A summary of the matrix components in normal skin is presented. Their primary roles in hemostasis, inflammation, proliferation, and remodeling phases of wound healing are briefly discussed. Identification of novel extracellular matrix in keloids is also provided. CONCLUSION: Abnormal scarring remains a challenging condition with unmet satisfactory treatments. Illumination of extracellular matrix composition and functions in wound healing process will allow for the development of targeted therapies in the future.
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Queloide , Cicatrização , Humanos , Pele/patologia , Queloide/patologia , Matriz Extracelular/patologia , InflamaçãoRESUMO
OBJECTIVES: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share many clinical manifestations and serological features. The aim of this study was to identify the common transcriptional profiling and composition of immune cells in peripheral blood in these autoimmune diseases (ADs). METHODS: We analysed bulk RNA-seq data for enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types from peripheral blood mononuclear cells (PBMCs) in 119 treatment-naive patients (41 RA, 38 pSS, 28 SLE and 12 polyautoimmunity) and 20 healthy controls. The single-cell RNA-seq (scRNA-seq) and flow cytometry had been performed to further define the immune cell subsets on PBMCs. RESULTS: Similar transcriptional profiles and common gene expression signatures associated with nucleosome assembly and haemostasis were identified across RA, SLE, pSS and polyautoimmunity. Distinct TF ensembles and gene regulatory network were mainly enriched in haematopoiesis. The upregulated cell-lineage-specific TFs PBX1, GATA1, TAL1 and GFI1B demonstrated a strong gene expression signature of megakaryocyte (MK) expansion. Gene expression-based cell type enrichment revealed elevated MK composition, specifically, CD41b+CD42b+ and CD41b+CD61+ MKs were expanded, further confirmed by flow cytometry in these ADs. In scRNA-seq data, MKs were defined by TFs PBX1/GATA1/TAL1 and pre-T-cell antigen receptor gene, PTCRA. Cellular heterogeneity and a distinct immune subpopulation with functional enrichment of antigen presentation were observed in MKs. CONCLUSIONS: The identification of MK expansion provided new insights into the peripheral immune cell atlas across RA, SLE, pSS and polyautoimmunity. Aberrant regulation of the MK expansion might contribute to the pathogenesis of these ADs.
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Artrite Reumatoide/sangue , Autoimunidade/genética , Lúpus Eritematoso Sistêmico/sangue , Megacariócitos/imunologia , Síndrome de Sjogren/sangue , Adulto , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Leucócitos Mononucleares , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , RNA-Seq , Síndrome de Sjogren/imunologia , Transcriptoma/imunologiaRESUMO
Fibroblasts in keloids undergo cell identity transition with altered transcriptional characteristics. However, the core transcription factors driving this cellular reprogramming remain largely unknown. Here, we report the results of transcriptional profiling from 48 keloid and 24 control dermal tissues. We identified 1187 upregulated differentially expressed genes (foldchange > 2, false discovery rate < 0.05) in keloids, which were mainly enriched in extracellular matrix organization and bone/cartilage development, with significantly increased expression of bone/cartilage-associated collagens (COL5A1, COL10A1, and COL11A1) and glycoproteins (ACAN, COMP, and SPARC). Deconvolution analysis also revealed significantly increased composition of osteoblasts in keloid dermis. A total of 92 upregulated transcription factors were screened out from differentially expressed genes and mainly enriched in transcription process and skeleton development. Additional sequencing of six keloid individuals with multiple regions and intersection further narrow the list with 10 transcription factors. Finally, AEBP1, CREB3L1, RUNX2, and ZNF469 have been identified as candidate core regulators in promoting the gaining of bone/cartilage-like characteristics in keloids. RNA-sequencing of full-skin keloids consolidated the existence of these four transcription factors. Immunohistochemistry was employed to verify the expression of AEBP1, CREB3L1, RUNX2, and ZNF469 in keloid fibroblasts. In conclusion, we bioinformatically discovered the increased expression of bone/cartilage-associated genes and candidate core transcription factors in keloids. Our findings promise to provide molecular clues to develop novel therapeutic modalities against skin fibrosis.
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Queloide , Carboxipeptidases/metabolismo , Cartilagem/metabolismo , Cartilagem/patologia , Colágeno/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Glicoproteínas/genética , Humanos , Queloide/metabolismo , RNA/metabolismo , Proteínas Repressoras/genética , Análise de Sequência de RNA , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: To investigate the causal link between early-life exposures and long-term health consequences, we established the Tianjin Birth Cohort (TJBC), a large-scale prospective cohort in northern China. METHODS: TJBC aims to enroll 10,000 families with follow-ups from pregnancy until children's six year-old. Pregnant women and their spouses were recruited through a three-tier antenatal healthcare system at early pregnancy, with follow-ups at mid-pregnancy, late pregnancy, delivery, 42 days after delivery, 6 months after delivery, and each year until 6 years old. Antenatal/neonatal examination, biological samples and questionnaires were collected. RESULTS: From August 2017 to January 2019, a total of 3,924 pregnant women have already been enrolled, and 1,697 women have given birth. We observed the prevalence of gestational diabetes mellitus as 18.1%, anemia as 20.4%, and thyroid hypofunction as 2.0%. In singleton live births, 5.6% were preterm birth (PTB), 3.7% were low birth weight, and 7.3% were macrosomia. Based on current data, we also identified maternal/paternal factors which increased the risk of PTB, including paternal age (OR 1.07; 95% CI, 1.01-1.14 for each year increase), vaginal bleeding during pregnancy (OR 2.82; 95% CI, 1.54-5.17) and maternal early-pregnancy BMI (OR 1.08; 95% CI, 1.01-1.15 for each kg/m2 increase). CONCLUSION: TJBC has the strength of collecting comprehensive maternal, paternal, and childhood information. With a diverse range of biological samples, we are also engaging with emerging new technologies for multi-omics research. The study would provide new insight into the causal link between macro/micro-environmental exposures of early life and short/long-term health consequences.
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Coorte de Nascimento , Nascimento Prematuro , Criança , China/epidemiologia , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Estudos ProspectivosRESUMO
In this paper, by approximating the non-local spatial dispersal equation by an associated reaction-diffusion system, an activator-inhibitor model with non-local dispersal is transformed into a reaction-diffusion system coupled with one ordinary differential equation. We prove that, to some extent, the non-locality-induced instability of the non-local system can be regarded as diffusion-driven instability of the reaction-diffusion system for sufficiently small perturbation. We study the structure of the spectrum of the corresponding linearized operator, and we use linear stability analysis and steady-state bifurcations to show the existence of non-constant steady states which generates non-homogeneous spatial patterns. As an example of our results, we study the bifurcation and pattern formation of a modified Klausmeier-Gray-Scott model of water-plant interaction.
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Conceitos Matemáticos , Modelos Biológicos , Difusão , PlantasRESUMO
Concurrent multiple primary extramammary Paget's disease (EMPD) is rare. Herein, we present two Chinese cases of concurrent primary EMPD involving both the genitalia and the axilla, and they also had a history of other malignancy. We also summarise the cases of multiple primary EMPD previously described in literature. Careful examination of all apocrine sweat gland-bearing sites and additional internal malignancies is recommended for patients with EMPD.
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Neoplasias Primárias Múltiplas , Doença de Paget Extramamária , Axila/patologia , Genitália/patologia , Humanos , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/patologiaRESUMO
This study aimed to encapsulate walnut peptides with different molecular weights (crude peptides, 5-10 kDa and < 5 kDa) within nanoliposomes. The peptides with molecular weight (MW) of 5-10 kDa (F2) was chosen as a representative sample to indicate the formation mechanism of nanoliposomes using scanning electron microscopy (SEM) and transmission electron microscope (TEM). The storage and simulated digestion experiment were carried out to evaluate the protective effect of nanoliposomes loading walnut peptides. Our results indicated that the amino acid composition was affected by peptide MW, and F2 exhibited the highest content of hydrophobic amino acids content. The MW of peptides also affected the distribution of the peptide of nanoliposomes, resulting in changes in particle size, ζ-potential, and encapsulation efficiency. The SEM exhibited that a high concentration of nanoliposomes might result in phospholipid fusion and larger particle diameters. The TEM showed individual nanoliposomes had spherical, smooth and full vesicle structures. The nanoliposomes could improve the stability of walnut peptides during storage. The maximum peptides retention after in vitro digestion was 61.6%, indicating a better sustained release in gastric digestion. The present study suggested that nanoliposomes can offer adequate protection to the walnut peptides during storage and digestion.
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Salinity stress is a threat to yield in many crops, including soybean (Glycine max L.). In this study, three soybean cultivars (JD19, LH3, and LD2) with different salt resistance were used to analyze salt tolerance mechanisms using physiology, transcriptomic, metabolomic, and bioinformatic methods. Physiological studies showed that salt-tolerant cultivars JD19 and LH3 had less root growth inhibition, higher antioxidant enzyme activities, lower ROS accumulation, and lower Na+ and Cl- contents than salt-susceptible cultivar LD2 under 100 mM NaCl treatment. Comparative transcriptome analysis showed that compared with LD2, salt stress increased the expression of antioxidant metabolism, stress response metabolism, glycine, serine and threonine metabolism, auxin response protein, transcription, and translation-related genes in JD19 and LH3. The comparison of metabolite profiles indicated that amino acid metabolism and the TCA cycle were important metabolic pathways of soybean in response to salt stress. In the further validation analysis of the above two pathways, it was found that compared with LD2, JD19, and LH3 had higher nitrogen absorption and assimilation rate, more amino acid accumulation, and faster TCA cycle activity under salt stress, which helped them better adapt to salt stress. Taken together, this study provides valuable information for better understanding the molecular mechanism underlying salt tolerance of soybean and also proposes new ideas and methods for cultivating stress-tolerant soybean.
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Glycine max/fisiologia , Tolerância ao Sal/fisiologia , Adaptação Fisiológica , Antioxidantes/metabolismo , Metaboloma , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/fisiologia , Estresse Salino , Glycine max/metabolismo , TranscriptomaRESUMO
OBJECTIVES: Familial aggregation of primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and co-aggregation of these autoimmune diseases (ADs) (also called familial autoimmunity) is well recognised. However, the genetic predisposition variants that explain this clustering remains poorly defined. METHODS: We used whole-exome sequencing on 31 families (9 pSS, 11 SLE, 6 RA and 5 mixed autoimmunity), followed by heterozygous filtering and cosegregation analysis of a family-focused approach to document rare variants predicted to be pathogenic by in silico analysis. Potential importance in immune-related processes, gene ontology, pathway enrichment and overlap analyses were performed to prioritise gene sets. RESULTS: A range from 1 to 50 rare possible pathogenic variants, including 39 variants in immune-related genes across SLE, RA and pSS families, were identified. Among this gene set, regulation of T cell activation (p=4.06×10-7) and T cell receptor (TCR) signalling pathway (p=1.73×10-6) were particularly concentrated, including PTPRC (CD45), LCK, LAT-SLP76 complex genes (THEMIS, LAT, ITK, TEC, TESPA1, PLCL1), DGKD, PRKD1, PAK2 and NFAT5, shared across 14 SLE, RA and pSS families. TCR-interactive genes P2RX7, LAG3, PTPN3 and LAX1 were also detected. Overlap analysis demonstrated that the antiviral immunity gene DUS2 variant cosegregated with SLE, RA and pSS phenotypes in an extended family, that variants in the TCR-pathway genes CD45, LCK and PRKD1 occurred independently in three mixed autoimmunity families, and that variants in CD36 and VWA8 occurred in both RA-pSS and SLE-pSS families. CONCLUSIONS: Our preliminary results define common genetic characteristics linked to familial pSS, SLE and RA and highlight rare genetic variations in TCR signalling pathway genes which might provide innovative molecular targets for therapeutic interventions for those three ADs.
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Artrite Reumatoide/genética , Autoimunidade/genética , Mutação em Linhagem Germinativa/imunologia , Lúpus Eritematoso Sistêmico/genética , Síndrome de Sjogren/genética , Linfócitos T/imunologia , Artrite Reumatoide/imunologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Síndrome de Sjogren/imunologiaRESUMO
OBJECTIVE: Idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) significantly increases morbidity and mortality. Lung ultrasound B-lines and Krebs von den Lungen-6 (KL-6) are identified as new sonographic and serum markers of ILD, respectively. The aim of our work was to assess the role of B-lines and KL-6 as markers of the severity of IIM-ILD. For this purpose, the correlation among B-lines score, serum KL-6 levels, high-resolution CT (HRCT) score, and pulmonary function tests were investigated in IIM-ILD patients. METHODS: Thirty-eight patients with IIM-ILD underwent chest HRCT scans, lung ultrasound and pulmonary function tests (independently performed within 1 week) examination. To assess severity and extent of ILD at HRCT, the Warrick score was used. The B-lines score denoting the extension of ILD was calculated by summing the number of B-lines on a total of 50 scanning sites. Serum KL-6 levels (U/ml) was measured by chemiluminescent enzyme immunoassay. RESULTS: A significant correlation was found between the B-lines score and serum KL-6 levels (r = 0.43, P < 0.01), and between the Warrick score and serum KL-6 levels (r = 0.45, P < 0.01). A positive correlation between B-lines score and the Warrick score (r = 0.87, P < 0.0001) was also confirmed. Both B-lines score and KL-6 levels inversely correlated to diffusion capacity for carbon monoxide (r = -0.77, P < 0.0001 and r = -0.42, P < 0.05, respectively) and total lung capacity (r = -0.73, P < 0.0001 and r = -0.36, P < 0.05, respectively). Moreover, B-lines correlated inversely with forced vital capacity (r = -0.73, P < 0.0001), forced expiratory volume in 1 s (r = -0.69, P < 0.0001). CONCLUSION: B-lines score and serum KL-6 levels correlate with HRCT findings and pulmonary function tests, supporting their use as measures of IIM-ILD severity.
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Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Mucina-1/sangue , Miosite/diagnóstico por imagem , Adulto , Biomarcadores/sangue , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/complicações , Testes de Função Respiratória , Índice de Gravidade de Doença , UltrassonografiaRESUMO
It has been commonly accepted that soybean domestication originated in East Asia. Although East Asia has the historical merit in soybean production, the USA has become the top soybean producer in the world since 1950s. Following that, Brazil and Argentina have been the major soybean producers since 1970s and 1990s, respectively. China has once been the exporter of soybean to Japan before 1990s, yet she became a net soybean importer as Japan and the Republic of Korea do. Furthermore, the soybean yield per unit area in East Asia has stagnated during the past decade. To improve soybean production and enhance food security in these East Asian countries, much investment has been made, especially in the breeding of better performing soybean germplasms. As a result, China, Japan, and the Republic of Korea have become three important centers for soybean genomic research. With new technologies, the rate and precision of the identification of important genomic loci associated with desired traits from germplasm collections or mutants have increased significantly. Genome editing on soybean is also becoming more established. The year 2019 marked a new era for crop genome editing in the commercialization of the first genome-edited plant product, which is a high-oleic-acid soybean oil. In this review, we have summarized the latest developments in soybean breeding technologies and the remarkable progress in soybean breeding-related research in China, Japan, and the Republic of Korea.
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Genoma de Planta , Genômica/métodos , Glycine max/crescimento & desenvolvimento , Glycine max/genética , Melhoramento Vegetal/normas , Plantas Geneticamente Modificadas/genética , Ásia Oriental , Fenótipo , Plantas Geneticamente Modificadas/crescimento & desenvolvimentoRESUMO
BACKGROUND: Anisodamine is used for the treatment of reperfusion injury in various organs. In this study, we investigated the effectiveness and mechanisms of action of anisodamine in promoting recovery from glycerol-induced acute kidney injury (AKI). METHODS: We compared the protective effects of atropine and anisodamine in the rat model of glycerol-induced AKI. We examined signaling pathways involved in oxidative stress, inflammation and apoptosis, as well as expression of kidney injury molecule-1 (KIM-1). Renal injury was assessed by measuring serum creatinine and urea, and by histologic analysis. Rhabdomyolysis was evaluated by measuring creatine kinase levels, and oxidative stress was assessed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels in kidney tissues. Inflammation was assessed by quantifying interleukin 6 (IL-6) and CD45 expression. Apoptosis and necrosis were evaluated by measuring caspase-3 (including cleaved caspase 3) and RIP3 levels, respectively. RESULTS: Glycerol administration resulted in a higher mean histologic damage score, as well as increases in serum creatinine, urea, creatine kinase, reactive oxygen species (ROS), MDA, IL-6, caspase-3 and KIM-1 levels. Furthermore, glycerol reduced kidney tissue SOD activity. All of these markers were significantly improved by anisodamine and atropine. However, the mean histologic damage score and levels of urea, serum creatinine, creatine kinase, ROS and IL-6 were lower in the anisodamine treatment group compared with the atropine treatment group. CONCLUSION: Pretreatment with anisodamine ameliorates renal dysfunction in the rat model of glycerol-induced rhabdomyolytic kidney injury by reducing oxidative stress, the inflammatory response and cell death.
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Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Glicerol/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Alcaloides de Solanáceas/uso terapêutico , Injúria Renal Aguda/metabolismo , Animais , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/uso terapêutico , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Alcaloides de Solanáceas/farmacologia , Solventes/toxicidade , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer. Little is known about the genetic changes that occur in esophageal cells during the development of ESCC. We performed next-generation sequence analyses of esophageal nontumor, intraepithelial neoplasia (IEN), and ESCC tissues from the same patients to track genetic changes during tumor development. METHODS: We performed whole-genome, whole-exome, or targeted sequence analyses of 227 esophageal tissue samples from 70 patients with ESCC undergoing resection at Shantou University Medical College in China from 2012 through 2015 (no patients had received chemotherapy or radiation therapy); we analyzed normal tissues, tissues with simple hyperplasia, dysplastic tissues (IEN), and ESCC tissues collected from different regions of the esophagus at the same time. We also obtained 1191 nontumor esophageal biopsy specimens from the Chaoshan region (a high-risk region for ESCC) of China (a high-risk region for ESCC) and performed immunohistochemical and histologic analyses to detect inflammation. RESULTS: IEN and ESCC tissues had similar mutations and copy number alterations, at similar frequencies; these differed from mutations detected in tissues with simple hyperplasia. IEN tissues had mutations associated with apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like-mediated mutagenesis (a DNA damage mutational signature). Genetic analyses indicated that most ESCCs were formed from early stage IEN clones. Trunk mutations (mutations shared by >10% of paired IEN and ESCC tissues) were in genes that regulate DNA repair and cell apoptosis, proliferation and adhesion. Mutations in TP53 and CDKN2A and copy number alterations in 11q (contains CCND1), 3q (contains SOX2), 2q (contains NFE2L2), and 9p (contains CDKN2A) were considered to be trunk variants; these were dominant mutations detected at high frequencies in clones of paired IEN and ESCC samples. In the esophageal biopsy samples from high-risk individuals (residing in the Chaoshan region), 68.9% had an evidence of chronic inflammation; the level of inflammation was correlated with atypical cell structures and markers of DNA damage. CONCLUSIONS: We analyzed mutations and gene copy number changes in nontumor, IEN, and ESCC samples, collected from 70 patients. IEN and ESCCs each had similar mutations and markers of genomic instability, including apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like. Genomic changes observed in precancerous lesions might be used to identify patients at risk for ESCC.
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Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Esofagite/metabolismo , Esôfago/patologia , Desaminases APOBEC/genética , Apoptose/genética , Adesão Celular/genética , Proliferação de Células/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 9/genética , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p18/genética , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Reparo do DNA/genética , Esofagite/patologia , Esôfago/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hiperplasia/genética , Fator 2 Relacionado a NF-E2/genética , Filogenia , Fatores de Transcrição SOXB1/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Self-organised patterns of vegetation are a characteristic feature of semi-deserts. In this paper, we find the internal competition reaction between plants can lead to the formation of spatial vegetation patterns, which is different from the normal formation mechanism of long-range competition and short-range facilitation. It is also found that the internal competition between biomass has an effect on the characters of banded vegetation. In particular, it is shown that the internal competition reaction leads to the decrease of the migration speed and the increase of the wavelength of the stripe patterns.
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Biomassa , Modelos Biológicos , Desenvolvimento Vegetal/fisiologia , Plantas/metabolismoRESUMO
Irregular uterine bleeding is a major side effect of long-acting progestogen-only contraceptives in women, and is the primary reason women discontinue their use. In this study, a mouse model of endometrial breakdown was established using a subcutaneous progesterone implant to understand how irregular bleeding begins. Although progestogens sustained decidualization, endometrial breakdown was still observed in this model. We, therefore, hypothesized that endometrial breakdown might involve functional progesterone withdrawal. Using co-immunoprecipitation assays, we observed the constitutive activation of nuclear factor kappa-b (NF-κB) p65 and its interaction with the progesterone receptor (PGR); moreover, transcriptional activity of the PGR was also repressed by NF-κB activity in primary mouse and human decidual stromal cells that mimic progesterone maintenance. Yet the ratio of PGR-B to PGR-A was not increased in the mouse model. In vivo comparison of endometrial breakdown induced by progesterone withdrawal to that seen during sustained progesterone exposure, in the presence of NF-κB inhibitors, revealed that NF-κB-mediated functional progesterone withdrawal is involved in endometrial breakdown in this implant model. These data prompt further studies to determine the homology of this functional progesterone withdrawal mechanism in human endometrium. Mol. Reprod. Dev. 83: 780-791, 2016 © 2016 Wiley Periodicals, Inc.