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The application of metal batteries is seriously affected by active ions transport and deposition stability during operation. This article takes water-based Zn metal electrodes as an example to analyze the factors that affect ion distribution and the impact of ion distribution on electrodeposition morphology through electrochemical model simulation calculation, in situ observation and electrochemical experiment: 1) high concentration will reduce the concentration polarization and the overpotential; 2) The passage of active ions through channels are facilitated by small anion (Cl-) rather than bigger one (SO4 2-), which means small deposition overpotential; 3) The transportability-reaction properties of cations (Zn2+, Li+, Na+ and H+) depends on their concentration, solvent coordination structure, and the energy changes during redox reactions. Based on the diffusion and reaction properties, a Li+ coupled Zn2+ electrolyte is designed to achieve the rapid transportation of doped ions to cover uneven growth sites and maintain a stable interface for the steady deposition of active Zn2+, guiding the interface design for high stability metal batteries in addition to the traditional addition of organic solvents.
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The shuttle effect limits the practical application of lithium-sulfur (Li-S) batteries with high specific capacity and cheap price. Herein, a three-dimensional carbon substrate containing Ni3 S2 nanoparticles is created to modify the separator. The in situ optical visualization battery proves that the material can realize the rapid conversion of Li2 S6 . Moreover, the impact of lithium-ion diffusion on the reactions in the cell is investigated, and the mechanism of Ni3 S2 @C in the cell is proposed based on the "adsorption-diffusion-conversion" mechanism. The "adsorption-diffusion-conversion" process of polysulfide is carried out on the surface of the composite separator, showing positive effects on the inhibition of polysulfide shuttle and the promotion of conversion. The separator is modified to improve sulfur utilization and reduce dead sulfur accumulation through a strategy of chemical immobilization and physical blocking. This helps to bridge the existing gaps of Li-S batteries.
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BACKGROUND: Bladder cancer is one of the most common malignant tumors of the urinary system and is associated with a poor prognosis once invasion and distant metastases occur. Epithelial-mesenchymal transition (EMT) drives metastasis and invasion in bladder cancer. Transforming growth factor ß1 (TGF-ß1) and stromal fibroblasts, especially cancer-associated fibroblasts (CAFs), are positive regulators of EMT in bladder cancer. However, it remains unclear how TGF-ß1 mediates crosstalk between bladder cancer cells and CAFs and how it induces stromal fibroblast-mediated EMT in bladder cancer. We aimed to investigate the mechanism of TGF-ß1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells. METHODS: Primary CAFs with high expression of fibroblast activation protein (FAP) were isolated from bladder cancer tissue samples. Subsequently, different conditioned media were used to stimulate the bladder cancer cell line T24 in a co-culture system. Gene set enrichment analysis, a human cytokine antibody array, and cytological assays were performed to investigate the mechanism of TGF-ß1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells. RESULTS: Among the TGF-ß family, TGF-ß1 was the most highly expressed factor in bladder cancer tissue and primary stromal fibroblast supernatant. In the tumor microenvironment, TGF-ß1 was mainly derived from stromal fibroblasts, especially CAFs. In stimulated bladder cells, stromal fibroblast-derived TGF-ß1 promoted bladder cancer cell migration, invasion, and EMT. Furthermore, TGF-ß1 promoted the activation of stromal fibroblasts, inducing CAF-like features, by upregulating FAP in primary normal fibroblasts and a normal fibroblast cell line. Stromal fibroblast-mediated EMT was induced in bladder cancer cells by TGF-ß1/FAP. Versican (VCAN), a downstream molecule of FAP, plays an essential role in TGF-ß1/FAP axis-induced EMT in bladder cancer cells. VCAN may also function through the PI3K/AKT1 signaling pathway. CONCLUSIONS: TGF-ß1 is a critical mediator of crosstalk between stromal fibroblasts and bladder cancer cells. We revealed a new mechanism whereby TGF-ß1 dominated stromal fibroblast-mediated EMT of bladder cancer cells via the FAP/VCAN axis and identified potential biomarkers (FAP, VCAN, N-cadherin, and Vimentin) of bladder cancer. These results enhance our understanding of bladder cancer invasion and metastasis and provide potential strategies for diagnosis, treatment, and prognosis.
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Fator de Crescimento Transformador beta1 , Neoplasias da Bexiga Urinária , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Fibroblastos/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Versicanas/metabolismoRESUMO
Heavy metals (HMs) from iron/steel smelting activities pose notable risks to human health, especially to those living around industrial facilities of North China Plain, the base of China's steel production. In this study, 78 outdoor windowsill dust samples were collected around a large-scale iron/steel smelter with more than 65 years of production history in the western North China Plain. Nine HMs were analysed to comprehensively assess the health risks by integrating Monte Carlo simulation, oral bioaccessibility, and source apportionment. Results showed serious pollution with Cd, Pb, and Zn based on their geo-accumulation index values and concentrations. Four potential sources including industrial sources (49.85%), traffic sources (21.78%), natural sources (20.58%), and coal combustion (7.79%) were quantitatively identified by multivariate statistical analysis. The oral bioaccessibilities of HMs determined by the physiologically based extraction test ranged from 0.02% to 65.16%. Zn, Mn, Cd, and Pb had higher bioaccessibilities than other HMs. After incorporating oral bioavailability adjustments, noncarcinogenic and carcinogenic risks were significantly reduced, especially for adults. The mean hazard index (HI) for children and adults was below the safety threshold (1.0), whereas the mean of the total carcinogenic risk (TCR) based on HM bioaccessibilities in the gastric phase remained above the acceptable level (1.0E-06) (children: 5.20E-06; adults: 1.16E-06). Traffic sources warranted increased concern as it substantially increased TCR. Cd was identified as the priority pollution in iron/steel smelting areas. Assessing source-oriented health risks associated with oral ingestion exposure can guide the management and control of HM contamination within iron/steel smelting-affected areas.
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The purpose of this study is to explore the evolution of brain edema after minimally invasive surgery in deep spontaneous cerebral hemorrhage (DSICH) treatment and to analyze the differences in edema after different surgical methods. The clinical data of 105 patients with DSICH treated at Renmin Hospital of Wuhan University from January 2020 to June 2022 were analyzed retrospectively. Among them, 54 patients were treated with minimally invasive puncture and drainage surgery (MIPDS group), and 51 were treated with neuroendoscopic surgery (NES group). Continuous computed tomography images of patients in the hospital and 3D Slicer software were used to quantitatively calculate the edematous area to explore the changes in perihematomal edema volume in the two groups after the operation. The peak volume of postoperative edema (37.36±10.51 mL) in the MIPDS group was more extensive than that in the NES group, and its net increase in edema volume was 16.86±10.01 mL more than that in the NES group. The relative edema index (0.86±0.26) was lower in the NES group than in the MIPDS group (P < 0.05). The peak of postoperative edema in the MIPDS group was at 6-8 days after the operation, and that in the NES group was most often at 3-5 days after the operation. There are differences in perihematomal edema of DSICH treated by different minimally invasive methods. Compared with the MIPDS group, the NES group showed earlier peak of cerebral edema and lower degree of cerebral edema. The absolute regression volume of edema in the MIDPs group was greater than that in the NEs group, but there was no difference in the regression rate of edema between the two groups.
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Edema Encefálico , Humanos , Edema Encefálico/etiologia , Neurocirurgiões , Estudos Retrospectivos , Edema/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Hemorragia CerebralRESUMO
OBJECTIVE: To evaluate the effectiveness and safety of microvascular decompression (MVD) using a fully transcranial neuroendoscopic approach. METHODS: Thirty-one patients who underwent MVD using a fully transcranial neuroendoscopic approach in our department between May 2016 and September 2019 were retrospectively reviewed. RESULTS: All patients successfully underwent MVD, and immediate pain relief was achieved in all 17 cases of trigeminal neuralgia (TGH) and 3 cases of glossopharyngeal neuralgia (GPN). Hemifacial spasm (HFS) was completely resolved in all 11 patients. No mortality or permanent complication was seen. CONCLUSIONS: The endoscope is a useful tool for confirming vascular conflict identified by the microscope and is helpful in detecting the vessel responsible for neuralgia without retracting the brain and nerves. MVD using a fully transcranial neuroendoscopic approach is an effective and safe alternative to endoscopic-assisted MVD and traditional MVD.
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Doenças do Nervo Glossofaríngeo , Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Neuroendoscopia , Neuralgia do Trigêmeo , Humanos , Estudos Retrospectivos , Espasmo Hemifacial/cirurgia , Neuralgia do Trigêmeo/cirurgia , Resultado do TratamentoRESUMO
For the first time, an eco-friendly and sustainable tandem [5C + 1C] cycloaromatization of α-alkenoyl ketene dithioacetals and nitroethane in water for the efficient synthesis of ortho-acylphenols was reported. In refluxing water, a range of α-alkenoyl ketene dithioacetals and nitroethane smoothly underwent tandem Michael addition/cyclization/aromatization reactions in the presence of 2.0 equivalents of DBU to provide various ortho-acylphenols in excellent yields. The green approach to ortho-acylphenols not only avoided the use of harmful organic solvents, which could result in serious environmental and safety issues, but also exhibited fascinating features such as good substrate scope, excellent yields, simple purification for desired products, ease of scale-up, and reusable aqueous medium.
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We report the use of a marking pen with metallic ink to assist body surface location in reflectance confocal microscopy (RCM). Not only is the marker waterproof, but the metallic ink appears brighter under RCM, thus assisting in identifying location.
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Tinta , Neoplasias Cutâneas , Humanos , Microscopia Confocal , Pele/diagnóstico por imagem , Pele/patologia , Neoplasias Cutâneas/patologiaRESUMO
Because sterilization of imaging probes is commonly impossible, the issue of probe contamination and cross-infection becomes an issue when using dermoscopy in the clinic. We describe a simple modification to reduce cross-infection during dermoscopy.
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Dermoscopia , Neoplasias Cutâneas , Dermoscopia/métodos , HumanosRESUMO
Andrographolide(ADE) has been demonstrated to inhibit tumor growth through direct cytotoxicity on tumor cells. However, its potential activity on tumor microenvironment (TME) remains unclear. Tumor-associated macrophages (TAMs), composed mainly of M2 macrophages, are the key cells that create an immunosuppressive TME by secretion of cytokines, thus enhancing tumor progression. Re-polarized subpopulations of macrophages may represent vital new therapeutic alternatives. Our previous studies showed that ADE possessed anti-metastasis and anoikis-sensitization effects. Here, we demonstrated that ADE significantly suppressed M2-like polarization and enhanced M1-like polarization of macrophages. Moreover, ADE inhibited the migration of M2 and tube formation in HUVECs under M2 stimulation. In vivo studies showed that ADE restrained the growth of MDA-MB-231 and HCC1806 human breast tumor xenografts and 4T-1 mammary gland tumors through TAMs. Wnt5a/ß-catenin pathway and MMPs were particularly associated with ADE's regulatory mechanisms to M2 according to RNA-seq and bioinformatics analysis. Moreoverï¼ western blot also verified the expressions of these proteins were declined with ADE exposure. Among the cytokines released by M2, PDGF-AA and CCL2 were reduced. Our current findings for the first time elucidated that ADE could modulate macrophage polarization and function through Wnt5a signaling pathway, thereby playing its role in inhibition of triple-negative breast cancer.
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Neoplasias da Mama , Diterpenos , Via de Sinalização Wnt , Feminino , Humanos , beta Catenina , Neoplasias da Mama/tratamento farmacológico , Microambiente Tumoral , Macrófagos Associados a Tumor , Diterpenos/farmacologia , Células Endoteliais da Veia Umbilical Humana , Células MDA-MB-231 , AnimaisRESUMO
Adoptive immunotherapy is a new potential method of tumour therapy, among which anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T cell), is a typical treatment agent for haematological malignancies. Previous clinical trials showed that the quality and phenotype of CAR-T cells expanded ex vivo would seriously affect the tumour treatment efficacy. Although magnetic beads are currently widely used to expand CAR-T cells, the optimal expansion steps and methods have not been completely established. In this study, the differences between CAR-T cells expanded with anti-CD3/CD28 mAb-coated beads and those expanded with cell-based aAPCs expressing CD19/CD64/CD86/CD137L/mIL-15 counter-receptors were compared. The results showed that the number of CD19-specific CAR-T cells with a 4-1BB and CD28 co-stimulatory domain was much greater with stimulation by aAPCs than that with beads. In addition, the expression of memory marker CD45RO was higher, whereas expression of exhausted molecules was lower in CAR-T cells expanded with aAPCs comparing with the beads. Both CAR-T cells showed significant targeted tumoricidal effects. The CAR-T cells stimulated with aAPCs secreted apoptosis-related cytokines. Moreover, they also possessed marked anti-tumour effect on NAMALWA xenograft mouse model. The present findings provided evidence on the safety and advantage of two expansion methods for CAR-T cells genetically modified by piggyBac transposon system.
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Antígenos CD19/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Animais , Western Blotting , Antígenos CD8/metabolismo , Linhagem Celular Tumoral , Eletroporação , Citometria de Fluxo , Humanos , Imunoterapia Adotiva/métodos , Células K562 , Masculino , Camundongos , Camundongos SCID , Plasmídeos/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
KEY MESSAGE: Combining GWAS, QTL-seq and transcriptome sequencing detected basal defense-related genes showing gDNA sequence variation and expression difference in diverse cotton lines, which might be the molecular mechanisms of VW resistance in G. hirsutum. Verticillium wilt (VW), which is caused by the soil-borne fungus Verticillium dahliae, is a major disease in cotton (Gossypim hirsutum) worldwide. To facilitate the understanding of the genetic basis for VW resistance in cotton, a genome-wide association study (GWAS), QTL-seq and transcriptome sequencing were performed. The GWAS of VW resistance in a panel of 120 core elite cotton accessions using the Cotton 63K Illumina Infinium SNP array identified 5 QTL from 18 significant SNPs meeting the 5% false discovery rate threshold on 5 chromosomes. All QTL identified through GWAS were found to be overlapped with previously reported QTL. By combining GWAS, QTL-seq and transcriptome sequencing, we identified eight candidate genes showing both gDNA sequence variation and expression difference between resistant and susceptible lines, most related to transcription factors (TFs), flavonoid biosynthesis and those involving in the plant basal defense and broad-spectrum disease resistance. Ten KASP markers were successfully validated in diverse cotton lines and could be deployed in marker-assisted breeding to enhance VW resistance. These results supported our inference that the gDNA sequence variation or expression difference of those genes involving in the basal defense in diverse cotton lines might be the molecular mechanisms of VW resistance in G. hirsutum.
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Resistência à Doença/genética , Genes de Plantas , Marcadores Genéticos , Gossypium/genética , Locos de Características Quantitativas , Transcriptoma , Verticillium/fisiologia , Mapeamento Cromossômico , Estudo de Associação Genômica Ampla , Gossypium/crescimento & desenvolvimento , Gossypium/microbiologia , Melhoramento Vegetal , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The enhanced release of inflammatory cytokines mediated by high mobility group box1 (HMGB1) leads to pain sensation, and has been implicated in the etiology of inflammatory pain. Paeonol (PAE), a major active phenolic component in Cortex Moutan, provides neuroprotective efficacy via exerting anti-inflammatory effect. However, the role and mechanism of PAE in inflammatory pain remain to be fully clarified. In this study, we showed that PAE treatment significantly ameliorated mechanical and thermal hyperalgesia of mice induced by complete Freund's adjuvant (CFA). The analgesic effect of PAE administration was associated with suppressing the enhanced expression of HMGB1 as well as the downstream signaling molecules including toll-like receptor 4 (TLR4), the nuclear NF-κB p65, TNF-α and IL-1ß after CFA insult in the anterior cingulate cortex (ACC), a key brain region responsible for pain processing. Furthermore, inhibition of HMGB1 activity by glycyrrhizin (GLY), an HMGB1 inhibitor, alleviated CFA-induced pain and also facilitated PAE-mediated analgesic effect in mice along with the decreased expression of TLR4, NF-κB p65, TNF-α and IL-1ß upon CFA injury. Collectively, we showed PAE exerted analgesic effect through inhibiting the HMGB1/TLR4/NF-κB p65 pathway and subsequent generation of cytokines TNF-α and IL-1ß in the ACC.
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Acetofenonas/farmacologia , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Acetofenonas/uso terapêutico , Animais , Proteína HMGB1/metabolismo , Hiperalgesia/metabolismo , Inflamação/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
Current research on the reconstruction of hyperspectral images from RGB images using deep learning mainly focuses on learning complex mappings through deeper and wider convolutional neural networks (CNNs). However, the reconstruction accuracy of the hyperspectral image is not high and among other issues the model for generating these images takes up too much storage space. In this study, we propose the double ghost convolution attention mechanism network (DGCAMN) framework for the reconstruction of a single RGB image to improve the accuracy of spectral reconstruction and reduce the storage occupied by the model. The proposed DGCAMN consists of a double ghost residual attention block (DGRAB) module and optimal nonlocal block (ONB). DGRAB module uses GhostNet and PRELU activation functions to reduce the calculation parameters of the data and reduce the storage size of the generative model. At the same time, the proposed double output feature Convolutional Block Attention Module (DOFCBAM) is used to capture the texture details on the feature map to maximize the content of the reconstructed hyperspectral image. In the proposed ONB, the Argmax activation function is used to obtain the region with the most abundant feature information and maximize the most useful feature parameters. This helps to improve the accuracy of spectral reconstruction. These contributions enable the DGCAMN framework to achieve the highest spectral accuracy with minimal storage consumption. The proposed method has been applied to the NTIRE 2020 dataset. Experimental results show that the proposed DGCAMN method outperforms the spectral accuracy reconstructed by advanced deep learning methods and greatly reduces storage consumption.
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KEY MESSAGE: An allene oxide cyclase gene which is involved in defense against biotic and abiotic stresses was cloned and characterized in sugarcane. Allene oxide cyclase (AOC), a key enzyme in jasmonate acid (JA) biosynthesis, affects the stereoisomerism and biological activity of JA molecules, and plays an important role in plant stress resistance. In this study, four SsAOC alleles (SsAOC1-SsAOC4), which shared similar gene structure and were located on Chr1A, Chr1B, Chr1C, and Chr1D, respectively, were mined from sugarcane wild species Saccharum spontaneum, and a homologous gene ScAOC1 (GenBank Accession Number: MK674849) was cloned from sugarcane hybrid variety Yacheng05-179 inoculated with Sporisorium scitamineum for 48 h. ScAOC1 and SsAOC1-SsAOC4 were alkaline, unstable, hydrophilic, and non-secretory proteins, which possess the same set of conserved motifs and were clustered into one group in the phylogenetic analysis. ScAOC1 was expressed in all sugarcane tissues, but with different levels. After infection by S. scitamineum, the transcripts of ScAOC1 were increased significantly both in the smut-susceptible (ROC22) and resistant (Yacheng05-179) varieties, but its transcripts were more accumulated and lasted for a longer period in the smut-resistant variety than in the smut-susceptible one. ScAOC1 was down-regulated under MeJA and NaCl treatments, but up-regulated under SA, ABA, PEG, and cold stresses. Transiently overexpressing ScAOC1 gene into Nicotiana benthamiana leaves regulated the responses of N. benthamiana to two pathogens Ralstonia solanacearum and Fusarium solani var. coeruleum. Furthermore, prokaryotic expression analysis showed overexpression of ScAOC1 in Escherichia coli BL21 could enhance its tolerance to NaCl, mannitol, and cold stimuli. These results indicated that ScAOC1 may play an active role in response to biotic and abiotic stresses in sugarcane.
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Oxirredutases Intramoleculares/genética , Proteínas de Plantas/genética , Saccharum/fisiologia , Estresse Fisiológico/fisiologia , Mapeamento Cromossômico , Resposta ao Choque Frio , Escherichia coli/genética , Evolução Molecular , Fusarium/patogenicidade , Regulação da Expressão Gênica de Plantas , Oxirredutases Intramoleculares/química , Oxirredutases Intramoleculares/metabolismo , Manitol/farmacologia , Família Multigênica , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Ralstonia solanacearum/patogenicidade , Sequências Reguladoras de Ácido Nucleico , Saccharum/efeitos dos fármacos , Saccharum/genética , Cloreto de Sódio/farmacologia , Nicotiana/genética , Nicotiana/microbiologiaRESUMO
Erythema papulatum centrifugum (EPC), also known as erythema papulosa semicircularis recidivans (EPSR), is distinct from eczema and other well-described figurate erythemas characterised by annular erythematous lesions. We report 7 cases of EPC and propose new diagnostic criteria including the following: (i) EPC is characterised by single or multiple recurrent expanding annular or semi annular erythema with central regression, surrounded by tiny red papules; (ii) the lesions regularly relapse and resolve; (iii) the histopathologic feature shows superficial perivascular inflammation with or without mild inflammation around sweat glands in the mid dermis and (iv) patients lack other associated cutaneous or internal abnormalities.
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Eritema/etiologia , Eritema/patologia , Dermatopatias Genéticas/etiologia , Dermatopatias Genéticas/patologia , Adulto , Eritema/terapia , Feminino , Humanos , Dermatopatias Genéticas/terapiaRESUMO
The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi-omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome-targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host-microbiome interactions. Combining these functional -omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi-omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.
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Bactérias/metabolismo , Microbioma Gastrointestinal , Perfilação da Expressão Gênica/métodos , Metabolômica/métodos , Microbiota , Proteômica/métodos , Bactérias/classificação , Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/microbiologia , Obesidade/genética , Obesidade/metabolismo , Obesidade/microbiologiaRESUMO
Several clinical immunotherapy trials with cytokine-induced killer (CIK) cells have been reported. However, molecular evidence of cell expansion, acquisition of tumor cytotoxicity, and safety of CIK cells is required before putting them to clinical use. Here, we performed dynamic transcriptomic analyses of CIKs generated from primary peripheral blood mononuclear cells exposed to interferon-γ, OKT3, and interleukin-2. CIK mRNAs were extracted and sequenced at days 0, 1, 7, and 14 and subjected to bioinformatics analyses. Using weighted correlation network analysis (WGCNA), we identified two major gene modules that mediate immune cell activation and mitosis. We found that activation and cytotoxicity of CIK cells likely rely on cluster of differentiation 8 (CD8) and its protein partner LCK proto-oncogene, Src family tyrosine kinase (LCK). A time-course series analysis revealed that CIK cells have relatively low immunogenicity because of decreased expression of some self-antigens. Importantly, we identified several crucial activating receptors and auxiliary adhesion receptors expressed on CIK cells that may function as tumor sensors. Interestingly, cytotoxicity-associated genes, including those encoding PRF1, GZMB, FASL, and several cytokines, were up-regulated in mature CIK cells. Most immune-checkpoint molecules and inflammatory tumor-promoting factors were down-regulated in the CIK cells, suggesting efficacy and safety in future clinical trials. Notably, insulin-like growth factor 1 (IGF-1) was highly expressed in CIK cells and may promote cytotoxicity, although it also could facilitate tumorigenesis. The transcriptomic atlas of CIK cells presented here may inform efforts to improve CIK-associated tumor cytotoxicity and safety in clinical trials.
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Células Matadoras Induzidas por Citocinas/metabolismo , Perfilação da Expressão Gênica , Ciclo Celular/genética , Ciclo Celular/imunologia , Linhagem Celular , Células Matadoras Induzidas por Citocinas/citologia , Células Matadoras Induzidas por Citocinas/imunologia , Humanos , Imunoterapia/efeitos adversos , Família Multigênica/genética , Família Multigênica/imunologia , Proto-Oncogene Mas , Segurança , Análise de Sequência de RNARESUMO
BACKGROUND The NKX2 gene family is made up of core transcription factors that are involved in the morphogenesis of the vertebrate heart. NKx2-5 plays a pivotal role in mouse cardiogenesis, and mutations in NKx2-5 result in an abnormal structure and function of the heart, including atrial septal defect and cardiac electrophysiological abnormalities. MATERIAL AND METHODS To investigate the genetic variation of NKX2-5 in Chinese patients with sporadic atrial septal defect, we sequenced the full length of the NKX2-5 gene in the participants of the study. Four hundred thirty-nine patients and 567 healthy unrelated individuals were recruited. Genomic DNA was extracted from the peripheral blood leukocytes of the participants. DNA samples from the participants were amplified by multiplex PCR and sequenced on an Illumina HiSeq platform. Variations were detected by comparison with a standard reference genome and annotation with a variant effect predictor. RESULTS Thirty variations were detected in Chinese patients with sporadic atrial septal defect, and 6 single nucleotide polymorphisms (SNPs) had a frequency greater than 1%. Among the 30 variations, the SNPs rs2277923 and rs3729753 were extremely prominent, with a high frequency and odds ratio in patients. CONCLUSIONS Single nucleotide variations are the prominent genetic variations of NKX2-5 in Chinese patients with sporadic atrial septal defect. The SNPs rs2277923 and rs3729753 are prominent single nucleotide variations (SNVs) in Chinese patients with sporadic atrial septal defect.