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1.
Front Public Health ; 12: 1345866, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596511

RESUMO

Background: Socioeconomic status inequality is an important variable in the emergence of urological diseases in humans. This study set out to investigate the association between the prevalence of overactive bladder (OAB) and the poverty income ratio (PIR) that served as a more influential indicator of socioeconomic status compared to education and occupation. Method: Data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2020 were used in this cross-sectional study. The association between the PIR and OAB was examined using weighted multivariate logistic regression and weighted restricted cubic splines (RCS). Additionally, interaction analysis was used for investigation to the connections between PIR and OAB in various covariate groups in order to confirm the stability of the results. Results: We observed a noteworthy inverse association between PIR and OAB after adjusting for potential confounding variables (OR = 0.87, 95% CI, 0.84-0.90, p < 0.0001). PIR was transformed into categorical variables, and the association held steady after that (1.0 < PIR <4.0 vs. PIR ≤ 1.0, OR = 0.70, 95% CI =0.63-0.77, p < 0.0001; PIR ≥ 4.0 vs. PIR ≤ 1.0, OR = 0.56, 95% CI =0.48-0.65, p < 0.0001). Additionally, RCS analysis showed that PIR and OAB had a negative nonlinear response relationship. Subgroup analyses showed that the inverse association between PIR and prevalence of OAB was stronger in obese than in nonobese individuals (P for interaction < 0.05). Conclusion: In our study, we observed a significant negative association between the PIR and the prevalence of OAB. In the future, PIR could be used as a reference standard to develop strategies to prevent and treat OAB.


Assuntos
Bexiga Urinária Hiperativa , Adulto , Humanos , Estudos Transversais , Bexiga Urinária Hiperativa/epidemiologia , Inquéritos Nutricionais , Classe Social , Renda
2.
Nucleic Acids Res ; 52(D1): D1407-D1417, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37739405

RESUMO

Advances in sequencing and imaging technologies offer a unique opportunity to unravel cell heterogeneity and develop new immunotherapy strategies for cancer research. There is an urgent need for a resource that effectively integrates a vast amount of transcriptomic profiling data to comprehensively explore cancer tissue heterogeneity and the tumor microenvironment. In this context, we developed the Single-cell and Spatially-resolved Cancer Resources (SCAR) database, a combined tumor spatial and single-cell transcriptomic platform, which is freely accessible at http://8.142.154.29/SCAR2023 or http://scaratlas.com. SCAR contains spatial transcriptomic data from 21 tumor tissues and single-cell transcriptomic data from 11 301 352 cells encompassing 395 cancer subtypes and covering a wide variety of tissues, organoids, and cell lines. This resource offers diverse functional modules to address key cancer research questions at multiple levels, including the screening of tumor cell types, metabolic features, cell communication and gene expression patterns within the tumor microenvironment. Moreover, SCAR enables the analysis of biomarker expression patterns and cell developmental trajectories. SCAR also provides a comprehensive analysis of multi-dimensional datasets based on 34 state-of-the-art omics techniques, serving as an essential tool for in-depth mining and understanding of cell heterogeneity and spatial location. The implications of this resource extend to both cancer biology research and cancer immunotherapy development.


Assuntos
Bases de Dados Factuais , Perfilação da Expressão Gênica , Neoplasias , Humanos , Diferenciação Celular , Perfilação da Expressão Gênica/métodos , Neoplasias/genética , Neoplasias/patologia , Transcriptoma , Microambiente Tumoral , Análise de Célula Única
3.
J Psychiatr Res ; 169: 49-57, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000184

RESUMO

OBJECTIVE: This study used event-related potential (ERP) and resting-state functional connectivity (rs-FC) approaches to investigate the neural mechanisms underlying the emotional attention bias in patients with chronic insomnia disorder (CID). METHODS: Twenty-five patients with CID and thirty-three demographically matched healthy controls (HCs) completed clinical questionnaires and underwent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) scans. EEG analysis examined the group differences in terms of reaction times, P3 amplitudes, event-related spectral perturbations, and inter-trial phase synchrony. Subsequently, seed-based rs-FC analysis of the amygdala nuclei (including the central-medial amygdala [CMA] and basolateral amygdala [BLA]) was performed. The relationship between P3 amplitude, rs-FC and clinical symptom severity in patients with CID was further investigated by correlation analysis. RESULTS: CID patients exhibited shorter reaction times than HCs in both standard and deviant stimuli, with the abnormalities becoming more pronounced as attention allocation increased. Compared to HCs, ERP analysis revealed increased P3 amplitude, theta wave power, and inter-trial synchrony in CID patients. The rs-FC analysis showed increased connectivity of the BLA-occipital pole, CMA-precuneus, and CMA-angular gyrus and decreased connectivity of the CMA-thalamus in CID patients. Notably, correlation analysis of the EEG and fMRI measurements showed a significant positive correlation between the P3 amplitude and the rs-FC of the CMA-PCU. CONCLUSION: This study confirms an emotional attention bias in CID, specifically in the neural mechanisms of attention processing that vary depending on the allocation of attentional resources. Abnormal connectivity in the emotion-cognition networks may constitute the neural basis of the abnormal scalp activation pattern.


Assuntos
Viés de Atenção , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Emoções , Lobo Parietal , Tonsila do Cerebelo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
4.
Nucleic Acids Res ; 52(D1): D998-D1009, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37930842

RESUMO

The nervous system is one of the most complicated and enigmatic systems within the animal kingdom. Recently, the emergence and development of spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) technologies have provided an unprecedented ability to systematically decipher the cellular heterogeneity and spatial locations of the nervous system from multiple unbiased aspects. However, efficiently integrating, presenting and analyzing massive multiomic data remains a huge challenge. Here, we manually collected and comprehensively analyzed high-quality scRNA-seq and ST data from the nervous system, covering 10 679 684 cells. In addition, multi-omic datasets from more than 900 species were included for extensive data mining from an evolutionary perspective. Furthermore, over 100 neurological diseases (e.g. Alzheimer's disease, Parkinson's disease, Down syndrome) were systematically analyzed for high-throughput screening of putative biomarkers. Differential expression patterns across developmental time points, cell types and ST spots were discerned and subsequently subjected to extensive interpretation. To provide researchers with efficient data exploration, we created a new database with interactive interfaces and integrated functions called the Spatiotemporal Cloud Atlas for Neural cells (SCAN), freely accessible at http://47.98.139.124:8799 or http://scanatlas.net. SCAN will benefit the neuroscience research community to better exploit the spatiotemporal atlas of the neural system and promote the development of diagnostic strategies for various neurological disorders.


Assuntos
Bases de Dados Genéticas , Doenças do Sistema Nervoso , Neurônios , Análise da Expressão Gênica de Célula Única , Animais , Neurônios/metabolismo , Atlas como Assunto , Doenças do Sistema Nervoso/genética
5.
Lung Cancer (Auckl) ; 14: 85-99, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025400

RESUMO

Purpose: Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent. Materials and Methods: We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis. Results: Seven distinct TAN subtypes were defined, of which, the N3 cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N3 might be a pro-tumorigenic TAN subtype. N1 and N5 clusters were considered to be well differentiated and mature neutrophils based on CXCR2 expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME. Conclusion: Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy.

6.
Nucleic Acids Res ; 51(21): 11634-11651, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37870468

RESUMO

Bromodomain-containing protein 9 (BRD9) is a specific subunit of the non-canonical SWI/SNF (ncBAF) chromatin-remodeling complex, whose function in human embryonic stem cells (hESCs) remains unclear. Here, we demonstrate that impaired BRD9 function reduces the self-renewal capacity of hESCs and alters their differentiation potential. Specifically, BRD9 depletion inhibits meso-endoderm differentiation while promoting neural ectoderm differentiation. Notably, supplementation of NODAL, TGF-ß, Activin A or WNT3A rescues the differentiation defects caused by BRD9 loss. Mechanistically, BRD9 forms a complex with BRD4, SMAD2/3, ß-CATENIN and P300, which regulates the expression of pluripotency genes and the activity of TGF-ß/Nodal/Activin and Wnt signaling pathways. This is achieved by regulating the deposition of H3K27ac on associated genes, thus maintaining and directing hESC differentiation. BRD9-mediated regulation of the TGF-ß/Activin/Nodal pathway is also demonstrated in the development of pancreatic and breast cancer cells. In summary, our study highlights the crucial role of BRD9 in the regulation of hESC self-renewal and differentiation, as well as its participation in the progression of pancreatic and breast cancers.


Assuntos
Células-Tronco Embrionárias Humanas , Neoplasias , Humanos , Fator de Crescimento Transformador beta/genética , Células-Tronco Embrionárias Humanas/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Células-Tronco Embrionárias/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Diferenciação Celular/genética , Ativinas/metabolismo , Via de Sinalização Wnt , Neoplasias/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
7.
Cell Death Dis ; 14(9): 636, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752152

RESUMO

Immunotherapy is considered a major breakthrough in the treatment of small cell lung cancer (SCLC), although its anti-tumor efficacy is limited. With a high degree of malignancy and high heterogeneity, SCLC is difficult to treat in the clinic. A new combination strategy is urgently needed to further improve the efficacy of immunotherapy in patients with SCLC. By immunofluorescence, 100 SCLC patients in a local cohort were classified into the SCLC-A (high ASCL1 expression; n = 36), SCLC-N (high NEUROD1 expression; n = 32), SCLC-P (high POU2F3 expression; n = 14), and SCLC-Y (high YAP1 expression; n = 18) subtypes. Each SCLC molecular subtype represented different prognoses, tumor microenvironment traits, and immunotherapy sensitivities. Analysis of both the local and public cohorts suggested that the SCLC-Y subtype exhibited the worst clinical outcome (p < 0.05) when compared with other subtypes. SCLC with high YAP1 expression was characterized by high PD-L1 expression, high stromal score, T-cell functional impairment, and a close relationship with immune-related pathways. YAP1 upregulated PD-L1 expression and suppressed T cell activation, thus leading to immune evasion. In in vitro experiments, blockade of YAP1 promoted cancer cell apoptosis, immune cell proliferation, T-cell activation, and cytotoxic T-cell infiltration, thus further potentiating the efficacy of immunotherapy in patients with the SCLC-Y subtype.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Antígeno B7-H1 , Terapia de Imunossupressão , Imunoterapia , Neoplasias Pulmonares/genética , Microambiente Tumoral
8.
Cell ; 186(19): 4216-4234.e33, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37714135

RESUMO

Chronic stimulation can cause T cell dysfunction and limit the efficacy of cellular immunotherapies. Improved methods are required to compare large numbers of synthetic knockin (KI) sequences to reprogram cell functions. Here, we developed modular pooled KI screening (ModPoKI), an adaptable platform for modular construction of DNA KI libraries using barcoded multicistronic adaptors. We built two ModPoKI libraries of 100 transcription factors (TFs) and 129 natural and synthetic surface receptors (SRs). Over 30 ModPoKI screens across human TCR- and CAR-T cells in diverse conditions identified a transcription factor AP4 (TFAP4) construct that enhanced fitness of chronically stimulated CAR-T cells and anti-cancer function in vitro and in vivo. ModPoKI's modularity allowed us to generate an ∼10,000-member library of TF combinations. Non-viral KI of a combined BATF-TFAP4 polycistronic construct enhanced fitness. Overexpressed BATF and TFAP4 co-occupy and regulate key gene targets to reprogram T cell function. ModPoKI facilitates the discovery of complex gene constructs to program cellular functions.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Exercício Físico , Humanos , Biblioteca Gênica , Imunoterapia , Pesquisa
9.
Nature ; 621(7977): 188-195, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37648854

RESUMO

γδ T cells are potent anticancer effectors with the potential to target tumours broadly, independent of patient-specific neoantigens or human leukocyte antigen background1-5. γδ T cells can sense conserved cell stress signals prevalent in transformed cells2,3, although the mechanisms behind the targeting of stressed target cells remain poorly characterized. Vγ9Vδ2 T cells-the most abundant subset of human γδ T cells4-recognize a protein complex containing butyrophilin 2A1 (BTN2A1) and BTN3A1 (refs. 6-8), a widely expressed cell surface protein that is activated by phosphoantigens abundantly produced by tumour cells. Here we combined genome-wide CRISPR screens in target cancer cells to identify pathways that regulate γδ T cell killing and BTN3A cell surface expression. The screens showed previously unappreciated multilayered regulation of BTN3A abundance on the cell surface and triggering of γδ T cells through transcription, post-translational modifications and membrane trafficking. In addition, diverse genetic perturbations and inhibitors disrupting metabolic pathways in the cancer cells, particularly ATP-producing processes, were found to alter BTN3A levels. This induction of both BTN3A and BTN2A1 during metabolic crises is dependent on AMP-activated protein kinase (AMPK). Finally, small-molecule activation of AMPK in a cell line model and in patient-derived tumour organoids led to increased expression of the BTN2A1-BTN3A complex and increased Vγ9Vδ2 T cell receptor-mediated killing. This AMPK-dependent mechanism of metabolic stress-induced ligand upregulation deepens our understanding of γδ T cell stress surveillance and suggests new avenues available to enhance γδ T cell anticancer activity.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Neoplasias , Receptores de Antígenos de Linfócitos T gama-delta , Linfócitos T , Humanos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular , Membrana Celular/metabolismo , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
10.
Clin Hemorheol Microcirc ; 85(1): 73-82, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37522202

RESUMO

PURPOSE: This research aims to present the findings of contrast-enhanced ultrasound (CEUS) in a series of patients with proven deep endometriosis (DE) and provide an updated literature review. MATERIALS AND METHODS: Between January 2018 and October 2022, seven patients with DE lesions had their imaging and medical records retrospectively reviewed. Clinical data, recorded images of a standardized conventional B-mode ultrasound, and Sonovue® CEUS were interpreted by two blinded, independent, experienced radiologists in consensus. The enhanced characteristics of the DE lesion on CEUS were also assessed using VueBox® software quantitatively. RESULTS: DE lesion appeared as irregular hypoechoic or heterogeneous on conventional ultrasound with dotted blood flow signal on color Doppler. Six of seven DE lesions showed heterogeneous hypo-enhancement in arterial phases. All the lesions showed a heterogeneous washout rapidly that began in the late arterial phase. In quantified analysis, the mean relative peak enhancement compared with adjacent tissue was 0.47±0.25. CONCLUSION: Our findings and literature review suggested that CEUS could be a feasible and promising non-invasive modality for diagnosing DE.


Assuntos
Meios de Contraste , Endometriose , Feminino , Humanos , Estudos Retrospectivos , Endometriose/diagnóstico por imagem , Ultrassonografia/métodos
11.
Food Chem X ; 18: 100645, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-36968310

RESUMO

Hairtail (Trichiurus lepturus) is a kind of abundant marine fish, and its by-products contain rich protein resources, which can be better exploited and utilized in the food industry. In this study, the glycoprotein of hairtail by-products (GHB) was extracted using ultrasonic-assisted salt solution extraction with hairtail by-products as the raw material. The anti-fatigue effect of GHB was explored by mouse behavior experiments (shuttle box test, open field test and load swimming test). The results showed that the active escape times of the GHB group increased compared with the blank group in the shuttle box test, and the GHB group stayed in the central area for more time in the open field test. At the same time, the exhaustive swimming time of high-dose-group mice was 122.01% longer than that of the blank control group. GHB can improve the memory learning ability and activity of mice, and exert its anti-fatigue effect by eliminating excessive free radicals, slowing the metabolism of amino acids and proteins, and increasing glycogen reserves. This study provides a theoretical basis for the function mechanism of glycoprotein of hairtail by-products and the development of supplementary material in functional foods.

12.
Transl Lung Cancer Res ; 12(2): 219-229, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36895926

RESUMO

Background: Despite immune checkpoint inhibitors (ICI) being widely used to treat patients with advanced non-small cell lung cancer (NSCLC), few studies examine the role of ICI in patients with proto-oncogene B-Raf, serine/threonine kinase (BRAF) mutations. Methods: A retrospective study was conducted for patients with BRAF-mutant NSCLC who received treatment at Shanghai Pulmonary Hospital between 2014 and 2022. Primary end point was progression-free survival (PFS). Secondary end point was best response (RECIST, version 1.1). Results: The study involved a total of 34 patients with 54 treatments recorded. The median PFS for the whole cohort was 5.8 months and the overall objective response rate (ORR) was 24%. Patients who were treated with ICI combined with chemotherapy reported a median PFS of 12.6 months and an ORR of 44%. Those who were treated with non-ICI therapy came with a median PFS of 5.3 months and an ORR of 14%. Specifically, patients had better clinical benefits with first-line ICI-combined therapy. The PFS was 18.5 months whereas that of non-ICI group was 4.1 months. The ORR was 56% in ICI-combined group and 10% in non-ICI cohort. Conclusions: The findings observed an evidential and significant susceptibility to ICIs combined therapy in patients with BRAF-mutant NSCLC, especially in first-line treatment.

13.
RSC Adv ; 13(4): 2372-2378, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36741139

RESUMO

Copper is an important interconnect material in integrated circuits (IC) due to its outstanding electrical and thermal properties. However, the development of the IC industry requires novel interconnect materials with higher conductivity. Here, uniform graphene oxide (GO) is deposited on copper by electrophoretic deposition (EPD) to obtain a GO-Cu bilayer structure at room temperature. (3-Mercaptopropyl) trimethoxysilane (MPTS) is self-assembled on the Cu anode surface, which protects the anode from oxidation during the EPD process. We find that the in situ hydrolysis of methoxy under the promotion of EPD voltage can facilitate the uniform deposition of GO and enhance the interface bonding force. In order to achieve better electrical performance, different reduction methods are conducted to reduce the structural disorder of GO. ERGO-Cu reduced by the electrochemical reduction method at -0.75 V for 1 min shows the lowest square resistance with a 16% resistance decrease compared with the GO-Cu structure and a 4.5% decrease compared with Cu substrate, due to the proper adjustment of the GO crystal structure. The room temperature fabricated ERGO-Cu bilayer structure provides a possibility for future interconnects with improved conductivity.

14.
J Immunother Cancer ; 11(2)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36854570

RESUMO

BACKGROUND: Immunotherapy for malignant tumors has made great progress, but many patients do not benefit from it. The complex intratumoral heterogeneity (ITH) hindered the in-depth exploration of immunotherapy. Conventional bulk sequencing has masked intratumor complexity, preventing a more detailed discovery of the impact of ITH on treatment efficacy. Hence, we initiated this study to explore ITH at the multi-omics spatial level and to seek prognostic biomarkers of immunotherapy efficacy considering the presence of ITH. METHODS: Using the segmentation strategy of digital spatial profiling (DSP), we obtained differential information on tumor and stromal regions at the proteomic and transcriptomic levels. Based on the consideration of ITH, signatures constructed by candidate proteins in different regions were used to predict the efficacy of immunotherapy. RESULTS: Eighteen patients treated with a bispecific antibody (bsAb)-KN046 were enrolled in this study. The tumor and stromal areas of the same samples exhibited distinct features. Signatures consisting of 11 and 18 differentially expressed DSP markers from the tumor and stromal areas, respectively, were associated with treatment response. Furthermore, the spatially resolved signature identified from the stromal areas showed greater predictive power for bsAb immunotherapy response (area under the curve=0.838). Subsequently, our stromal signature was validated in an independent cohort of patients with non-small cell lung cancer undergoing immunotherapy. CONCLUSION: We deciphered ITH at the spatial level and demonstrated for the first time that genetic information in the stromal region can better predict the efficacy of bsAb treatment. TRIAL REGISTRATION NUMBER: NCT03838848.


Assuntos
Anticorpos Biespecíficos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ecossistema , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Multiômica , Proteômica
15.
Nucleic Acids Res ; 51(D1): D1150-D1159, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36305818

RESUMO

It is a challenge to efficiently integrate and present the tremendous amounts of single-cell data generated from multiple tissues of various species. Here, we create a new database named SPEED for single-cell pan-species atlas in the light of ecology and evolution for development and diseases (freely accessible at http://8.142.154.29 or http://speedatlas.net). SPEED is an online platform with 4 data modules, 7 function modules and 2 display modules. The 'Pan' module is applied for the interactive analysis of single cell sequencing datasets from 127 species, and the 'Evo', 'Devo', and 'Diz' modules provide comprehensive analysis of single-cell atlases on 18 evolution datasets, 28 development datasets, and 85 disease datasets. The 'C2C', 'G2G' and 'S2S' modules explore intercellular communications, genetic regulatory networks, and cross-species molecular evolution. The 'sSearch', 'sMarker', 'sUp', and 'sDown' modules allow users to retrieve specific data information, obtain common marker genes for cell types, freely upload, and download single-cell datasets, respectively. Two display modules ('HOME' and 'HELP') offer easier access to the SPEED database with informative statistics and detailed guidelines. All in all, SPEED is an integrated platform for single-cell RNA sequencing (scRNA-seq) and single-cell whole-genome sequencing (scWGS) datasets to assist the deep-mining and understanding of heterogeneity among cells, tissues, and species at multi-levels, angles, and orientations, as well as provide new insights into molecular mechanisms of biological development and pathogenesis.


Assuntos
Bases de Dados Factuais , Análise de Célula Única , Humanos , Animais , Evolução Biológica , Plantas/genética , Ecologia
16.
Front Genet ; 13: 1002699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386809

RESUMO

Cancer immune function and tumor microenvironment are governed by long noncoding RNAs (lncRNAs). Nevertheless, it has yet to be established whether lncRNAs play a role in tumor-associated neutrophils (TANs). Here, a computing framework based on machine learning was used to identify neutrophil-specific lncRNA with prognostic significance in squamous cell carcinoma and lung adenocarcinoma using univariate Cox regression to comprehensively analyze immune, lncRNA, and clinical characteristics. The risk score was determined using LASSO Cox regression analysis. Meanwhile, we named this risk score as "TANlncSig." TANlncSig was able to distinguish between better and worse survival outcomes in various patient datasets independently of other clinical variables. Functional assessment of TANlncSig showed it is a marker of myeloid cell infiltration into tumor infiltration and myeloid cells directly or indirectly inhibit the anti-tumor immune response by secreting cytokines, expressing immunosuppressive receptors, and altering metabolic processes. Our findings highlighted the value of TANlncSig in TME as a marker of immune cell infiltration and showed the values of lncRNAs as indicators of immunotherapy.

17.
Cancer Commun (Lond) ; 42(10): 937-970, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075878

RESUMO

In China, lung cancer is a primary cancer type with high incidence and mortality. Risk factors for lung cancer include tobacco use, family history, radiation exposure, and the presence of chronic lung diseases. Most early-stage non-small cell lung cancer (NSCLC) patients miss the optimal timing for treatment due to the lack of clinical presentations. Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China. The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC, thus prolonging survival in patients with positive drivers. In the exploration of immune escape mechanisms, programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China. In the Chinese Society of Clinical Oncology's guidelines for NSCLC, maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy. Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC. In this review, we summarized recent advances in NSCLC in China in terms of epidemiology, biology, molecular pathology, pathogenesis, screening, diagnosis, targeted therapy, and immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Receptor de Morte Celular Programada 1/metabolismo
18.
Small ; 18(28): e2201334, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35723177

RESUMO

In vivo simultaneous visualization of multiple biomarkers is critical to accurately diagnose disease and decipher fundamental processes at a certain pathological evolution, which however is rarely exploited. Herein, a multimodal activatable imaging probe (P-125 I) is reported with activatable fluoro-photoacoustic and radioactive signal for in vivo imaging of biomarkers (i.e., hepsin and prostate-specific membrane antigen (PSMA)) associated with prostate cancer diagnosis and prognosis. P-125 I contains a near-infrared (NIR) dye that is caged with a hepsin-cleavable peptide sequence and linked with a radiolabeled PSMA-targeted ligand (PSMAL). After systemic administration, P-125 I actively targets the tumor site via specific recognition between PSMA and PSMAL moiety and in-situ generates of activated fluoro-photoacoustic signal after reacting with hepsin to release the free dye (uncaged state). P-125 I achieves precisely early detection of prostate cancer and renal clearance to alleviate toxicity issues. In addition, the accumulated radioactive and activated photoacoustic signal of probe correlates well with the respective expression level of PSMA and hepsin, which provides valuable foreseeability for cancer progression and prognosis. Thus, this study presents a multimodal activatable probe for early detection and in-depth deciphering of prostate cancer.


Assuntos
Sondas Moleculares , Neoplasias da Próstata , Biomarcadores Tumorais , Diagnóstico por Imagem/métodos , Corantes Fluorescentes , Humanos , Rim , Masculino , Imagem Molecular/métodos , Neoplasias da Próstata/diagnóstico por imagem
19.
Materials (Basel) ; 15(5)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35269195

RESUMO

SiO2-TiO2-C aerogel photocatalysts with different carbon loadings were synthesized by using sol-gel chemistry. The anatase crystal and nonmetal carbon dopant were introduced during the sol preparation and formed by hydrothermal treatment, which can simultaneously enhance the adsorption ability and visible light photo-activity. A high surface area (759 g cm-3) SiO2-TiO2-C aerogel composite can remove up to 80% tetracycline hydrochloride within 180 min under visible light. The characterization of the gel structures shows that the homogeneous dispersion of O, Si, Ti and C in the skeleton, indicating that hydrothermal synthesis could provide a very feasible way for the preparation of composite materials. n(C):n(Ti) molar ratio of 3.5 gives the best catalytic performance of the hybrid aerogel, and the cyclic test still confirms over 60% degradation activity after seven use cycles. All catalysis reaction followed the pseudo-first-order rate reaction with high correlation coefficient. The electrons and holes in the compound could be effectively restrained with doping proper amount of C, and ESR results indicate that the oxidation process was dominated by the hydroxyl radical (•OH) and superoxide radical (•O2-) generated in the system.

20.
Transl Cancer Res ; 11(2): 339-357, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35281414

RESUMO

Background: The interaction between cancer cells and stromal cells has a significant contribution in tumorigenesis and tumor development, and plays an anti-tumor immune effect under the regulation of drug resistance-related genes, which affects the outcome of patients. Coiled-coil domain-containing protein 73 (CCDC73), DLG associated protein 1 (DLGAP1), dermatan sulfate epimerase like (DSEL), estrogen receptor 1 (ESR1), and SEC14-like 5 (SEC14L5) were identified as drug resistance-related genes in lung cancer. However, these genes have no clear value in lung cancer in terms of expression and prognosis. Methods: ONCOMINE, GEPIA, UALCAN, cBioPortal, GeneMANIA, STRING, and TIMER were utilized in this study. Results: The transcriptional expression level of DLGAP1 was remarkably decreased in lung cancer tissues, while the transcriptional level of SEC14L5 was significantly increased. The pathological stage of lung adenocarcinoma (LUAD) was tightly correlated with the expression of SEC14L5. The lung cancer patients with high transcription level of CCDC73 gene tended to have a good prognosis. The function of drug resistance-related genes is mainly related to RNA polymerization. Our results showed that infiltration of six types of immune cells (dendritic cells, macrophages, neutrophils, B cells, CD4+ T cells, and CD8+ T cells) significantly correlated with the expression of these drug resistance-related genes. Conclusions: Novel screening for immunotherapy targets and prognostic biomarkers in lung cancer may draw inspiration from our results.

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