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BACKGROUND: Improving immunotherapy efficacy for EGFR-negative lung adenocarcinoma (LUAD) patients remains a critical challenge, and the therapeutic effect of immunotherapy is largely determined by the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the top-ranked immune infiltrating cells in the TME, and M2-TAMs exert potent roles in tumor promotion and chemotherapy resistance. An M2-TAM-based prognostic signature was constructed by integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to reveal the immune landscape and select drugs in EGFR-negative LUAD. METHODS: M2-TAM-based biomarkers were obtained from the intersection of bulk RNA-seq data and scRNA-seq data. After consensus clustering of EGFR-negative LUAD into different clusters based on M2-TAM-based genes, we compared the prognosis, clinical features, estimate scores, immune infiltration, and checkpoint genes among the clusters. Next, we combined univariate Cox and LASSO regression analyses to establish an M2-TAM-based prognostic signature. RESULTS: CCL20, HLA-DMA, HLA-DRB5, KLF4, and TMSB4X were verified as prognostic M2-like TAM-related genes by univariate Cox and LASSO regression analyses. IPS and TMB analyses revealed that the high-risk group responded better to common immunotherapy. CONCLUSION: The study shows the potential of the M2-like TAM-related gene signature in EGFR-negative LUAD, explores the immune landscape based on M2-like TAM-related genes, and predict immunotherapy response of patients with EGFR-negative LUAD, providing a new insight for individualized treatment.
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Adenocarcinoma de Pulmão , Receptores ErbB , Neoplasias Pulmonares , Macrófagos Associados a Tumor , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Receptores ErbB/genética , Prognóstico , Microambiente Tumoral/imunologia , Masculino , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fator 4 Semelhante a Kruppel , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Previous studies have shown that necroptosis-related long noncoding RNA (lncRNA) risk models can be used to predict prognosis and immune infiltration in patients with esophageal cancer. However, further analysis of the regulatory mechanisms of necroptosis-related lncRNAs used in risk models remains to be conducted. The purpose of the present study was to identify valuable necroptosis-related lncRNAs in esophageal cancer and to verify their molecular and cellular functions. METHODS: Esophageal cancer data were downloaded from The Cancer Genome Atlas (TCGA). The expression of eight genes (LINC00299, AC090912.2, AC244197.2, AL158166.1, AC079684.1, AP003696.1, AC079684.1 and AP003696.1) in the necroptosis-related lncRNA risk model, their relationships with clinicopathological stage, and their diagnostic receiver operating characteristic (ROC) curves were analyzed. The prognostic value of these lncRNAs for overall survival (OS) and disease specific survival (DSS) was analyzed, and time-dependent ROC curves were generated. The AP003696.1 target gene (lncRNA ENSG00000253385.1) was further investigated through immune infiltration analysis, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analyses, and gene coexpression analysis. Finally, in vitro functional assays based on lncRNA ENSG00000253385.1 were conducted to explore its regulatory role in esophageal cancer. RESULTS: A bioinformatics approach was used to study the eight genes in the necroptosis-related lncRNA risk model. AP003696.1 (lncRNA ENSG00000253385.1) was highly expressed in esophageal cancer tissues, and its high expression was correlated with poor OS and DFdS. Both univariate and multivariate Cox regression analyses revealed that lncRNA ENSG00000253385.1 is an independent prognostic factor. The lncRNA ENSG00000253385.1 gene was demonstrated to play a definite role in the invasion of esophageal cancer immune cells and in signaling pathways in these cells. In vitro cell functional assays revealed that lncRNA ENSG00000253385.1 expression was elevated in the KYSE150 and KYSE410 esophageal cancer cell lines. Small interfering RNA (siRNA)-mediated silencing of lncRNA ENSG00000253385.1 significantly inhibited the proliferation, migration, and invasion of KYSE150 and KYSE410 cells, as well as promoted their apoptosis. CONCLUSIONS: The ENSG00000253385.1 gene may be a key gene in the occurrence, development, and prognosis of esophageal cancer. These findings provide new ideas and references for the screening of therapeutic targets, as well as the development of targeted drugs, for esophageal cancer treatment.
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Incomplete recovery, baseline drift, and a long response time have been impeding the practical applications of transition metal dichalcogenide (TMD)-based gas sensors. Here, we report WS2 sensors with significantly improved gas recovery, rapid response, and negligible baseline drift by the incorporation of black phosphorus (BP) as well as the decoration of Pt to detect NO2 for the first time. Compared to bare WS2, the BP-WS2 sensors show higher sensitivity, better repeatability, and more excellent selectivity towards NO2 at the optimal operating temperature of 50 °C. Furthermore, the optimized 30%BP-WS2/Pt sensors exhibit a continuous enhancement in the recovery level and sensitivity with negligible baseline drift. The 30%BP-WS2/Pt sensor also exhibits a shorter response time of 28 s than 49.5 s for its counterpart WS2 sensor towards 32 ppm NO2. The enhanced sensing properties are primarily due to the combined effects of more adsorption sites provided by BP, the spill-over effect of Pt catalysis, and the WS2/BP heterostructure. Therefore, the Pt-decorated 30%BP-WS2 sensor exhibits prominent gas-sensing properties of high gas sensitivity, a low detection limit of 100 ppb, good selectivity, and fast response. Our strategy provides a new route for designing and optimizing TMD-based gas sensors with excellent gas-sensing performance.
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BACKGROUND: The dominant subclass of non-small-cell lung cancer (NSCLC) is lung adenocarcinoma (LUAD). The tumor microenvironment (TME) is a crucial feature of carcinogenesis and progression in LUAD. Furthermore, immune and stromal components of TME are crucial factors to investigating and curing LUAD. Thus, the study assessed the value of TME-related genes for LUAD prognosis and immune infiltration. METHODS: All data were downloaded from TCGA and GEO databases. The immune and stromal scores were downloaded from ESTIMATE, and the association between the scores and prognosis was explored by Kaplan-Meier survival analysis. Protein-protein interaction (PPI) network and univariate Cox regression were used to find TME-related differentially expressed genes (DEGs), and HLA-DMA was regarded as a prognostic hub gene. Western blot analyses, qRT-PCR, and immunofluorescence were applied to verify HLA-DMA expression in clinical samples. NSCLC cell lines were used to verify the effect of HLA-DMA on cell proliferation and cell cycle distribution. At last, the alteration of immunotherapy response and TME transition caused by HLA-DMA different expression were further studied. RESULTS: The immune score was positively correlated with survival. The functional analyses suggested that TME-related DEGs may be involved in the immune response. The expression level of HLA-DMA was decreased in LUAD. In addition, HLA-DMA expression was associated with several clinical features and was positively associated with survival. Furthermore, HLA-DMA may suspend cell proliferation by regulating cell cycle. HLA-DMA expression was closely associated with immune infiltration and positively correlated with TMB, indicating that patients with high HLA-DMA level were more suitable for immunotherapy. CONCLUSION: These results reveal that HLA-DMA might act as a biomarker for immune infiltration and immunotherapy response.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Prognóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Ciclo Celular/genética , Adenocarcinoma de Pulmão/genética , Microambiente Tumoral/genéticaRESUMO
The spin-valley coupling between circularly polarized light and valley excitons in transition metal dichalcogenides provides the opportunity to generate and manipulate spin information by exploiting the valley degree of freedom. Here, we demonstrate a room-temperature valley-addressable tungsten disulfide monolayer laser in which the spin of lasing is controlled by the spin of pump without magnetic fields. This effect was achieved by integrating a tungsten disulfide monolayer into a photonic cavity that supports two orthogonal spin modes with high quality factors. The spin-pumped lasing effectively broke the population symmetry of valley excitons, resulting in highly coherent emission with valley-switchable radiation modes due to distinct laser thresholds. Our scheme provides a nanophotonic platform to develop versatile coherent spin-light sources operating at room temperature by actively manipulating spin-valley coupling in light-matter interactions.
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Direct-bandgap transition metal dichalcogenide monolayers are appealing candidates to construct atomic-scale spin-optical light sources owing to their valley-contrasting optical selection rules. Here we report on a spin-optical monolayer laser by incorporating a WS2 monolayer into a heterostructure microcavity supporting high-Q photonic spin-valley resonances. Inspired by the creation of valley pseudo-spins in monolayers, the spin-valley modes are generated from a photonic Rashba-type spin splitting of a bound state in the continuum, which gives rise to opposite spin-polarized ±K valleys due to emergent photonic spin-orbit interaction under inversion symmetry breaking. The Rashba monolayer laser shows intrinsic spin polarizations, high spatial and temporal coherence, and inherent symmetry-enabled robustness features, enabling valley coherence in the WS2 monolayer upon arbitrary pump polarizations at room temperature. Our monolayer-integrated spin-valley microcavities open avenues for further classical and non-classical coherent spin-optical light sources exploring both electron and photon spins.
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Esophageal carcinoma (ESCA) is one of the most common malignancies in the world, and has high morbidity and mortality rates. Necrosis and long noncoding RNAs (lncRNAs) are involved in the progression of ESCA; however, the specific mechanism has not been clarified. The aim of the present study was to investigate the role of necrosis-related lncRNAs (nrlncRNAs) in patients with ESCA by bioinformatics analysis, and to establish a nrlncRNA model to predict ESCA immune infiltration and prognosis. To form synthetic matrices, ESCA transcriptome data and related information were obtained from The Cancer Genome Atlas. A nrlncRNA model was established by coexpression, univariate Cox (Uni-Cox), and least absolute shrinkage and selection operator analyses. The predictive ability of this model was evaluated by Kaplan-Meier, receiver operating characteristic (ROC) curve, Uni-Cox, multivariate Cox regression, nomogram and calibration curve analyses. A model containing eight nrlncRNAs was generated. The areas under the ROC curves for 1-, 3- and 5-year overall survival were 0.746, 0.671 and 0.812, respectively. A high-risk score according to this model could be used as an indicator for systemic therapy use, since the half-maximum inhibitory concentration values varied significantly between the high-risk and low-risk groups. Based on the expression of eight prognosis-related nrlncRNAs, the patients with ESCA were regrouped using the 'ConsensusClusterPlus' package to explore potential molecular subgroups responding to immunotherapy. The patients with ESCA were divided into three clusters based on the eight nrlncRNAs that constituted the risk model: The most low-risk group patients were classified into cluster 1, and the high-risk group patients were mainly concentrated in clusters 2 and 3. Survival analysis showed that Cluster 1 had a better survival than the other groups (P=0.016). This classification system could contribute to precision treatment. Furthermore, two nrlncRNAs (LINC02811 and LINC00299) were assessed in the esophageal epithelial cell line HET-1A, and in the human esophageal cancer cell lines KYSE150 and TE1. There were significant differences in the expression levels of these lncRNAs between tumor and normal cells. In conclusion, the present study suggested that nrlncRNA models may predict the prognosis of patients with ESCA, and provide guidance for immunotherapy and chemotherapy decision making. Furthermore, the present study provided strategies to promote the development of individualized and precise treatment for patients with ESCA.
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Immunotherapy-based regiments have potential as first-line treatment for advanced gastric esophageal cancer. The present study aimed to conduct a meta-analysis of the association between the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with unresectable locally advanced or metastatic gastric esophageal cancer. Subgroup analysis of patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) was conducted to identify the characteristics of patients with immune benefit and to provide a decision-making basis for clinical practice. PubMed, Embase, Cochrane Library and other databases were searched to collect randomized controlled trials of immunotreatment-based regimens (experimental group) versus conventional first-line chemotherapy regimens (control group) for unresectable locally advanced or metastatic gastric esophageal cancer. The main outcome measures included progression-free survival (PFS), overall survival (OS), objective response rate, disease control rate and safety, and the secondary outcomes were the differences in OS and PFS between patients with PD-L1 CPS ≥10 and those with PD-L1 CPS <10. In addition, Asian and non-Asian populations were analysed. Nine studies with a total of 6,820 patients were included. The OS of patients treated with immunotherapy-based regimens was significantly longer than that of those treated with chemotherapy alone [HR=0.74; 95% CI (0.69, 0.80); P<0.00001]. The OS of patients with PD-L1 CPS ≥10 and PD-L1 CPS <10 in the experimental group was significantly longer than that of patients in the control group [HR=0.68; 95% CI (0.59, 0.77); P<0.00001 and HR=0.73; 95% CI (0.62, 0.87); P=0.0005]. The PFS of patients being treated with immunotherapy-based regimens was significantly longer than that of those treated with chemotherapy alone [HR=0.71; 95% CI (0.59, 0.86); P=0.0003]. In addition, the PFS of patients with PD-L1 CPS ≥10 and PD-L1 CPS <10 in the experimental group was significantly longer than that of patients in the control group [HR=0.67; 95% CI (0.49, 0.92); P=0.01 and HR=0.63; 95% CI (0.48, 0.83); P=0.001]. There was no significant difference in the overall incidence of adverse events and the incidence of grade 3 or above adverse events between the experimental and control groups [RR=1; 95% CI (0.99, 1.02); P=0.65 and RR=0.97; 95% CI (0.84, 1.12); P=0.69, respectively]. In conclusion, treatment with immunotherapy-based regimens may prolong the OS of patients with unresectable locally advanced or metastatic gastric esophageal cancer and this treatment regimen is safe compared with chemotherapy alone.
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OBJECTIVE: To estimate 30-day hospital readmission rates among persons living with HIV (PLWH) at the Nantong Infectious Disease Hospital in China and analyse the related risk factors. METHODS: A single-centre retrospective cohort study was conducted. There were 894 PLWH records obtained from the electronic medical record (EMR) system at the Nantong Infectious Disease Hospital in China, from October 2013 to February 2018. The 30-day readmission rates were calculated, and the risk factors were analysed by generalised estimating equations (GEEs). RESULTS: A total of 1153 hospitalizations from 894 patients were recorded between October 2013 and February 2018. The median time of 30-day readmissions was 13 days (interquartile range (IQR), 6-23). The reasons for all causes, acquired immunodeficiency syndrome (AIDS)-defining illnesses (ADIs), and non-AIDS-defining infections (non-ADIs) were 9.08, 13.52, and 7.91%, respectively. The results from the GEE analysis demonstrated that the risk factors associated with 30-days readmissions were as follows: no antiretroviral therapy (ART) prior to hospitalisations (odds ratio (OR) = 1.90, 95% confidence interval (CI): 1.21-3.00), low CD4 counts (OR = 2.17, 95% CI: 1.33-3.54), and multiple comorbidities (OR = 6.45, 95% CI: 1.62-25.73). CONCLUSION: Early detection of HIV infection and early initiation of ART treatment are the keys to controlling 30-day readmissions.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Readmissão do Paciente , Estudos Retrospectivos , Fatores de Risco , Síndrome da Imunodeficiência Adquirida/complicações , Hospitais , China/epidemiologiaRESUMO
OBJECTIVE: To investigate the role of inositol-requiring enzyme 1(IRE1) in autophagy of human gastric cancer cells induced by vitamin E succinate(VES). METHODS: Human gastric cancer SGC-7901 cells were cultured in vitro and divided into solvent control group(0.1% ethanol absolute), different doses(5, 10, 15 and 20 µg/mL) VES group, 4µ8C group, and VES + 4µ8C group. The endoplasmic reticulum stress-related molecules glucose regulated protein 78(GRP78) and C/EBP homologous protein(CHOP), autophagy marker microtubule associated Protein1 light chain 3(LC3), Beclin-1, unfolded protein response branching pathway Inositol-requiring enzyme 1(IRE1), X box-binding protein 1(XBP1), c-Jun n-terminal kinase(JNK) and p-JNK were detected by Western blot in the solvent control group and different doses of VES group. IRE1 was inhibited by 4µ8C. The expressions of IRE1, XBP1, JNK, p-JNK, GRP78 and CHOP were detected by Western blot, and the expressions of LC3 and Beclin-1 were detected. RESULTS: The expression of GRP78(1.16±0.06) and CHOP(1.36±0.11) in 20 µg/mL VES group were significantly higher than those in solvent control group GRP78(0.36±0.10) and CHOP(0.48±0.05)(P<0.001). The expression of Beclin-1(1.09±0.20) and LC3-â ¡/LC3-â (1.29±0.03) in 20 µg/mL VES group were significantly higher than those in solvent control group(0.27±0.07) and LC3-â ¡/LC3-â (0.43±0.06)(P<0.001). The expression levels of IRE1(1.07±0.20), XBP1(1.33±0.07) and p-JNK/JNK(1.19±0.31) in 20 µg/mL VES group were significantly higher than those in the solvent control group(P<0.01). After IRE1 is inhibited: The expression level of IRE1(0.63±0.27), XBP1(0.74±0.09), p-JNK/JNK(0.35±0.04), GRP78(0.66±0.02), CHOP(0.51±0.02), LC3-â ¡/LC3-â (0.72±0.01), Beclin-1(0.70±0.15) was significantly lower than that of VES group(P<0.05). CONCLUSION: VES may participate in the regulation of autophagy in gastric cancer cells by upregulating IRE1 pathway.
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Neoplasias Gástricas , alfa-Tocoferol , Humanos , Chaperona BiP do Retículo Endoplasmático , Proteína Beclina-1 , Apoptose , Proteínas Serina-Treonina Quinases/fisiologia , Estresse do Retículo Endoplasmático , Autofagia , InositolRESUMO
Esophageal squamous cell carcinoma (ESCC) is a common malignancy with high morbidity and mortality. Although circular RNAs (circRNAs) play important roles in various cancers including ESCC, the role of the circRNA mannosidase alpha class 1A member 2 (circMAN1A2) in ESCC has been rarely studied. This study aimed to explore the role of circMAN1A2 in ESCC. CircMAN1A2 expression in ESCC tissues and cells was evaluated, and the relationship between circMAN1A2 expression and prognosis in patients with ESCC was analyzed. C-C chemokine ligand 5 (CCL5) was found to be a downstream target of circMAN1A2 by analysing the Agilent Microarray. Next, we performed in vitro and in vivo xenotransplantation assays to explore the role of circMAN1A2 in ESCC. We observed that high circMAN1A2 expression is associated with poor prognosis in patients with ESCC. Suppression of circMAN1A2 expression inhibits the proliferation, migration, and invasiveness of ESCC via regulating CCL5. Our results suggest that circMAN1A2 can promote the progression of ESCC by regulating CCL5. Thus, circMAN1A2 might be a novel diagnostic biomarker of ESCC, and targeting circMAN1A2 using inhibitors could be a potential therapeutic strategy to treat ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Esofágicas/patologia , Ligantes , Manosidases/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genéticaRESUMO
An individual based randomized controlled trial (RCT) was designed to evaluate the impact of a customized short message service (SMS) intervention on HIV-related high-risk behaviors among Men who have sex with men (MSM). In total, 631 HIV-negative MSM were enrolled at baseline and divided into intervention and control groups randomly. Nine months later, the intervention group who received additional customized SMS intervention reported significantly lower rates of multiple partners, unclear partner infection status and condomless anal intercourse compared to the control group who received the routine intervention only. Six months post stopping the SMS intervention, the rates of unclear partner infection status and condomless anal intercourse still remained lower report in the intervention group. Our study shown that the customized SMS interventions can significantly reduce the HIV-related high-risk behaviors among MSM and with sustained effects over a period of time.
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Infecções por HIV , Minorias Sexuais e de Gênero , Envio de Mensagens de Texto , Masculino , Humanos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Assunção de Riscos , Comportamento Sexual , China/epidemiologia , Parceiros SexuaisRESUMO
Control over multiple optical elements that can be dynamically rearranged to yield substantial three-dimensional structural transformations is of great importance to realize reconfigurable plasmonic nanoarchitectures with sensitive and distinct optical feedback. In this work, we demonstrate a transformable plasmonic helix system, in which multiple gold nanoparticles (AuNPs) can be directly transported by DNA swingarms to target positions without undergoing consecutive stepwise movements. The swingarms allow for programmable AuNP translocations in large leaps within plasmonic nanoarchitectures, giving rise to tailored circular dichroism spectra. Our work provides an instructive bottom-up solution to building complex dynamic plasmonic systems, which can exhibit prominent optical responses through cooperative rearrangements of the constituent optical elements with high fidelity and programmability.
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Pancreatic cancer is one of the most challenging cancer types in clinical treatment worldwide. This study aimed to understand the tumorigenesis mechanism and explore potential therapeutic targets for patients with pancreatic cancer. Single-cell data and expression profiles of pancreatic cancer samples and normal tissues from multiple databases were included. Comprehensive bioinformatics analyses were applied to clarify tumor microenvironment and identify key genes involved in cancer development. Immense difference of cell types was shown between tumor and normal samples. Four cell types (B cell_1, B cell_2, cancer cell_3, and CD1C+_B dendritic cell_3) were screened to be significantly associated with prognosis. Three ligand-receptor pairs, including CD74-MIF, CD74-COPA, and CD74-APP, greatly contributed to tumorigenesis. High expression of BUB1 (BUB1 Mitotic Checkpoint Serine/Threonine Kinase) was closely correlated with worse prognosis. CD1C+_B dendritic cell_3 played a key role in tumorigenesis and cancer progression possibly through CD74-MIF. BUB1 can serve as a prognostic biomarker and a therapeutic target for patients with pancreatic cancer. The study provided a novel insight into studying the molecular mechanism of pancreatic cancer development and proposed a potential strategy for exploiting new drugs.
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Neoplasias Pancreáticas , Proteínas Serina-Treonina Quinases , Carcinogênese , Humanos , Terapia de Alvo Molecular , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
Glioma is a prevalent malignancy among brain tumors with high modality and low prognosis. Ferroptosis has been identified to play a crucial role in the progression and treatment of cancers. KAT6B, as a histone acetyltransferase, is involved in multiple cancer development. However, the function of KAT6B in glioma is still elusive. Here, we aimed to evaluate the effect of KAT6B on ferroptosis in glioma cells and explored the potential mechanisms. We observed that the expression of KAT6B was enhanced in clinical glioma samples. The viability of glioma cells was repressed by erastin and the overexpression of KAT6B rescued the phenotype in the cells. Meanwhile, the apoptosis of glioma cells was induced by the treatment of erastin, while the overexpression of KAT6B blocked the effect in the cells. The levels of lipid ROS and iron were promoted by the treatment of erastin and the overexpression of KAT6B could reverse the effect in the cells. Mechanically, we identified that the expression of STAT3 was repressed by the KAT6B knockdown in glioma cells. The KAT6B was able to enrich on the promoter of STAT3 in glioma cells. Meanwhile, ChIP assay showed that the knockdown of KAT6B inhibited the enrichment of histone H3 lysine 23 acetylation (H3K23ac) and RNA polymerase II (RNA pol II) on STAT3 promoter in the cells. Depletion of STAT3 reversed KAT6B-regulated viability, apoptosis, and ferroptosis of glioma cells. Thus, we concluded that KAT6B contributes to glioma progression by repressing ferroptosis via epigenetically inducing STAT3.
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BACKGROUND: Obesity is associated with type 2 diabetes mellitus (T2DM). However, the obesity index that is most closely related to type 2 diabetes remains controversial. Therefore, the aim of this study was to compare the associations of five anthropometric indices (body mass index [BMI], body adiposity index, waist circumference [WC], waist-to-hip ratio, and waist-to-height ratio [WHtR]) with T2DM among Chinese adults divided into four groups according to sex and age. METHODS: A total of 4007 adult participants (1669 men and 2338 women) were included in the study. Odds ratios (ORs) and 95% confidence intervals were used with binary logistic regression models to estimate the risk of T2DM for each obesity index. Furthermore, we compared the area under the receiver operating characteristic curve (AUC) of each obesity index for the criterion of T2DM under the influence of risk factors. RESULTS: WC had the highest OR (3.211 and 1.452) and AUC (0.783 and 0.614) in both age groups of men. However, WHtR (OR = 2.366, AUC = 0.771) and BMI (OR = 1.596, AUC = 0.647) were the optimal criteria for predicting T2DM among females in the 18-59 and ≥ 60 years age groups, respectively. CONCLUSIONS: This study suggests that there is a positive association between obesity-related anthropometric indices and T2DM in different sex and age groups. WC appears to be the optimal anthropometric index for predicting T2DM in men. The optimal obesity indices related to T2DM were WHtR and BMI for women aged 18-59 and ≥ 60 years, respectively.
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Diabetes Mellitus Tipo 2 , Índice de Massa Corporal , China/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Obesidade/diagnóstico , Obesidade/epidemiologia , Curva ROC , Fatores de Risco , Circunferência da Cintura , Razão Cintura-Estatura , Relação Cintura-QuadrilRESUMO
Planar, thin-layered chiral plasmonic superstructures with complex two-dimensional (2D) patterns, namely, double-layered binary stars (bi-stars) and pinwheels, were realized through DNA programmable 2D supramolecular self-assembly of gold nanorods (AuNRs). The chirality of the chiral superstructures was defined by a finite number of AuNR pairs as enantiomeric motifs, and their sizes (â¼240 nm) were precisely defined by the underlying DNA template. These planar, thin-layered chiral nanoparticle superstructures exhibited prescribed shapes and sizes at the dried state on the substrate surface and are characteristic of giant anisotropy of chiroptical responses, with enhanced g-factors from the axial incident excitation as compared to the in-plane excitation. This work will inspire possibilities for the construction of 2D chiral materials, for example, chiral metasurfaces, for the on-chip manipulation of chiral light-matter interactions via programmable self-assembly of nanoparticles.
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Nanopartículas Metálicas , Nanotubos , DNA , Ouro , EstereoisomerismoRESUMO
The crucial roles of the long noncoding RNAs (lncRNAs) in the development of ovarian cancer (OC) have been extensively studied. According to the prediction result from the Kaplan-Meier Plotter database, high expression of lncRNA proteasome subunit α type-3 antisense RNA1 (PSMA3-AS1) is associated with the poor prognosis in patients with OC. Thus, the study aimed to investigate the role of lncRNA PSMA3-AS1 in OC. Reverse transcription quantitative polymerase chain reaction analysis revealed that PSMA3-AS1 expression was significantly upregulated in OC cells and tissues. PSMA3-AS1 silencing inhibited OC cell proliferation, migration, and invasion, as shown by results of cell counting kit-8, colony formation, wound healing, and Transwell assays, respectively. Additionally, PSMA3-AS1 deficiency suppressed tumor growth in vivo. Mechanistically, luciferase reporter and RNA pulldown assays implied that PSMA3-AS1 served as a competing endogenous RNA for miR-378a-3p to upregulate the expression of polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). GALNT3 was a target gene of miR-378a-3p in OC. Moreover, PSMA3-AS1 activated the PI3K/Akt pathway by upregulating GALNT3 expression. Overall, PSMA3-AS1 promotes OC cell proliferation, migration, invasion, and xenograft tumor growth by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis.
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MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Bacteriano , RNA Longo não Codificante/genéticaRESUMO
In living organisms, proteins are organized prevalently through a self-association mechanism to form dimers and oligomers, which often confer new functions at the intermolecular interfaces. Despite the progress on DNA-assembled artificial systems, endeavors have been largely paid to achieve monomeric nanostructures that mimic motor proteins for a single type of motion. Here, we demonstrate a DNA-assembled building block with rotary and walking modules, which can introduce new motion through dimerization and oligomerization. The building block is a chiral system, comprising two interacting gold nanorods to perform rotation and walking, respectively. Through dimerization, two building blocks can form a dimer to yield coordinated sliding. Further oligomerization leads to higher-order structures, containing alternating rotation and sliding dimer interfaces to impose structural twisting. Our hierarchical assembly scheme offers a design blueprint to construct DNA-assembled advanced architectures with high degrees of freedom to tailor the optical responses and regulate multi-motion on the nanoscale.