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Time-resolved or time-correlation measurements using cathodoluminescence (CL) reveal the electronic and optical properties of semiconductors, such as their carrier lifetimes, at the nanoscale. However, halide perovskites, which are promising optoelectronic materials, exhibit significantly different decay dynamics in their CL and photoluminescence (PL). We conducted time-correlation CL measurements of CsPbBr3 using Hanbury Brown-Twiss interferometry and compared them with time-resolved PL. The measured CL decay time was on the order of subnanoseconds and was faster than PL decay at an excited carrier density of 2.1 × 1018 cm-3. Our experiment and analytical model revealed the CL dynamics induced by individual electron incidences, which are characterized by highly localized carrier generation followed by a rapid decrease in carrier density due to diffusion. This carrier diffusion can play a dominant role in the CL decay time for undoped semiconductors, in general, when the diffusion dynamics are faster than the carrier recombination.
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As demand for higher integration density and smaller devices grows, silicon-based complementary metal-oxide-semiconductor (CMOS) devices will soon reach their ultimate limits. 2D transition metal dichalcogenides (TMDs) semiconductors, known for excellent electrical performance and stable atomic structure, are seen as promising materials for future integrated circuits. However, controlled and reliable doping of 2D TMDs, a key step for creating homogeneous CMOS logic components, remains a challenge. In this study, a continuous electrical polarity modulation of monolayer WS2 from intrinsic n-type to ambipolar, then to p-type, and ultimately to a quasi-metallic state is achieved simply by introducing controllable amounts of vanadium (V) atoms into the WS2 lattice as p-type dopants during chemical vapor deposition (CVD). The achievement of purely p-type field-effect transistors (FETs) is particularly noteworthy based on the 4.7 at% V-doped monolayer WS2, demonstrating a remarkable on/off current ratio of 105. Expanding on this triumph, the first initial prototype of ultrathin homogeneous CMOS inverters based on monolayer WS2 is being constructed. These outcomes validate the feasibility of constructing homogeneous CMOS devices through the atomic doping process of 2D materials, marking a significant milestone for the future development of integrated circuits.
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Nicotine exposure from smoking constitutes a significant global public health concern. Furthermore, smoking represents a pivotal risk factor for head and neck squamous cell carcinoma (HNSCC). However, the influence of nicotine on HNSCC remains relatively underexplored. Our aim was to unravel the molecular mechanisms that underlie the effect of nicotine on the metastatic cascade of HNSCC. In this study, we discovered a significant association between smoking and HNSCC metastasis and prognosis. Nicotine significantly enhanced HNSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Analysis of TCGA-HNSCC and FDEENT-HNSCC cohorts revealed reduced miR-375-3p levels in HNSCC tumor tissues, particularly among current smokers. Additionally, miR-375-3p level was strongly correlated with both lymph node metastasis and tumor stage. By downregulating miR-375-3p, nicotine promotes HNSCC cell metastasis in vitro and hematogenous metastatic capacity in vivo. Utilizing transcriptomic sequencing, molecular docking, dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH), we demonstrated that miR-375-3p specifically binds to 3' untranslated region (3'UTR) of NTRK2 mRNA. Thus, this study uncovers a novel nicotine-induced mechanism involving miR-375-3p-mediated NTRK2 targeting, which promotes HNSCC metastasis. These findings have implications for improving the prognosis of patients with HNSCC, especially in smokers.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Receptores de Aminoácido , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Nicotina/toxicidade , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Simulação de Acoplamento Molecular , Hibridização in Situ Fluorescente , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , Células Epiteliais/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de CélulasRESUMO
Background: Breast cancer (BRCA) is a common malignancy in women, and its resistance to immunotherapy is a major challenge. Abnormal expression of genes is important in the occurrence and development of BRCA and may also affect the prognosis of patients. Although many BRCA prognosis model scores have been developed, they are only applicable to a limited number of disease subtypes. Our goal is to develop a new prognostic score that is more accurate and applicable to a wider range of BRCA patients. Methods: BRCA patient data from The Cancer Genome Atlas database was used to identify breast cancer-related genes (BRGs). Differential expression analysis of BRGs was performed using the 'limma' package in R. Prognostic BRGs were identified using co-expression and univariate Cox analysis. A predictive model of four BRGs was established using Cox regression and the LASSO algorithm. Model performance was evaluated using K-M survival and receiver operating characteristic curve analysis. The predictive ability of the signature in immune microenvironment and immunotherapy was investigated. In vitro experiments validated POLQ function. Results: Our study identified a four-BRG prognostic signature that outperformed conventional clinicopathological characteristics in predicting survival outcomes in BRCA patients. The signature effectively stratified BRCA patients into high- and low-risk groups and showed potential in predicting the response to immunotherapy. Notably, significant differences were observed in immune cell abundance between the two groups. In vitro experiments demonstrated that POLQ knockdown significantly reduced the viability, proliferation, and invasion capacity of MDA-MB-231 or HCC1806 cells. Conclusion: Our 4-BRG signature has the potential as an independent biomarker for predicting prognosis and treatment response in BRCA patients, complementing existing clinicopathological characteristics.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Prognóstico , Mama , Biologia Computacional , Imunoterapia , Microambiente Tumoral/genéticaRESUMO
Precise synthesis of all-inorganic lead halide perovskite nanowire heterostructures and superlattices with designable modulation of chemical compositions is essential for tailoring their optoelectronic properties. Nevertheless, controllable synthesis of perovskite nanostructure heterostructures remains challenging and underexplored to date. Here, we report a rational strategy for wafer-scale synthesis of one-dimensional periodic CsPbCl3/CsPbI3 superlattices. We show that the highly parallel array of halide perovskite nanowires can be prepared roughly as horizontally guided growth on an M-plane sapphire. A periodic patterning of the sapphire substrate enables position-selective ion exchange to obtain highly periodic CsPbCl3/CsPbI3 nanowire superlattices. This patterning is further confirmed by micro-photoluminescence investigations, which show that two separate band-edge emission peaks appear at the interface of a CsPbCl3/CsPbI3 heterojunction. Additionally, compared with the pure CsPbCl3 nanowires, photodetectors fabricated using these periodic heterostructure nanowires exhibit superior photoelectric performance, namely, high ION/IOFF ratio (104), higher responsivity (49 A/W), and higher detectivity (1.51 × 1013 Jones). Moreover, a spatially resolved visible image sensor based on periodic nanowire superlattices is demonstrated with good imaging capability, suggesting promising application prospects in future photoelectronic imaging systems. All these results based on the periodic CsPbCl3/CsPbI3 nanowire superlattices provides an attractive material platform for integrated perovskite devices and circuits.
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High synthesis temperatures and specific growth substrates are typically required to obtain crystalline or oriented inorganic functional thin films, posing a significant challenge for their utilization in large-scale, low-cost (opto-)electronic applications on conventional flexible substrates. Here, we explore a pulse irradiation synthesis (PIS) to prepare thermoelectric metal chalcogenide (e.g., Bi2Se3, SnSe2, and Bi2Te3) films on multiple polymeric substrates. The self-propagating combustion process enables PIS to achieve a synthesis temperature as low as 150 °C, with an ultrafast reaction completed within one second. Beyond the photothermoelectric (PTE) property, the thermal coupling between polymeric substrates and bismuth selenide films is also examined to enhance the PTE performance, resulting in a responsivity of 71.9 V/W and a response time of less than 50 ms at 1550 nm, surpassing most of its counterparts. This PIS platform offers a promising route for realizing flexible PTE or thermoelectric devices in an energy-, time-, and cost-efficient manner.
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Inorganic semiconductors typically have limited p-type behavior due to the scarcity of holes and the localized valence band maximum, hindering the progress of complementary devices and circuits. In this work, we propose an inorganic blending strategy to activate the hole-transporting character in an inorganic semiconductor compound, namely tellurium-selenium-oxygen (TeSeO). By rationally combining intrinsic p-type semimetal, semiconductor, and wide-bandgap semiconductor into a single compound, the TeSeO system displays tunable bandgaps ranging from 0.7 to 2.2 eV. Wafer-scale ultrathin TeSeO films, which can be deposited at room temperature, display high hole field-effect mobility of 48.5 cm2/(Vs) and robust hole transport properties, facilitated by Te-Te (Se) portions and O-Te-O portions, respectively. The nanosphere lithography process is employed to create nanopatterned honeycomb TeSeO broadband photodetectors, demonstrating a high responsibility of 603 A/W, an ultrafast response of 5 µs, and superior mechanical flexibility. The p-type TeSeO system is highly adaptable, scalable, and reliable, which can address emerging technological needs that current semiconductor solutions may not fulfill.
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The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.
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Trióxido de Arsênio , Carcinoma Hepatocelular , Morte Celular Imunogênica , Neoplasias Hepáticas , Proteínas de Membrana , Nucleotidiltransferases , Trióxido de Arsênio/farmacologia , Trióxido de Arsênio/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Humanos , Animais , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos , Morte Celular Imunogênica/efeitos dos fármacos , Linhagem Celular Tumoral , Interferons/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVE: To establish the diagnostic accuracy of RASSF1A (Ras association domain family 1 isoform) methylation using bronchial aspirates as an auxiliary method for diagnosing lung cancer through a systematic review and meta-analysis. METHODS: Studies published prior to October 30, 2022, were retrieved from the Embase, PubMed, Web of Science, and Wan Fang databases using the keywords "lung cancer", "RASSF1A", "methylation", and "bronchial aspirates". A fixed or random effect model was used to calculate the combined sensitivity, specificity, positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), along with the respective 95% confidence intervals (CIs) and the area under the curve (AUC) with Q index. The threshold effect was defined by using the Spearman correlation coefficient, and the Deeks funnel plot was generated to evaluate publication bias. RESULTS: Among the 12 trials that met the inclusion criteria, a total of 2388 participants were involved. The pooled results for the diagnosis of lung cancer were as follows, when compared to the pathological diagnosis: sensitivity of 0.47 (95% CI: 0.45-0.50), specificity of 0.96 (95% CI: 0.95-0.97), positive LR of 12.18 (95% CI: 8.96-16.55), negative LR of 0.56 (95% CI: 0.52-0.61), DOR of 24.05 (95% CI: 17.29-33.47), and AUC of 0.78 (Q index = 0.72), respectively. The sensitivity of the RASSF1A methylation assay was relatively low in a detailed subgroup analysis, fluctuating between 0.39 and 0.90, indicating a limitation in its diagnostic value for lung cancer. The RASSF1A methylation assay, on the other hand, demonstrated excellent specificity, suggesting a high exclusion value. Of note, the diagnostic sensitivity, specificity, DOR, and AUC for small cell lung cancer were 0.90 (0.84-0.94), 0.95 (0.94-0.97), 249.5 (103.94-598.8), and 0.98, respectively, showing that RASSF1A methylation was a promising biomarker for diagnosing small cell lung cancer with both high diagnostic and exclusion value. Furthermore, RASSF1A methylation using bronchial washings and bronchial aspirates showed a high AUC of 0.998 and 0.93, respectively, indicating excellent diagnostic performance. CONCLUSIONS: The methylation of RASSF1A in bronchial aspirates demonstrated a high level of diagnostic accuracy and has the potential to be a valuable supplementary diagnostic method, especially for identifying small cell lung cancer.