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Electromigration, as a common reason for interconnect failure, is becoming increasingly important in the ongoing decrease in the integrated circuit manufacturing process. A study is being carried out utilizing the ab initio calculational method to gain a deeper understanding of electromigration, with a focus on the atom diffusion process in the Ag-Pd alloy system, a commonly used interconnect material. We begin by establishing that the primary mechanism of diffusion is step-edge diffusion on the (111) surface. Following this, we examine the current-induced force exerted on the migrating Ag atom. The Pd substitutional defect reveals an effect that increases the energy barrier of diffusion and decreases the current-induced force that powers the directional migration.
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Retina-inspired visual sensors play a crucial role in the realization of neuromorphic visual systems. Nevertheless, significant obstacles persist in the pursuit of achieving bidirectional synaptic behavior and attaining high performance in the context of photostimulation. In this study, we propose a reconfigurable all-optical controlled synaptic device based on the IGZO/SnO/SnS heterostructure, which integrates sensing, storage and processing functions. Relying on the simple heterojunction stack structure and the role of energy band engineering, synaptic excitatory and inhibitory behaviors can be observed under the light stimulation of ultraviolet (266 nm) and visible light (405, 520 and 658 nm) without additional voltage modulation. In particular, junction field-effect transistors based on the IGZO/SnO/SnS heterostructure were fabricated to elucidate the underlying bidirectional photoresponse mechanism. In addition to optical signal processing, an artificial neural network simulator based on the optoelectrical synapse was trained and recognized handwritten numerals with a recognition rate of 91%. Furthermore, we prepared an 8 × 8 optoelectrical synaptic array and successfully demonstrated the process of perception and memory for image recognition in the human brain, as well as simulated the situation of damage to the retina by ultraviolet light. This work provides an effective strategy for the development of high-performance all-optical controlled optoelectronic synapses and a practical approach to the design of multifunctional artificial neural vision systems.
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Understanding the intrinsic mechanisms underpinning cancer metabolism and therapeutic resistance is of central importance for effective nutrition-starvation therapies. Here, we report that Interleukin 1A (IL1A) mRNA and IL-1α protein facilitate glutathione (GSH) synthesis to counteract oxidative stress and resistance against nutrition-starvation therapy in oral squamous cell carcinoma (OSCC). The expression of IL1A mRNA was elevated in the case of OSCC associated with unfavorable clinical outcomes. Both IL1A mRNA and IL-1α protein expression were increased under glucose-deprivation in vitro and in vivo. The transcription of IL1A mRNA was regulated in an NRF2-dependent manner in OSCC cell lines under glucose-deprivation. Moreover, the IL-1α conferred resistance to oxidative stress via GSH synthesis in OSCC cell lines. The intratumoral administration of siRNAs against IL1A mRNA markedly reversed GSH production and sensitized OSCC cells to Anlotinib in HN6 xenograft models. Overall, the current study demonstrates novel evidence that the autocrine IL-1α favors endogenous anti-oxidative process and confers therapeutic resistance to nutrition-starvation in OSCCs.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Estrés Oxidativo , Glutatión/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Línea Celular TumoralRESUMEN
Seven previously undescribed lanostane triterpenoids, ganoderic acid M1 (1), M2 (2), M3 (3), M4 (4), M5 (5), M6 (6), and M7 (7), together with eight known compounds, were isolated from mycelia of the basidiomycete Ganoderma sinense (Ganodermataceae). The structures of all compounds were elucidated by spectroscopic analysis. The possible biosynthetic pathway of these fifteen triterpenoids was proposed. Some of the compounds were evaluated for their anti-inflammatory activity by measuring the production of nitric oxide (NO), TNF-α, and IL-6 in RAW264.7 macrophage cells induced by lipopolysaccharide. Lanosta-7,9(11),24-trien-3ß,15α,22ß-triacetoxy-26-oic acid (14) exhibited the strongest inhibition of NO production with an IC50 of 0.6 ± 0.1 µM and completely inhibited the secretion of TNF-α and IL-6 at 10 µM. The structure-activity relationship of the anti-inflammatory activity is discussed.
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Ganoderma , Triterpenos , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Cuerpos Fructíferos de los Hongos/química , Triterpenos/química , Ganoderma/química , Esteroides/química , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Estructura MolecularRESUMEN
For traditional wide-bandgap semiconductor materials, a high-temperature process is unavoidable for improving crystallization quality, so the substrate of the device is greatly limited. In this work, zinc-tin oxide (a-ZTO) amorphous oxide processed by the pulsed laser deposition method was utilized as the n-type layer, which exhibits considerable electron mobility and optical transparency, and can be deposited at room temperature. At the same time, by combining p-type CuI grown by the thermal evaporation method, a vertically structured ultraviolet photodetector based on CuI/ZTO heterojunction was obtained. The detector demonstrates self-powered properties, with an on-off ratio exceeding 104, and rapid response with a rise time of 2.36 ms and a fall time of 1.49 ms. Also, the photodetector shows long-term stability with 92% retention after 5000 s cyclic lighting and maintains reproducible response in frequency dependence measurement. Furthermore, the flexible photodetector on poly(ethylene terephthalate) (PET) substrates was constructed, exhibiting fast response and durability in the bending state. This is the first time that the heterostructure based on CuI has been applied in the flexible photodetector. The excellent results indicate that the combination of amorphous oxide and CuI has the potential for ultraviolet photodetectors, and will broaden the application range of high-performance flexible/transparent optoelectronic devices in the future.
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Lichen natural products are a tremendous source of new bioactive chemical entities for drug discovery. The ability to survive in harsh conditions can be directly correlated with the production of some unique lichen metabolites. Despite the potential applications, these unique metabolites have been underutilized by pharmaceutical and agrochemical industries due to their slow growth, low biomass availability, and technical challenges involved in their artificial cultivation. At the same time, DNA sequence data have revealed that the number of encoded biosynthetic gene clusters in a lichen is much higher than in natural products, and the majority of them are silent or poorly expressed. To meet these challenges, the one strain many compounds (OSMAC) strategy, as a comprehensive and powerful tool, has been developed to stimulate the activation of silent or cryptic biosynthetic gene clusters and exploit interesting lichen compounds for industrial applications. Furthermore, the development of molecular network techniques, modern bioinformatics, and genetic tools is opening up a new opportunity for the mining, modification, and production of lichen metabolites, rather than merely using traditional separation and purification techniques to obtain small amounts of chemical compounds. Heterologous expressed lichen-derived biosynthetic gene clusters in a cultivatable host offer a promising means for a sustainable supply of specialized metabolites. In this review, we summarized the known lichen bioactive metabolites and highlighted the application of OSMAC, molecular network, and genome mining-based strategies in lichen-forming fungi for the discovery of new cryptic lichen compounds.
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BACKGROUND: Treatment options are limited for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). We aimed to evaluate the preliminary results of the efficacy and safety of all-trans retinoic acid (ATRA) combined with low-dose apatinib in patients with R/M ACCHN according to a secondary analysis of a phase II study. METHODS: Patients from a phase II study (NCT02775370) who orally administered 500 milligram (mg) apatinib daily until treatment-related adverse events (AEs) intolerance or progression occurred were eligible for inclusion. Patients were further treated with combination therapy of ATRA (25 mg/m2 /day) and apatinib (250 mg/day) between March 2019 and October 2021 until progression of disease (PD). RESULTS: A total of 16 patients were included with nine (56.3%) males and aged 35-69 years old. All recruited patients previously received anti-angiogenic therapy then withdrew due to toxicities or progression occurred. The objective response rate (ORR) and disease control rate (DCR) were 18.8% and 100%, respectively. During a median follow-up of 23.9 months (range:17.8-31.7 months), 11 (68.8%) patients developed PD and one of them died in 20.9 months. The median of progression-free survival (PFS) was 16.3 months (95% CI: 7.2-25.4 months), and the 6-month, 12-month, and 24-month PFS rates were 100%, 81.3%, and 33.3%, respectively. The grade 3 adverse events were albuminuria (n = 2, 12.5%) and hand-foot syndrome (n = 1, 6.25%). CONCLUSION: All-trans retinoic acid combined with low-dose apatinib might be a potential efficacy therapeutic option for patients with R/M ACCHN. This finding will be further confirmed by our registered ongoing trial, the APLUS study (NCT04433169).
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Antineoplásicos , Carcinoma Adenoide Quístico , Carcinoma , Neoplasias de Cabeza y Cuello , Neoplasias Pulmonares , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Femenino , Antineoplásicos/efectos adversos , Carcinoma Adenoide Quístico/tratamiento farmacológico , Tretinoina/efectos adversos , Carcinoma/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias Pulmonares/patologíaRESUMEN
Research on tumour cell-derived small extracellular vesicles (sEVs) that regulate tumour microenvironment (TME) has provided strategies for targeted therapy of head and neck squamous cell carcinoma (HNSCC). Herein, we demonstrated that sEVs derived from HNSCC cancer cells carried CD73 (sEVsCD73 ), which promoted malignant progression and mediated immune evasion. The sEVsCD73 phagocytosed by tumour-associated macrophages (TAMs) in the TME induced immunosuppression. Higher CD73high TAMs infiltration levels in the HNSCC microenvironment were correlated with poorer prognosis, while sEVsCD73 activated the NF-κB pathway in TAMs, thereby inhibiting immune function by increasing cytokines secretion such as IL-6, IL-10, TNF-α, and TGF-ß1. The absence of sEVsCD73 enhanced the sensitivity of anti-PD-1 therapy through reversed immunosuppression. Moreover, circulating sEVsCD73 increased the risk of lymph node metastasis and worse prognosis. Taken together, our study suggests that sEVsCD73 derived from tumour cells contributes to immunosuppression and is a potential predictor of anti-PD-1 responses for immune checkpoint therapy in HNSCC.
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5'-Nucleotidasa/inmunología , Vesículas Extracelulares , Neoplasias de Cabeza y Cuello , Vesículas Extracelulares/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Terapia de Inmunosupresión , Macrófagos/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Microambiente TumoralRESUMEN
The oral squamous cell cancer (OSCC) incidence in young patients has increased since the end of the last century; however, the underlying mechanism is still unclear. Oral microbiota dysbiosis was proven to be a tumorigenesis factor, and we propose that there is a distinct bacterial composition in young patients that facilitates the progression of OSCC. Twenty elderly (>60 years old) and 20 young (<50 years old) subjects were included in this study. OSCC tissue was collected during surgery, sent for 16S rDNA sequencing and analyzed by the QIIME 2 pipeline. The results showed that Ralstonia, Prevotella, and Ochrobactrum were significantly enriched in younger OSCC tissue microbiota, while Pedobacter was more abundant in elderly OSCC tissues. Fusobacterium had high relative abundance in both cohorts. At the phylum level, Proteobacteria was the dominant taxon in all samples. The functional study showed that there were significant differences in the taxa abundance from metabolic and signaling pathways. The results indicated that the microbiota of younger OSCC tissues differed from that of elderly OSCC tissues by both taxon composition and function, which partially explains the distinct roles of bacteria during tumorigenesis in these two cohorts. These findings provide insights into different mechanisms of the microbiota-cancer relationship with regard to aging.
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BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease worldwide. Much progress has been made in exploring mechanisms and improving the therapy of HNSCC, but only a few studies have focused on the role of ferroptosis on HNSCC progression. The current study aimed to reveal the underlining mechanisms that caveolin-1 (CAV1)-ROS (reactive oxygen species)-ferroptosis axis affect the process of HNSCC and discover novo therapeutic targets or strategies. METHODS: The role of CAV1 in ferroptosis was analyzed by FerrDb, and its clinical significance was examined by TCGA dataset of HNSCC. The expressions of caveolin-1 (CAV1) in HNSCC tissues were measured by immunohistochemistry, western blot, and real-time PCR assay. Three siRNA sequences were designed to silence CAV1 mRNA in HNSCC cells. Cell proliferation, colony formation, wound-healing, and transwell assays were used to examine the proliferation, migration, and invasion of cancer cells. ROS evaluation and intracellular Fe2+ content assays were performed to examine the levels of ferroptosis. RESULTS: Through the analysis with published data, CAV1 was found to overexpress in HNSCC than normal tissues, and was one of the vital suppressors of ferroptosis pathway. Our study showed that CAV1 was over expressed in HNSCC tissues and the high level of CAV1 predicted poorer prognosis. Further experiments indicated that CAV1 could inhibit the ferroptosis of cancer cells and promote the proliferation, migration and invasion. CONCLUSIONS: Overexpression of CAV1 in HNSCC inhibited the process of ferroptosis, leading to aggressive phenotypes, as well as worse prognosis. The regulatory pathway of CAV1 and ferroptosis are potential targets for designing diagnostic and combined therapeutic strategies for HNSCC patients.
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Ferroptosis , Neoplasias de Cabeza y Cuello , Caveolina 1/genética , Línea Celular Tumoral , Neoplasias de Cabeza y Cuello/genética , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
5-period ZnO/Zn0.9Mg0.1O multiple quantum wells (MQWs) were employed as active layers to fabricate the p-GaN/MQWs/n-ZnO diode by molecular beam epitaxy. It exhibited an efficient UV emission around 370 nm at room temperature. Calculated band structures and carrier distributions showed that electrons were restricted to overflow to the p-type layer, and carriers were confined in the high-quality MQWs well layer.
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Graphitic carbon nitride (g-C3N4) has been regarded as an intriguing photocatalyst applying to hydrogen generation but suffering rapid recombination of photoinduced electron-hole pairs and insufficient absorption under visible light. We developed a novel one-pot thermal copolymerization method of melamine as a precursor and 7,7,8,8-tetracyanoquinodimethane (TCNQ) as a comonomer to synthesize modified g-C3N4 (abbreviated as X% TCNQ) for the first time, aiming to directly incorporate TCNQ molecular into carbon nitride skeleton for the substitution of low-electronegative carbon for high-electronegative nitride atom. Results revealed that the as-prepared photocatalysts by copolymerization of melamine with TCNQ retained the original framework of g-C3N4, and dramatically altered the electronic and optical properties of carbon nitride. Various measurements confirmed that as-synthesized samples exhibited larger specific surface areas, faster photogenerated charge transfer and broader optical absorption by decreasing the π-deficiency and extending the π-conjugated system, thus facilitating the photocatalytic activity. Specifically, the 0.3% TCNQ exhibited as high as seven times than the pristine g-C3N4 on photocatalytic H2 generation and kept its photoactivity for five circles. This work highlights a feasible approach of chemical protocols for the molecular design to synthesize functional carbon nitride photocatalysts by copolymerizing appropriate g-C3N4 precursor and comonomers.
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ZnO has broad applications in optoelectronic devices, including ultraviolet light emitters and photodetectors. Herein we report the impact of MoO3 surface functionalization on the photoresponse of epitaxially grown ZnO. Under illumination with 350 nm UV light, the photocurrent of ZnO is found to be enhanced by 2.87 times after the deposition of 0.2 nm MoO3. As corroborated by in situ ultraviolet photoelectron spectroscopy and X-ray photoelectron spectroscopy results, the enhanced photoresponse derives from MoO3 related gap states within the band gap of ZnO and larger upward band bending at the interface, which is attributed to the strong electron transfer from ZnO to MoO3. Moreover, photoluminescence results reveal that the recombination probability of the photo-generated charge carriers in ZnO is reduced after MoO3 surface functionalization.
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Photocatalytic hydrogen evolution by water splitting has become a very effective way to solve the energy crisis. For use in that process, graphitic carbon nitride (g-C3N4) has drawn much attention for its response in the visible region. However, its insufficient sunlight absorption efficiency and easy recombination of photoinduced carriers restrict its photocatalytic activity. Herein, we demonstrate a two-step liquid ultrasonic method in water to synthesize a series of tetracyanoquinodimethane (TCNQ)-C3N4 photocatalysts aiming to form a conjugated structure by 7,7,8,8-TCNQ. g-C3N4 was treated with APTES firstly on its surface in order to give a better interface contact with TCNQ. Benefiting from the conjugation effect between TCNQ and g-C3N4, the separation and transport efficiency of photogenerated carriers were significantly improved. Besides, introducing TCNQ also broadened the absorption region. Both of these points lead to the enhancement of photocatalytic H2 production rate, with the optimized 5% TCNQ-C3N4 giving a rate nearly 9.48 times that of pure g-C3N4. Also, 5% TCNQ-C3N4 (U) was prepared with unmodified g-C3N4, which exhibited a rate only 6.87 times that of pure g-C3N4, thus validating the necessity of surface modification. Our work reveals that the rational conjugated structure could modulate the electrical and optical properties of g-C3N4, yielding an improvement of photocatalytic activities.
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Plasmonic noble metal has been applied in photocatalytic materials, and TiO2 with plasmonic noble metal has been studied for a long time. In this work, we have fabricated incomplete covered Au/Ag alloy nanoshuttle-TiO2 nanomaterials with 268.7 µmol g-1 h-1 H2-evolution in a simple solution method. The considerable photocatalytic performance is mainly due to the enhanced surface plasmon resonance effect of Au/Ag alloy nanoshuttles. It has been found that TiO2 clusters attached to the Au/Ag nanoshuttles surface migrate under electrons irradiation and cover the exposed Au/Ag NS surface to achieve thermodynamic stability, which results in instability of photocatalytic performance. The mechanism has been discussed in detail.
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Understanding of the carrier concentration properties of current spreading layers in LED devices is important although difficult to achieve. Here, we present a solution to determine the carrier concentration for current spreading layers in ZnO-based LEDs, based on Raman spectroscopy. Raman spectra and lineshape fitting indicate a hole concentration below 1×1018 cm-3 in the p-type region and an electron concentration of 1.21×1019 cm-3 in n-type. The results from Raman spectroscopy are further qualitatively confirmed by the electroluminescence spectrum and device simulation, which demonstrates its possible application in carrier concentration assessment in multilayered structures.
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In this work, tin oxide (SnO2) nanoarrays (NAs) with a novel morphology were fabricated by a hydrothermal method. Each SnO2 nanorod (NR) consisted of a bunch of nearly ten primary NRs with a width of 4-7 nm. On this basis, gold (Au) nanoparticles (NPs) were used to induce the growth of smaller and more orderly SnO2 NAs. The prepared ultraviolet (UV) detectors based on SnO2 NAs have high responsivity and high external quantum efficiency (EQE) under 20 µW cm-2 UV light with only 1 V external bias voltage.
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This paper reports observations and analysis of the Rb2 31Π g state. A total of 323 rovibrational term values spanning the range of the rotational quantum number J = 7 through 77 and the vibrational quantum number v = 2 through 23 (about 1/3 of the potential well depth) were measured using the optical-optical double resonance technique. The term values are simulated within a model of a piece-wise multi-parameter potential energy function based on the generalized splines. This function not only enables a reproduction of the experimental data with a reasonable quality but also approximates the available ab initio function in its whole range with a uniform accuracy.
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Non-polar ZnO thin films are grown on m-plane sapphire substrates by plasma-assisted molecular beam epitaxy. Emission enhancement from non-polar ZnO thin films coated with Al/AlOx has been studied by photoluminescence spectroscopy. AlOx has been used to mediate the surface plasmon (SP) energy of Al nanoparticles. Taking advantage of the resonant coupling between the UV emission of non-polar ZnO film and Al nanoparticle SPs, an 84-fold enhancement of the UV emission and an 8.3-fold enhancement of internal quantum efficiency (ηint) have been achieved under the optimized sputtering time and energy of SPs.
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A series of ZnO nanorod (NR)-reduced graphene oxide (rGO) nanocomposites (NCs) (i.e., ZnO-rGO NCs) with varying rGO loadings were fabricated by electrostatic self-assembly of positively charged ZnO NRs with negatively charged graphene oxide (GO), followed by the hydrothermal reduction of GO to rGO. When compared with bare ZnO NRs, ZnO-5% rGO exhibited significant photoactivity 6 times higher in the photodegradation of rhodamine B (RhB), and 2 times higher than ZnO-5% rGO(H) synthesized by hard integration of GO and ZnO NRs. In the same manner, ZnO-5% rGO exhibited a significant photoactivity 3 times higher in photodegrading phenol, which is 2 times higher than ZnO-5% rGO(H). Furthermore, the adsorption properties of ZnO-rGO NCs towards RhB and phenol were significantly different as a result of the opposite charges of the two pollutants in aqueous solution, which also led to the formation of different key free radicals during the degradation reaction. Based on various characterization techniques, it is concluded that the enhanced photoactivity and photostability of ZnO-5% rGO originated from the synergistic effects between ZnO NRs and rGO nanosheets including higher specific surface area, enhanced photogenerated carrier separation, and strengthened protection effects from intimate rGO coupling. However, these synergistic effects were weaker in ZnO-5% rGO(H) which reflects the key importance of surface charge modification in producing a well-contacted interface.