ABSTRACT
As a non-volatile semiconductor memory technology, phase-change memory has a wide range of application prospects as a result of the excellent comprehensive performance. In this paper, multilayer thin films based on Sb2Te3 material were designed and prepared by inserting the Sn15Sb85 layer. The thermal and electrical properties of superlattice-like Sb2Te3/Sn15Sb85 phase-change films can be adjusted by controlling the thickness ratio of Sb2Te3/Sn15Sb85. In comparison to the monolayer Sb2Te3 film, the multilayer layer Sb2Te3/Sn15Sb85 materials have a higher crystallization temperature, larger crystallization activation energy, and longer data lifetime, indicating the great improvement of thermal stability. The changes in the phase structure and vibrational modes of multilayer Sb2Te3/Sn15Sb85 films were characterized by X-ray diffraction and Raman spectroscopy, respectively. The presence of Sn15Sb85 layers restrains grain growth and refines the grain size. The multilayer Sb2Te3/Sn15Sb85 films exhibit better surface flatness, smaller surface potential undulation, and lower thickness variations than single-layer Sb2Te3. Phase-change memory cells based on the [Sb2Te3 (1 nm)/Sn15Sb85 (9 nm)]5 thin film has a lower threshold voltage (1.9 V) and threshold current (3.1 µA) compared to the Ge2Sb2Te5 film. Meanwhile, the electrical heating model of a phase-change memory cell based on a [Sb2Te3 (1 nm)/Sn15Sb85 (9 nm)]5 multilayer structure was established by multiphysics coupling analysis, proving the great improvement in heat transfer performance and efficiency. The experimental and theoretical studies confirm that the insertion of the Sn15Sb85 layer can significantly improve the crystallization properties of Sb2Te3 films, paving the way for optimizing the phase-change materials by regulating the microstructural parameters.
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Trace iron ions (Fe(III)) are commonly found in water and wastewater, where free chlorine is very likely to coexist with Fe(III) affecting the disinfectant's stability and N-DBPs' fate during UV/chlorine disinfection, and yet current understanding of these mechanisms is limited. This study investigates the effects of Fe(III) on the formation and toxicity alteration of halonitromethanes (HNMs), dichloroacetonitrile (DCAN), and dichloroacetamide (DCAcAm) from polyethyleneimine (PEI) during UV/chlorine disinfection. Results reveal that the maxima concentrations of HNMs, DCAN, and DCAcAm during UV/chlorine disinfection with additional Fe(III) were 1.39, 1.38, and 1.29 times higher than those without additional Fe(III), instead of being similar to those of Fe(III) inhibited the formation of HNMs, DCAN and DCAcAm during chlorination disinfection. Meanwhile, higher Fe(III) concentration, acidic pH, and higher chlorine dose were more favorable for forming HNMs, DCAN, and DCAcAm during UV/chlorine disinfection, which were highly dependent on the involvement of HO· and Cl·. Fe(III) in the aquatic environment partially hydrolyzed to the photoactive Fe(III)hydroxyl complexes Fe(OH)2+ and [Fe(H2O)6]3+, which undergone UV photoactivation and coupling reactions with HOCl to achieve effective Fe(III)/Fe(II) interconversion, a process that facilitated the sustainable production of HO·. Extensive product analysis and comparison verified that the HO· production enhanced by the Fe(III)/Fe(II) internal cycle played a primary role in increasing HNMs, DCAN, and DCAcAm productions during UV/chlorine disinfection. Note that the incorporation of Fe(III) increased the cytotoxicity and genotoxicity of HNMs, DCAN, and DCAcAm formed during UV/chlorine disinfection, and yet Fe(III) did not have a significant effect on the acute toxicity of water samples before, during, and after UV/chlorine disinfection. The new findings broaden the knowledge of Fe(III) affecting HNMs, DCAN, and DCAcAm formation and toxicity alteration during UV/chlorine disinfection.
Subject(s)
Disinfection , Disinfection/methods , Ultraviolet Rays , Chlorine/chemistry , Polyethyleneimine/chemistry , Acetonitriles/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/toxicity , Iron/chemistry , Water Purification/methods , Acetamides/chemistry , Acetamides/toxicity , Disinfectants/chemistryABSTRACT
Extracellular matrix (ECM) stiffening is a typical characteristic of cartilage aging, which is a quintessential feature of knee osteoarthritis (KOA). However, little is known about how ECM stiffening affects chondrocytes and other molecules downstream. This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane (PDMS) substrates. It demonstrated that epigenetic Parkin regulation by histone deacetylase 3 (HDAC3) represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology. We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro, while the stiffness ECM downregulated HDAC3, prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis (OA) in mice. Contrarily, intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice. The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals, promoted the Parkin acetylation and hyperactivated mitophagy, and damaged chondrocyte health. These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM, suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.
Subject(s)
Cellular Senescence , Chondrocytes , Down-Regulation , Extracellular Matrix , Histone Deacetylases , Osteoarthritis , Animals , Chondrocytes/metabolism , Chondrocytes/pathology , Histone Deacetylases/metabolism , Histone Deacetylases/genetics , Extracellular Matrix/metabolism , Osteoarthritis/pathology , Humans , Mice , Cellular Senescence/drug effects , Mice, Inbred C57BL , Mitophagy/drug effects , Male , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Acetylation , Cells, CulturedABSTRACT
The twist engineering of moiré superlattice in van der Waals heterostructures of transition metal dichalcogenides can manipulate valley physics of interlayer excitons (IXs), paving the way for next-generation valleytronic devices. However, the twist angle-dependent control of excitonic potential on valley polarization is not investigated so far in electrically controlled heterostructures and the physical mechanism underneath needs to be explored. Here, we demonstrate the dependence of both polarization switching and degree of valley polarization on the moiré period. We also find the mechanisms to reveal the modulation of twist angle on the exciton potential and the electron-hole exchange interaction, which elucidate the experimentally observed twist angle-dependent valley polarization of IXs. Furthermore, we realize the valley-addressable devices based on polarization switch. Our work demonstrates the manipulation of the valley polarization of IXs by tunning twist angle in electrically controlled heterostructures, which opens an avenue for electrically controlling the valley degrees of freedom in twistronic devices.
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Samantaray et al [...].
ABSTRACT
The limited ionic conductivity at room temperature and the constrained electrochemical window of poly(ethylene oxide) (PEO) pose significant obstacles that hinder its broader utilization in high-energy-density lithium metal batteries. The garnet-type material Li6.4 La3 Zr1.4 Ta0.6 O12 (LLZTO) is recognized as a highly promising active filler for enhancing the performance of PEO-based solid polymer electrolytes (SPEs). However, its performance is still limited by its high interfacial resistance. In this study, a novel hybrid filler-designed SPE is employed to achieve excellent electrochemical performance for both the lithium metal anode and the LiFePO4 cathode. The solid composite membrane containing hybrid fillers achieves a maximum ionic conductivity of 1.9 × 10-4 S cm-1 and a Li+ transference number of 0.67 at 40 °C, respectively. Additionally, the Li/Li symmetric cells demonstrate a smooth and stable process for 2000 h at a current density of 0.1 mA cm-2 . Furthermore, the LiFePO4 /Li battery delivers a high-rate capacity of 159.2 mAh g-1 at 1 C, along with a capacity retention of 95.2% after 400 cycles. These results validate that employing a composite of both active and inactive fillers is an effective strategy for achieving superior performance in all-solid-state lithium metal batteries (ASSLMBs).
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The limited ionic conductivity and unstable interface due to poor solid-solid interface pose significant challenges to the stable cycling of solid-state batteries (SSBs). Herein, an interfacial plasticization strategy is proposed by introducing a succinonitrile (SN)-based plastic curing agent into the polyacrylonitrile (PAN)-based composite polymer electrolytes (CPE) interface. The SN at the interface strongly plasticizes the PAN in the CPE, which reduces the crystallinity of the PAN drastically and enables the CPE to obtain a low modulus surface, but it still maintains a high modulus internally. The reduced crystallinity of PAN provides more amorphous regions, which are favorable for Li+ transport. The gradient modulus structure not only ensures intimate interfacial contact but also favors the suppression of Li dendrites growth. Consequently, the interfacial plasticized CPE (SF-CPE) obtains a high ionic conductivity of 4.8 × 10-4 S cm-1 as well as a high Li+ transference number of 0.61. The Li-Li symmetric cell with SF-CPE can cycle for 1000 h at 0.1 mA cm-2, the LiFeO4 (LFP)-Li full-cell demonstrates a high capacity retention of 86.1% after 1000 cycles at 1 C, and the LiCoO2 (LCO)-Li system also exhibits an excellent cycling performance. This work provides a novel strategy for long-life solid-state batteries.
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Toxicity significantly influences the successful development of drugs. Based on the toxicity prediction method (carrier protein binding information-toxicity relationship) previously established by the our group, this paper introduces information on the interaction between pesticides and environmental markers (SOD) into the model for the first time, so that the toxicity prediction model can not only predict the toxicity of pesticides to humans and animals, but also predict the toxicity of pesticides to the environment. Firstly, the interaction of acetolactate synthase inhibitor herbicides (ALS inhibitor herbicides) with human serum albumin (HSA) and superoxide dismutase (SOD) was investigated systematically from theory combined with experiments by spectroscopy methods and molecular docking, and important fluorescence parameters were obtained. Then, the fluorescence parameters, pesticides acute toxicity LD50 and structural splitting information were used to construct predictive modeling of ALS inhibitor herbicides based on the carrier protein binding information (R2 = 0.977) and the predictive modeling of drug acute toxicity based on carrier protein binding information and conformational relationship (R2 = 0.991), which had effectively predicted pesticides toxicity in humans and animals. To predict potential environmental toxicity, the predictive modeling of drug acute toxicity based on superoxide dismutase binding information was established (R2 = 0.883) by ALS inhibitor herbicides-SOD binding information, which has a good predictive ability in the potential toxicity of pesticides to the environment. This study lays the foundation for developing low toxicity pesticides.
Subject(s)
Herbicides , Pesticides , Animals , Humans , Herbicides/toxicity , Herbicides/metabolism , Serum Albumin, Human/metabolism , Molecular Docking Simulation , Protein Binding , Enzyme Inhibitors/toxicity , Carrier Proteins , Superoxide Dismutase/metabolism , Spectrometry, FluorescenceABSTRACT
Background: The continuous exploration of oligometastatic disease has led to the remarkable achievements of local consolidative therapy (LCT) and favorable outcomes for this disease. Thus, this study investigated the potential benefits of LCT in patients with single-organ metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: Patients with single-organ metastatic PDAC diagnosed between 2010 - 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to minimize selection bias. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates. Results: A total of 12900 patients were identified from the database, including 635 patients who received chemotherapy combined with LCT with a 1:1 PSM with patients who received only chemotherapy. Patients with single-organ metastatic PDAC who received chemotherapy in combination with LCT demonstrated extended median overall survival (OS) by approximately 57%, more than those who underwent chemotherapy alone (11 vs. 7 months, p < 0.001). Furthermore, the multivariate Cox regression analysis revealed that patients that received LCT, younger age (< 65 years), smaller tumor size (< 50 mm), and lung metastasis (reference: liver) were favorable prognostic factors for patients with single-organ metastatic PDAC. Conclusion: The OS of patients with single-organ metastatic pancreatic cancer who received LCT may be prolonged compared to those who received only chemotherapy. Nevertheless, additional prospective randomized clinical trials are required to support these findings.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Aged , Cross-Sectional Studies , Propensity Score , Prospective Studies , Pancreatic Neoplasms/drug therapy , RegistriesABSTRACT
This work presents the optimization of the crystallization behavior and reliability of Sn15Sb85thin films by doping Sm element. The phase transition behaviors induced by thermal were investigated byin situresistance measurement. With the addition of Sm element, Sn15Sb85film exhibits the superior crystallization temperature (232 °C) and data conservation (172.32 °C for 10 years), larger activation energy of crystallization (4.91 eV) and crystalline resistance (â¼103Ω), which contributes to the increased thermal stability of the amorphous state and decrease in the programming energy. The Sm-doping can broaden the energy band gap from 0.55 to 1.07 eV. The amorphous Sm and Sn compositions could retard grain growth and refine grain size from 21.13 to 11.13 nm, combining with x-ray diffraction and x-ray photoelectron spectroscopy. The surface morphology of Sn15Sb85film becomes smoother after Sm doping as determined by atomic force microscopy images, resulting in the improved interfacial reliability. Phase change memory devices based on Sm0.095(Sn15Sb85)0.905films can successfully achieve the complete SET and RESET reversible operation process with high operating speed (200 ns) and low power consumption (1.6 × 10-10J). The results suggest that doping the proper concentration of Sm element will be an effectual solution to adapt and optimize the crystallization properties of Sn15Sb85phase change material.
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Single photon emission of quantum emitters (QEs) carrying internal degrees of freedom such as spin and angular momentum plays an important role in quantum optics. Recently, QEs in two-dimensional semiconductors have attracted great interest as promising quantum light sources. However, whether those QEs are characterized by the same valley physics as delocalized valley excitons is still under debate. Moreover, the potential applications of such QEs still need to be explored. Here we show experimental evidence of valley symmetry breaking for neutral QEs in WSe2 monolayer by interacting with chiral plasmonic nanocavities. The anomalous magneto-optical behaviour of the coupled QEs suggests that the polarization state of emitted photon is modulated by the chiral nanocavity instead of the valley-dependent optical selection rules. Calculations of cavity quantum electrodynamics further show the absence of intrinsic valley polarization. The cavity-dependent circularly polarized single-photon output also offers a strategy for future applications in chiral quantum optics.
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We report the slow-light enhanced spin-resolved in-plane emission from a single quantum dot (QD) in a photonic crystal waveguide (PCW). The slow light dispersions in PCWs are designed to match the emission wavelengths of single QDs. The resonance between two spin states emitted from a single QD and a slow light mode of a waveguide is investigated under a magnetic field with Faraday configuration. Two spin states of a single QD experience different degrees of enhancement as their emission wavelengths are shifted by combining diamagnetic and Zeeman effects with an optical excitation power control. A circular polarization degree up to 0.81 is achieved by changing the off-resonant excitation power. Strongly polarized photon emission enhanced by a slow light mode shows great potential to attain controllable spin-resolved photon sources for integrated optical quantum networks on chip.
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Solid-state electrolytes have been widely investigated for lithium batteries since they provide a high degree of safety. However, their low ionic conductivity and substantial growth of lithium dendrites hamper their commercial applications. Garnet-type Li6.4La3Zr1.4Ta0.6O12 (LLZTO) is one of the most promising active fillers to advance the performance of the solid polymer electrolyte. Nevertheless, their performance is still limited due to their large interfacial resistance. Herein, we embedded the amorphous Li2O2 (LO) into LLZTO particles via the quenching process and successfully achieved an interfacial layer of Li2O2 around LLZTO particles (LLZTO@LO). Amorphous Li2O2 acts as a binder and showed an excellent affinity for Li+ ions which promotes their fast transference. Moreover, the stable and dense interfacial Li2O2 layer enhances interfacial contact and suppresses the lithium dendrite growth during the long operation cycling process. The PEO/10LLZTO@2LO solid composite polymer electrolyte (SCPE) showed the highest ionic conductivity of 3.2 × 10-4 S cm-1 at 40 °C as compared to pristine LLZTO-based SCPE. Moreover, the Liâ(PEO/10LLZTO@2LO) âLi symmetric cell showed a stable and smooth long lifespan up to 1100 h at 40 °C. Furthermore, the LiFePO4//Li full battery with PEO/10LLZTO@2LO SCPE demonstrated stable cycling performance for 400 cycles. These results constitute a significant step toward the practical application of solid-state lithium metal batteries (SS-LMBs).
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Structural instability at high voltage severely restricts the reversible capacity of the LiCoO2 cathode. Moreover, the main difficulties in achieving high-rate performance of LiCoO2 are the long Li+ diffusion distance and slow Li+ intercalation/extraction during the cycle. Thus, we designed a modification strategy of nanosizing and tri-element co-doping to synergistically enhance the electrochemical performance of LiCoO2 at high voltage (4.6 V). Mg, Al, and Ti co-doping maintains the structural stability and phase transition reversibility, which promotes the cycling performance of LiCoO2. After 100 cycles at 1 C, the capacity retention of the modified LiCoO2 reached 94.3%. In addition, the tri-elemental co-doping increases Li+ interlayer spacing and enhances Li+ diffusivity by tens of times. Simultaneously, nanosize modification decreases Li+ diffusion distance, leading to a significantly enhanced rate capacity of 132 mA h g-1 at 10 C, much better than that of the unmodified LiCoO2 (2 mA h g-1). After 600 cycles at 5 C, the specific capacity remains at 135 mA h g-1 with a capacity retention of 91%. The nanosizing co-doping strategy synchronously enhanced the rate capability and cycling performance of LiCoO2.
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High levels of proinflammatory cytokines, macrophage polarization status and immune-mediated angiogenesis play pivotal roles in the pathogenesis of inflammatory bowel disease (IBD). Thalidomide, an anti-inflammatory, immunomodulatory and antiangiogenic agent, is used off-label for treatment of IBD. The therapeutic potential of thalidomide is limited by its poor solubility and side effects associated with its systemic exposure. To address these issues and promote its therapeutic effects on IBD, thalidomide nanocrystals (Thali NCs) were prepared and coated with polydopamine (PDA), a potential macrophage polarization modulator, to form PDA coated Thali NCs (Thali@PDA). Thali@PDA possessed a high drug loading and displayed average particle size of 764.7 ± 50.30 nm. It showed a better anti-colitis effect than bare thalidomide nanocrystals at the same dose of thalidomide. Synergistic effects of polydopamine on anti-inflammatory and anti-angiogenic activities of thalidomide were observed. Furthermore, PDA coating could direct polarization of macrophages towards M2 phenotype, which boosted therapeutic effects of Thali@PDA on IBD. Upon repeated dosing of Thali@PDA for one week, symptoms of IBD in mice were significantly relieved, and histomorphology of the colitis colons were normalized. Key proinflammatory cytokine levels in the inflamed intestines were significantly decreased. Toxicity study also revealed that Thali@PDA is a safe formulation.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Nanoparticles , Mice , Animals , Thalidomide/pharmacology , Angiogenesis Inhibitors/adverse effects , Colitis/chemically induced , Colitis/drug therapy , Colitis/pathology , Anti-Inflammatory Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Macrophages , Cytokines , Dextran Sulfate/pharmacologyABSTRACT
Since China's speedy economic development, the problems of energy consumption and environmental pollution have become increasingly prominent. A question worth in-depth study is whether ecological civilization (EC) construction, one of the main policies to solve China's severe environmental and ecological problems, affects carbon dioxide emissions (CDE). In this study, we use a novel method proposed by Hsiao et al. (2012) to estimate the average treatment effect by using panel data to study the impact of establishing the EC pilot zones of China on CDE. The results show that, although EC construction is effective in reducing CDE, the impact varies from region to region. The study findings can provide a scientific basis to promote the experience of EC construction better and improve its CDE effect.
Subject(s)
Carbon Dioxide , Economic Development , Carbon Dioxide/analysis , Civilization , Environmental Pollution/analysis , ChinaABSTRACT
Objective@#To understand physical fitness among primary and middle school students in Henan Province, so as to provide theoretical basis for physical fitness promotion among primary and middle school students.@*Methods@#Based on data of National Survey on Student Physical Fitness and Health in Henan Province in 2019, a total of 42 734 students were investigated. The Z value of each physical fitness index were calculated by Z method, physical fitness index (PFI) was obtained to reflect the physical fitness condition synthetically. Physical fitness of different groups were compared, and associated factors of PFI were analyzed by multiple linear regression.@*Results@#Lung capacity, grip strength, standing long jump, 50 m run, 50 m×8 shuttle run and PFI in boys were [(2 552.1±1 226.5)mL, (26.0±13.9)N, (171.0±43.7)cm, (9.3±1.8)s, (132.1±22.6)s, (1.4±3.6)], respectively, which were significantly higher than that of girls [(1 965.2±765.3)mL, (19.1±8.2)N, (142.4±26.6)cm, (10.5±1.4)s, (136.9±21.1)s, (-1.4±3.2)]( t =59.35,62.66,81.87,-74.92,-16.72,85.96, P <0.01). The seated forward flexion of boys [(7.0±7.5)cm] was significantly lower than that of girls[(11.8±7.1)cm], the difference was statistically significant ( t =-68.57, P <0.01). Significant sex differences were observed in physical fitness at different age ( P <0.01). There was a certain gap between urban boys and rural boys in terms of strength quality, endurance quality and flexibility quality, and the physical quality of urban girls was better than that of rural girls as a whole. The detection rates of poor eyesight, malnutrition, overweight and obesity, anemia and high blood pressure of primary and middle school students were 68.0%, 5.4%, 26.0%, 15.9% and 18.0%, respectively. Region, sex, age and nutritional status(malnutrition,overweight and obesity) were the influencing factors of PFI( β =-0.23,-2.92,-0.11,-1.19, -0.78 , P <0.05).@*Conclusion@#Physical fitness among primary and middle school students varies in gender, age group, region and disease condition in Henan Province. Scientific intervention should be administered, especially for rural, female students, senior students, undernourished and overweight and obese students, to improve health awareness and physical fitness.
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Single charge control of localized excitons (LXs) in two-dimensional transition metal dichalcogenides (TMDCs) is crucial for potential applications in quantum information processing and storage. However, traditional electrostatic doping method by applying metallic gates onto TMDCs may cause inhomogeneous charge distribution, optical quenching, and energy loss. Herein, by locally controlling the ferroelectric polarization of the ferroelectric thin film BiFeO3 (BFO) with a scanning probe, we can deterministically manipulate the doping type of monolayer WSe2 to achieve p-type and n-type doping. This nonvolatile approach can maintain the doping type and hold the localized excitonic charges for a long time without applied voltage. Our work demonstrated that the ferroelectric polarization of BFO can control the charges of LXs effectively. Neutral and charged LXs have been observed in different ferroelectric polarization regions, confirmed by magnetic optical measurement. Highly circular polarization degree with 90% photon emission from these quantum emitters was achieved in high magnetic fields. Controlling the single charge of LXs in a non-volatile way shows a great potential for deterministic photon emission with desired charge states for photonic long-term memory.
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Idiopathic pulmonary arterial hypertension (IPAH) is a disease with complex etiology. Currently, IPAH treatment is limited, and patients' prognosis is poor. This study aimed to explore new therapeutic targets in IPAH through bioinformatics. Two data sets (GSE113439 and GSE130391) meeting the requirements were obtained from the Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) were identified and analyzed by NetworkAnalyst platform. By enriching Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), we examined the function of DEGs. A protein-protein interaction (PPI) network was constructed to identify central genes using the CytoNCA plug-in. Finally, four central genes, ASPM, CENPE, NCAPG, and TOP2A, were screened out. We selected NCAPG for protein-level verification. We established an animal model of PAH and found that the expression of NCAPG was significantly increased in the lung tissue of PAH rats. In vitro experiments showed that the expression of NCAPG was significantly increased in proliferative pulmonary arterial smooth muscle cells (PASMCs). When NCAPG of PASMCs was knocked down, the cell proliferation was inhibited, which suggested that NCAPG was related to the proliferation of PASMCs. Therefore, these results may provide new therapeutic targets for IPAH.
Subject(s)
Cell Cycle Proteins , Myocytes, Smooth Muscle , Pulmonary Arterial Hypertension , Animals , Cell Cycle Proteins/genetics , Cell Proliferation , Computational Biology , Familial Primary Pulmonary Hypertension/metabolism , Humans , Myocytes, Smooth Muscle/cytology , Nerve Tissue Proteins/metabolism , Pulmonary Arterial Hypertension/genetics , Pulmonary Artery/cytology , RatsABSTRACT
Melanoma is a malignant skin cancer that is prone to metastasis in the early stage and has a poor prognosis. Immunomodulatory therapy for melanoma has been a hot research topic in recent years. However, low immune cell infiltration and loss of tumor immunogenicity may occur in tumors, resulting in low response rates to immunotherapy. Thus, immunomodulatory therapy is usually used in combination with chemotherapy and radiotherapy. Development of combined therapeutic strategies with low systemic toxicity, high immune responsiveness and long-term inhibition of metastasis and recurrence of melanoma is the goal of current research. In this study, the insoluble immune adjuvant imiquimod (R837) was prepared as nanocrystals and coated with polydopamine (PDA) to form R837@PDA, which was then loaded into chitosan hydrogel (CGP) to form the drug-loaded gel system, R837@PDA@CGP (RPC), to combine immunomodulation effects, induction of immunogenic cell death (ICD) effects and immune-enhancement effects. After treatment with RPC, ICD in melanoma was induced, and the infiltration rate of cytotoxic T cells (CTLs) in melanoma was also significantly enhanced, which turned the tumor itself into an in situ vaccine and boosted the cancer-immunity cycle at the tumor site. Therefore, melanoma growth, metastasis and recurrence were notably inhibited.