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Atomically dispersed catalysts have been shown highly active for preferential oxidation of carbon monoxide in the presence of excess hydrogen (PROX). However, their stability has been less than ideal. We show here that the introduction of a structural component to minimize diffusion of the active metal center can greatly improve the stability without compromising the activity. Using an Ir dinuclear heterogeneous catalyst (DHC) as a study platform, we identify two types of oxygen species, interfacial and bridge, that work in concert to enable both activity and stability. The work sheds important light on the synergistic effect between the active metal center and the supporting substrate and may find broad applications for the use of atomically dispersed catalysts.
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Monóxido de Carbono , Hidrógeno , Monóxido de Carbono/química , Oxidación-Reducción , Catálisis , Hidrógeno/química , Platino (Metal)/químicaRESUMEN
Lysosomal dysfunction can drive carcinogenesis. Lysosomal-associated membrane protein 3 (LAMP3), is a member of the Lysosome Associated Membrane Proteins and is involved in the malignant phenotype such as tumour metastasis and drug resistance, while the mechanisms that regulate the malignant progression of tumour remain vague. Our study aims to provide a more systematic and comprehensive understanding of the role of LAMP3 in the progression of various cancers by various databases.We explored the role of LAMP3 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Multiple online web platforms and software were used for data analysis, including HPA, TIMER, TISIDB, GEPIA, UALCAN, Kaplan-Meier plotter, DAVID and TIGER. The immunohistochemistry was used to quantify the LAMP3 and PD-L1 expression levels in cancer.High LAMP3 expression was found in most cancers and differentially expressed across molecular and immune subtypes. The expression of LAMP3 was involved in the immune-associated processes of Antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and the immune-associated pathways of T cell receptor and B cell receptor signalling pathways in most cancers. It also correlated with genetic markers of immunomodulators in various cancers. LAMP3 and PD-L1 expression in BRCA and HNSC tissues was higher than that in corresponding adjacent normal tissues by immunohistochemistry. There is a significant correlation between the expression of LAMP3 and PD-L1.Our study elucidates that LAMP3 has different expression patterns and genetic alteration patterns in different tumours. It is a potential biomarker for immune-related cancer diagnosis, prognosis and efficacy prediction.
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Antígeno B7-H1 , Neoplasias , Humanos , Proteína 3 de la Membrana Asociada a Lisosoma , Pronóstico , Proteínas de Membrana de los LisosomasRESUMEN
Lung cancer is a leading cause of cancer-related deaths worldwide. Recent studies have identified pyroptosis, a type of programmed cell death, as a critical process in the development and progression of lung cancer. In this study, we investigated the effect of EEBR, a new compound synthesized by our team, on pyroptosis in non-small cell lung cancer cells (NSCLC) and the underlying molecular mechanisms. Our results demonstrated that EEBR significantly reduced the proliferation and metastasis of NSCLC cells in vitro. Moreover, EEBR-induced pyroptosis in NSCLC cells, as evidenced by cell membrane rupture, the release of cytokines such as interleukin-18 and interleukin-1 beta and the promotion of Gasdermin D cleavage in a Caspase-1-dependent manner. Furthermore, EEBR promoted the nuclear translocation of NF-κB and upregulated the protein level of NLRP3. Subsequent studies revealed that EEBR-induced pyroptosis was suppressed by the inhibition of NF-κB. Finally, EEBR effectively suppressed the growth of lung cancer xenograft tumours by promoting NSCLC pyroptosis in animal models. Taken together, our findings suggest that EEBR induces Caspase-1-dependent pyroptosis through the NF-κB/NLRP3 signalling cascade in NSCLC, highlighting its potential as a candidate drug for NSCLC treatment.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Humanos , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Piroptosis , Caspasa 1/metabolismo , Inflamasomas/metabolismoRESUMEN
BACKGROUND: TSTA3 gene encoding GDP-L-fucose synthase has recently been proved to be closely related to the prognosis of patients with various tumors. However, its role in lung cancer is still unclear. The purpose of this study is to explore the expression level, prognostic effect, potential function and mechanism of TSTA3 in lung cancer. METHODS: Based on TCGA database, Kaplan-Meier and COX regression was used to analyze the relationship between TSTA3 expression and prognosis of lung cancer patients. Immunohistochemistry was used to determine the TSTA3 protein expression in lung cancer and normal tissues. The function of TSTA3 in lung squamous cell carcinoma (LUSC) cell was determined by CCK8, colony formation, transwell assay in vitro and subcutaneous xenografts in vivo. Transcriptome analysis, Lyso-Tracker Red staining and rescue experiment were used to explore the possible underlying mechanism. RESULTS: The expression of TSTA3 was significantly increased in lung cancer, especially in LUSC, and was significantly correlated with the malignant characteristics of LUSC. COX regression analysis showed that the high expression of TSTA3 was an independent prognostic factor in LUSC patients. This was also confirmed by immunohistochemical staining. Compared with the control group, the proliferation, colony formation, invasion and migration ability of LUSC cells with TSTA3 overexpression was enhanced. Similarly, the ability of cell proliferation, colony formation, invasion and migration were weakened after transient knockdown of TSTA3. In vivo experiment showed that compared with control group, TSTA3 overexpression significantly promoted the growth of tumor and shortened survival time. In addition, transcriptome sequencing analysis showed that the differentially expressed genes between TSTA3 overexpression and control group was mainly concentrated in the lysosome pathway. Further study found that TSTA3 might affect the proliferation, invasion and migration of LUSC by regulating the expression of lysosome-associated membrane protein 2 (LAMP2) in LUSC. CONCLUSION: The expression level of TSTA3 in LUSC is significantly higher than that in normal tissues. High expression of TSTA3 is associated with poor prognosis of LUSC patients. TSTA3 may affect the proliferation, invasion and migration of LUSC by regulating LAMP2.
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Using sunlight to produce valuable chemicals and fuels from carbon dioxide (CO2 ), i.e., artificial photosynthesis (AP) is a promising strategy to achieve solar energy storage and a negative carbon cycle. However, selective synthesis of C2 compounds with a high CO2 conversion rate remains challenging for current AP technologies. We performed CO2 photoelectroreduction over a graphene/silicon carbide (SiC) catalyst under simulated solar irradiation with ethanol (C2 H5 OH) selectivity of>99 % and a CO2 conversion rate of up to 17.1â mmol gcat -1 h-1 with sustained performance. Experimental and theoretical investigations indicated an optimal interfacial layer to facilitate the transfer of photogenerated electrons from the SiC substrate to the few-layer graphene overlayer, which also favored an efficient CO2 to C2 H5 OH conversion pathway.
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The recent proposal of antidoping scheme breaks new ground in conceiving conversely functional materials and devices; yet, the few available examples belong to the correlated electron systems. Here, we demonstrate both theoretically and experimentally that the main group oxide BaBiO3 is a model system for antidoping using oxygen vacancies. The first-principles calculations show that the band gap systematically increases due to the strongly enhanced Bi-O breathing distortions away from the vacancies and the annihilation of Bi 6s/O 2p hybridized conduction bands near the vacancies. Our further spectroscopic experiments confirm that the band gap increases systematically with electron doping, with a maximal gap enhancement of â¼75% when the film's stoichiometry is reduced to BaBiO2.75. These results unambiguously demonstrate the remarkable antidoping effect in a material without strong electron correlations and underscores the importance of bond disproportionation in realizing such an effect.
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Nanoscale zerovalent iron (nZVI) is considered as a highly efficient material for sequestrating arsenite, but the origin of its high efficacy as well as the chemical transformations of arsenite during reaction is not well understood. Here, we report an in situ X-ray absorption spectroscopy (XAS) study to investigate the complex mechanism of nZVI reaction with arsenite under anaerobic conditions at the time scale from seconds to days. The time-resolved XAS analysis revealed a gradual oxidation of AsIII to AsV in the course of minutes to hours in both the solid and liquid phase for the high (above 0.5 g/L) nZVI dose system. When the reaction time increased up to 60 days, AsV became the dominant species. The quick-scanning extended X-ray absorption fine structure (QEAXFS) was introduced to discover the transient intermediate at the highly reactive stage, and a small red-shift in As K-edge absorption edge was observed. The QEAXFS combined with density functional theory (DFT) calculation suggested that the red-shift is likely due to the electron donation in a Fe-O-As complex and possible active sites of As sequestrations include Fe(OH)4 and 4-Fe cluster. This is the first time that the transient reaction intermediate was identified in the As-nZVI sequestration system at the fast-reacting early stage. This study also demonstrated usefulness of in situ monitoring techniques in environmental water research.
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ArsenitosRESUMEN
The optical design of a Hettrick-Underwood-style soft X-ray spectrometer with Wolter type 1 mirrors is presented. The spectrometer with a nominal length of 3.1â m can achieve a high resolving power (resolving power higher than 10000) in the soft X-ray regime when a small source beam (<3â µm in the grating dispersion direction) and small pixel detector (5â µm effective pixel size) are used. Adding Wolter mirrors to the spectrometer before its dispersive elements can realize the spatial imaging capability, which finds applications in the spectroscopic studies of spatially dependent electronic structures in tandem catalysts, heterostructures, etc. In the pump-probe experiments where the pump beam perturbs the materials followed by the time-delayed probe beam to reveal the transient evolution of electronic structures, the imaging capability of the Wolter mirrors can offer the pixel-equivalent femtosecond time delay between the pump and probe beams when their wavefronts are not collinear. In combination with some special sample handing systems, such as liquid jets and droplets, the imaging capability can also be used to study the time-dependent electronic structure of chemical transformation spanning multiple time domains from microseconds to nanoseconds. The proposed Wolter mirrors can also be adopted to the existing soft X-ray spectrometers that use the Hettrick-Underwood optical scheme, expanding their capabilities in materials research.
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The exciton-phonon coupling in highly oriented pyrolytic graphite is studied using resonant inelastic x-ray scattering (RIXS) spectroscopy. With â¼70 meV energy resolution, multiple low energy excitations associated with coupling to phonons can be clearly resolved in the RIXS spectra. Using resonance dependence and the closed form for RIXS cross section without considering the intermediate state mixing of phonon modes, the dimensionless coupling constant g is determined to be 5 and 0.35, corresponding to the coupling strength of 0.42 eV+/-20 meV and 0.20 eV+/-20 meV, for zone center and boundary phonons, respectively. The reduced g value for the zone-boundary phonon may be related to its double resonance nature.
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In this article, the capabilities of soft and hard X-ray techniques, including X-ray absorption (XAS), soft X-ray emission spectroscopy (XES), resonant inelastic soft X-ray scattering (RIXS), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD), and their application to solid-state hydrogen storage materials are presented. These characterization tools are indispensable for interrogating hydrogen storage materials at the relevant length scales of fundamental interest, which range from the micron scale to nanometer dimensions. Since nanostructuring is now well established as an avenue to improve the thermodynamics and kinetics of hydrogen release and uptake, due to properties such as reduced mean free paths of transport and increased surface-to-volume ratio, it becomes of critical importance to explicitly identify structure-property relationships on the nanometer scale. X-ray diffraction and spectroscopy are effective tools for probing size-, shape-, and structure-dependent material properties at the nanoscale. This article also discusses the recent development of in-situ soft X-ray spectroscopy cells, which enable investigation of critical solid/liquid or solid/gas interfaces under more practical conditions. These unique tools are providing a window into the thermodynamics and kinetics of hydrogenation and dehydrogenation reactions and informing a quantitative understanding of the fundamental energetics of hydrogen storage processes at the microscopic level. In particular, in-situ soft X-ray spectroscopies can be utilized to probe the formation of intermediate species, byproducts, as well as the changes in morphology and effect of additives, which all can greatly affect the hydrogen storage capacity, kinetics, thermodynamics, and reversibility. A few examples using soft X-ray spectroscopies to study these materials are discussed to demonstrate how these powerful characterization tools could be helpful to further understand the hydrogen storage systems.
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Interfaces between metal electrodes and π-conjugated polymers play an important role in the organic optoelectronic devices. In this paper, the molecular orientation of the pristine poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (APFO3) films, chemical reactions and the electronic structure during the interface formation of Ca/APFO3 have been investigated in detail using synchrotron radiation photoemission spectroscopy (SRPES), X-ray photoemission spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. It is shown that the APFO3 film has a high degree of orientational ordering with its aromatic ring tilted at an angle of 43° from the substrate, and the 9,9-dioctyl fluorene unit (F8) is almost in the same plane as the benzothiazole unit (BT). Upon vapor-deposition of Ca onto APFO3 at room temperature, Ca dopes electrons into APFO3 and induces the downward band bending of APFO3. Moreover, Ca can diffuse into the APFO3 subsurface and react with N, S and C atoms of APFO3. Finally, the barrier of electron injection at the Ca/APFO3 interface is derived by the energy level alignment diagram. These results enable us to gain comprehensive insights into APFO3 and will facilitate the reasonable design of high performance devices based on APFO3.
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Lithium/sulfur (Li/S) cells have attracted much attention due to their higher theoretical specific capacity and energy compared to those of current lithium-ion cells. However, the application of Li/S cells is still hampered by short cycle life. Sulfur-graphene oxide (S-GO) nanocomposites have shown promise as cathode materials for long-life Li/S cells because oxygen-containing functional groups on the surface of graphene oxide were successfully used as sulfur immobilizers by forming weak bonds with sulfur and polysulfides. While S-GO showed much improved cycling performance, the capacity decay still needs to be improved for commercially viable cells. In this study, we attempt to understand the capacity fading mechanism based on an ex situ study of the structural and chemical evolution of S-GO nanocomposite cathodes with various numbers of cycles using scanning electron microscopy (SEM), near edge X-ray absorption fine structure (NEXAFS) and X-ray photoelectron spectroscopy (XPS). It is found that both the surface morphologies and chemical structures of the cathode materials change considerably with increasing number of cycles. These changes are attributed to several unexpected chemical reactions of lithium with S-GO nanocomposites occurring during the discharge-charge processes with the formation of Li2CO3, Li2SO3, Li2SO4, and COSO2Li species. These reactions result in the loss of recyclable active sulfur on the surface of the electrode, and thus capacity fades while coulombic efficiency is near 100%. Moreover, the reaction products accumulate on the cathode surface, forming a compact blocking insulating layer which may make the diffusion of Li ions into/out of the cathode difficult during the discharge-charge process and thus lead to lower utilization of sulfur at higher rates. We think that these two observations are significant contributors to the capacity and rate capability degradation of the Li/S-GO cells. Therefore, for the rechargeable Li/S-GO cells, we suggest that the content of oxygen-containing functional groups on GO should be optimized and more stable functional groups need to be identified for further improvement of the cycling performance. The information we gain from this study may provide general insights into the fundamental understanding of the degradation mechanisms of other rechargeable Li/S cells using similar oxygen-containing functional groups as sulfur immobilizers.
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OBJECTIVE: This study evaluates intratympanic lidocaine's efficacy and safety for tinnitus relief in sudden sensorineural hearing loss (SSNHL) patients. METHODS: In a double-blind randomized controlled trial, 100 SSNHL patients with unilateral tinnitus received either intratympanic lidocaine or saline plus usual care. Treatment impact was assessed at 1 and 3 months using the Tinnitus Handicap Inventory, subjective visual analog scale, pure-tone audiometry. RESULTS: The lidocaine group demonstrated significant tinnitus relief according to the Tinnitus Handicap Inventory and visual analog scale, without pure-tone audiometry improvement or serious adverse events throughout the study period. CONCLUSION: Intratympanic lidocaine provides a safe, efficacious treatment option for SSNHL tinnitus. Further studies should refine the dosage and delivery parameters because of SSNHL's heterogenous nature.
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Anestésicos Locales , Audiometría de Tonos Puros , Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Inyección Intratimpánica , Lidocaína , Acúfeno , Humanos , Acúfeno/tratamiento farmacológico , Método Doble Ciego , Masculino , Femenino , Lidocaína/administración & dosificación , Lidocaína/uso terapéutico , Persona de Mediana Edad , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Adulto , Resultado del Tratamiento , Pérdida Auditiva Súbita/tratamiento farmacológico , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , AncianoRESUMEN
To address the problems of unstable efficiency, long treatment period, and high energy consumption during microplastics (MPs) removal by traditional coagulation-flotation technology, a gel coagulation-spontaneous flotation (GCSF) process is proposed that employs laminarin (LA) as the crosslinker and polyaluminum chloride (PAC)/polyaluminum ferric chloride (PAFC) as the coagulant to remove MPs. Herein, the effects of GCSF chemical conditions on microplastic-humic acid composite pollutants (MP-HAs) removal were investigated, and the removal mechanisms were analyzed through theoretical calculations and floc structure characterization. Results showed that an LA to PAC/PAFC ratio of 2.5:1 achieved the highest removal of HA (86 %) and MPs (93 %-99 %) in short coagulation (< 1 min) and spontaneous flotation (< 9 min) period. PAC-LA exhibited strong removal ability for MP-HAs while PAFC-LA induced fast flotation speed. The peak intensity and peak shift in Fourier-transformed infrared and X-ray photo-electron spectra indicated that the removal mechanisms of MPs include hydrogen bond adsorption and the sweeping effect, mainly relying on -OH/-C = O on the MPs surface and entrapment of gel flocs with a high degree of aggregation, respectively. The extended Derjaguin-Landau-Verwey-Overbeek calculation also revealed that interactions between PAC/PAFC-LA and MP-HAs were mainly polar interaction (hydrogen bonding) and intermolecular attraction interaction (Lifshitz-van der Waals force), and the sweep effect was reflected by intermolecular interaction. In addition, density function theory calculations indicated that -OH in LA mainly adsorbs DO through a double hydrogen bond configuration, and the crosslinking ligand FeO6/AlO6 assists in DO absorption by -OH.
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Microplásticos , Microplásticos/química , Contaminantes Químicos del Agua/química , Carbono/química , FloculaciónRESUMEN
Objectives: To identify the long-term spatiotemporal trend of ozone-related chronic obstructive pulmonary disease (COPD) burden by sex and country and to explore potential drivers. Methods: We retrieved data of ozone-related COPD death and disability adjusted life year (DALY) from the Global Burden of Disease 2019. We used a linear regression of natural logarithms of age-standardized rates (ASRs) with calendar year to examine the trends in ASRs and a panel regression to identify country-level factors associated with the trends. Results: Global ozone-attributable COPD deaths increased from 117,114 to 208,342 among men and from 90,265 to 156,880 among women between 1990 and 2019. Although ASRs of ozone-related COPD death and DALY declined globally, they increased in low and low-middle Socio-demographic Index (SDI) regions, with faster rise in women. Elevated average maximum temperature was associated with higher ozone-attributable COPD burden, while more green space was associated with lower burden. Conclusion: More efforts are needed in low and low-middle SDI regions, particularly for women, to diminish inter-country inequality in ozone-attributable COPD. Global warming may exacerbate the burden. Expanding green space may mitigate the burden.
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Carga Global de Enfermedades , Salud Global , Ozono , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Ozono/efectos adversos , Femenino , Masculino , Análisis Espacio-Temporal , Persona de Mediana Edad , Anciano , Años de Vida Ajustados por Discapacidad , Contaminantes Atmosféricos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Factores Sexuales , Contaminación del Aire/efectos adversosRESUMEN
This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11.
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Adenocarcinoma del Pulmón , Sistema de Transporte de Aminoácidos y+ , Ferroptosis , Neoplasias Pulmonares , Factores de Empalme de ARN , Regulación hacia Arriba , Humanos , Ferroptosis/genética , Factores de Empalme de ARN/metabolismo , Factores de Empalme de ARN/genética , Ratones , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Animales , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Progresión de la Enfermedad , Masculino , Femenino , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Ratones DesnudosRESUMEN
ILC3s have been identified as crucial immune regulators that play a role in maintaining host homeostasis and modulating the antitumor response. Emerging evidence supports the idea that LTi cells play an important role in initiating lymphoid tissue development, while other ILC3s can promote host defense and orchestrate adaptive immunity, mainly through the secretion of specific cytokines and crosstalk with other immune cells or tissues. Additionally, dysregulation of ILC3-mediated overexpression of cytokines, changes in subset abundance, and conversion toward other ILC subsets are closely linked with the occurrence of tumors and inflammatory diseases. Regulation of ILC3 cytokines, ILC conversion and LTi-induced TLSs may be a novel strategy for treating tumors and intestinal or extraintestinal inflammatory diseases. Herein, we discuss the development of ILCs, the biology of ILC3s, ILC plasticity, the correlation of ILC3s and adaptive immunity, crosstalk with the intestinal microenvironment, controversial roles of ILC3s in intestinal diseases and potential applications for treatment.
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Enfermedades Intestinales , Neoplasias , Humanos , Linfocitos , Inmunidad Innata , Citocinas , Inmunoterapia , Microambiente TumoralRESUMEN
Triple negative breast cancer (TNBC) presents a formidable challenge due to the lack of effective treatment modalities. Immunotherapy stands as a promising therapeutic approach; however, the emergence of drug resistance mechanisms within tumor cells, particularly those targeting apoptosis and pyroptosis, has hampered its clinical efficacy. SHP2 is intricately involved in diverse physiological processes, including immune cell proliferation, infiltration, and tumor progression. Nevertheless, the precise contribution of SHP2 to tumor cell pyroptosis resistance remains inadequately understood. Herein, we demonstrate that SHP2 inhibition hampers the proliferative, migratory, and invasive capabilities of TNBC, accompanied by noticeable alterations in cellular membrane architecture. Mechanistically, we provide evidence that SHP2 depletion triggers the activation of Caspase-1 and GSDMD, resulting in GSDMD-dependent release of LDH, IL-1ß, and IL-18. Furthermore, computational analyses and co-localization investigations substantiate the hypothesis that SHP2 may hinder pyroptosis through direct binding to JNK, thereby impeding JNK phosphorylation. Our cellular experiments further corroborate these findings by demonstrating that JNK inhibition rescues pyroptosis induced by SHP2 knockdown. Strikingly, in vivo experiments validate the suppressive impact of SHP2 knockdown on tumor progression via enhanced JNK phosphorylation. Additionally, SHP2 knockdown augments tumor sensitivity to anti-PD-1 therapy, thus reinforcing the pro-pyroptotic effects and inhibiting tumor growth. In summary, our findings elucidate the mechanism by which SHP2 governs TNBC pyroptosis, underscoring the potential of SHP2 inhibition to suppress cell pyroptosis resistance and its utility as an adjunctive agent for tumor immunotherapy.
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Inhibidores de Puntos de Control Inmunológico , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Piroptosis , Neoplasias de la Mama Triple Negativas , Humanos , Caspasa 1 , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Fosforilación , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
BACKGROUND: Colorectal cancer (CRC) is the most common type of gastrointestinal tumor, but the available pharmacological treatment is insufficient. As a traditional Chinese medicine, the green walnut husks (QLY) exhibit anti-inflammatory, analgesic, anti-bacterial and anti-tumor effects. However, the effects and molecular mechanisms of QLY extracts on CRC were not yet made known. OBJECTIVE: This study aims to provide efficient and low toxicity drugs for the treatment of CRC. The purpose of this study is to explore the anti-CRC effect and mechanism of QLY, providing preliminary data support for clinical research of QLY. METHODS: Western blotting, Flow cytometry, immunofluorescence, Transwell, MTT, Cell proliferation assay, and xenograft model were used to perform the research. RESULTS: In this study, the potential of QLY to inhibit the proliferation, migration invasion and induce apoptosis of the mouse colorectal cancer cell line CT26 in vitro was identified. The xenograft tumor model of CRC noted that QLY suppressed tumor growth without sacrificing body weight in mice. In addition, QLY-induced apoptosis in tumor cells through NLRC3/PI3K/AKT signaling pathway was revealed. CONCLUSION: QLY regulates the levels of mTOR, Bcl-2 and Bax by affecting the NLRC3/PI3K/AKT pathway to promote apoptosis of tumor cells, suppressing cell proliferation, invasion and migration, and subsequently preventing the progression of colon cancer.
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Neoplasias Colorrectales , Juglans , Humanos , Animales , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Colorrectales/metabolismo , Apoptosis , Proliferación Celular , Línea Celular Tumoral , Movimiento Celular , Péptidos y Proteínas de Señalización Intercelular/uso terapéuticoRESUMEN
The past decade has witnessed the development of layered-hydroxide-based self-supporting electrodes, but the low active mass ratio impedes its all-around energy-storage applications. Herein, the intrinsic limit of layered hydroxides is broken by engineering F-substituted ß-Ni(OH)2 (Ni-F-OH) plates with a sub-micrometer thickness (over 700 nm), producing a superhigh mass loading of 29.8 mg cm-2 on the carbon substrate. Theoretical calculation and X-ray absorption spectroscopy analysis demonstrate that Ni-F-OH shares the ß-Ni(OH)2 -like structure with slightly tuned lattice parameters. More interestingly, the synergy modulation of NH4 + and F- is found to serve as the key enabler to tailor these sub-micrometer-thickness 2D plates thanks to the modification effects on the (001) plane surface energy and local OH- concentration. Guided by this mechanism, the superstructures of bimetallic hydroxides and their derivatives are further developed, revealing they are a versatile family with great promise. The tailored ultrathick phosphide superstructure achieves a superhigh specific capacity of 7144 mC cm-2 and a superior rate capability (79% at 50 mA cm-2 ). This work highlights a multiscale understanding of how exceptional structure modulation happens in low-dimensional layered materials. The as-built unique methodology and mechanisms will boost the development of advanced materials to better meet future energy demands.