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Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.
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Menopause is a normal physiological process accompanied by changes in various physiological states. The incidence of vascular calcification (VC) increases each year after menopause and is closely related to osteoporosis (OP). Although many studies have investigated the links between VC and OP, the interaction mechanism of the two under conditions of estrogen loss remains unclear. MicroRNAs (miRNAs), which are involved in epigenetic modification, play a critical role in estrogen-mediated mineralization. In the past several decades, miRNAs have been identified as biomarkers or therapeutic targets in diseases. Thus, we hypothesize that these small molecules can provide new diagnostic and therapeutic approaches. In this review, we summarize the close interactions between VC and OP and the role of miRNAs in their interplay.
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MicroRNAs , Pós-Menopausa , Calcificação Vascular , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Feminino , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Pós-Menopausa/genética , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , Estrogênios/metabolismo , Biomarcadores/metabolismo , Osteoporose/genética , Osteoporose/metabolismo , Epigênese GenéticaRESUMO
The Python-based program, XMECP, is developed for realizing robust, efficient, and state-of-the-art minimum energy crossing point (MECP) optimization in multiscale complex systems. This article introduces the basic capabilities of the XMECP program by theoretically investigating the MECP mechanism of several example systems including (1) the photosensitization mechanism of benzophenone, (2) photoinduced proton-coupled electron transfer in the cytosine-guanine base pair in DNA, (3) the spin-flip process in oxygen activation catalyzed by an iron-containing 2-oxoglutarate-dependent oxygenase (Fe/2OGX), and (4) the photochemical pathway of flavoprotein adjusted by the intensity of an external electric field. MECPs related to multistate reaction and multistate reactivity in large-scale complex biochemical systems can be well-treated by workflows suggested by the XMECP program. The branching plane updating the MECP optimization algorithm is strongly recommended as it provides derivative coupling vector (DCV) with explicit calculation and can equivalently evaluate contributions from non-QM residues to DCV, which can be nonadiabatic coupling or spin-orbit coupling in different cases. In the discussed QM/MM examples, we also found that the influence on the QM region by DCV can occur through noncovalent interactions and decay with distance. In the example of DNA base pairs, the nonadiabatic coupling occurs across the π-π stacking structure formed in the double-helix system. In contrast to general intuition, in the example of Fe/2OGX, the central ferrous and oxygen part contribute little to the spin-orbit coupling; however, a nearby arginine residue, which is treated by molecular mechanics in the QM/MM method, contributes significantly via two hydrogen bonds formed with α-ketoglutarate (α-KG). This indicates that the arginine residue plays a significant role in oxygen activation, driving the initial triplet state toward the productive quintet state, which is more than the previous knowledge that the arginine residue can bind α-KG at the reaction site by hydrogen bonds.
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Preeclampsia (PE) is considered as a disease of placental origin. However, the specific mechanism of placental abnormalities remains elusive. This study identified thrombospondin-1 (THBS1) is downregulated in preeclamptic placentae and negatively correlated with blood pressure. Functional studies show that THBS1 knockdown inhibits proliferation, migration, and invasion and increases the cycle arrest and apoptosis rate of HTR8/SVneo cells. Importantly, THBS1 silencing induces necroptosis in HTR8/SVneo cells, accompanied by the release of damage-associated molecular patterns (DAMPs). Necroptosis inhibitors necrostatin-1 and GSK'872 restore the trophoblast survival while pan-caspase inhibitor Z-VAD-FMK has no effect. Mechanistically, the results show that THBS1 interacts with transforming growth factor B-activated kinase 1 (TAK1), which is a central modulator of necroptosis quiescence and affects its stability. Moreover, THBS1 silencing up-regulates the expression of neuronal precursor cell-expressed developmentally down-regulated 4 (NEDD4), which acts as an E3 ligase of TAK1 and catalyzes K48-linked ubiquitination of TAK1 in HTR8/SVneo cells. Besides, THBS1 attenuates PE phenotypes and improves the placental necroptosis in vivo. Taken together, the down-regulation of THBS1 destabilizes TAK1 by activating NEDD4-mediated, K48-linked TAK1 ubiquitination and promotes necroptosis and DAMPs release in trophoblast cells, thus participating in the pathogenesis of PE.
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MAP Quinase Quinase Quinases , Necroptose , Ubiquitina-Proteína Ligases Nedd4 , Pré-Eclâmpsia , Trombospondina 1 , Trofoblastos , Ubiquitinação , Humanos , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/genética , Feminino , Gravidez , Trofoblastos/metabolismo , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , Necroptose/genética , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Ubiquitina-Proteína Ligases Nedd4/genética , Trombospondina 1/metabolismo , Trombospondina 1/genética , Adulto , Placenta/metabolismoRESUMO
As an iron dependent regulatory cell death process driven by excessive lipid peroxides (LPO), ferroptosis is recognized as a powerful weapon for pancreatic cancer (PC) therapy. However, the tumor microenvironment (TME) with hypoxia and elevated glutathione (GSH) expression not only inhibits LPO production, but also induces glutathione peroxidase 4 (GPX4) mediated LPO clearance, which greatly compromise the therapeutic outcomes of ferroptosis. To address these issues, herein, a novel triple-enhanced ferroptosis amplifier (denoted as Zal@HM-PTBC) is rationally designed. After intravenous injection, the overexpressed H2O2/GSH in TME induces the collapse of Zal@HM-PTBC and triggers the production of oxygen and reactive oxygen species (ROS), which synergistically amplify the degree of lipid peroxidation (broaden sources). Concurrently, GSH consumption because of the degradation of the hollow manganese dioxide (HM) significantly weakens the activity of GPX4, resulting in a decrease in LPO clearance (reduce expenditure). Moreover, the loading and site-directed release of zalcitabine further promotes autophagy-dependent LPO accumulation (enhance effectiveness). Both in vitro and in vivo results validated that the ferroptosis amplifier demonstrated superior specificity and favorable therapeutic responses. Overall, this triple-enhanced LPO accumulation strategy demonstrates the ability to facilitate the efficacy of ferroptosis, injecting vigorous vitality into the treatment of PC.
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Ferroptose , Glutationa , Peróxidos Lipídicos , Neoplasias Pancreáticas , Ferroptose/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Animais , Peróxidos Lipídicos/metabolismo , Humanos , Linhagem Celular Tumoral , Glutationa/metabolismo , Camundongos , Compostos de Manganês/química , Óxidos/química , Espécies Reativas de Oxigênio/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Camundongos Nus , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
Although metal-organic polyhedra (MOPs) expansion has been studied to date, it is still a rare occurrence for their porous intermolecular assembly for iodine capture. The major limitation is the lack of programmable and controllable methods for effectively constructing and utilizing the exterior cavities. Herein, the goal of programmable porous intermolecular assembly is realized in the first family of aluminum oxo polyhedrons (AlOPs) using ligands with directional H-bonding donor/acceptor pairs and auxiliary alcohols as structural regulation sites. The approach has the advantage of avoiding the use of expensive edge-directed ditopic and face-directed tritopic ligands in the general synthesis strategy of MOPs. Combining theoretical calculations and experiments, the intrinsic relationship is revealed between alcohol ligands and the growth mechanism of AlOPs. The maximum I2 uptake based on the mass gain during sorption corresponds to 2.35 g g-1, representing the highest reported I2 sorption by an MOP. In addition, it can be easily regenerated and maintained the iodine sorption capacity, revealing its further potential application. This method of constructing stable and programmable porous materials will provide a new way to solve problems such as radionuclide capture.
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Citrinin derivatives have been found to have various pharmacological activities, such as anti-inflammatory, anti-tumor, and antioxidant effects. Dicitrinone G (DG) was a new citrinin dimer isolated from marine-derived fungus Penicillium sp. GGF 16-1-2 which has potential activity. Here, we aim to investigate whether DG has anti-pancreatic cancer activity. In xenograft tumor model, 2 × 106 BXPC-3 cells were injected into the hind flank of NU/NU nude mice by subcutaneously for 2 weeks followed by treating with DG (0.25, 0.5, 1 mg/kg) and 5-FU (30 mg/kg) for 4 weeks. Tumor volume and weight were measured, and the expression of CD31, IL-18, NLRP3, and Caspase-1 in tumor tissue were detected. In vitro, HUVECs were treated with conditioned medium (CM) derived from BXPC-3 cells, the effects of DG on angiogenesis were detected by tube formation and western blot analysis. In vivo studies showed that the tumor growth and angiogenesis were greatly suppressed. The tumor weight inhibition rates of DG and 5-FU groups were about 42.36%, 38.94%, 43.80%, and 31.88%. Furthermore, the expression of CD31 and Caspase-1 were decreased. In vitro, CM derived from BXPC-3 cells which treated with DG could inhibit the tube formation and expression of pro-angiogenic NICD in HUVECs. Our study suggests that DG could suppress angiogenesis via the NLRP3/IL-18 pathway and may have the potential to inhibit tumor development.
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Citrinina , Penicillium , Animais , Camundongos , Humanos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Camundongos Nus , Angiogênese , Caspase 1/metabolismo , Fluoruracila/farmacologiaRESUMO
OBJECTIVE: To evaluate the effectiveness of Tai Chi on cognitive function in older adults with mild cognitive impairment. METHODS: A systematic search of eight English and five Chinese electronic databases was conducted to identify randomized controlled trials of Tai Chi as the intervention. The main outcomes included executive function, episodic memory, visuospatial function, working memory, concentration, memory complaints, and global cognition. The Cochrane RoB tool was used to assess bias in the study. Meta-analysis was conducted using Review Manager 5.4. Narrative syntheses were performed if meta-analysis was inappropriate. RESULTS: A total of eleven trials (905 participants) were included. Meta-analysis showed that Tai Chi significantly and moderately affected executive function (SMD = -1.01, 95% CI: -1.54 to -0.47, p < 0.001), episodic memory (SMD = 0.59, 95% CI: 0.24 to 0.94, p = 0.001), visuospatial function (SMD = 0.38, 95% CI: 0.15 to 0.60, p < 0.001), and global cognition (SMD = 0.57, 95% CI: 0.14 to 1.00, p = 0.01).One study showed that Tai Chi could improve verbal fluency. CONCLUSIONS: This review reveals that Tai Chi can improve executive function, episodic memory, visuospatial function, and global cognition in older adults with mild cognitive impairment, but not working memory, concentration, or memory complaints. These findings are consist with existing reviews about the effectiveness of Tai Chi. Long-duration (> 1500 min) Tai Chi is more effective for improving global cognition. However, the findings should be interpreted with caution due to the potential risk of bias and limited sample sizes of the included studies. Future trials should examine the effectiveness of standardized Tai Chi intervention on cognitive outcomes in older adults with mild cognitive impairment.
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Disfunção Cognitiva , Tai Chi Chuan , Humanos , Idoso , Ensaios Clínicos Controlados Aleatórios como Assunto , Cognição , Disfunção Cognitiva/terapia , Função ExecutivaRESUMO
The reactive oxygen species (ROS) produced through the Fenton reaction, induces lipid peroxide (LPO), causing cellular structural damage and ultimately triggering ferroptosis. However, the generation of ROS in the tumor microenvironment (TME) is limited by the catalytic efficiency of the Fenton reaction. Herein, a novel hollow mesoporous silica nanoparticle (HMSN) combined with multi-metal sulfide-doped mesoporous silica nanocatalyzers (NCs) was developed, namely MxSy-HMSN NCs (M represents Cu Mn and Fe, S denotes sulfur). The MxSy-HMSN can dramatically enhanced the ferroptosis by: (1) facilitating the conversion of H2O2 to ·OH through Fenton or Fenton-like reactions through co-catalysis; (2) weakening ROS scavenging systems by depleting the over expressed glutathione (GSH) in TME; (3) providing exceptional photothermal therapy to augment ferroptosis. The MxSy-HMSN can also act as smart cargos for anticancer drug-doxorubicin (DOX). The release of DOX is responsive to GSH/pH/Near-infrared Light (NIR) irradiation at the tumor lesion, significantly improving therapeutic outcomes while minimizing side effects. Additionally, the MxSy-HMSN has demonstrated excellent magnetic resonance imaging (MRI) potential. This smart MxSy-HMSN offer a synergetic approach combining ferroptosis with chemo-photothermal therapy and magnetic resonance imaging (MRI) diagnose, which could be an informative guideline for the design of future NCs.
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Antineoplásicos , Ferroptose , Neuropatia Hereditária Motora e Sensorial , Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Fototerapia/métodos , Medicina de Precisão , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Doxorrubicina/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/química , Dióxido de Silício/química , Neuropatia Hereditária Motora e Sensorial/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Background: As China amends its "zero COVID" strategy, a sudden increase in the number of infections may overwhelm medical resources and its impact has not been quantified. Specific mitigation strategies are needed to minimize disruption to the healthcare system and to prepare for the next possible epidemic in advance. Method: We develop a stochastic compartmental model to project the burden on the medical system (that is, the number of fever clinic visits and admission beds) of China after adjustment to COVID-19 policy, which considers the epidemiological characteristics of the Omicron variant, age composition of the population, and vaccine effectiveness against infection and severe COVD-19. We also estimate the effect of four-dose vaccinations (heterologous and homologous), antipyretic drug supply, non-pharmacological interventions (NPIs), and triage treatment on mitigating the domestic infection peak. Result: As to the impact on the medical system, this epidemic is projected to result in 398.02 million fever clinic visits and 16.58 million hospitalizations, and the disruption period on the healthcare system is 18 and 30 days, respectively. Antipyretic drug supply and booster vaccination could reduce the burden on emergency visits and hospitalization, respectively, while neither of them could not reduce to the current capacity. The synergy of several different strategies suggests that increasing the heterologous booster vaccination rate for older adult to over 90% is a key measure to alleviate the bed burden for respiratory diseases on the basis of expanded healthcare resource allocation. Conclusion: The Omicron epidemic followed the adjustment to COVID-19 policy overloading many local health systems across the country at the end of 2022. The combined effect of vaccination, antipyretic drug supply, triage treatment, and PHSMs could prevent overwhelming medical resources.
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Antipiréticos , COVID-19 , Humanos , Idoso , Antipiréticos/uso terapêutico , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , China/epidemiologia , Febre , PolíticasRESUMO
BACKGROUND: Although the majority of pregnancies with preeclampsia are characterised by elevated blood pressure, preeclampsia is often associated with nephrotic syndrome with similar symptoms such as high proteinuria and bilateral lower limb oedema. In this study, we compared the maternal-foetal outcomes of pregnant women with preeclampsia in a population with nephrotic syndrome and explored the factors that contribute to the corresponding outcomes and disease development. METHODS: A total of 90 pregnant women were included in this study, of whom 30 had nephrotic syndrome and were diagnosed with preeclampsia during pregnancy, and 60 had nephrotic syndrome alone. Descriptive statistical analyses of baseline data were performed to analyse the effect of combined preeclampsia on maternal and foetal pregnancy outcomes using unadjusted and adjusted logistic regression models. RESULTS: In this study, the baseline data of the two study populations demonstrated no differences except for the history of caesarean section and 24-h proteinuria results, which were significantly different (P < 0.05). The risk of preterm birth in the nephrotic syndrome with preeclampsia group was 8.25 (95% CI:3.041-22.084 P < 0.05); for a low birth weight, the risk was 6.00 (95% CI:2.302-15.638 P < 0.05); for foetal distress,the risk was 5.667 (95% CI:2.070-15.514 P < 0.05); and the risk of foetal birth restriction was 7.429 (95% CI: 2.642-20.885 P < 0.05). A risk-based analysis of adverse maternal outcomes yielded a risk of miscarriage of 2.200 (95% CI: 0.584-8.291; P > 0.05). After adjusting the model for each outcome, significant risks of preterm labour, foetal birth restriction, and low birth weight were revealed (P < 0.05). CONCLUSION: Combined preeclampsia has a significantly higher risk of adverse pregnancy outcomes for the foetus.Therefore, the prevention and control of eclampsia in pregnant women should be improved to ensure maternal and neonatal health.
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Síndrome Nefrótica , Pré-Eclâmpsia , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/diagnóstico , Nascimento Prematuro/epidemiologia , Síndrome Nefrótica/complicações , Síndrome Nefrótica/epidemiologia , Cesárea , Resultado da Gravidez/epidemiologia , Proteinúria/epidemiologiaRESUMO
Zeolitic metal-organic frameworks (ZMOFs) have emerged as one of the most promsing catalysts for energy conversion, but they suffer from either weak bonding between metal-organic cubes (MOCs) that decrease their stability during catalysis processes or low activity due to inadequate active sites. In this work, through ligand-directing strategy, we successfully obtain an unprecedented bismuth-based ZMOF (Bi-ZMOF) featuring a ACO topological crystal structure with strong coordination bonding between the Bi-based cages. As a result, it enables efficient reduction of CO2 to formic acid (HCOOH) with Faradaic efficiency as high as 91 %. A combination of in situ surface-enhanced infrared absorption spectroscopy and density functional theory calculation reveals that the Bi-N coordination contributes to facilitating charge transfer from N to Bi atoms, which stabilize the intermediate to boost the reduction efficiency of CO2 to HCOOH. This finding highlights the importance of the coordination environment of metal active sites on electrocatalytic CO2 reduction. We believe that this work will offer a new clue to rationally design zeolitic MOFs for catalytic reaction.
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Noroviruses (NoVs) are the leading viral pathogens globally causing acute gastroenteritis (AGE) in humans, posing a significant global health threat and economic burden. Recent investigations revealed that human NoVs had been detected in different animals, which raises concerns about whether NoVs are potential zoonotic diseases. This study developed a novel luciferase immunosorbent assay (LISA) to detect GII.6 NoV IgG based on P protein of VP1. The LISA showed high specificity (99.20%) and sensitivity (92.00%) with 4-16 times more sensitivity compared with an ELISA. NoV-LISA was reproducible with human serum regarding the inter- and intra-assay coefficient of variance values. Potential cross-reactivity was also evaluated using mice serum immunized by other antigens, which showed that NoV-LISA could differentiate GII.6 NoV from rotavirus and various genotypes of NoV. Specific GII.6 NoV IgG was widely detected in different domestic and wild animals, including dogs, pigs, bats, rats, and home shrews, with various IgG-positive rates ranging from 2.5 to 74.4%. In conclusion, our newly developed NoV-LISA assay is suitable for NoV-specific IgG detection in humans and animals. The wide distribution of IgG antibodies against human NoV indicates potential zoonotic transmission between humans and animals.
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Purpose: The Tunisian stool-associated parvovirus [Tusavirus (TuV)] is a novel member of the genus Protoparvovirus, which may be linked to diarrhea. Herein, we investigated the prevalence of TuV in different populations and analyzed its genetic and bioinformatic characteristics. Methods: This study was conducted in a tertiary hospital in Guangzhou (China) from February 2018 to July 2022. Demographic and clinical information and stool samples were collected from individuals who visited the hospital. ProtScale, SwissModel, Datamonkey, and other tools were used to analyze and predict the physicochemical parameters, tertiary structure, selection pressure, and B-cell epitopes of capsid viral protein 2 of TuV (VP2-TuV). Results: A total of 3,837 participants were enrolled, among which two stool samples from patients with chronic illnesses were tested positive for TuV DNA. However, no positive sample was detected among patients with diarrhea. Two near-complete genome sequences were amplified. The genetic analysis revealed the presence of diversity among TuVs isolated from distinct host species. Bioinformatics analysis revealed that VP2-TuV exhibited hydrophilic properties and lacked transmembrane domains and signal peptides. The secondary structure of VP2-TuV was composed mainly of random coils and ß-strands. Selective-pressure analysis of the VP2 region suggested that TuV primarily underwent negative selection during evolution. Negatively selected codon sites coincided with residues comprising of B-cell epitopes, suggesting minimal changes in the immunogenicity of TuV over time. Conclusion: TuV was detected in patients with chronic diseases but not in patients with diarrhea. The putative roles of TuV in the pathogenicity of human diseases and zoonotic viruses must be determined by additional studies.
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Endometriosis is characterized by the presence of endometrial tissue outside the uterus that not only causes severe pelvic pain and infertility but also increased risk for ovarian carcinogenesis in women of reproductive age. Here, we found that angiogenesis was increased and accompanied with up-regulation of Notch1 in human endometriotic tissue sample, which is associated with pyroptosis induced by activation of endothelial NLRP3 inflammasome. Further, in endometriosis model induced in wild type and NLRP3-deficient (NLRP3-KO) mice, we found that deficiency of NLRP3 suppressing the development of endometriosis. In vitro, inhibiting the activation of NLRP3 inflammasome prevents LPS/ATP-induced tube formation in endothelial cells. Meanwhile, knockdown NLRP3 expression by gRNA disrupt the interaction between Notch1 and HIF-1α under the inflammatory microenvironment. This study demonstrates that activation of NLRP3 inflammasome-mediated pyroptosis affects angiogenesis in endometriosis via Notch1-dependent manner.
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Endometriose , Inflamassomos , Humanos , Feminino , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células Endoteliais/metabolismo , Piroptose , Transdução de SinaisRESUMO
Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy with diverse histological types. This study aimed to detect neoantigens in ccRCC to develop mRNA vaccines and distinguish between ccRCC immunological subtypes for construction of an immune landscape to select patients suitable for vaccination. Using The Cancer Genome Atlas SpliceSeq database, The Cancer Genome Atlas, and the International Cancer Genome Consortium cohorts, we comprehensively analysed potential tumour antigens of ccRCC associated with aberrant alternative splicing, somatic mutation, nonsense-mediated mRNA decay factors, antigen-presenting cells, and overall survival. Immune subtypes (C1/C2) and nine immune gene modules of ccRCC were identified by consistency clustering and weighted correlation network analysis. The immune landscape as well as molecular and cellular characteristics of immunotypes were assessed. Rho-guanine nucleotide exchange factor 3 (ARHGEF3) was identified as a new ccRCC antigen for development of an mRNA vaccine. A higher tumour mutation burden, differential expression of immune checkpoints, and immunogenic cell death were observed in cases with the C2 immunotype. Cellular characteristics increased the complexity of the immune environment, and worse outcomes were observed in ccRCC cases with the C2 immunotype. We constructed the immune landscape for selecting patients with the C2 immunotype suitable for vaccination.
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Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Seleção de Pacientes , Vacinas Sintéticas , RNA Mensageiro/genética , Neoplasias Renais/genética , Vacinas de mRNARESUMO
Metal molecular rings are a class of compounds with aesthetically pleasing symmetry and fundamentally useful properties. The reported work generally focuses on the ring center cavity, and there is little known about those on the ring waist. Herein, we report the discovery of porous aluminum molecular rings and their performance and contribution to the cyanosilylation reaction. We develop a facile ligand induced aggregation and solvent regulation strategy towards AlOC-58NC and AlOC-59NT with high purity, high yield (75% and 70%, respectively) and gram-level scale-up. These molecular rings exhibit a "two-tier" pore feature involving the general central cavity and newly observed equatorial semi-open cavities. AlOC-59NT with two types of one-dimensional channels showed good catalytic activity. The interaction of the aluminum molecular ring catalyst with the substrate has been crystallographically characterized and theoretically confirmed, showing a ring adaptability process that involves the capture and binding of the substrate. This work provides new ideas for the assembly of porous metal molecular rings and to understand the overall reaction pathway involving aldehydes and is expected to inspire the design of low-cost catalysts through structural modifications.
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The photocatalytic hydrogenation of CO2 by Cu-deposited ZnO (Cu/ZnO) polar surfaces is investigated through density functional theory (DFT) calculations combined with experimental work. The DFT results demonstrate that, without Cu-loading, CO2 and H2 present weak physisorption on the clean ZnO polar surface, except that H2 undergoes strong chemisorption on the ZnO(0001Ì) surface. Cu deposition on the ZnO polar surface could remarkably enhance the CO2 chemisorption ability, due to the induced charge redistribution on the interface of the Cu/ZnO polar surface systems. Additionally, a Cu-nanoisland, which was simulated using a Cu(111) slab model, exhibited strong ability to chemically adsorb H2. Thus, H2 may act as an adsorption competitor to CO2 on the Cu/ZnO(0001Ì), while, in contrast, CO2 and H2 (syngas) may have more opportunity to simultaneously adsorb on Cu/ZnO(0001) to promote the CO2 hydrogenation. These facet-dependent properties lead us to assume that Cu/ZnO(0001) should be a favorable photocatalyst for CO2 hydrogenation. This assumption is further verified by our photocatalysis experiment based on a ZnO single crystal. According to the theoretical and experimental results, the optimal HCOO* reaction pathway for the photocatalytic hydrogenation of CO2 on Cu/ZnO(0001) is proposed. In this optimal HCOO* path, the hydrogenation of CO2* step and hydrogenation of HCOO* step could be promoted by the coupling of a photo-generated spillover proton and a photoelectron on the interface of Cu/ZnO(0001). This research demonstrates the feasibility of the photocatalytic reduction of CO2 on Cu/ZnO(0001), and will help to develop related high-efficiency catalysts.
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Background: Resilience is one of the most important variables associated with adaptive ability. The resilience scale for the oldest-old age (RSO) has been designed to measure the resilience among the oldest-old people. Originally developed in Japan, this scale has not been used in China. The objective of this study was to translate the RSO into Chinese and investigate its validity and reliability among the community's oldest-old adults aged ≥80 years. Methods: A total of 473 oldest-old people who came from communities were recruited by convenience sampling for the assessment of construct validity using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). In addition, internal consistency reliability, test-retest reliability, face validity, and content validity were used to evaluate the psychometric characteristics of RSO. Results: The RSO demonstrated good face validity and content validity. The content validity index of the Chinese version of the RSO was 0.890. Moreover, one factor was extracted by exploratory factor analysis, which accounted for 61.26% of the variance. The RSO had high internal consistency with a Cronbach's alpha = 0.927. The test-retest reliability was 0.785. The item-total correlations ranged from 0.752 to 0.832. Conclusion: The results of the study indicate that the Chinese version of the RSO questionnaire has good reliability and validity and can be recommended for use by health and social service agencies as a method for assessing the resilience of the oldest-old in the community.