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1.
Mol Cell Proteomics ; 23(6): 100769, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38641227

RESUMEN

The understanding of dynamic plasma proteome features in hybrid immunity and breakthrough infection is limited. A deeper understanding of the immune differences between heterologous and homologous immunization could assist in the future establishment of vaccination strategies. In this study, 40 participants who received a third dose of either a homologous BBIBP-CorV or a heterologous ZF2001 protein subunit vaccine following two doses of inactivated coronavirus disease 2019 vaccines and 12 patients with BA2.2 breakthrough infections were enrolled. Serum samples were collected at days 0, 28, and 180 following the boosting vaccination and breakthrough and then analyzed using neutralizing antibody tests and mass spectrometer-based proteomics. Mass cytometry of peripheral blood mononuclear cell samples was also performed in this cohort. The chemokine signaling pathway and humoral response markers (IgG2 and IgG3) associated with infection were found to be upregulated in breakthrough infections compared to vaccination-induced immunity. Elevated expression of IGKV, IGHV, IL-17 signaling, and the phagocytosis pathway, along with lower expression of FGL2, were correlated with higher antibody levels in the boosting vaccination groups. The MAPK signaling pathway and Fc gamma R-mediated phagocytosis were more enriched in the heterologous immunization groups than in the homologous immunization groups. Breakthrough infections can trigger more intensive inflammatory chemokine responses than vaccination. T-cell and innate immune activation have been shown to be closely related to enhanced antibody levels after vaccination and therefore might be potential targets for vaccine adjuvant design.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Proteómica , SARS-CoV-2 , Humanos , Proteómica/métodos , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Masculino , Estudios Longitudinales , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunización Secundaria , Vacunación , Estudios de Cohortes , Proteoma , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Infección Irruptiva
2.
Genomics ; 116(5): 110906, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39084477

RESUMEN

Enhancers are crucial in gene expression regulation, dictating the specificity and timing of transcriptional activity, which highlights the importance of their identification for unravelling the intricacies of genetic regulation. Therefore, it is critical to identify enhancers and their strengths. Repeated sequences in the genome are repeats of the same or symmetrical fragments. There has been a great deal of evidence that repetitive sequences contain enormous amounts of genetic information. Thus, We introduce the W2V-Repeated Index, designed to identify enhancer sequence fragments and evaluates their strength through the analysis of repeated K-mer sequences in enhancer regions. Utilizing the word2vector algorithm for numerical conversion and Manta Ray Foraging Optimization for feature selection, this method effectively captures the frequency and distribution of K-mer sequences. By concentrating on repeated K-mer sequences, it minimizes computational complexity and facilitates the analysis of larger K values. Experiments indicate that our method performs better than all other advanced methods on almost all indicators.

3.
Nano Lett ; 24(29): 9065-9073, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38985516

RESUMEN

The metal oxide electron transport layers (ETLs) of n-i-p perovskite solar cells (PSCs) are dominated by TiO2 and SnO2, while the efficacy of the other metal oxide ETLs still lags far behind. Herein, an emerging, economical, and environmentally friendly metal oxide, antimony oxide (Sb2Ox, x = 2.17), prepared by chemical bath deposition is reported as an alternative ETL for PSCs. The deposited Sb2Ox film is amorphous and very thin (∼10 nm) but conformal on rough fluorine-doped tin oxide substrates, showing matched energy levels, efficient electron extraction, and then reduced nonradiative recombination in PSCs. The champion PSC based on the Sb2Ox ETL delivers an impressive power conversion efficiency of 24.7% under one sun illumination, which represents the state-of-the-art performance of all metal oxide ETL-based PSCs. Additionally, the Sb2Ox-based devices show improved operational and thermal stability compared to their SnO2-based counterparts. Armed with these findings, we believe this work offers an optional ETL for perovskites-based optoelectronic devices.

4.
J Am Chem Soc ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196853

RESUMEN

A powerful Pt-catalyzed asymmetric diboration/desymmetric double-allylboration cascade reaction has been developed for the construction of synthetically useful, densely functionalized hydrindanes with five stereocenters, including three quaternary ones, in good yields and excellent enantiomeric excess (ee) values within a single synthetic operation. A unified strategy utilizing this key tandem methodology enabled the concise asymmetric total synthesis of cyathane diterpene (-)-Cyathin B2 in 14 steps from commercially available starting materials, thereby demonstrating its remarkable potential in the synthesis of hydrindane-containing natural products and pharmaceuticals.

5.
J Am Chem Soc ; 146(11): 7198-7203, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38456819

RESUMEN

A new and efficient synthesis of rubriflordilactone A has been realized. The key transformations include the following: (1) an intramolecular Prins cyclization to establish the seven-membered ring containing two contiguous stereocenters; (2) a Mukaiyama hydration/oxa-Michael cascade to construct the B-ring; and (3) an unprecedented stereocontrol intermolecular o-QM type [4 + 2]-cycloaddition to rapidly assemble core structure of rubriflordilactone A.

6.
Apoptosis ; 29(5-6): 768-784, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38493408

RESUMEN

Hepatocellular carcinoma (HCC) is a common cause of cancer-associated death worldwide. The mitochondrial unfolded protein response (UPRmt) not only maintains mitochondrial integrity but also regulates cancer progression and drug resistance. However, no study has used the UPRmt to construct a prognostic signature for HCC. This work aimed to establish a novel signature for predicting patient prognosis, immune cell infiltration, immunotherapy, and chemotherapy response based on UPRmt-related genes (MRGs). Transcriptional profiles and clinical information were obtained from the TCGA and ICGC databases. Cox regression and LASSO regression analyses were applied to select prognostic genes and develop a risk model. The TIMER algorithm was used to investigate immunocytic infiltration in the high- and low-risk subgroups. Here, two distinct clusters were identified with different prognoses, immune cell infiltration statuses, drug sensitivities, and response to immunotherapy. A risk score consisting of seven MRGs (HSPD1, LONP1, SSBP1, MRPS5, YME1L1, HDAC1 and HDAC2) was developed to accurately and independently predict the prognosis of HCC patients. Additionally, the expression of core MRGs was confirmed by immunohistochemistry (IHC) staining, single-cell RNA sequencing, and spatial transcriptome analyses. Notably, the expression of prognostic MRGs was significantly correlated with sorafenib sensitivity in HCC and markedly downregulated in sorafenib-treated HepG2 and Huh7 cells. Furthermore, the knockdown of LONP1 decreased the proliferation, invasion, and migration of HepG2 cells, suggesting that upregulated LONP1 expression contributed to the malignant behaviors of HCC cells. To our knowledge, this is the first study to investigate the consensus clustering algorithm, prognostic potential, immune microenvironment infiltration and drug sensitivity based on the expression of MRGs in HCC. In summary, the UPRmt-related classification and prognostic signature could assist in determining the prognosis and personalized therapy of HCC patients from the perspectives of predictive, preventative and personalized medicine.


Asunto(s)
Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Mitocondrias , Sorafenib , Respuesta de Proteína Desplegada , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/diagnóstico , Respuesta de Proteína Desplegada/efectos de los fármacos , Pronóstico , Sorafenib/farmacología , Sorafenib/uso terapéutico , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Femenino , Línea Celular Tumoral
7.
Funct Integr Genomics ; 24(1): 14, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38236308

RESUMEN

Cytochrome P450s are a large family of protein-encoding genes in plant genomes, many of which have not yet been comprehensively characterized. Here, a novel P450 gene, CYP82D47, was isolated and functionally characterized from cucumber (Cucumis sativus L.). Quantitative real-time reverse-transcription polymerase chain reaction analysis revealed that CYP82D47 expression was triggered by salicylic acid (SA) and ethephon (ETH). Expression analysis revealed a correlation between CYP82D47 transcript levels and plant defense responses against powdery mildew (PM) and Fusarium oxysporum f. sp. cucumerinum (Foc). Although no significant differences were observed in disease resistance between CYP82D47-RNAi and wild-type cucumber, overexpression (OE) of CYP82D47 enhanced PM and Foc resistance in cucumber. Furthermore, the expression levels of SA-related genes (PR1, PR2, PR4, and PR5) increased in CYP82D47-overexpressing plants 7 days post fungal inoculation. The levels of ETH-related genes (EIN3 and EBF2) were similarly upregulated. The observed enhanced resistance was associated with the upregulation of SA/ETH-signaling-dependent defense genes. These findings indicate the crucial role of CYP82D47 in pathogen defense in cucumber. CYP82D47-overexpressing cucumber plants exhibited heightened susceptibility to both diseases. The study results offer important insights that could aid in the development of disease-resistant cucumber cultivars and elucidate the molecular mechanisms associated with the functions of CYP82D47.


Asunto(s)
Cucumis sativus , Fusarium , Compuestos Organofosforados , Cucumis sativus/genética , Regulación hacia Arriba , Resistencia a la Enfermedad/genética , Ácido Salicílico/farmacología
8.
Small ; 20(32): e2308959, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38501792

RESUMEN

Hitherto, highly concentrated electrolyte is the overarching strategy for revitalizing the usage of amide - in lithium-metal batteries (LMBs), which simultaneously mitigates the reactivity of amide toward Li and regulates uniform Li deposition via forming anion-solvated coordinate structure. However, it is undeniable that this would bring the cost burden for practical electrolyte preparation, which stimulates further electrolyte design toward tailoring anion-abundant Li+ solvation structure in stable amide electrolytes under a low salt content. Herein, a distinct method is conceived to design anions-enriched Li+ solvation structure in dilute amide-electrolyte (1 m Li-salt concentration) with the aid of integrating perfluoropolyethers (PFPE-MC) with anion-solvating ability and B/F-involved additives. The optimized electrolyte based on N,N-Dimethyltrifluoroacetamide (FDMAC) exhibits outstanding compatibility with Li and NCM622 cathode, facilitates uniform Li deposition along with robust solid electrolyte interphase (SEI) formation. Accordingly, both the lab-level LMB coin cell and practical pouch cell based on this dilute FDMAC electrolyte deliver remarkable performances with improved capacity and cyclability. This work pioneers the feasibility of diluted amide as electrolyte in LMB, and provides an innovative strategy for highly stable Li deposition via manipulating solvation structure within diluent electrolyte, impelling the electrolyte engineering development for practical high-energy LMBs.

9.
Small ; : e2402320, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38881259

RESUMEN

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

10.
J Transl Med ; 22(1): 58, 2024 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-38221609

RESUMEN

BACKGROUND: Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood. METHODS: In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells. RESULTS: Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy. CONCLUSION: The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.


Asunto(s)
Síndrome de Liberación de Citoquinas , Inmunoterapia Adoptiva , Melatonina , Antígenos CD19 , Tratamiento Basado en Trasplante de Células y Tejidos , Síndrome de Liberación de Citoquinas/terapia , Factores Inmunológicos/farmacología , Inmunoterapia Adoptiva/efectos adversos , Melatonina/farmacología , Recurrencia Local de Neoplasia , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Animales , Ratones
11.
Toxicol Appl Pharmacol ; 483: 116839, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38290667

RESUMEN

Actin filaments form unique structures with robust actin bundles and cytoskeletal networks affixed to the extracellular matrix and interact with neighboring cells, which are crucial structures for cancer cells to acquire a motile phenotype. This study aims to investigate a novel antitumor mechanism by which Tanshinone IIA (Tan IIA) modulates the morphology and migration of liver cancer cells via actin cytoskeleton regulation. 97H and Huh7 exhibited numerous tentacle-like protrusions that interacted with neighboring cells. Following treatment with Tan IIA, 97H and Huh7 showed a complete absence of cytoplasmic protrusion and adherens junctions, thereby effectively impeding their migration capability. The fluorescence staining of F-actin and microtubules indicated that these tentacle-like protrusions and cell-cell networks were actin-based structures that led to morphological changes after Tan IIA treatment by retracting and reorganizing beneath the membrane. Tan IIA can reverse the actin depolymerization and cell morphology alterations induced by latrunculin A. Tan IIA down-regulated actin and Rho GTPases expression significantly, as opposed to inducing Rho signaling activation. Preventing the activity of proteasomes and lysosomes had no discernible impact on the modifications in cellular structure and protein expression induced by Tan IIA. However, as demonstrated by the puromycin labeling technique, the newly synthesized proteins were significantly inhibited by Tan IIA. In conclusion, Tan IIA can induce dramatic actin cytoskeleton remodeling by inhibiting the protein synthesis of actin and Rho GTPases, resulting in the suppression of tumor growth and migration. Targeting the actin cytoskeleton of Tan IIA is a promising strategy for HCC treatment.


Asunto(s)
Abietanos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Actinas , Proteínas de Unión al GTP rho/farmacología , Proliferación Celular , Carcinoma Hepatocelular/tratamiento farmacológico , Citoesqueleto , Citoesqueleto de Actina , Línea Celular Tumoral , Apoptosis
12.
Cancer Cell Int ; 24(1): 235, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970064

RESUMEN

BACKGROUND: Colorectal cancer is among the most common malignant tumors affecting the gastrointestinal tract. Liver metastases, a complication present in approximately 50% of colorectal cancer patients, are a considerable concern. Recently, studies have revealed the crucial role of miR-455 in tumor pathogenesis. However, the effect of miR-455 on the progression of liver metastases in colorectal cancer remains controversial. As an antagonist of bone morphogenetic protein(BMP), Gremlin 1 (GREM1) may impact organogenesis, body patterning, and tissue differentiation. Nevertheless, the role of miR-455 in regulating GREM1 in colorectal cancer liver metastases and how miR-455/GREM1 axis influences tumour immune microenvironment is unclear. METHODS: Bioinformatics analysis shows that miR-455/GREM1 axis plays crucial role in liver metastasis of intestinal cancer and predicts its possible mechanism. To investigate the impact of miR-455/GREM1 axis on the proliferation, invasion, and migration of colorectal cancer cells, colony formation assay, wound healing and transwell assay were examined in vitro. The Dual-Luciferase reporter gene assay and RNA pull-down assay confirmed a possible regulatory effect between miR-455 and GREM1. In vivo, colorectal cancer liver metastasis(CRLM) model mice was established to inquiry the effect of miR-455/GREM1 axis on tumor growth and macrophage polarization. The marker of macrophage polarization was tested using immunofluorescence(IF) and quantitative real-time polymerase chain reaction(qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), cytokines were detected in culture medium supernatants. RESULTS: We found that miR-455 and BMP6 expression was increased and GREM1 expression was decreased in liver metastase compared with primary tumor. miR-455/GREM1 axis promotes colorectal cancer cells proliferation, migration, invasion via affected PI3K/AKT pathway. Moreover, downregulating GREM1 augmented BMP6 expression in MC38 cell lines, inducing M2 polarization of macrophages, and promoting liver metastasis growth in CRLM model mice. CONCLUSION: These data suggest that miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization. These results offer valuable insights and direction for future research and treatment of CRLM.

13.
J Magn Reson Imaging ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39052258

RESUMEN

BACKGROUND: There is increasing interest in utilizing AI-generated content for gadolinium-free contrast-enhanced breast MRI. PURPOSE: To develop a generative model for gadolinium-free contrast-enhanced breast MRI and evaluate the diagnostic utility of the generated scans. STUDY TYPE: Retrospective. POPULATION: Two hundred seventy-six women with 304 breast MRI examinations (49 ± 13 years, 243/61 for training/testing). FIELD STRENGTH/SEQUENCE: ZOOMit diffusion-weighted imaging (DWI), T1-weighted volumetric interpolated breath-hold examination (T1W VIBE), and axial T2 3D SPACE at 3.0 T. ASSESSMENT: A generative model was developed to generate contrast-enhanced scans using precontrast T1W VIBE and DWI images. The generated and real images were quantitatively compared using the structural similarity index (SSIM), mean absolute error (MAE), and Dice similarity coefficient. Three radiologists with 8, 5, and 5 years of experience independently rated the image quality and lesion visibility on AI-generated and real images within various subgroups using a five-point scale. Four breast radiologists, with 8, 8, 5, and 5 years of experience, independently and blindly interpreted four reading protocols: unenhanced MRI protocol alone and combined with AI-generated scans, abbreviated MRI protocol, and full-MRI protocol. STATISTICAL ANALYSIS: Results were assessed using t-tests and McNemar tests. Using pathology diagnosis as reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each reading protocol. A P value <0.05 was considered significant. RESULTS: In the test set, the generated images showed similarity to the real images (SSIM: 0.935 ± 0.047 [SD], MAE: 0.015 ± 0.012 [SD], and Dice coefficient: 0.726 ± 0.177 [SD]). No significant difference in lesion visibility was observed between real and AI-generated scans of the mass, non-mass, and benign lesion subgroups. Adding AI-generated scans to the unenhanced MRI protocol slightly improved breast cancer detection (sensitivity: 92.86% vs. 85.71%, NPV: 76.92% vs. 70.00%); achieved non-inferior diagnostic utility compared to the AB-MRI protocol and full-protocol (sensitivity: 92.86%, 95.24%; NPV: 75.00%, 81.82%). DATA CONCLUSION: AI-generated gadolinium-free contrast-enhanced breast MRI has potential to improve the sensitivity of unenhanced MRI in detecting breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

14.
Cell Commun Signal ; 22(1): 272, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750472

RESUMEN

BACKGROUND: In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. METHODS: Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. RESULTS: Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß, and caused further DNA damage and promoted the apoptosis rate of tumor cells. CONCLUSIONS: Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.


Asunto(s)
Glioma , Glicoproteínas de Membrana , Microglía , Receptores Inmunológicos , Transducción de Señal , Animales , Humanos , Ratones , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Técnicas de Silenciamiento del Gen , Glioma/genética , Glioma/patología , Glioma/metabolismo , Inflamación/genética , Inflamación/patología , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones Endogámicos C57BL , Microglía/metabolismo , Microglía/patología , FN-kappa B/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Transducción de Señal/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética
15.
Langmuir ; 40(22): 11541-11547, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38767530

RESUMEN

Methyl acetate (MA) is a suitable solvent for low-temperature electrolyte solutions, but its poor stability against lithium metal is a big problem. Herein, a simple and cheap solution of LiPF6 dissolved in MA was successfully employed for Li4Ti5O12/graphite dual-ion batteries (DIBs). This cell has a long cycle life with 93.1% capacity retention after 1000 cycles. Moreover, it has superior performance at low temperatures (-40 °C) compared to other reported DIBs. The storage behavior of PF6- solvated by MA in graphite cathode has been investigated in detail by in situ X-ray diffraction (XRD) in combination with electrochemical dilatometry (ECD).

16.
Langmuir ; 40(22): 11353-11370, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38771257

RESUMEN

The essential role of electrolyte solutions in traditional electrochemical energy storage devices is crucial to enhancing their performance. Consequently, a wide array of electrolyte mixtures along with diverse electrodes have been extensively explored across different models of secondary batteries. Fascinatingly, the role of ethyl methyl carbonate (EMC) as a key cosolvent in the electrolyte mixture of commercial lithium-ion batteries with a graphite anode is garnering growing attention in alternative rechargeable dual-ion batteries utilizing graphite cathodes. In this context, the advancement and function of EMC as a solvent in electrolyte mixtures for lithium-ion and dual-ion batteries were extensively and thoroughly examined in this analysis, encompassing the genesis, synthesis process, and diverse characteristics for the practical uses of these batteries. Here, the review aims to guide readers in understanding EMC's function and impact as a cosolvent in electrolyte mixtures for both major secondary lithium-ion and dual-ion batteries, considering their distinct physicochemical characteristics.

17.
Langmuir ; 40(25): 13177-13182, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38863368

RESUMEN

LiPF6 dissolved in dimethyl carbonate (DMC) is one of the cheapest groups of electrolyte solutions in dual-ion batteries. Generally, the discharge capacity of anion storage delivered by the graphite cathode grows with increasing LiPF6 concentration. This fact is consistent with the irreversible storage of DMC-solvated PF6-, and then, the underlying mechanism is clarified by the electrochemical tests and ex situ X-ray diffraction (XRD) measurements of graphite cathodes as well as infrared (IR) and Raman spectroscopy characterizations of solutions. Moreover, quaternary ammonium salts have facile dissociation, which can effectively regulate the solvation state of the anion and the interaction between ion pairs in the electrolyte. A small amount of tetrabutylammonium hexafluorophosphate (TBAPF6) is introduced into the highly concentrated LiPF6-DMC solution to improve the performance of the graphite cathode. The discharge capacity of the Li/graphite cell has increased by approximately 50%. This effect is also correlated with the solvation state of the anion. This study provides an insightful clue for the choice of electrolyte solution in dual-ion batteries.

18.
Langmuir ; 40(2): 1418-1424, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38158394

RESUMEN

A straightforward hybrid approach of a blend cathode is put forward to alleviate self-discharged anion-graphite intercalation compounds in dual-ion batteries. The self-discharge mechanism of the LiNi0.5Mn1.5O4/graphite blend cathode is investigated by conventional electrochemical tests and in situ X-ray diffraction measurements. A charging behavior between electrode materials during self-discharge has been discovered. This work will contribute to advancing the practical implementation of dual-ion batteries and provide valuable theoretical support for the research of blend electrodes.

19.
J Org Chem ; 89(3): 1703-1708, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38227772

RESUMEN

Visible-light-induced three-component 1,2-alkylpyridylation of alkenes with unactivated alkyl iodides and aryl cyanides is reported via a photocatalytic halogen-atom transfer (XAT) strategy. This metal-free protocol utilizes readily available tertiary alkylamine as the terminal reductant to smoothly convert alkyl iodides into the corresponding carbon radical species. The reaction features a broad substrate scope, excellent functional group tolerance, high efficiency, and mild reaction conditions. The practicability of this methodology is further demonstrated in the late-stage difunctionalization of bioactive molecules.

20.
Crit Care ; 28(1): 162, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741134

RESUMEN

BACKGROUND: The effect of the periurethral cleansing range on catheter-associated urinary tract infection (CAUTI) occurrence remains unknown. The purpose of this study was to evaluate the efficacy of expanded periurethral cleansing for reducing CAUTI in comatose patients. METHODS: In this randomized controlled trial, eligible patients in our hospital were enrolled and allocated randomly to the experimental group (expanded periurethral cleansing protocol; n = 225) or the control group (usual periurethral cleansing protocol; n = 221). The incidence of CAUTI on days 3, 7, and 10 after catheter insertion were compared, and the pathogen results and influencing factors were analyzed. RESULTS: The incidences of CAUTI in the experimental and control groups on days 3, 7, and 10 were (5/225, 2.22% vs. 7/221, 3.17%, P = 0.54), (12/225, 5.33% vs. 18/221, 8.14%, P = 0.24), and (23/225, 10.22% vs. 47/221, 21.27%, P = 0.001), respectively; Escherichia coli and Candida albicans were the most common species in the two groups. The incidences of bacterial CAUTI and fungal CAUTI in the two groups were 11/225, 4.89% vs. 24/221, 10.86%, P = 0.02) and (10/225, 4.44% vs. 14/221, 6.33%, P = 0.38), respectively. The incidences of polymicrobial CAUTI in the two groups were 2/225 (0.89%) and 9/221 (4.07%), respectively (P = 0.03). The percentages of CAUTI-positive females in the two groups were 9.85% (13/132) and 29.52% (31/105), respectively (P < 0.05). The proportion of CAUTI-positive patients with diabetes in the experimental and control groups was 17.72% (14/79), which was lower than the 40.85% (29/71) in the control group (P < 0.05). CONCLUSION: Expanded periurethral cleansing could reduce the incidence of CAUTI, especially those caused by bacteria and multiple pathogens, in comatose patients with short-term catheterization (≤ 10 days). Female patients and patients with diabetes benefit more from the expanded periurethral cleansing protocol for reducing CAUTI.


Asunto(s)
Infecciones Relacionadas con Catéteres , Coma , Infecciones Urinarias , Humanos , Femenino , Infecciones Urinarias/prevención & control , Infecciones Urinarias/epidemiología , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Catéteres/prevención & control , Infecciones Relacionadas con Catéteres/epidemiología , Adulto , Anciano , Cateterismo Urinario/efectos adversos , Cateterismo Urinario/métodos , Uretra
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