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Efficient photocatalytic CO2 reduction coupled with the photosynthesis of pure H2O2 is a challenging and significant task. Herein, using classical CO2 photoreduction site iron porphyrinate as the linker, Ag(I) clusters were spatially separated and evenly distributed within a new metal-organic framework (MOF), namely Ag27TPyP-Fe. With water as electron donors, Ag27TPyP-Fe exhibited remarkable performances in artificial photosynthetic overall reaction with CO yield of 36.5 µmol g-1 h-1 and ca. 100% selectivity, as well as H2O2 evolution rate of 35.9 µmol g-1 h-1. Since H2O2 in the liquid phase can be more readily separated from the gaseous products of CO2 photoreduction, high-purity H2O2 with a concentration up to 0.1 mM was obtained. Confirmed by theoretical calculations and the established energy level diagram, the reductive iron(II) porphyrinates and oxidative Ag(I) clusters within an integrated framework functioned synergistically to achieve artificial photosynthesis. Furthermore, photoluminescence spectroscopy and photoelectrochemical measurements revealed that the robust connection of Ag(I) clusters and iron porphyrinate ligands facilitated efficient charge separation and rapid electron transfer, thereby enhancing the photocatalytic activity.
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BACKGROUND: Checkpoint inhibitor therapy has demonstrated overall survival benefit in multiple tumor types. Tumor mutational burden (TMB) is a predictive biomarker for response to immunotherapies. This study evaluated the efficacy of nivolumab+ipilimumab in multiple tumor types based on TMB status evaluated using either tumor tissue (tTMB) or circulating tumor DNA in the blood (bTMB). PATIENTS AND METHODS: Patients with metastatic or unresectable solid tumors with high (≥10 mutations per megabase) tTMB (tTMB-H) and/or bTMB (bTMB-H) who were refractory to standard therapies were randomized 2:1 to receive nivolumab+ipilimumab or nivolumab monotherapy in an open-label, phase 2 study (CheckMate 848; NCT03668119). tTMB and bTMB were determined by the Foundation Medicine FoundationOne® CDx test and bTMB Clinical Trial Assay, respectively. The dual primary endpoints were objective response rate (ORR) in patients with tTMB-H and/or bTMB-H tumors treated with nivolumab+ipilimumab. RESULTS: In total, 201 patients refractory to standard therapies were randomized: 135 had tTMB-H and 125 had bTMB-H; 82 patients had dual tTMB-H/bTMB-H. In patients with tTMB-H, ORR was 38.6% (95% CI 28.4% to 49.6%) with nivolumab+ipilimumab and 29.8% (95% CI 17.3% to 44.9%) with nivolumab monotherapy. In patients with bTMB-H, ORR was 22.5% (95% CI 13.9% to 33.2%) with nivolumab+ipilimumab and 15.6% (95% CI 6.5% to 29.5%) with nivolumab monotherapy. Early and durable responses to treatment with nivolumab+ipilimumab were seen in patients with tTMB-H or bTMB-H. The safety profile of nivolumab+ipilimumab was manageable, with no new safety signals. CONCLUSIONS: Patients with metastatic or unresectable solid tumors with TMB-H, as determined by tissue biopsy or by blood sample when tissue biopsy is unavailable, who have no other treatment options, may benefit from nivolumab+ipilimumab. TRIAL REGISTRATION NUMBER: NCT03668119.
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Protocolos de Quimioterapia Combinada Antineoplásica , Ipilimumab , Neoplasias , Nivolumab , Humanos , Nivolumab/uso terapéutico , Nivolumab/administración & dosificación , Nivolumab/farmacología , Femenino , Ipilimumab/uso terapéutico , Ipilimumab/administración & dosificación , Ipilimumab/farmacología , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Mutación , Anciano de 80 o más Años , Metástasis de la NeoplasiaRESUMEN
Polyphenol oxidase (PPO) activity drives walnut fruit browning, but the roles of its only two-family genes, JrPPO1 and JrPPO2, remain unclear. This study explores the spatiotemporal expression and enzymatic characteristics of JrPPO1 and JrPPO2 in walnut. Treatment with the PPO activator CuSO4 and H2O2 accelerated fruit browning and up-regulated JrPPO1/2 expression, whereas treatment with the PPO inhibitor ascorbic acid delayed browning, down-regulating JrPPO1 and up-regulating JrPPO2 expression. Compared to mJrPPO1, mJrPPO2 can exhibited better enzyme activity at higher temperatures (47 °C) and in more acidic environments (pH 4.25). mJrPPO2 exhibited a higher substrate specificity over mJrPPO1, and the preferred substrates are catechol, chlorogenic acid, and epicatechin. Additionally, mJrPPO2 adapted better to low concentration of oxygen (as low as 1.0% O2) and slightly elevated CO2 levels compared to mJrPPO1. Subcellular localization and spatiotemporal expression patterns showed that JrPPO1 is only expressed in green tissues and located in chloroplasts, while JrPPO2 is also located in chloroplasts, partly associated with membranes, and is expressed in both green and non-green tissues. Silencing JrPPO1/2 with virus-induced gene silencing (VIGS) reduced fruit browning, maintained higher total phenols, and decreased MDA production. Notably, silencing JrPPO1 had a greater impact on browning than JrPPO2, indicating JrPPO1's greater contribution to PPO activity and fruit browning in walnut fruits. Consequently, JrPPO1 can be effectively regulated both at the molecular level and by manipulating environmental conditions, to achieve the objective of controlling fruit browning.
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Catecol Oxidasa , Frutas , Regulación de la Expresión Génica de las Plantas , Juglans , Proteínas de Plantas , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Frutas/genética , Frutas/metabolismo , Juglans/genética , Juglans/metabolismo , Catecol Oxidasa/metabolismoRESUMEN
Physical exercise is recognized for its beneficial effects on brain health and executive function, particularly through the careful manipulation of key exercise parameters, including type, intensity, and duration. The aim of this systematic review and meta-analysis was to delineate the optimal types, intensities, and durations of exercise that improve cognitive functions in older adults with mild cognitive impairment (MCI) or dementia. A comprehensive search was conducted in Scopus, Web of Science, and PubMed from their inception until December 2023. The methodological quality and publication bias of the included studies were assessed using the PEDro scale and Egger's regression test, respectively. Separate meta-analyses were performed to assess the overall impact of exercise on cognitive assessments and to explore the effects of different exercise types (i.e., aerobic, resistance, dual-task, mind-body, and multi-component exercises) and intensities (i.e., low, moderate, and high) on executive function. Results were presented as standardized mean differences (SMD) and 95% confidence intervals (95% CI). A meta-regression analysis was conducted to examine the correlation between exercise duration and mean effects. In total, 15,087 articles were retrieved from three databases, of which 35 studies were included in our final analyses. The results indicated high overall methodological quality (PEDro score = 8) but a potential for publication bias (t = 2.08, p = 0.045). Meta-analyses revealed that all types of exercise (SMD = 0.691, CI [0.498 to 0.885], p < 0.001) and intensities (SMD = 0.694, CI [0.485 to 0.903], p < 0.001) show significant effects favoring exercise. Notably, dual-task exercises (SMD = 1.136, CI [0.236 to 2.035], p < 0.001) and moderate-intensity exercises (SMD = 0.876, CI [0.533 to 1.219], p < 0.001) exhibited the greatest effect. No significant correlation was observed between exercise duration and SMD (R² = 0.038, p = 0.313). Overall, our meta-analyses support the role of physical exercise in enhancing executive function in older adults with MCI or dementia. It is essential to carefully tailor exercise parameters, particularly type and intensity, to meet the specific needs of older adults with MCI or dementia. Such customization is crucial for optimizing executive function outcomes and improving overall brain health.
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To mitigate the greenhouse effect, a number of porous organic polymers (POPs) has been developed for carbon capture. Considering the permanent quadrupole of symmetrical CO2 molecules, the integration of electron-rich groups into POPs is a feasible way to enhance the dipole-quadrupole interactions between host and guest. To comprehensively explore the effect of pore environment, including specific surface area, pore size, and number of heteroatoms, on carbon dioxide adsorption capacity, we synthesized a series of microporous POPs with different content of ß-ketoenamine structures via Schiff-base condensation reactions. These materials exhibit high BET specific surface areas, high stability, and excellent CO2 adsorption capacity. It is worth mentioning that the CO2 adsorption capacity and CO2/N2 selectivity of TAPPy-TFP reaches 3.87 mmol g-1 and 27. This work demonstrates that the introduction of ß-ketoenamine sites directly through condensation reaction is an effective strategy to improve the carbon dioxide adsorption performance of carbon dioxide.
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Amino acid homeostasis is interconnected with the immune network of plants. During plant-pathogen interaction, amino acid transporters (AATs) have been shown to be involved in plant immune responses. However, the molecular mechanism by which how AATs function in this process remains elusive. In this study, we identify OsMP1 that acts as a quantitative trait locus against blast fungus from a joint analysis of GWAS and QTL mapping in rice. Heterogeneous expression of OsMP1 in yeast supports its function in transporting a wide range of amino acids, including Thr, Ser, Phe, His and Glu. OsMP1 could also mediate 15N-Glu efflux and influx in Xenopus oocyte cells. The expression of OsMP1 is dramatically induced by Magnaporthe oryzae in the resistant landrace Heikezijing, while remaining unresponsive in the susceptible landrace Suyunuo. Overexpressing OsMP1 in Suyunuo enhances disease resistance to blast fungus and leaf-blight bacterium without yield penalty. Furthermore, the overexpression of OsMP1 leads to increased accumulation of Thr, Ser, Phe and His in the leaves. And the heightened levels of these amino acids contribute to reduced disease susceptibility, which is associated with upregulated jasmonic acid pathway. Thus, our results elucidate the pivotal role of OsMP1 in disease resistance and provide a potential target for breeding more resistant rice cultivars without compromising yield.
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The intratumoral microbiome (TM) refers to the microorganisms in the tumor tissues, including bacteria, fungi, viruses, and so on, and is distinct from the gut microbiome and circulating microbiota. TM is strongly associated with tumorigenesis, progression, metastasis, and response to therapy. This paper highlights the current status of TM. Tract sources, adjacent normal tissue, circulatory system, and concomitant tumor co-metastasis are the main origin of TM. The advanced techniques in TM analysis are comprehensively summarized. Besides, TM is involved in tumor progression through several mechanisms, including DNA damage, activation of oncogenic signaling pathways (phosphoinositide 3-kinase [PI3K], signal transducer and activator of transcription [STAT], WNT/ß-catenin, and extracellular regulated protein kinases [ERK]), influence of cytokines and induce inflammatory responses, and interaction with the tumor microenvironment (anti-tumor immunity, pro-tumor immunity, and microbial-derived metabolites). Moreover, promising directions of TM in tumor therapy include immunotherapy, chemotherapy, radiotherapy, the application of probiotics/prebiotics/synbiotics, fecal microbiome transplantation, engineered microbiota, phage therapy, and oncolytic virus therapy. The inherent challenges of clinical application are also summarized. This review provides a comprehensive landscape for analyzing TM, especially the TM-related mechanisms and TM-based treatment in cancer.
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Crack generation and propagation are critical aspects of grinding processes for hard and brittle materials. Despite extensive research, the impact of residual cracks from coarse grinding on the cracks generated during fine grinding remains unexplored. This study aims to bridge this gap by examining the propagation law of existing cracks under indentation using the extended finite element method. The results reveal that prefabricated cracks with depths less than the crack depth produced on an undamaged surface tend to extend further without surpassing the latter. Conversely, deeper prefabricated cracks do not exhibit significant expansion. A novel method combining indentation and prefabricated cracks with fracture strength tests is proposed to determine crack propagation. Silicon wafers with varying damaged surfaces are analyzed, and changes in fracture strength, measured by the ball-on-ring method, are utilized to determine crack propagation. The experimental results confirm the proposed crack evolution law, validated by damage assessments across different grinding processes, which is suitable for crack damage. The findings demonstrate that residual cracks from coarse grinding are negligible in predicting the maximum crack depth during fine grinding. This research provides a crucial foundation for optimizing the wafer thinning process in 3D stacked chip manufacturing, establishing that changes in fracture strength are a reliable indicator of crack propagation feasibility.
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BACKGROUND: Colorectal cancer (CRC) patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) status are conventionally perceived as unresponsive to adjuvant chemotherapy (ACT). The mitochondrial transcription factor A (TFAM) is required for mitochondrial DNA copy number (mtDNA-CN) expression. In light of previous findings indicating that the frequent truncating-mutation of TFAM affects the chemotherapy resistance of MSI CRC cells, this study aimed to explore the potential of mtDNA-CN as a predictive biomarker for ACT efficacy in dMMR CRC patients. METHODS: Levels of MtDNA-CN were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) in a cohort of 308 CRC patients with dMMR comprising 180 stage II and 128 stage III patients. Clinicopathologic and therapeutic data were collected. The study examined the association between mtDNA-CN levels and prognosis, as well as the impact of ACT benefit on dMMR CRC patients. Subgroup analyses were performed based mainly on tumor stage and mtDNA-CN level. Kaplan-Meier and Cox regression models were used to evaluate the effect of mtDNA-CN on disease-free survival (DFS) and overall survival (OS). RESULTS: A substantial reduction in mtDNA-CN expression was observed in tumor tissue, and higher mtDNA-CN levels were correlated with improved DFS (73.4% vs 85.7%; P = 0.0055) and OS (82.5% vs 90.3%; P = 0.0366) in dMMR CRC patients. Cox regression analysis identified high mtDNA-CN as an independent protective factor for DFS (hazard ratio [HR] 0.547; 95% confidence interval [CI] 0.321-0.934; P = 0.0270) and OS (HR 0.520; 95% CI 0.272-0.998; P = 0.0492). Notably, for dMMR CRC patients with elevated mtDNA-CN, ACT significantly improved DFS (74.6% vs 93.4%; P = 0.0015) and OS (81.0% vs 96.7%; P = 0.0017), including those with stage II or III disease. CONCLUSIONS: The mtDNA-CN levels exhibited a correlation with the prognosis of stage II or III CRC patients with dMMR. Elevated mtDNA-CN emerges as a robust prognostic factor, indicating improved ACT outcomes for stages II and III CRC patients with dMMR. These findings suggest the potential utility of mtDNA-CN as a biomarker for guiding personalized ACT treatment in this population.
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Biomarcadores de Tumor , Neoplasias Colorrectales , Variaciones en el Número de Copia de ADN , Reparación de la Incompatibilidad de ADN , ADN Mitocondrial , Inestabilidad de Microsatélites , Estadificación de Neoplasias , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , ADN Mitocondrial/genética , Femenino , Masculino , Quimioterapia Adyuvante , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Anciano , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , AdultoRESUMEN
Background: Diffuse large B-cell lymphoma (DLBCL) is the predominant type of malignant B-cell lymphoma. Although various treatments have been developed, the limited efficacy calls for more and further exploration of its characteristics. Methods: Datasets from the Gene Expression Omnibus (GEO) database were used for identifying the tumor purity of DLBCL. Survival analysis was employed for analyzing the prognosis of DLBCL patients. Immunohistochemistry was conducted to detect the important factors that influenced the prognosis. Drug-sensitive prediction was performed to evaluate the value of the model. Results: VCAN, CD3G, and C1QB were identified as three key genes that impacted the outcome of DLBCL patients both in GEO datasets and samples from our center. Among them, VCAN and CD3G+ T cells were correlated with favorable prognosis, and C1QB was correlated with worse prognosis. The ratio of CD68 + macrophages and CD8 + T cells was associated with better prognosis. In addition, CD3G+T cells ratio was significantly correlated with CD68 + macrophages, CD4 + T cells, and CD8 +T cells ratio, indicating it could play an important role in the anti-tumor immunity in DLBCL. The riskScore model constructed based on the RNASeq data of VCAN, C1QB, and CD3G work well in predicting the prognosis and drug sensitivity. Conclusions: VCAN, CD3G, and C1QB were three key genes that influenced the tumor purity of DLBCL, and could also exert certain impact on drug sensitivity and prognosis of DLBCL patients. Funding: This work is supported by the Shenzhen High-level Hospital Construction Fund and CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-062).
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Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/inmunología , Pronóstico , Femenino , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Covalent organic frameworks are a class of crystalline porous polymers formed by linking organic units into periodically aligned skeletons and pores. Here we report a strategy for wiring these frameworks with conducting polymers via wall engineering and polymerization. We anchored each edge site with one pyrrole unit, which is densely packed along the z direction yet protruded from pore walls. This assembly enables the polymerization of pyrrole units to form polypyrrole and creates a new polypyrrole chain conformation. The resultant framework constitutes six single file polypyrrole chains in each pore and develop spatially segregated yet built-in single molecular wires with exceptional stable polarons. Hall effect measurements revealed that the materials are p-type semiconductors, increase conductivity by eight orders of magnitude compared to the pristine frameworks, and achieve a carrier mobility as large as 13.2 cm2 V-1 s-1. Our results open an avenue to π electronic frameworks by interlayer molecular wiring with conducting polymers.
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BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.
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Electrocatalytic carbon dioxide reduction reaction (CO2RR) is an effective way of converting CO2 into value-added products using renewable energy, whose activity and selectivity can be in principle maneuvered by tuning the microenvironment near catalytic sites. Here, we demonstrate a strategy for tuning the microenvironment of CO2RR by learning from the natural chlorophyll and heme. Specifically, the conductive covalent organic frameworks (COFs) linked by piperazine serve as versatile supports for single-atom catalysts (SACs), and the pendant groups modified on the COFs can be readily tailored to offer different push-pull electronic effects for tunable microenvironment. As a result, while all the COFs exhibit high chemical structure stability under harsh conditions and good conductivity, the addition of -CH2NH2 can greatly enhance the activity and selectivity of CO2RR. As proven by experimental characterization and theoretical simulation, the electron-donating group (-CH2NH2) not only reduces the surface work function of COF, but also improves the adsorption energy of the key intermediate *COOH, compared with the COFs with electron-withdrawing groups (-CN, -COOH) near the active sites. This work provides insights into the microenvironment modulation of CO2RR electrocatalysts at the molecular level.
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We identify a population of Protogenin-positive (PRTG+ve) MYChigh NESTINlow stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RLVZ). Oncogenic transformation of early Prtg+ve rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG+ve stem cells grow adjacent to a human-specific interposed vascular plexus in the RLVZ, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTGhigh compartment of Gr3-MB in vivo using either the diphtheria toxin system or chimeric antigen receptor T cells constitutes effective therapy. Human Gr3-MBs likely arise from early embryonic RLVZ PRTG+ve stem cells inhabiting a specific perivascular niche. Targeting the PRTGhigh compartment and/or the perivascular niche represents an approach to treat children with Gr3-MB.
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Meduloblastoma , Células Madre Neoplásicas , Humanos , Meduloblastoma/patología , Meduloblastoma/metabolismo , Animales , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Ratones , Rombencéfalo/metabolismo , Rombencéfalo/embriología , Neoplasias Cerebelosas/metabolismo , Neoplasias Cerebelosas/patología , Células Endoteliales/metabolismo , Nicho de Células Madre , Células Madre/metabolismo , Técnicas de Cocultivo , Estructuras Embrionarias , Metencéfalo/embriologíaRESUMEN
Soil freeze-thaw processes and snowmelt infiltration have a significant impact on the hydrological cycle and ecosystem productivity in alpine pastoral areas. To investigate the driving mechanism of snow on soil freeze-thaw processes, a meteorological station was established in the southern part of Namatso Lake, Tibet to collect environmental data. The study included analyzing the relationship between soil temperature and humity, as well as assessing soil freeze-thaw characteristics and the evolution of soil frost heave over time. The freeze-thaw frequency was significantly 43% lower at the surface soil, and the freeze-thaw intensity decreased when the ground was snow-covered. During the initial freezing period, precipitation and soil humidity remain relatively low, and soil moisture decreases linearly with decreasing soil temperature, which occurs in the phenomenon of soil freeze-shrink. During the initial thawing period, snowmelt infiltration impacts soil humidity, and soil frost heave increases logarithmically, reaching a maximum of 5.2 mm, driven by freeze-thaw. Soil moisture decreases under topsoil evaporation in the later stage and again follows a linear trend with the soil temperature. This study not only reveals the correlation between soil temperature and humidity during different freeze-thaw periods but also enhances the understanding of soil deformation patterns under the influence of snow accumulation.
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Metabolic dysfunction-associated steatohepatitis (MASH) is a severe metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by abnormal hepatic steatosis and inflammation. Previous studies have shown that Patchouli alcohol (PA), the primary component of Pogostemonis Herba, can alleviate digestive system diseases. However, its protection against MASH remains unclear. This study explored the protective effects and underlying mechanism of PA against high-fat diet-induced MASH in rats. Results showed that PA considerably reduced body weight, epididymal fat, and liver index and attenuated liver histological injury in MASH rats. PA alleviated hepatic injury by inhibiting steatosis and inflammation. These effects are associated with the improvement of SREBP-1c- and PPARα-mediated lipid metabolism and inhibition of the STING-signaling pathway-mediated inflammatory response. Moreover, PA-inhibited hepatic endoplasmic reticulum (ER) stress and mitochondrial dysfunction, reducing SREBP-1c and STING expressions and enhance PPARα expression. PA treatment had the strongest effect on the regulation of mitogen fusion protein 2 (Mfn2) in inhibiting mitochondrial dysfunction. Mfn2 is an important structural protein for binding ERs and mitochondria to form mitochondria-associated ER membranes (MAMs). MASH-mediated disruption of MAMs was inhibited after PA treatment-induced Mfn2 activation. Therefore, the pharmacological effect of PA on MASH is mainly attributed to the inhibition of MAM disruption-induced hepatic steatosis and inflammation. The findings of this study may have implications for MASH treatment that do not neglect the role of Mfn2-mediated MAMs.
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Dieta Alta en Grasa , Estrés del Retículo Endoplásmico , Retículo Endoplásmico , PPAR alfa , Ratas Sprague-Dawley , Sesquiterpenos , Animales , Masculino , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Ratas , Sesquiterpenos/uso terapéutico , Sesquiterpenos/farmacología , PPAR alfa/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hígado/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Hígado Graso/patología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Metabolismo de los Lípidos/efectos de los fármacos , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Pogostemon , Transducción de Señal/efectos de los fármacosRESUMEN
The pore shapes of two-dimensional covalent organic frameworks (2D COFs) significantly limit their practical applications in separation and catalysis. Although various 2D COFs with polygonal pores have been well developed, constructing COFs with pentagonal pores remains an enormous challenge. In this work, we developed one kind of pentagonal COFs with the mcm topological structure for the first time, through the rational combination of C4 and C2 symmetric building blocks. The resulting pentagonal COFs exhibit high crystallinity, excellent porosity, and strong robustness. Moreover, the inbuilt porphyrin units render these COFs as efficient electrocatalytic catalysts toward oxygen reduction reaction with a half-wave potential of up to 0.81 V, which ranks as one of the highest values among COFs-based electrocatalysts. This work not only verified the possibility of constructing 2D COFs with pentagonal pores but also developed a strategy for the construction of functional 2D COFs for interesting applications.
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Molecular sieving is an ideal separation mechanism, but controlling pore size, restricting framework flexibility, and avoiding strong adsorption are all very challenging. Here, we report a flexible adsorbent showing molecular sieving at ambient temperature and high pressure, even under high humidity. While typical guest-induced transformations are observed, a high transition pressure of 16.6â atm is observed for C2H4 at 298â K because of very weak C2H4 adsorption (~16â kJ mol-1). Also, C2H6 is completely excluded below the pore-opening pressure of 7.7â atm, giving single-component selectivity of ca. 300. Quantitative high-pressure column breakthrough experiments using 1 : 1â C2H4/C2H6 mixtures at 10â atm as input confirm molecular sieving with C2H4 adsorption of 0.73â mmol g-1 or 32â cm3(STP) cm-3 and negligible C2H6 adsorption of 0.001(2) mmol g-1, and the adsorbent can be completely regenerated by inert gas purging. Furthermore, it is highly hydrophobic with negligible water adsorption, and the C2H4/C2H6 separation performance is unaffected at high humidity.
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Nanoimprinting large-area structures, especially high-density features like meta lenses, poses challenges in achieving defect-free nanopatterns. Conventional high-resolution molds for nanoimprinting are often expensive, typically constructed from inorganic materials such as silicon, nickel (Ni), or quartz. Unfortunately, replicated nanostructures frequently suffer from breakage or a lack of definition during demolding due to the high adhesion and friction at the polymer-mold interface. Moreover, mold degradation after a limited number of imprinting cycles, attributed to contamination and damaged features, is a common issue. In this study, a disruptive approach is presented to address these challenges by successfully developing an anti-sticking nanocomposite mold. This nanocomposite mold is created through the co-deposition of nickel atoms and low surface tension polytetrafluoroethylene (PTFE) nanoparticles via electroforming. The incorporation of PTFE enhances the ease of polymer release from the mold. The resulting Ni-PTFE nanocomposite mold exhibits exceptional lubrication properties and a significantly reduced surface energy. This robust nanocomposite mold proves effective in imprinting fine, densely packed nanostructures down to 100 nm using thermal nanoimprinting for at least 20 cycles. Additionally, UV nanoimprint lithography (UV-NIL) is successfully performed with this nanocomposite mold. This work introduces a novel and cost-effective approach to reusable high-resolution molds, ensuring defect-reduction production in nanoimprinting.