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Intrinsic neural activities are characterized as endless spontaneous fluctuation over multiple time scales. However, how the intrinsic brain organization changes over time under local perturbation remains an open question. By means of statistical physics, we proposed an approach to capture whole-brain dynamics based on estimating time-varying nonreversibility and k-means clustering of dynamic varying nonreversibility patterns. We first used synthetic fMRI to investigate the effects of window parameters on the temporal variability of varying nonreversibility. Second, using real test-retest fMRI data, we examined the reproducibility, reliability, biological, and physiological correlation of the varying nonreversibility substates. Finally, using repetitive transcranial magnetic stimulation-fMRI data, we investigated the modulation effects of repetitive transcranial magnetic stimulation on varying nonreversibility substate dynamics. The results show that: (i) as window length increased, the varying nonreversibility variance decreased, while the sliding step almost did not alter it; (ii) the global high varying nonreversibility states and low varying nonreversibility states were reproducible across multiple datasets and different window lengths; and (iii) there were increased low varying nonreversibility states and decreased high varying nonreversibility states when the left frontal lobe was stimulated, but not the occipital lobe. Taken together, these results provide a thermodynamic equilibrium perspective of intrinsic brain organization and reorganization under local perturbation.
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Mapeo Encefálico , Encéfalo , Reproducibilidad de los Resultados , Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Estimulación Magnética Transcraneal/métodos , Lóbulo FrontalRESUMEN
Developing a highly active catalyst that can efficiently capture and convert carbon dioxide (CO2) into high-value-added energy materials remains a severe challenge, which inspires us to explore effective metal-organic frameworks (MOFs) with high chemical stability and high-density active sites. Herein, we report a robust 3D lead(II)-organic framework of {(Me2NH2)2[Pb5(PTTPA)2(H2O)3]·2DMF·3H2O}n (NUC-111) with unreported [Pb10(COO)22(H2O)6] clusters (abbreviated as {Pb10}) as nodes (H6PTTPA = 4,4',4â³-(pyridine-2,4,6-triyl)triisophthalic acid). After thermal activation, NUC-111a is functionalized by the multifarious symbiotic acid-base active sites of open Pb2+ sites and uncoordinated pyridine groups on the inner surface of the void volume. Gas adsorption tests confirm that NUC-111a displays a higher separation performance for mixed gases of f CO2 and CH4 with the selectivity of CO2/CH4 at 273 K and 101 kPa being 31 (1:99, v/v), 23 (15:85, v/v), and 8 (50:50, v/v), respectively. When the temperature rises to 298 K, the selectivity of CO2/CH4 at 101 kPa is 26 (1:99, v/v), 22 (15:85, v/v), and 11 (50:50, v/v). Moreover, activated NUC-111a exhibited excellent catalytic performance, stability, and recyclability for the cycloaddition of CO2 with epoxides under mild conditions. Hence, this work provides valuable insight into designing MOFs with multifunctionality for CO2 capture, separation, and conversion.
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Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive approach to modulate brain activity and behavior in humans. Still, how individual resting-state brain dynamics after rTMS evolves across different functional configurations is rarely studied. Here, using resting state fMRI data from healthy subjects, we aimed to examine the effects of rTMS to individual large-scale brain dynamics. Using Topological Data Analysis based Mapper approach, we construct the precise dynamic mapping (PDM) for each participant. To reveal the relationship between PDM and canonical functional representation of the resting brain, we annotated the graph using relative activation proportion of a set of large-scale resting-state networks (RSNs) and assigned the single brain volume to corresponding RSN-dominant or a hub state (not any RSN was dominant). Our results show that (i) low-frequency rTMS could induce changed temporal evolution of brain states; (ii) rTMS didn't alter the hub-periphery configurations underlined resting-state brain dynamics; and (iii) the rTMS effects on brain dynamics differ across the left frontal and occipital lobe. In conclusion, low-frequency rTMS significantly alters the individual temporo-spatial dynamics, and our finding further suggested a potential target-dependent alteration of brain dynamics. This work provides a new perspective to comprehend the heterogeneous effect of rTMS.
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Encéfalo , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Lóbulo Occipital , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiologíaRESUMEN
In order to achieve the high adsorption and catalytic performance of CO2, the direct self-assembly of robust defect-engineered MOFs is a scarcely reported and challenging proposition. Herein, a highly robust nanoporous indium(III)-organic framework of {[In2(CPPDA)(H2O)3](NO3)·2DMF·3H2O}n (NUC-107) consisting of two kinds of inorganic units of chain-shaped [In(COO)2(H2O)]n and watery binuclear [In2(COO)4(H2O)8] was generated by regulating the growth environment. It is worth mentioning that [In2(COO)4(H2O)8] is very rare in terms of its richer associated water molecules, implying that defect-enriched metal ions in the activated host framework can serve as strong Lewis acid. Compared to reported skeleton of [In4(CPPDA)2(µ3-OH)2(DMF)(H2O)2]n (NUC-66) with tetranuclear clusters of [In4(µ3-OH)2(COO)10(DMF)(H2O)2] as nodes, the void volume of NUC-107 (50.7%) is slightly lower than the one of NUC-66 (52.8%). However, each In3+ ion in NUC-107 has an average of 1.5 coordinated small molecules (H2O), which far exceeds the average of 0.75 in NUC-66 (H2O and DMF). After thermal activation, NUC-107a characterizes the merits of unsaturated In3+ sites, free pyridine moieties, solvent-free nanochannels (10.2 × 15.7 Å2). Adsorption tests prove that the host framework of NUC-107a has a higher CO2 adsorption (113.2 cm3/g at 273 K and 64.8 cm3/g at 298 K) than NUC-66 (91.2 cm3/g at 273 K and 53.0 cm3/g at 298 K). Catalytic experiments confirmed that activated NUC-107a with the aid of n-Bu4NBr was capable of efficiently catalyzing the cycloaddition of CO2 with epoxides into corresponding cyclic carbonates under the mild conditions. Under the similar conditions of 0.10 mol% MOFs, 0.5 mol% n-Bu4NBr, 0.5 MP CO2, 60 °C and 3 h, compared with NUC-66a, the conversion of SO to SC catalyzed by NUC-107a increased by 21%. Hence, this work offers a valuable perspective that the in situ creation of robust defect-engineered MOFs can be realized by regulating the growth environment.
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We investigate the "roughness" of the energy landscape of a system that diffuses in a heterogeneous medium with a random position-dependent friction coefficient α(x). This random friction acting on the system stems from spatial inhomogeneity in the surrounding medium and is modeled using the generalized Caldira-Leggett model. For a weakly disordered medium exhibiting a Gaussian random diffusivity D(x) = kBT/α(x) characterized by its average value ⟨D(x)⟩ and a pair-correlation function ⟨D(x1)D(x2)⟩, we find that the renormalized intrinsic diffusion coefficient is lower than the average one due to the fluctuations in diffusivity. The induced weak internal friction leads to increased roughness in the energy landscape. When applying this idea to diffusive motion in liquid water, the dissociation energy for a hydrogen bond gradually approaches experimental findings as fluctuation parameters increase. Conversely, for a strongly disordered medium (i.e., ultrafast-folding proteins), the energy landscape ranges from a few to a few kcal/mol, depending on the strength of the disorder. By fitting protein folding dynamics to the escape process from a metastable potential, the decreased escape rate conceptualizes the role of strong internal friction. Studying the energy landscape in complex systems is helpful because it has implications for the dynamics of biological, soft, and active matter systems.
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This case report presents a detailed analysis of a 31-year-old male patient who presented with a complex array of clinical symptoms, including proteinuria, hematuria, edema, and kidney insufficiency. Despite undergoing multiple tests, the results for anti-glomerular basement membrane antibodies yielded negative findings. Subsequently, kidney biopsy pathology revealed a distinct diagnosis of atypical anti-glomerular basement membrane (anti-GBM) disease with membrane hyperplasia. Treatment was initiated with a comprehensive approach involving high doses of corticosteroids therapy and cyclophosphamide (CTX). However, contrary to expectations, the patient's kidney function exhibited rapid deterioration following this therapeutic regimen. The culmination of these complications necessitated a pivotal transition to maintenance hemodialysis. This case underscores the intricate challenges associated with diagnosing and managing rare and atypical presentations of kidney disorders. The negative anti-GBM antibody results and subsequent identification of atypical anti-GBM nephropathy highlight the need for tailored diagnostic strategies to discern subtle nuances within complex clinical scenarios. Additionally, the unexpected response to the treatment regimen emphasizes the potential variability in individual patient responses, underlining the necessity for vigilant monitoring and adaptable treatment strategies. This case report contributes to the evolving understanding of atypical kidney pathologies and the complexities involved in their management.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular , Masculino , Humanos , Adulto , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/complicaciones , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Hiperplasia/patología , Riñón/patología , Autoanticuerpos , Proteinuria/etiología , Proteinuria/complicaciones , Ciclofosfamida/uso terapéuticoRESUMEN
To investigate the effect and mechanism of polydatin on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF-α, LPS, IL-6 and IL-1ß in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α-diversity, ß-diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx-induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM-treated or untreated ABx mice. The histopathological changes and collagen I and α-SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM-induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin-treated BLM mice effectively alleviated lung fibrosis in BLM-treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM-induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect.
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Microbioma Gastrointestinal , Fibrosis Pulmonar , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/terapia , Fibrosis Pulmonar/metabolismo , Bleomicina/farmacología , Pulmón/patología , Fibrosis , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ratones Endogámicos C57BLRESUMEN
To improve the catalytic performance of metal-organic frameworks (MOFs), creating higher defects is now considered as the most effective strategy, which can not only optimize the Lewis acidity of metal ions but also create more pore space to enhance diffusion and mass transfer in the channels. Herein, the exquisite combination of scarcely reported [In2(CO2)5(H2O)2(DMF)2] clusters and 2,6-bis(2,4-dicarboxylphenyl)-4-(4-carboxylphenyl)pyridine (H5BDCP) under solvothermal conditions generated a highly robust nanoporous framework of {[In2(BDCP)(DMF)2(H2O)2](NO3)}n (NUC-65) with nanocaged voids (14.1 Å) and rectangular nanochannels (15.94 Å × 11.77 Å) along the a axis. It is worth mentioning that an In(1) ion displays extremely low tetra-coordination modes after the thermal removal of its associated four solvent molecules of H2O and DMF. Activated {[In2(BDCP)](Br)}n (NUC-65Br), as a defective material because of its extremely unsaturated metal centers, could be generated by bromine ion exchange, solvent exchange, and vacuum drying. Catalytic experiments proved that the conversion of epichlorohydrin with 1 atm CO2 into 4-(chloromethyl)-1,3-dioxolan-2-one catalyzed by 0.11 mol % NUC-65Br could reach 99% at 65 °C within 24 h. Moreover, with the aid of 5 mol % cocatalyst n-Bu4NBr, heterogeneous NUC-65Br owns excellent universal catalytic performance in most epoxides under mild conditions. In addition, NUC-65Br, as a heterogeneous catalyst, exhibits higher activity and better selectivity for Knoevenagel condensation of aldehydes and malononitrile. Hence, this work offers a fresh insight into the design of structure defect cationic metal-organic frameworks, which can be better applied to various fields because of their promoted performance.
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With the introduction of Eu3+ ions as the secondary fluorescent signal reporter and sensing active sites, a dual-emission ratiometric sensor of Eu3+@NiMOF (Eu3+ functional NiMOF) for hippuric acid (HA) detection in urine and serum was fabricated via the postsynthetic encapsulating strategy. Based on the two emission signals at 441 nm (turn-on) and 628 nm (turn-off), the produced Eu3+@NiMOF ratiometric sensor provided enhanced sensitivity, higher selectivity, and 9.7 times lower limits of detection (LOD) for the detection of HA (2.38 µM, 0.42 µg·mL-1) than that of the pristine NiMOF. Considering the high sensitivity and visualization results, further exploration of intelligent applications in the HA sensing process was carried out by constructing a tandem combinational logic gate to improve the practicability and convenience with the help of a smartphone. This work provides a promising approach for developing MOF-based ratiometric sensors to detect biomarkers.
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Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Colorantes Fluorescentes/química , Hipuratos , AntibacterianosRESUMEN
Overexpression of tumor necrosis factor-α (TNF-α) is implicated in many inflammatory diseases, including septic shock, hepatitis, asthma, insulin resistance and autoimmune diseases, such as rheumatoid arthritis and Crohn's disease. The TNF-α signaling pathway is a valuable target, and anti-TNF-α drugs are successfully used to treat autoimmune and inflammatory diseases. Here, we study anti-inflammatory activity of an anti-TNF-α peptide (SN1-13, DEFHLELHLYQSW). In the cellular level assessment, SN1-13 inhibited TNF-α-induced cytotoxicity and blocks TNF-α-triggered signaling activities (IC50 = 15.40 µM). Moreover, the potential binding model between SN1-13 and TNF-α/TNFRs conducted through molecular docking revealed that SN1-13 could stunt TNF-α mediated signaling thought blocking TNF-α and its receptor TNFR1 and TNFR2. These results suggest that SN1-13 would be a potential lead peptide to treat TNF-α-mediated inflammatory diseases.
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FN-kappa B , Factor de Necrosis Tumoral alfa , Humanos , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Simulación del Acoplamiento Molecular , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inflamación/tratamiento farmacológico , Péptidos/farmacología , Péptidos/uso terapéuticoRESUMEN
To detect the effects of long non-coding ribonucleic acid (lncRNA) actin filament-associated protein 1-antisense RNA1 (AFAP1-AS1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) A549 cells and its mechanism. 1) The expression of lncRNA AFAP1-AS1 in NSCLC A549 cells was detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). 2) The changes in proliferation and apoptosis of A549 cells after low expression of lncRNA AFAP1-AS1 were detected using cell counting kit-8 (CCK-8) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. 3) The changes in Wnt signaling pathway proteins in A549 cells after low expression of lncRNA AFAP1-AS1 were detected using Western blotting. 1) The expression of lncRNA AFAP1-AS1 rose in A549 cells (P<0.01). 2) After low expression of lncRNA AFAP1-AS1, the growth of A549 cells was inhibited, and apoptosis was promoted. 3) After low expression of lncRNA AFAP1-AS1, the mRNA and protein expressions of glycogen synthase kinase (GSK) and ß-catenin declined (P<0.05). Lowly-expressed AFAP1-AS1 inhibits the proliferation and promotes the apoptosis of NSCLC A549 cells via inhibiting the Wnt signaling pathway.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , ARN Largo no Codificante , Vía de Señalización Wnt , Humanos , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Vía de Señalización Wnt/genéticaRESUMEN
Xuanbai Chengqi Decoction (XBCQD), a classic traditional Chinese medicine, has been widely used to treat COVID-19 in China with remarkable curative effect. However, the chemical composition and potential therapeutic mechanism is still unknown. Here, we used multiple open-source databases and literature mining to select compounds and potential targets for XBCQD. The COVID-19 related targets were collected from GeneCards and NCBI gene databases. After identifying putative targets of XBCQD for the treatment of COVID-19, PPI network was constructed by STRING database. The hub targets were extracted by Cytoscape 3.7.2 and MCODE analysis was carried out to extract modules in the PPI network. R 3.6.3 was used for GO enrichment and KEGG pathway analysis. The effective compounds were obtained via network pharmacology and bioinformatics analysis. Drug-likeness analysis and ADMET assessments were performed to select core compounds. Moreover, interactions between core compounds and hub targets were investigated through molecular docking, molecular dynamic (MD) simulations and MM-PBSA calculations. As a result, we collected 638 targets from 61 compounds of XBCQD and 845 COVID-19 related targets, of which 79 were putative targets. Based on the bioinformatics analysis, 10 core compounds and 34 hub targets of XBCQD for the treatment of COVID-19 were successfully screened. The enrichment analysis of GO and KEGG indicated that XBCQD mainly exerted therapeutic effects on COVID-19 by regulating signal pathways related to viral infection and inflammatory response. Meanwhile, the results of molecular docking showed that there was a stable binding between the core compounds and hub targets. Moreover, MD simulations and MM-PBSA analyses revealed that these compounds exhibited stable conformations and interacted well with hub targets during the simulations. In conclusion, our research comprehensively explained the multi-component, multi-target, and multi-pathway intervention mechanism of XBCQD in the treatment of COVID-19, which provided evidence and new insights for further research.
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COVID-19 , Medicamentos Herbarios Chinos , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Simulación de Dinámica Molecular , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Emodin is a natural anthraquinone compound, which is the main component found in the traditional Chinese herb Polygonum cuspidatum. The anti-fibrosis effects of Emodin have been reported. This study aimed to explore the specific mechanism of Emodin in the epithelial-mesenchymal transition (EMT) of pulmonary fibrosis. The pulmonary fibrosis mice models were constructed with bleomycin, the EMT models of alveolar epithelial cells were stimulated by TGF-ß1, and Emodin was used for intervention. c-MYC and miR-182-5p were overexpressed or silenced by cell transfection. Our results demonstrated that Emodin attenuated pulmonary fibrosis induced by bleomycin in mice, and inhibited EMT, meanwhile downregulated c-MYC, upregulated miR-182-5p, and downregulated ZEB2 in vitro and vivo. Next, overexpression of c-MYC promoted EMT, while silencing c-MYC and overexpressing miR-182-5p inhibited EMT. Then, c-MYC negatively regulated the expression of miR-182-5p with a direct binding relationship. And miR-182-5p inhibited ZEB2 expression in a targeted manner. Finally, Emodin inhibited EMT that had been promoted by overexpression of c-MYC. In conclusion, Emodin could attenuate pulmonary fibrosis and EMT by regulating the c-MYC/miR-182-5p/ZEB2 axis, which might provide evidence for the application of Emodin in the treatment of pulmonary fibrosis.
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Emodina , MicroARNs , Fibrosis Pulmonar , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Transición Epitelial-Mesenquimal , MicroARNs/metabolismo , Emodina/farmacología , Bleomicina/efectos adversosRESUMEN
The abuse of antibiotics and lack of new antibacterial drugs has led to the emergence of superbugs that raise fears of untreatable infections. The Cathelicidin family of antimicrobial peptide (AMP) with varying antibacterial activities and safety is considered to be a promising alternative to conventional antibiotics. In this study, we investigated a novel Cathelicidin peptide named Hydrostatin-AMP2 from the sea snake Hydrophis cyanocinctus. The peptide was identified based on gene functional annotation of the H. cyanocinctus genome and bioinformatic prediction. Hydrostatin-AMP2 showed excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria, including standard and clinical Ampicillin-resistant strains. The results of the bacterial killing kinetic assay demonstrated that Hydrostatin-AMP2 had faster antimicrobial action than Ampicillin. Meanwhile, Hydrostatin-AMP2 exhibited significant anti-biofilm activity including inhibition and eradication. It also showed a low propensity to induce resistance as well as low cytotoxicity and hemolytic activity. Notably, Hydrostatin-AMP2 apparently decreased the production of pro-inflammatory cytokines in the LPS-induced RAW264.7 cell model. To sum up, these findings indicate that Hydrostatin-AMP2 is a potential peptide candidate for the development of new-generation antimicrobial drugs fighting against antibiotic-resistant bacterial infections.
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Antiinfecciosos , Hydrophiidae , Animales , Catelicidinas/química , Antibacterianos/farmacología , Bacterias Gramnegativas , Bacterias Grampositivas , Antiinfecciosos/farmacología , Antiinflamatorios/farmacología , Bacterias , Ampicilina , Pruebas de Sensibilidad MicrobianaRESUMEN
Developing efficient and sensitive MOF-based luminescence sensors for bioactive molecule detection is of great significance and remains a challenge. Benefiting from favorable chemical and thermal stability, as well as excellent luminescence performance, a porous Zn(II)Ho(III) heterometallic-organic framework (ZnHoMOF) was selected here as a bifunctional luminescence sensor for the early diagnosis of a toluene exposure biomarker of hippuric acid (HA) through "turn-on" luminescence enhancing response and the daily monitoring of NFT/NFZ antibiotics through "turn-off" quenching effects in aqueous media with high sensitivity, acceptable selectivity, good anti-interference, exceptional recyclability performance, and low detection limits (LODs) of 0.7 ppm for HA, 0.04 ppm for NFT, and 0.05 ppm for NFZ. Moreover, the developed sensor was employed to quantify HA in diluted urine samples and NFT/NFZ in natural river water with satisfactory results. In addition, the sensing mechanisms of ZnHoMOF as a dual-response chemosensor in efficient detection of HA and NFT/NFZ antibiotics were conducted from the view of photo-induced electron transfer (PET), as well as inner filter effects (IFEs), with the help of time-dependent density functional theory (TD-DFT) and spectral overlap experiments.
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Antibacterianos , Nitrofuranos , Luminiscencia , BiomarcadoresRESUMEN
The catalytic performance of metal-organic framework (MOF)-based catalysts can be enhanced by increasing their catalytic sites, which prompts us to explore the multicore cluster-based skeletons by using designed functional ligands. Herein, the exquisite combination of [Tb4(µ2-OH)2(CO2)8] cluster and 2,6-bis(2,4-dicarboxylphenyl)-4-(4-carboxylphenyl)pyridine (H5BDCP) ligand generated a highly robust nanoporous framework of {[Tb4(BDCP)2(µ2-OH)2]·3DMF·5H2O}n (NUC-58), in which each four {Tb4} clusters are woven together to generate an elliptical nanocage (aperature ca. 12.4 Å). As far as we know, NUC-58 is an excellent nanocage-cluster-based {Tb4}-organic framework with the outstanding confined pore environments of a large specific surface area, high porosity, and plentiful coexisting Lewis acid-base sites of Tb3+, µ2-OH and Npyridine atoms. Performed experiments exhibited that NUC-58 owns a better catalytic performance for the cycloaddition reactions under mild conditions with a high turnover number and turnover frequency. Furthermore, NUC-58, as an eminent heterogeneous catalyst, can enormously boost the Knoevenagel condensation reactions. Thus, this work opens a path for the precise design of polynuclear metal cluster-based MOFs with excellent catalysis, stability, and regenerative behavior.
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The high catalytic activity of metal-organic frameworks (MOFs) can be realized by increasing their effective active sites, which prompts us to perform the functionalization on selected linkers by introducing a strong Lewis basic group of fluorine. Herein, the exquisite combination of paddle-wheel [Cu2(CO2)4(H2O)] clusters and meticulously designed fluorine-funtionalized tetratopic 2',3'-difluoro-[p-terphenyl]-3,3â³,5,5â³-tetracarboxylic acid (F-H4ptta) engenders one peculiar nanocaged {Cu2}-organic framework of {[Cu2(F-ptta)(H2O)2]·5DMF·2H2O}n (NUC-54), which features two types of nanocaged voids (9.8 Å × 17.2 Å and 10.1 Å × 12.4 Å) shaped by 12 paddle-wheel [Cu2(COO)4H2O)2] secondary building units, leaving a calculated solvent-accessible void volume of 60.6%. Because of the introduction of plentifully Lewis base sites of fluorine groups, activated NUC-54a exhibits excellent catalytic performance on the cycloaddition reaction of CO2 with various epoxides under mild conditions. Moreover, to expand the catalytic scope, the deacetalization-Knoevenagel condensation reactions of benzaldehyde dimethyl acetal and malononitrile were performed using the heterogenous catalyst of NUC-54a. Also, NUC-54a features high recyclability and catalytic stability with excellent catalytic performance in subsequent catalytic tests. Therefore, this work not only puts forward a new solution for developing high-efficiency heterogeneous catalysts, but also enriches the functionalization strategies for nanoporous MOFs.
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Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.
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Colitis , Enfermedades Inflamatorias del Intestino , Animales , Diferenciación Celular , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colon , Sulfato de Dextran , Modelos Animales de Enfermedad , Glucósidos , Enfermedades Inflamatorias del Intestino/patología , Ratones , Ratones Endogámicos C57BL , Factor de Transcripción STAT3/metabolismo , Estilbenos , Linfocitos T Reguladores/metabolismo , Células Th17 , Ácido Trinitrobencenosulfónico/metabolismoRESUMEN
N6-methyladenosine (m6A) modification is one of the most prevalent RNA modification forms of eukaryotic mRNA and is an important post-transcriptional mechanism for regulating genes. However, the role of m6A modification in the regulation of severe asthma has never been reported. Thus, we aimed to investigate the m6A regulator-mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma. In this study, 87 healthy controls and 344 severe asthma cases from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) programme were used to systematically evaluate the m6A modification patterns mediated by 27 m6A regulators and to investigate the effects of m6A modification on immune microenvironment characteristics. We found that 16 m6A regulators were abnormal and identified two key m6A regulators (YTHDF3 and YTHDC1) and three m6A modification patterns. The study of infiltration characteristics of immune microenvironment found that pattern 2 had more infiltrating immune cells and more active immune response. Besides, it was found that the eosinophils which are very important for severe asthma were affected by YTHDF3 and EIF3B. We also verified key m6A regulators with merip-seq and found that they were mainly distributed in exons and enriched in 3'UTR. In conclusion, our findings suggested that m6A modification plays a key role in severe asthma, and may be able to guide the future strategy of immunotherapy.
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Adenosina/análogos & derivados , Asma/etiología , Asma/metabolismo , Microambiente Celular/genética , Microambiente Celular/inmunología , ARN Mensajero/genética , Adenosina/metabolismo , Animales , Asma/diagnóstico , Biomarcadores , Biología Computacional , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Metilación , Ratones , Modelos Biológicos , ARN Mensajero/metabolismo , Curva ROC , Índice de Severidad de la Enfermedad , TranscriptomaRESUMEN
The target for the self-assembly of functional microporous metal-organic frameworks (MOFs) could be realized by employing ligand-directed and/or template-induced strategies, which prompted us to explore the synthetic technique of d10 secondary-building-unit-based nanoporous frameworks. Here, the exquisite combination of a paddle-wheel [Mn2(CO2)6(OH2)2] cluster and a TDP6- ligand contributes one robust honeycomb framework of {(Me2NH2)2[Mn2(TDP)(H2O)2]·3H2O·3DMF}n (NUC-31; DMF = N,N-dimethylformamide), whose activated state with the removal of associated aqueous molecules characterizes the outstanding physicochemical properties of nanochannels, penta- and tetracoordinated Mn2+ serving as highly open metal sites, rich Lewis base sites (rows of CâO groups and Npyridine atoms), and excellent thermal stability. Moreover, it is worth mentioning that Lewis acid-base sites on the inner surface of the channels in activated NUC-31 successfully form one unprecedented canal-shaped acid-base confined space with evenly distributed open metal sites of Mn2+ and Npyridine atoms as the canal bottom as well as two rows of CâO groups serving as dyke dams. Catalytic experiments displayed that activated NUC-31 could serve as an efficient heterogeneous catalyst for the chemical fixation of CO2 with epoxides into cyclic carbonates under mild conditions. Furthermore, NUC-31 could effectively catalyze the reaction Knoevenagel condensation, which should be ascribed to the synergistic polarization effect aroused from its plentiful Lewis base sites in the confined channel space. Hence, these results demonstrate that the employment of ligand-directed and template-dependent strategies could overcome the self-assembled barriers of functional microporous MOFs and achieve unexpected frameworks.