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The first wide-view image of multiple structural and phase transformations for MOFs from crystal state transformations further to the extreme limit approaching liquid/glass phase, was presented based on a square-layer framework of [Co2(pybz)2(CH3COO)2]·DMF (Co2). The process involves i) an initial crystalline transformation brings to a 3-fold interpenetrated and ordered vacancies contained framework [Co(pybz)2(CH3OH)2]·2CH3OH (CoM) due to in-situ disassemble-reassemble, ii) thermal induced departure of a pair of cis-form coordinated methanol in CoM leads to amorphous framework (a-dCoM), iii) glass transition (Tg = 566 K) to super-cooled liquid (scl-dCoM, spanning 38 K), iv) obtaining MOF glass g-dCoM upon quenching the super-cooled liquid, and v) re-crystallization of super-cooled liquid to six-fold interpenetrated dia-net framework [Co(pybz)2]6n (rec-dCoM) under heating above 604 K. The access to glass from CoM, provides a new self-perturbation strategy to create more MOF glasses without melting. The wider pore size distribution in amorphous/glassy MOFs than crystalline precursor realized the first time selective hydrocarbon gas separation by breakthrough experiments, which bring efficient separation of 1:99 C2H2/C2H4 by either a-dCoM or g-dCoM and produce polymer grade C2H4 with purity ≥ 99.5% after a single adsorption process. Furthermore, the mixture of 50:50 C3H6/C3H8 can be separated by a-dCoM.
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BACKGROUND: The bacterium Eikenella, classified as a gram-negative member of the phylum Proteobacteria, is distinguished by its rarity, corrosive nature, facultative anaerobic properties, and conditional pathogenicity. It represents the sole species within its genus-Eikenella corrodens (E. corrodens)-and can be found colonizing both human and animal oral and nasopharyngeal regions. Additionally, it occasionally inhabits the gastrointestinal or urogenital tracts. However, its slow growth rate can be attributed to its high nutritional requirements. However, there is an uneven distribution of construction and diagnostic capacity in China which poses undeniable challenges for the clinical examination and analysis of this case, especially in the basic hospitals. CASE SUMMARY: Here we presented a case of empyema associated with E. corrodens infection in a 67-year-old male patient without any previous history of infectious diseases in our primary hospital in Dongguan district of China. The patient was admitted due to recurrent worsening cough, sputum production, and dyspnea for 3 d, which had persisted for over 20 years. Moreover, the patient experienced a one-hour episode of unconsciousness. Upon admission, immediate comprehensive examinations were conducted on the patient which subsequently led to his admission to the intensive care unit. Meanwhile, the patient presented with drowsiness and profuse sweating along with bilateral conjunctival edema observed during initiation of non-invasive ventilation, suggesting empyema. A significant amount of coffee-colored malodorous pleural fluid was drained during the procedure above and sent to the laboratory department for inspection. Finally, laboratory culture results confirmed the presence of E. corrodens infection in the pleural fluid sample. The patient received antimicrobial therapy until died on day 22 in the hospital. CONCLUSION: In this report, we presented a case of empyema associated with E. corrodens infection. Multiple courses of morphological examination, viable culture analysis, and biochemical identification revealed its difficulties in detecting distinctive characteristics, as well as a detection model worth promoting. It's just that there were still certain deficiencies in terms of morphological assessment, biochemical identification, and drug susceptibility testing.
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Background: Interactions among tumor, immune, and vascular niches play major roles in driving glioblastoma (GBM) malignancy and treatment responses. The composition, heterogeneity, and localization of extracellular core matrix proteins (CMPs) that mediate such interactions, however, are not well understood. Methods: Here, through computational genomics and proteomics approaches, we analyzed the functional and clinical relevance of CMP expression in GBM at bulk, single cell, and spatial anatomical resolution. Results: We identified genes encoding CMPs whose expression levels categorize GBM tumors into CMP expression-high (M-H) and CMP expression-low (M-L) groups. CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, infiltration of pro-tumor immune cells, and immune checkpoint gene expression. Anatomical and single-cell transcriptome analyses indicate that matrisome gene expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells driving GBM progression. Finally, we identified a 17-gene CMP expression signature, termed Matrisome 17 (M17) signature that further refines the prognostic value of CMP genes. The M17 signature is a significantly stronger prognostic factor compared to MGMT promoter methylation status as well as canonical subtypes, and importantly, potentially predicts responses to PD1 blockade. Conclusion: The matrisome gene expression signature provides a robust stratification of GBM patients by survival and potential biomarkers of functionally relevant GBM niches that can mediate mesenchymal-immune cross talk. Patient stratification based on matrisome profiles can contribute to selection and optimization of treatment strategies.
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BACKGROUND: Individual susceptibility to sodium valproate (VPA)-induced tremors may be due to genetic polymorphisms in the gene encoding the uridine diphosphate glucuronosyltransferase (UGT) enzyme, which affec the drug's clinical efficacy and cause toxic side effects. This study aimed to investigate the association between UGT1A6 polymorphisms and VPA-induced tremors in patients with epilepsy. METHODS: In total, 128 patients with epilepsy were enrolled. Patients with epilepsy who received VPA were divided into tremor and non-tremor groups. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the genotype of UGT1A6 polymorphisms. RESULTS: Carriers of the UGT1A6 A541G mutant genotype conferred a higher risk of tremor than wild-type carriers (odds ratio 2.128, P = 0.045). Logistic regression analysis showed that the A541G mutant genotype was a significant genetic risk factor for VPA-induced tremors. This suggests that individual susceptibility to VPA-induced tremors may result, at least partially, from genetic variation in UGT1A6 A541G. CONCLUSIONS: Patients with epilepsy carrying the UGT1A6 A541G mutant genotype may have VPA-induced tremors, and early detection of this genotype will help guide the clinical individualizsation of VPA treatment.
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Anticonvulsivantes , Epilepsia , Glucuronosiltransferase , Tremor , Ácido Valproico , Humanos , Glucuronosiltransferase/genética , Ácido Valproico/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia/genética , Masculino , Feminino , Tremor/genética , Tremor/induzido quimicamente , Anticonvulsivantes/efeitos adversos , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Genótipo , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Polimorfismo GenéticoRESUMO
Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.
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An efficient palladium-catalyzed reaction of [60]fullerene with benzoic acids via carboxylic acid group-directed C-H bond activation is achieved. The obtained [60]fullerene-fused lactones can undergo a retro Baeyer-Villiger reaction to provide [60]fullerene-fused ketones via apparent reduction in the presence of triflic acid. A representative ketone product obtained by the reduction reaction can be employed as an overcoating layer for the electron-transporting layer in an n-type perovskite solar cell.
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Thoracic aortic dissection (TAD) is a severe disease, characterized by numerous apoptotic vascular smooth muscle cells (VSMCs). EDIL3/Del-1 is a secreted protein involved in macrophage efferocytosis in acute inflammation. Here, we aimed to investigate whether EDIL3 promoted the internalization and degradation of apoptotic VSMCs during TAD. The levels of EDIL3 were decreased in the serum and aortic tissue from TAD mice. Global edil3 knockout (edil3-/-) mice and edil3-/- bone marrow chimeric mice exhibited a considerable exacerbation in ß-aminopropionitrile monofumarate (BAPN)-induced TAD, accompanied with increased apoptotic VSMCs accumulating in the damaged aortic tissue. Two types of phagocytes, RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were used for in vitro efferocytosis assay. edil3-deficient phagocytes exhibited inefficient internalization and degradation of apoptotic VSMCs. Instead, EDIL3 promoted the internalization phase through interacting with phosphatidylserine (PtdSer) on apoptotic VSMCs and binding to the macrophage ITGAV/αv-ITGB3/ß3 integrin. In addition, EDIL3 accelerated the degradation phase through activating LC3-associated phagocytosis (LAP). Mechanically, following the engulfment, EDIL3 enhanced the activity of SMPD1/acid sphingomyelinase in the phagosome through blocking ITGAV-ITGB3 integrin, which facilitates phagosomal reactive oxygen species (ROS) production by NAPDH oxidase CYBB/NOX2. Furthermore, exogenous EDIL3 supplementation alleviated BAPN-induced TAD and promoted apoptotic cell clearance. EDIL3 may be a novel factor for the prevention and treatment of TAD.Abbreviations: BAPN: ß-aminopropionitrile monofumarate; BMDM: bone marrow-derived macrophage; C12FDG: 5-dodecanoylaminofluorescein-di-ß-D-galactopyranoside; CTRL: control; CYBB/NOX2: cytochrome b-245, beta polypeptide; DCFH-DA: 2',7'-dichlorofluorescin diacetate; EDIL3/Del-1: EGF-like repeats and discoidin I-like domains 3; EdU: 5-ethynyl-2'-deoxyuridine; EVG: elastic van Gieson; H&E: hematoxylin and eosin; IL: interleukin; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NAC: N-acetylcysteine; PtdSer: phosphatidylserine; rEDIL3: recombinant EDIL3; ROS: reactive oxygen species; SMPD1: sphingomyelin phosphodiesterase 1; TAD: thoracic aortic dissection; TEM: transmission electron microscopy; VSMC: vascular smooth muscle cell; WT: wild-type.
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Regulated cell death (RCD) is a complex process that involves several cell types and plays a crucial role in vascular diseases. Vascular smooth muscle cells (VSMCs) are the predominant elements of the medial layer of blood vessels, and their regulated death contributes to the pathogenesis of vascular diseases. The types of regulated VSMC death include apoptosis, necroptosis, pyroptosis, ferroptosis, parthanatos, and autophagy-dependent cell death (ADCD). In this review, we summarize the current evidence of regulated VSMC death pathways in major vascular diseases, such as atherosclerosis, vascular calcification, aortic aneurysm and dissection, hypertension, pulmonary arterial hypertension, neointimal hyperplasia, and inherited vascular diseases. All forms of RCD constitute a single, coordinated cell death system in which one pathway can compensate for another during disease progression. Pharmacologically targeting RCD pathways has potential for slowing and reversing disease progression, but challenges remain. A better understanding of the role of regulated VSMC death in vascular diseases and the underlying mechanisms may lead to novel pharmacological developments and help clinicians address the residual cardiovascular risk in patients with cardiovascular diseases.
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An electrochemical microsensor for mesothelin (MSLN) based on an acupuncture needle (AN) was constructed in this work. To prepare the microsensor, MSLN was self-assembled on 4-mercaptophenylboronic acid (4-MPBA) by an interaction force between the external cis-diol and phenylboronic acid. This was followed by the gradual electropolymerization of thionine (TH) and eriochrome black T (EBT) around the anchored protein. The thickness of the surface imprinted layers influenced the sensing performance and needed to be smaller than the height of the anchored protein. The polymerized EBT was not electrically active, but the polymerized TH provided a significant electrochemical signal. Therefore, electron transfer smoothly proceeded through the eluted nanocavities. The imprinted nanocavities were highly selective toward MSLN, and the rebinding of insulating proteins reduced the electrochemical signal of the embedded pTH. The functionalized interface was characterized by SEM and electrochemical methods, and the preparation conditions were studied. After optimization, the sensor showed a linear response in the range of 0.1 to 1000 ng mL-1 with a detection limit of 10 pg mL-1, indicating good performance compared with other reported methods. This microsensor also showed high sensitivity and stability, which can be attributed to the fine complementation of the imprinted organic nanocavities. The sensitivity of this sensor was related to the nanocavities used for electron transport around the AuNPs. In the future, microsensors that can directly provide electrochemical signals are expected to play important roles especially on AN matrices.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Eletrodos , Limite de Detecção , Mesotelina , Fenotiazinas , Fenotiazinas/química , Humanos , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Polímeros Molecularmente Impressos/química , Agulhas , Ouro/química , Proteínas Ligadas por GPI/análiseRESUMO
BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.
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LDL-Colesterol , Colesterol , Lipoproteína(a) , Triglicerídeos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Triglicerídeos/sangue , Fatores de Risco , LDL-Colesterol/sangue , Lipoproteína(a)/sangue , Colesterol/sangue , Hipolipemiantes/uso terapêutico , Apolipoproteínas B/sangue , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , Biomarcadores/sangueRESUMO
Organic-inorganic hybrid perovskite solar cells (PSCs) have recently been demonstrated to be promising renewable harvesters because of their prominent photovoltaic power conversion efficiency (PCE), although their stability and efficiency still have not reached commercial criteria. Trouble-oriented analyses showcase that defect reduction among the grain boundaries and interfaces in the prepared perovskite polycrystalline films is a practical strategy, which has prompted researchers to develop functional molecules for interface passivation. Herein, the pyridine-based bifunctional molecule dimethylpyridine-3,5-dicarboxylate (DPDC) was employed as the interface between the electron-transport layer and perovskite layer, which achieved a champion PCE of 21.37% for an inverted MAPbI3-based PSC, which was greater than 18.64% for the control device. The mechanistic studies indicated that the significantly improved performance was mainly attributed to the remarkably enhanced fill factor with a value greater than 83%, which was primarily due to the nonradiative recombination suppression offered by the passivation effect of DPDC. Moreover, the promoted carrier mobility together with the enlarged crystal size contributed to a higher short-circuit current density. In addition, an increase in the open-circuit voltage was also observed in the DPDC-treated PSC, which benefited from the improved work function for reducing the energy loss during carrier transport. Furthermore, the DPDC-treated PSC showed substantially enhanced stability, with an over 80% retention rate of its initial PCE value over 300 h even at a 60% relative humidity level, which was attributed to the hydrophobic nature of the DPDC molecule and effective defect passivation. This work is expected not only to serve as an effective strategy for using a pyridine-based bifunctional molecule to passivate perovskite interfaces to enhance photovoltaic performance but also to shed light on the interface passivation mechanism.
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Chiral analysis with simple devices is of great importance for analytical chemistry. Based on the photothermal (PT) effect, a simple chiral sensor with a portable laser device as the light source and a thermometer as the detection tool was developed for the chiral recognition of tryptophan (Trp) isomers and the sensitive sensing of one isomer (L-Trp). Gold nanorods (GNRs), which have outstanding photo-thermal conversion ability due to their localized surface plasma resonance (LSPR) effect, are used as PT reagents, and biomacromolecules bovine serum albumin (BSA) are used as natural chiral sources, and thus, GNRs@BSA was obtained through Au-S bonds. The resultant GNRs@BSA displays higher affinity toward L-Trp than D-Trp owing to the inherent chirality of BSA. Under the irradiation of near-infrared (NIR) light, the temperature of GNRs@BSA//L-Trp is greatly lower than that of GNRs@BSA//D-Trp due to its greatly decreased thermal conductivity, and thus chiral discrimination of Trp isomers can be achieved. In addition, the developed PT effect-based chiral sensor can be used for sensitive detection of L-Trp, and the linear range and limit of detection (LOD) are 1 µM-10 mM and 0.43 µM, respectively.
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Ouro , Limite de Detecção , Nanotubos , Soroalbumina Bovina , Triptofano , Ouro/química , Soroalbumina Bovina/química , Nanotubos/química , Triptofano/análise , Triptofano/química , Estereoisomerismo , Bovinos , Animais , Temperatura , Espectrometria de FluorescênciaRESUMO
Remodeling retinal Müller glial fate, including gliosis inhibition and pro-reprogramming, represents a crucial avenue for treating degenerative retinal diseases. Stem cell transplantation exerts effects on modulating retinal Müller glial fate. However, the optimized stem cell products and the underlying therapeutic mechanisms need to be investigated. In the present study, we found that retinal progenitor cells from human embryonic stem cell-derived retinal organoids (hERO-RPCs) transferred extracellular vesicles (EVs) into Müller cells following subretinal transplantation into RCS rats. Small EVs from hERO-RPCs (hERO-RPC-sEVs) were collected and were found to delay photoreceptor degeneration and protect retinal function in RCS rats. hERO-RPC-sEVs were taken up by Müller cells both in vivo and in vitro, and inhibited gliosis while promoting early dedifferentiation of Müller cells. We further explored the miRNA profiles of hERO-RPC-sEVs, which suggested a functional signature associated with neuroprotection and development, as well as the regulation of stem cell and glial fate. Mechanistically, hERO-RPC-sEVs might regulate the fate of Müller cells by miRNA-mediated nuclear factor I transcription factors B (NFIB) downregulation. Collectively, our findings offer novel mechanistic insights into stem cell therapy and promote the development of EV-centered therapeutic strategies.
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Células Ependimogliais , Vesículas Extracelulares , MicroRNAs , Organoides , Degeneração Retiniana , Vesículas Extracelulares/metabolismo , Animais , MicroRNAs/genética , Humanos , Degeneração Retiniana/terapia , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Células Ependimogliais/metabolismo , Organoides/metabolismo , Ratos , Retina/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Transplante de Células-Tronco/métodos , Gliose , Diferenciação Celular , Células-Tronco/metabolismo , Células-Tronco/citologiaRESUMO
BACKGROUND: Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor-like repeats and discoidin I-like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear. METHODS AND RESULTS: A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL-1ß (interleukin 1ß) and TGF-ß (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin-induced EndMT by promoting Smad4 deubiquitination in HUVECs. CONCLUSIONS: Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.
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Cardiomiopatia Dilatada , Animais , Humanos , Camundongos , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatia Dilatada/metabolismo , Moléculas de Adesão Celular/metabolismo , Discoidinas , Fator de Crescimento Epidérmico , Transição Epitelial-Mesenquimal , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina Tiolesterase , Proteases Específicas de Ubiquitina/metabolismoRESUMO
Introduction: The goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD). Methods: We used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice. Results: Proteomic profiling of mice brains exposed to fasudil revealed the activation of the mitochondrial tricarboxylic acid (TCA) cycle and blood-brain barrier (BBB) gap junction metabolic pathways. We also observed a significant negative correlation between the brain levels of phosphorylated tau (pTau) at residue 396 and both fasudil and its metabolite hydroxyfasudil. Conclusions: Our results provide evidence on the activation of proteins and pathways related to mitochondria and BBB functions by fasudil treatment and support its further development and therapeutic potential for AD.
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Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin-1 (MaR1), one of metabolites from Omega-3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)-infused mouse model. In addition, MaR1-treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin-dependent protein kinase II/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension.
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INTRODUCTION: The rapid growth of omics technologies has led to the use of bioinformatics as a powerful tool for unravelling scientific puzzles. However, the obstacles of bioinformatics are compounded by the complexity of data processing and the distinct nature of omics data types, particularly in terms of visualization and statistics. OBJECTIVES: We developed a comprehensive and free platform, CFViSA, to facilitate effortless visualization and statistical analysis of omics data by the scientific community. METHODS: CFViSA was constructed using the Scala programming language and utilizes the AKKA toolkit for the web server and MySQL for the database server. The visualization and statistical analysis were performed with the R program. RESULTS: CFViSA integrates two omics data analysis pipelines (microbiome and transcriptome analysis) and an extensive array of 79 analysis tools spanning simple sequence processing, visualization, and statistics available for various omics data, including microbiome and transcriptome data. CFViSA starts from an analysis interface, paralleling a demonstration full course to help users understand operating principles and scientifically set the analysis parameters. Once analysis is conducted, users can enter the task history interface for figure adjustments, and then a complete series of results, including statistics, feature tables and figures. All the graphic layouts were printed with necessary statistics and a traceback function recording the options for analysis and visualization; these statistics were excluded from the five competing methods. CONCLUSION: CFViSA is a user-friendly bioinformatics cloud platform with detailed guidelines for integrating functions in multi-omics analysis with real-time visualization adjustment and complete series of results provision. CFViSA is available at http://www.cloud.biomicroclass.com/en/CFViSA/.
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Biologia Computacional , Perfilação da Expressão Gênica , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Bases de Dados Factuais , Transcriptoma , SoftwareRESUMO
Efficient discrimination of amino acids (AAs) isomers is of significant importance for life science and analytical chemistry. Here, a dual-mode chiral discrimination strategy is proposed for visual and electrochemical chiral discrimination of tryptophan (Trp) isomers. Shikimic acid chiral ionic liquids (SCIL) is coordinated with copper ions (Cu2+), and the obtained SCIL-Cu2+ can form ternary complexes with the Trp isomers. Owing to the inherent chirality of SCIL and the reverse homochirality of L-Trp and D-Trp, the ternary complex of SCIL-Cu-D-Trp has higher stability than SCIL-Cu-L-Trp, as revealed by the calculated stability constants (K) and changes in Gibbs free energy (ΔG). The difference in the stability can be utilized for the chiral discrimination of L-Trp and D-Trp, resulting in discernible differences in colors and the electrochemical signals of the Trp isomers. Besides Trp, the isomers of phenylalanine (Phe) can also be discriminated by the proposed dual-mode chiral discrimination strategy with the SCIL-Cu2+ complex.
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We report the synthesis and structural characterization of a 2D metal-organic framework with AB-packing layers, [Co2(pybz)2(CH3COO)2]·DMF (Co2, pybz= 4-(4-pyridyl)benzoate), containing a stable (4,4)-grid network fabricated by paddle-wheel nodes, ditopic pybz, and acetate ligands. After removal of the guest, the layer structure is retained but reorganized into an ABCD packing mode in the activated phase (Co2a). Consequently, the intralayer square windows (7.2 × 5.0 Å2) close, while the interlayer separation is decreased slightly from 3.69 to 3.45 Å, leaving a narrow gap. Importantly, the dangling methyl group of the acetate with H-bonds to the adjacent layers and also the well-distributed π-π interactions between the aromatic rings of neighboring layers facilitate the structural stability. These weak supramolecular interactions further allow for favorable dynamic exfoliation of the layers, which promotes efficient adsorption of C2H2 (41.6 cm3 g-1) over CO2 with an adsorption ratio of 6.3 (0.5 bar, 298 K). The effective separation performance of equimolar C2H2/CO2 was verified by cycling breakthrough experiments and was even tolerable to moisture (R.H = 52%). DFT calculations, in situ PXRD, and PDF characterization reveal that the favorable retention of C2H2 rather than that of CO2 is due to its H-bond formation with the paddle-wheel oxygen atoms that triggers the increase in interlayer separation during C2H2 adsorption.