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1.
Proc Natl Acad Sci U S A ; 121(22): e2317205121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38776369

RESUMO

Understanding the operando defect-tuning performance of catalysts is critical to establish an accurate structure-activity relationship of a catalyst. Here, with the tool of single-molecule super-resolution fluorescence microscopy, by imaging intermediate CO formation/oxidation during the methanol oxidation reaction process on individual defective Pt nanotubes, we reveal that the fresh Pt ends with more defects are more active and anti-CO poisoning than fresh center areas with less defects, while such difference could be reversed after catalysis-induced step-by-step creation of more defects on the Pt surface. Further experimental results reveal an operando volcano relationship between the catalytic performance (activity and anti-CO ability) and the fine-tuned defect density. Systematic DFT calculations indicate that such an operando volcano relationship could be attributed to the defect-dependent transition state free energy and the accelerated surface reconstructing of defects or Pt-atom moving driven by the adsorption of the CO intermediate. These insights deepen our understanding to the operando defect-driven catalysis at single-molecule and subparticle level, which is able to help the design of highly efficient defect-based catalysts.

2.
Mol Cell ; 71(6): 1064-1078.e5, 2018 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-30197300

RESUMO

ß-hydroxybutyrate (ß-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether ß-HB alters the senescence pathway in vascular cells remains unknown. Here we report that ß-HB promotes vascular cell quiescence, which significantly inhibits both stress-induced premature senescence and replicative senescence through p53-independent mechanisms. Further, we identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a direct binding target of ß-HB. ß-HB binding to hnRNP A1 markedly enhances hnRNP A1 binding with Octamer-binding transcriptional factor (Oct) 4 mRNA, which stabilizes Oct4 mRNA and Oct4 expression. Oct4 increases Lamin B1, a key factor against DNA damage-induced senescence. Finally, fasting and intraperitoneal injection of ß-HB upregulate Oct4 and Lamin B1 in both vascular smooth muscle and endothelial cells in mice in vivo. We conclude that ß-HB exerts anti-aging effects in vascular cells by upregulating an hnRNP A1-induced Oct4-mediated Lamin B1 pathway.


Assuntos
Ácido 3-Hidroxibutírico/farmacologia , Senescência Celular/efeitos dos fármacos , Animais , Células Cultivadas , Regulação da Expressão Gênica , Ribonucleoproteína Nuclear Heterogênea A1/efeitos dos fármacos , Ribonucleoproteína Nuclear Heterogênea A1/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fator 3 de Transcrição de Octâmero/efeitos dos fármacos , Fator 3 de Transcrição de Octâmero/metabolismo , RNA Mensageiro , Ativação Transcricional , Regulação para Cima
3.
Proc Natl Acad Sci U S A ; 120(25): e2301011120, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37307468

RESUMO

As a sustainable approach for N2 fixation, electrocatalytic N2 reduction reaction (N2RR) to produce ammonia (NH3) is highly desirable with a precise understanding to the structure-activity relationship of electrocatalysts. Here, firstly, we obtain a novel carbon-supported oxygen-coordinated single-Fe-atom catalyst for highly efficient production of ammonia from electrocatalytic N2RR. Based on such new type of N2RR electrocatalyst, by combining operando X-ray absorption spectra (XAS) with density function theory calculation, we reveal significantly that the as-prepared active coordination structure undergoes a potential-driven two-step restructuring, firstly from FeSAO4(OH)1a to FeSAO4(OH)1a'(OH)1b with the adsorption of another -OH on FeSA at open-circuit potential (OCP) of 0.58 VRHE, and subsequently restructuring from FeSAO4(OH)1a'(OH)1b to FeSAO3(OH)1a″ due to the breaking of one Fe-O bond and the dissociation of one -OH at working potentials for final electrocatalytic process of N2RR, thus revealing the first potential-induced in situ formation of the real electrocatalytic active sites to boost the conversion of N2 to NH3. Moreover, the key intermediate of Fe-NNHx was detected experimentally by both operando XAS and in situ attenuated total reflection-surface-enhanced infrared absorption spectra (ATR-SEIRAS), indicating the alternating mechanism followed by N2RR on such catalyst. The results indicate the necessity of considering the potential-induced restructuring of the active sites on all kinds of electrocatalysts for such as highly efficient ammonia production from N2RR. It also paves a new way for a precise understanding to the structure-activity relationship of a catalyst and helps the design of highly efficient catalysts.

4.
Proc Natl Acad Sci U S A ; 119(14): e2114639119, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35349346

RESUMO

SignificanceHere, with single-molecule fluorescence microscopy, we study the catalytic behavior of individual Pt atoms at single-turnover resolution, and then reveal the unique catalytic properties of Pt single-atom catalyst and the difference in catalytic properties between individual Pt atoms and Pt nanoparticles. Further density functional theory calculation indicates that unique catalytic properties of Pt single-atom catalyst could be attributed intrinsically to the unique surface properties of Pt1-based active sites.


Assuntos
Nanopartículas , Platina , Catálise , Cinética , Platina/química , Propriedades de Superfície
5.
Nano Lett ; 24(15): 4682-4690, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563501

RESUMO

Multienzyme assemblies mediated by multivalent interaction play a crucial role in cellular processes. However, the three-dimensional (3D) programming of an enzyme complex with defined enzyme activity in vitro remains unexplored, primarily owing to limitations in precisely controlling the spatial topological configuration. Herein, we introduce a nanoscale 3D enzyme assembly using a tetrahedral DNA framework (TDF), enabling the replication of spatial topological configuration and maintenance of an identical edge-to-edge distance akin to natural enzymes. Our results demonstrate that 3D nanoscale enzyme assemblies in both two-enzyme systems (glucose oxidase (GOx)/horseradish peroxidase (HRP)) and three-enzyme systems (amylglucosidase (AGO)/GOx/HRP) lead to enhanced cascade catalytic activity compared to the low-dimensional structure, resulting in ∼5.9- and ∼7.7-fold enhancements over homogeneous diffusional mixtures of free enzymes, respectively. Furthermore, we demonstrate the enzyme assemblies for the detection of the metabolism biomarkers creatinine and creatine, achieving a low limit of detection, high sensitivity, and broad detection range.


Assuntos
Enzimas Imobilizadas , Glucose Oxidase , Enzimas Imobilizadas/química , Peroxidase do Rábano Silvestre/química , Glucose Oxidase/química , DNA/química
6.
Am J Respir Cell Mol Biol ; 70(1): 39-49, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37713305

RESUMO

Increasing evidence suggests that mitochondrial dysfunction in pulmonary endothelial cells (ECs) plays a causative role in the initiation and progression of pulmonary hypertension (PH); how mitochondria become dysfunctional in PH remains elusive. Mitochondria-derived vesicles (MDVs) are small subcellular vesicles that excise from mitochondria. Whether MDV deregulation causes mitochondrial dysfunction in PH is unknown. The aim of this study was to determine MDV regulation in ECs and to elucidate how MDV deregulation in ECs leads to PH. MDV formation and mitochondrial morphology/dynamics were examined in ECs of EC-specific liver kinase B1 (LKB1) knockout mice (LKB1ec-/-), in monocrotaline-induced PH rats, and in lungs of patients with PH. Pulmonary ECs of patients with PH and hypoxia-treated pulmonary ECs exhibited increased mitochondrial fragmentation and disorganized mitochondrial ultrastructure characterized by electron lucent-swelling matrix compartments and concentric layering of the cristae network, together with defective MDV shedding. MDVs actively regulated mitochondrial membrane dynamics and mitochondrial ultrastructure via removing mitofission-related cargoes. The shedding of MDVs from parental mitochondria required LKB1-mediated mitochondrial recruitment of Rab9 GTPase. LKB1ec-/- mice spontaneously developed PH with decreased mitochondrial pools of Rab9 GTPase, defective MDV shedding, and disequilibrium of the mitochondrial fusion-fission cycle in pulmonary ECs. Aerosol intratracheal delivery of adeno-associated virus LKB1 reversed PH, together with improved MDV shedding and mitochondrial function in rats in vivo. We conclude that LKB1 regulates MDV shedding and mitochondrial dynamics in pulmonary ECs by enhancing mitochondrial recruitment of Rab9 GTPase. Defects of LKB1-mediated MDV shedding from parental mitochondria instigate EC dysfunction and PH.


Assuntos
Hipertensão Pulmonar , Doenças Mitocondriais , Ratos , Humanos , Camundongos , Animais , Hipertensão Pulmonar/metabolismo , Células Endoteliais/metabolismo , Mitocôndrias , GTP Fosfo-Hidrolases/metabolismo , Camundongos Knockout , Doenças Mitocondriais/complicações , Doenças Mitocondriais/metabolismo
7.
J Cell Mol Med ; 28(3): e18097, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38164738

RESUMO

Current studies have indicated that insufficient trophoblast epithelial-mesenchymal transition (EMT), migration and invasion are crucial for spontaneous abortion (SA) occurrence and development. Exosomal miRNAs play significant roles in embryonic development and cellular communication. Hereon, we explored the roles of serum exosomes derived from SA patients on trophoblast EMT, migration and invasion. Exosomes were isolated from normal control (NC) patients with abortion for unplanned pregnancy and SA patients, then characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. Exosomal miRNA profiles were identified by miRNA sequencing. The effects of serum exosomes on trophoblast migration and invasion were detected by scratch wound healing and transwell assays, and other potential mechanisms were revealed by quantitative real-time PCR (RT-PCR), western blotting and dual-luciferase reporter assay. Finally, animal experiments were used to explore the effects of exosomal miR-410-3p on embryo absorption in mice. The serum exosomes from SA patients inhibited trophoblast EMT and reduced their migration and invasion ability in vitro. The miRNA sequencing showed that miR-410-3p was upregulated in SA serum exosomes. The functional experiments showed that SA serum exosomes restrained trophoblast EMT, migration and invasion by releasing miR-410-3p. Mechanistically, SA serum exosomal miR-410-3p inhibited trophoblast cell EMT, migration and invasion by targeting TNF receptor-associated factor 6 (TRAF6) at the post-transcriptional level. Besides, SA serum exosomal miR-410-3p inhibited the p38 MAPK signalling pathway by targeting TRAF6 in trophoblasts. Moreover, milk exosomes loaded with miR-410-3p mimic reached the maternal-fetal interface and aggravated embryo absorption in female mice. Clinically, miR-410-3p and TRAF6 expression were abnormal and negatively correlated in the placental villi of SA patients. Our findings indicated that exosome-derived miR-410-3p plays an important role between SA serum and trophoblasts in intercellular communication, suggesting a novel mechanism by which serum exosomal miRNA regulates trophoblasts in SA patients.


Assuntos
Aborto Espontâneo , Exossomos , MicroRNAs , Humanos , Feminino , Gravidez , Camundongos , Animais , Exossomos/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Placenta/metabolismo , MicroRNAs/genética , Trofoblastos/metabolismo , Transição Epitelial-Mesenquimal/genética , Proliferação de Células , Movimento Celular/genética
8.
J Am Chem Soc ; 146(18): 12410-12422, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38669207

RESUMO

Synthetic nanoparticles as lipid nanoparticles (LNPs) are widely used as drug delivery vesicles. However, they hold several drawbacks, including low biocompatibility and unfavorable immune responses. Naturally occurring extracellular vesicles (EVs) hold the potential as native, safe, and multifunctional nanovesicle carriers. However, loading of EVs with large biomolecules remains a challenge. Here, we present a controlled loading methodology using DNA-mediated and programmed fusion between EVs and messenger RNA (mRNA)-loaded liposomes. The fusion efficiency is characterized at the single-particle level by real-time microscopy through EV surface immobilization via lipidated biotin-DNA handles. Subsequently, fused EV-liposome particles (EVLs) can be collected by employing a DNA strand-replacement reaction. Transferring the fusion reaction to magnetic beads enables us to scale up the production of EVLs one million times. Finally, we demonstrated encapsulation of mCherry mRNA, transfection, and improved translation using the EVLs compared to liposomes or LNPs in HEK293-H cells. We envision this as an important tool for the EV-mediated delivery of RNA therapeutics.


Assuntos
Vesículas Extracelulares , Lipossomos , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Células HEK293 , Lipossomos/química , RNA Mensageiro/química , RNA Mensageiro/genética , DNA/química , Nanopartículas/química
9.
Biochem Biophys Res Commun ; 720: 150131, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38763124

RESUMO

Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe2O4-PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe2O4, denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 µg/mL). In the animal model of MDR S. aureus infected wound, after 100 µL SBC@ZIF-8+NIR (150 µg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing.


Assuntos
Antibacterianos , Estruturas Metalorgânicas , Fotoquimioterapia , Antibacterianos/farmacologia , Antibacterianos/química , Fotoquimioterapia/métodos , Animais , Camundongos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Biofilmes/efeitos dos fármacos , Terapia Fototérmica , Staphylococcus aureus/efeitos dos fármacos , Nanopartículas/química , Testes de Sensibilidade Microbiana , Compostos Férricos/química , Compostos Férricos/farmacologia , Compostos de Estanho/química , Compostos de Estanho/farmacologia , Zeolitas/química , Zeolitas/farmacologia
10.
PLoS Pathog ; 18(7): e1010702, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35881621

RESUMO

Puccinia striiformis f. sp. tritici (Pst) secretes an array of specific effector proteins to manipulate host immunity and promote pathogen colonization. In a previous study, we functionally characterized a glycine-serine-rich effector PstGSRE1 with a glycine-serine-rich motif (m9). However, the mechanisms of glycine-serine-rich effectors (GSREs) remain obscure. Here we report a new glycine-serine-rich effector, PstGSRE4, which has no m9-like motif but inhibits the enzyme activity of wheat copper zinc superoxide dismutase TaCZSOD2, which acts as a positive regulator of wheat resistance to Pst. By inhibiting the enzyme activity of TaCZSOD2, PstGSRE4 reduces H2O2 accumulation and HR areas to facilitate Pst infection. These findings provide new insights into the molecular mechanisms of GSREs of rust fungi in regulating plant immunity.


Assuntos
Basidiomycota , Triticum , Basidiomycota/fisiologia , Cobre/metabolismo , Glicina/farmacologia , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Doenças das Plantas/microbiologia , Puccinia , Serina/metabolismo , Superóxido Dismutase/metabolismo , Triticum/microbiologia , Zinco/metabolismo
11.
FASEB J ; 37(10): e23206, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37718485

RESUMO

There is a higher expression level of epidermal growth factor receptor (EGFR) in up to 90% of advanced head and neck squamous cell carcinoma (HNSCC) tissue than in normal surrounding tissues. However, the role of RNA-binding proteins (RBPs) in EGFR-associated metastasis of HNSCC remains unclear. In this study, we reveal that RBPs, specifically nucleolin (NCL) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), correlated with the mesenchymal phenotype of HNSCC. The depletion of RBPs significantly attenuated EGF-induced HNSCC metastasis. Intriguingly, the EGF-induced EMT markers, such as fibronectin, were regulated by RBPs through the ERK and NF-κB pathway, followed by the enhancement of mRNA stability of fibronectin through the 5' untranslated region (5'-UTR) of the gene. The upregulation of fibronectin triggered the integrin signaling activation to enhance tumor cells' attachment to endothelial cells and increase endothelial permeability. In addition, the concurrence of EGFR and RBPs or EGFR and fibronectin was associated with overall survival and disease-free survival of HNSCC. The in vivo study showed that depletion of NCL, hnRNPA2B1, and fibronectin significantly inhibited EGF-promoted extravasation of tumor cells into lung tissues. The depletion of fibronectin or treatment with integrin inhibitors dramatically attenuated EGF-induced HNSCC metastatic nodules in the lung. Our data suggest that the RBPs/fibronectin axis is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis.


Assuntos
Fibronectinas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Fibronectinas/genética , Células Endoteliais , Fator de Crescimento Epidérmico , Receptores ErbB/genética , Regiões 5' não Traduzidas , Integrinas , Neoplasias de Cabeça e Pescoço/genética
12.
Cell Commun Signal ; 22(1): 207, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566153

RESUMO

Super enhancers (SEs) consist of clusters of enhancers, harboring an unusually high density of transcription factors, mediator coactivators and epigenetic modifications. SEs play a crucial role in the maintenance of cancer cell identity and promoting oncogenic transcription. Super enhancer lncRNAs (SE-lncRNAs) refer to either transcript from SEs locus or interact with SEs, whose transcriptional activity is highly dependent on SEs. Moreover, these SE-lncRNAs can interact with their associated enhancer regions in cis and modulate the expression of oncogenes or key signal pathways in cancers. Inhibition of SEs would be a promising therapy for cancer. In this review, we summarize the research of SE-lncRNAs in different kinds of cancers so far and decode the mechanism of SE-lncRNAs in carcinogenesis to provide novel ideas for the cancer therapy.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Super Intensificadores , Elementos Facilitadores Genéticos/genética , Neoplasias/genética , Fatores de Transcrição/genética
13.
Biomacromolecules ; 25(3): 1871-1886, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38324764

RESUMO

Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.


Assuntos
Acrilamidas , Durapatita , Alicerces Teciduais , Durapatita/química , Alicerces Teciduais/química , Gelatina/química , Osteogênese , Biomimética , Regeneração Óssea , Impressão Tridimensional , Engenharia Tecidual
14.
Pharmacol Res ; 204: 107189, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38649124

RESUMO

Spinal cord injury (SCI) is a complex problem in modern medicine. Fibroblast activation and fibroscarring after SCI impede nerve recovery. Non-coding RNA plays an important role in the progression of many diseases, but the study of its role in the progression of spinal fibrosis is still emerging. Here, we investigated the function of circular RNAs, specifically antisense to the cerebellar degeneration-related protein 1 (CDR1as), in spinal fibrosis and characterized its molecular mechanism and pathophysiology. The presence of CDR1as in the spinal cord was verified by sequencing and RNA expression assays. The effects of inhibition of CDR1as on scar formation, inflammation and nerve regeneration after spinal cord injury were investigated in vivo and in vitro. Further, gene expression of miR-7a-5p and protein expression of transforming Growth Factor Beta Receptor II (TGF-ßR2) were measured to evaluate their predicted interactions with CDR1as. The regulatory effects and activation pathways were subsequently verified by miR-7a-5p inhibitor and siCDR1as. These results indicate that CDR1as/miR-7a-5p/TGF-ßR2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases.


Assuntos
Fibrose , MicroRNAs , RNA Circular , RNA Longo não Codificante , Transdução de Sinais , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Proteínas Smad/metabolismo , Proteínas Smad/genética , Regeneração Nervosa , Feminino , Masculino , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Camundongos Endogâmicos C57BL , Camundongos , Recuperação de Função Fisiológica
15.
Inorg Chem ; 63(23): 10611-10618, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38801713

RESUMO

Uranium [U(VI)] mining activity resulted in the discharge of uranium containing acid wastewater. It is necessary for immobilizing the uranium from wastewater to avoid its environmental pollution. In this work, a novel hydrothermal mineralization strategy is proposed for uranium stabilization. Three reaction systems such as Mg3(PO4)2 + UO22+, Mg2+ + PO43- + UO22+, and Mg2+ + PO43- + Mg3(PO4)2 + UO22+ were designed to investigate the uranium mineralization and stabilization performance. The consumed molar quantities of magnesium and phosphate were calculated to understand the mineralization mechanisms. The molar ratios of Mg/U and P/U in the experimental results were in agreement with those of thermodynamic calculation in the presence of dissolved Mg2+ and PO43- under the hydrothermal process. The calculated saturated index indicated the facile crystallization of uranium into the saleeite and chernikovite through hydrothermal mineralization at the pH value of 5 and 473 K. Crystallization into saleeite and chernikovite contributed to uranium stabilization, resulting in the negligible leaching rate of 5% due to the high crystallinity of 97.23%. Thus, hydrothermal mineralization of uranium crystallization into saleeite and chernikovite was promising for uranium stabilization with long-term stability.

16.
Cell Mol Life Sci ; 80(9): 264, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37615725

RESUMO

The SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase that has been reported to regulate carcinogenesis and inflammation. However, its role in vascular smooth muscle cell (VSMC) homeostasis and vascular diseases has not been determined. Here, we investigated the role of SMYD2 in VSMC phenotypic modulation and vascular intimal hyperplasia and elucidated the underlying mechanism. We observed that SMYD2 expression was downregulated in injured carotid arteries in mice and phenotypically modulated VSMCs in vitro. Using an SMC-specific SMYD2 knockout mouse model, we found that SMYD2 ablation in VSMCs exacerbated neointima formation after vascular injury in vivo. Conversely, SMYD2 overexpression inhibited VSMC proliferation and migration in vitro and attenuated arterial narrowing in injured vessels in mice. SMYD2 downregulation promoted VSMC phenotypic switching accompanied with enhanced proliferation and migration. Mechanistically, genome-wide transcriptome analysis and loss/gain-of-function studies revealed that SMYD2 up-regulated VSMC contractile gene expression and suppressed VSMC proliferation and migration, in part, by promoting expression and transactivation of the master transcription cofactor myocardin. In addition, myocardin directly interacted with SMYD2, thereby facilitating SMYD2 recruitment to the CArG regions of SMC contractile gene promoters and leading to an open chromatin status around SMC contractile gene promoters via SMYD2-mediated H3K4 methylation. Hence, we conclude that SMYD2 is a novel regulator of VSMC contractile phenotype and intimal hyperplasia via a myocardin-dependent epigenetic regulatory mechanism.


Assuntos
Músculo Liso Vascular , Proteínas Nucleares , Animais , Camundongos , Carcinogênese , Hiperplasia/genética , Camundongos Knockout , Proteínas Nucleares/genética
17.
Chemotherapy ; : 1-12, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38797169

RESUMO

INTRODUCTION: The aim of the study was to conduct a systematic review to explore the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) for patients with hepatocellular carcinoma (HCC). METHODS: Chinese and English databases (PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and VIP database) were searched from database inception to August 15, 2023. Studies comparing TACE combined with PVE versus TACE alone for patients with HCC were included. The degree of heterogeneity was assessed using I2 statistics and a Q test. The effect size was represented by risk ratio and mean difference (MD), and the effect size range was estimated using a 95% confidence interval (CI). RESULTS: Eight eligible studies were included in the systematic review, involving 689 participants. The results showed that the future liver residual (FLR) of patients treated with TACE combined with PVE was significantly higher than that of those treated with PVE alone (MD = 3.99%; 95% CI: 1.03-6.94). Furthermore, compared with PVE alone, TACE combined with PVE had a positive effect on disease-free survival (odds ratio [OR] = 2.16; 95% CI: 1.20-3.88), recurrence rate (OR = 0.79; 95% CI: 0.07-9.42), and complications (OR = 0.53; 95% CI: 0.30-0.96). There was no statistically significant impact on mortality with TACE combined with PVE treatment. CONCLUSION: The combination of TACE with PVE can significantly reduce the FLR of patients with HCC, with higher disease-free survival, lower recurrence rate, and fewer complications.

18.
Sleep Breath ; 28(3): 1415-1422, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38427222

RESUMO

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common respiratory disease with potential lethality. At present, the commonly used treatment method is continuous positive airway pressure ventilation, but with the prolongation of the course of the disease, the effect of single ventilation on the improvement of oxidative stress levels is not good. Lipoic acid is a commonly used antioxidant in clinics. In this paper, lipoic acid combined with continuous positive airway pressure ventilation is used to explore whether it has a better therapeutic effect on patients. AIM: To probe into the clinical efficacy of lipoic acid combined with continuous positive airway pressure ventilation in the therapy of OSAHS. METHODS: 82 patients with OSAHS who were cured in our hospital from March 2021 to September 2022 were prospectively collected as subjects. Based on different treatment methods, patients were grouped into a control group (43 cases) and an observation group (39 cases). The control group was treated with continuous positive airway pressure (CPAP), and the observation group was treated with lipoic acid based on control group. The therapeutic effects were measured by apnea hypopnea index (AHI), oxygen saturation (SpO2), mean oxygen saturation (MSpO2), serum malondialdehyde (MDA), superoxide dismutase (SOD), hypoxia inducible factor-1α (HIF-1α) levels, peripheral blood γ-aminobutyric acid, melatonin levels. RESULTS: The clinical effectiveness of the observation group was better (P < 0.05). After treatment, AHI, the levels of MDA and HIF-1α in the observation group were lower and SpO2, MSpO2 and the level of SOD, γ- aminobutyric acid, and melatonin were higher than those in the control group (P < 0.05). The levels of γ- aminobutyric acid and melatonin were negatively correlated with the severity of symptoms, ESS, and AIS scores (P < 0.05). CONCLUSIONS: The clinical effect of lipoic acid combined with CPAP in the treatment of OSAHS is better, and it has a positive effect on the levels of γ-aminobutyric acid and melatonin in peripheral blood. Lipoic acid was added to the original method for treatment, and the therapeutic effect was greatly improved.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Melatonina , Apneia Obstrutiva do Sono , Ácido Tióctico , Ácido gama-Aminobutírico , Humanos , Ácido Tióctico/uso terapêutico , Melatonina/sangue , Melatonina/uso terapêutico , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Ácido gama-Aminobutírico/sangue , Terapia Combinada , Antioxidantes , Resultado do Tratamento , Estudos Prospectivos
19.
Biotechnol Lett ; 46(1): 37-46, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38064043

RESUMO

Metabolic Engineering of yeast is a critical approach to improving the production capacity of cell factories. To obtain genetically stable recombinant strains, the exogenous DNA is preferred to be integrated into the genome. Previously, we developed a Golden Gate toolkit YALIcloneNHEJ, which could be used as an efficient modular cloning toolkit for the random integration of multigene pathways through the innate non-homologous end-joining repair mechanisms of Yarrowia lipolytica. We expanded the toolkit by designing additional building blocks of homologous arms and using CRISPR technology. The reconstructed toolkit was thus entitled YALIcloneHR and designed for gene-specific knockout and integration. To verify the effectiveness of the system, the gene PEX10 was selected as the target for the knockout. This system was subsequently applied for the arachidonic acid production, and the reconstructed strain can accumulate 4.8% of arachidonic acid. The toolkit will expand gene editing technology in Y. lipolytica, which would help produce other chemicals derived from acetyl-CoA in the future.


Assuntos
Sistemas CRISPR-Cas , Yarrowia , Sistemas CRISPR-Cas/genética , Yarrowia/genética , Yarrowia/metabolismo , Ácido Araquidônico/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Engenharia Metabólica
20.
Aesthetic Plast Surg ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995348

RESUMO

BACKGROUND: In Asia, the demand for cosmetic facial treatments has surged due to technological advancements, increased social acceptability, and affordability. Poly-L-lactic acid (PLLA) fillers, known for their biocompatibility and biodegradability, have emerged as a popular choice for facial contouring, yet studies specifically addressing their use in Asian populations are scarce. METHODS: This retrospective study examined 30 Chinese patients who underwent facial contouring with PLLA fillers, focusing on product composition, injection techniques, and safety measures. A comprehensive clinical evaluation was performed, including the Global Aesthetic Improvement Scale (GAIS) and Global Impression of Change Scale (GICS) for effectiveness and patient satisfaction, respectively. RESULTS: No significant difference in GAIS scores was observed between injectors and blinded evaluators over a 12-month period, indicating consistent effectiveness. Patient satisfaction remained high, with GICS scores reflecting positive outcomes. The safety profile was favorable, with no serious adverse events reported. The study highlighted the importance of anatomical knowledge to avoid complications, particularly in areas prone to blindness. CONCLUSIONS: PLLA fillers offer a safe, effective option for facial contour correction in the Asian population, achieving high patient satisfaction and maintaining results over time. The study underscores the need for tailored approaches in cosmetic procedures for Asians, considering their unique facial structures and aesthetic goals. Further research with larger, multicenter cohorts is recommended to validate these findings and explore long-term effects. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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