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1.
Environ Res ; 262(Pt 2): 119945, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276836

RESUMO

Soil Pb contamination is inevitable, as a result of phosphate mining. It is essential to explore more effective Pb remediation approaches in phosphate mining wasteland soil to ensure their viability for a gradual return of soil quality for cultivation. In this study, a Pb-resistant urease-producing bacterium, Serratia marcescens W1Z1, was screened for remediation using microbially induced carbonate precipitation (MICP). Magnesium polypeptide (MP) was prepared from soybean meal residue, and the combined remediation of Pb contamination with MP and MICP in phosphate mining wasteland soil was studied. Remediation of Pb using a combination of MP with MICP strain W1Z1 (WM treatment) was the most effective, with the least exchangeable Pb at 30.37% and the most carbonate-bound Pb at 40.82%, compared to the other treatments, with a pH increase of 8.38. According to the community analysis, MP moderated the damage to microbial abundance and diversity caused by MICP. Total nitrogen (TN) was positively correlated with Firmicutes, pH, and carbonate-bound Pb. Serratia inoculated with strain W1Z1 were positively correlated with bacteria belonging to the Firmicutes phylum and negatively correlated with bacteria belonging to Proteobacteria. The available phosphate (AP) in the phosphate mining wasteland soil could encapsulate the precipitated Pb by ion exchange with carbonate, making it more stable. Combined MP-MICP remediation of Pb contamination in phosphate mining wasteland soil was effective and improved the soil microenvironment.

2.
Nat Chem Biol ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300230

RESUMO

Clustered regularly interspaced short palindromic repeats-Cas13 effectors are used for RNA editing but the adeno-associated virus (AAV) packaging limitations because of their big sizes hinder their therapeutic application. Here we report the identification of the Cas13j family, with LepCas13j (529 aa) and ChiCas13j (424 aa) being the smallest and most highly efficient variants for RNA interference. The miniaturized Cas13j proteins enable the development of compact RNA base editors. Chi-RESCUE-S, by fusing dChiCas13j with hADAR2dd, demonstrates high efficiency and specificity in A-to-G and C-to-U conversions. Importantly, this system is compatible with single-AAV packaging without the need for protein sequence truncation. It successfully corrected pathogenic mutations, such as APOC3D65N and SCN9AR896Q, to the wild-type forms. In addition, we developed an optimized system, Chi-RESCUE-S-mini3, which pioneered efficient in vivo C-to-U RNA editing of PCSK9 in mice through single-AAV delivery, resulting in reduced total cholesterol levels. These results highlight the potential of Cas13j to treat human diseases.

3.
Angew Chem Int Ed Engl ; : e202412903, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264260

RESUMO

The difluorobenzothiadizole (ffBT) unit is one of the most classic electron-accepting building blocks used to construct D-A copolymers for applications in organic solar cells (OSCs). Historically, ffBT-based polymers have achieved record power conversion efficiencies (PCEs) in fullerene-based OSCs owing to their strong temperature-dependent aggregation (TDA) characteristics. However, their excessive miscibility and rapid aggregation kinetics during film formation have hindered their performance with state-of-the-art non-fullerene acceptors (NFAs). Herein, we synthesized two ffBT-based copolymers, PffBT-2T and PffBT-4T, incorporating different π-bridges to modulate intermolecular interactions and aggregation tendencies. Experimental and theoretical studies revealed that PffBT-4T exhibits reduced electrostatic potential differences and miscibility with L8-BO compared to PffBT-2T. This facilitates improved phase separation in the active layer, leading to enhanced molecular packing and optimized morphology. Moreover, PffBT-4T demonstrated a prolonged nucleation and crystal growth process, leading to enhanced molecular packing and optimized morphology. Consequently, PffBT-4T-based devices achieved a remarkable PCE of 17.5%, setting a new record for ffBT-based photovoltaic polymers. Our findings underscore the importance of conjugate backbone modulation in controlling aggregation behavior and film formation kinetics, providing valuable insights for the design of high-performance polymer donors in organic photovoltaics.

4.
Diabetes Metab Syndr Obes ; 17: 3355-3363, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262434

RESUMO

Aim: Although the interplay of insulin resistance (IR) and low muscle mass is increasingly recognized, it remains unknown whether the triglyceride-glucose (TyG) index, as an indicator of IR, is associated with low muscle mass in patients with type 2 diabetes (T2D). Our study aimed to investigate the association between TyG index and low muscle mass in hospitalized T2D patients. Methods: This cross-sectional study involved 2687 hospitalized participants with T2D. The TyG index was calculated by fasting plasma glucose (FPG) and triglyceride levels. The outcome variables were defined as appendicular skeletal muscle mass index (ASMI) and low muscle mass. To explore the relationship between TyG index and low muscle mass, we conducted the multivariate linear regression, multivariate logistic regression, and subgroup analysis. Results: In the fully adjusted multivariate linear regression, there was a negative correlation between TyG index (ß=-0.10, 95% CI: -0.14, -0.06) and ASMI. TyG index (OR = 1.34, 95% CI: 1.08, 1.65) had a more significant association with low muscle mass compared to FPG (OR = 1.05, 95% CI: 1.01, 1.09) and glycated hemoglobin A1c (OR = 1.07, 95% CI: 0.99, 1.15). The statistical significance of the trend persisted among the TyG index quartile groups. Subgroup analysis revealed stronger positive associations between TyG index and low muscle mass in females, individuals aged 60 years or older, those with a body mass index of 28kg/m2 or higher, and HbA1c levels of 6.5% or higher, as well as those with hypertension and dyslipidemia. Conclusion: A higher TyG index level is positively associated with a higher risk of low muscle mass, suggesting that TyG index could be a potential biomarker of low muscle mass in hospitalized T2D patients.

5.
J Hazard Mater ; 479: 135728, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39236535

RESUMO

Bisphenols (BPs) are recognized as endocrine disrupting compounds and have garnered increasing attention due to their widespread utilization. However, the varying biological toxicities and underlying mechanisms of BPs with different functional groups remain unknown. In the present study, the toxic effects of four BPs (BPA, BPS, BPAF, and TBBPA) on a photosynthetic microalgae Chromochloris zofingiensis were compared. Results showed that halogen-containing BPs exhibited higher cellular uptake, leading to more severe oxidative stress, lower photosynthetic efficiency, and greater accumulation of starch and lipids. Specifically, TBBPA with bromine groups showed a greater toxicity than BPAF with fluorine groups, possibly due to the incomplete debromination in C. zofingiensis. Transcriptomic analysis revealed that halogen-containing BPs triggered greater number of differentially expressed genes (DEGs), and only 64 common DEGs were found among different BPs, indicating that the effects of BPs with different functional groups varied greatly. Genes involved in endocytosis, peroxisomes, and endoplasmic reticulum protein processing pathways were mostly upregulated across different BPs, while photosynthesis-related genes showed varied expression, possibly due to their distinct functional groups. Additionally, SIN3A, ZFP36L, CHMP, and ATF2 emerged as potential key regulatory genes. Overall, this study thoroughly explained how functional groups impact the toxicity and biodegradation of BPs in C. zofingiensis.


Assuntos
Biodegradação Ambiental , Fenóis , Fenóis/toxicidade , Fenóis/metabolismo , Fotossíntese/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Microalgas/efeitos dos fármacos , Microalgas/metabolismo , Clorófitas/metabolismo , Clorófitas/efeitos dos fármacos , Clorófitas/genética , Disruptores Endócrinos/toxicidade , Disruptores Endócrinos/metabolismo , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/metabolismo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo
6.
Front Plant Sci ; 15: 1395999, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39328795

RESUMO

Introduction: The thickening of radish taproots is primarily determined by secondary growth driven by the vascular cambium and is a highly intricate process regulated by plant hormones, transcription factors, and many metabolic pathways. Gibberellin (GA), a plant hormone associated with cell elongation, is essential in secondary growth. However, the mechanism through which exogenous GA3 regulates secondary taproot growth in radishes remains unclear. Methods: Integrated morphological, anatomical, hormonal, and transcriptomic analyses of taproots in radishes treated with GA3 and its biosynthesis inhibitor paclobutrazol (PBZ) were performed to explore their effects on taproot secondary growth and key regulatory pathways. Results: GA3 significantly hindered taproot thickening by inhibiting the formation and maintenance of the vascular cambium, and PBZ promoted root development by increasing root length rather than root diameter. Transcriptome analysis revealed 2,014, 948, and 1,831 differentially expressed genes identified from the control vs. GA3, control vs. PBZ, and GA3 vs. PBZ comparisons, respectively. Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis revealed that differentially expressed genes were primarily involved in the biosyntheses of secondary metabolites and metabolic pathways. GA3 significantly increased the levels of endogenous indole-acetic acid and the expression of auxin synthesis and signal transduction genes. Discussion: Exogenous GA3 significantly inhibited the expression of genes involved in the maintenance and differentiation of vascular cambium, including WOX14, ER/ERL1, and XCP2. Exogenous GA3 affects root thickening in radishes primarily by regulating hormone signal transduction pathways, vascular cambium activity, and substance and energy metabolisms. Our findings provide insights into the mechanisms underlying taproot thickening in radishes and provide a valuable gene database for future studies.

7.
Talanta ; 282: 126905, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39341059

RESUMO

Labor pain has an important impact on maternal labor experience, mood, and postpartum depression. It is of great emotional significance to pay attention to the pain stress response of pregnant women and take necessary intervention measures in the labor process to weaken the sense of delivery experience and reduce the risk of complications. To better understand the molecular alteration of pain and stress changes during the delivery, we analyzed the metabolomic and proteomic of the plasma collected during the labor process at different stages, revealing the significant changes in metabolites and proteins and the key regulatory pathways. The KEGG enrichment analysis showed the differentially expressed metabolites and differentially expressed proteins were mainly enriched in glutamate metabolism, glutathione metabolism, oxidative phosphorylation, glycolysis/gluconeogenesis, and citrate cycle (TCA cycle). In particular, the glutathione metabolism played a major role in the metabolic pathway of the whole labor process. The result demonstrated the potential significance of the glutathione metabolic pathway in pain regulation.

8.
Chem Commun (Camb) ; 60(70): 9412-9415, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39136093

RESUMO

The impact of molecular point groups on phase transition materials has been seldom discussed. Two organic cations with different symmetries were incorporated into a [SnCl6]2- framework. By breaking the symmetry of cations, a novel hybrid material with two successive phase transitions featuring a rare "on-off-on" nonlinear optical switch was obtained.

9.
Micromachines (Basel) ; 15(8)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39203668

RESUMO

This paper presents the design, simulation, fabrication, and characterization of a novel large-scan-range electrothermal micromirror integrated with a pair of position sensors. Note that the micromirror and the sensors can be manufactured within a single MEMS process flow. Thanks to the precise control of the fabrication of the grid-based large-size Al/SiO2 bimorph actuators, the maximum piston displacement and optical scan angle of the micromirror reach 370 µm and 36° at only 6 Vdc, respectively. Furthermore, the working principle of the sensors is deeply investigated, where the motion of the micromirror is reflected by monitoring the temperature variation-induced resistance change of the thermistors on the substrate during the synchronous movement of the mirror plate and the heaters. The results show that the full-range motion of the micromirror can be recognized by the sensors with sensitivities of 0.3 mV/µm in the piston displacement sensing and 2.1 mV/° in the tip-tilt sensing, respectively. The demonstrated large-scan-range micromirror that can be monitored by position sensors has a promising prospect for the MEMS Fourier transform spectrometers (FTS) systems.

10.
Cancer Immunol Immunother ; 73(10): 193, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105794

RESUMO

OBJECTIVE: Most recurrent glioblastoma (rGBM) patients do not benefit from immune checkpoint inhibition, emphasizing the necessity for response biomarkers. This study evaluates whether tumor in situ fluid (TISF) circulating tumor DNA (ctDNA) could serve as a biomarker for response to low-dose bevacizumab (Bev) plus anti-PD-1 therapy in rGBM patients, aiming to enhance systemic responses to immunotherapy. METHODS: In this phase II trial, 32 GBM patients with first recurrence after standard therapy were enrolled and then received tislelizumab plus low-dose Bev each cycle. TISF samples were analyzed for ctDNA using a 551-gene panel before each treatment. RESULTS: The median progression-free survival (mPFS) and overall survival (mOS) were 8.2 months (95% CI, 5.2-11.1) and 14.3 months (95% CI, 6.5-22.1), respectively. The 12-month OS was 43.8%, and the objective response rate was 56.3%. Patients with more than 20% reduction in the mutant allele fraction and tumor mutational burden after treatment were significantly associated with better prognosis compared to baseline TISF-ctDNA. Among detectable gene mutations, patients with MUC16 mutation, EGFR mutation & amplification, SRSF2 amplification, and H3F3B amplification were significantly associated with worse prognosis. CONCLUSIONS: Low-dose Bev plus anti-PD-1 therapy significantly improves OS in rGBM patients, offering guiding significance for future individualized treatment strategies. TISF-ctDNA can monitor rGBM patients' response to combination therapy and guide treatment. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT05540275.


Assuntos
Bevacizumab , Neoplasias Encefálicas , DNA Tumoral Circulante , Glioblastoma , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso , Adulto , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Prognóstico
11.
Chemosphere ; 363: 142911, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39038709

RESUMO

Quantum dots (QDs) are widely utilized semiconductor nanocrystal materials with both nanotoxicity and composition-related toxicity. To determine the toxicological impacts and underlying mechanisms of QDs with different compositions on microalgae, carbon QDs (CQDs) and CdSe QDs were used in the present study. Results showed that QDs composed of CdSe were more toxic than QDs composed of carbon, which inhibited cell growth, with reductions in chl b content, chlorophyll fluorescence parameters, and increases in lipids and starch (two major storage substances). In addition, CdSe QDs elevated reactive oxygen species (ROS), resulting in oxidative damage, while CQDs had little effect on antioxidants. Comparative transcriptome analysis showed that gene expression was accelerated by CdSe QDs, and there was a compensatory upregulation of porphyrin metabolism, potentially to support chlorophyll synthesis. In addition, an MYB transcription factor was predicted by weighted gene co-expression network analysis (WGCNA) to serve as regulator in nanoparticle toxicity, while glutathione peroxidase (GPX) and dual-specificity tyrosine phosphorylation regulated kinases 2/3/4 (DYRK2/3/4) may be key mediators of the composition-related toxicity of CdSe QDs. This study highlights the critical role of QDs' composition in determining their impacts on aquatic microalgae, providing a theoretical reference for selecting appropriate QDs materials for various industrial applications.


Assuntos
Compostos de Cádmio , Carbono , Pontos Quânticos , Espécies Reativas de Oxigênio , Compostos de Selênio , Pontos Quânticos/toxicidade , Pontos Quânticos/química , Carbono/química , Carbono/toxicidade , Compostos de Cádmio/toxicidade , Compostos de Cádmio/química , Espécies Reativas de Oxigênio/metabolismo , Compostos de Selênio/toxicidade , Compostos de Selênio/química , Microalgas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Clorofila , Clorófitas/efeitos dos fármacos , Antioxidantes/metabolismo , Antioxidantes/toxicidade
12.
J Colloid Interface Sci ; 675: 700-711, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38996700

RESUMO

HYPOTHESIS: Simple single-chain amphiphiles (sodium monododecyl phosphate, SDP) and organic small molecules (isopentenol, IPN), both of primitive relevance, are proved to have been the building blocks of protocells on the early Earth. How do SDP-based membrane and coexisting IPN come together in specific ways to produce more complex chemical entities? What kind of cell-like behavior can be endowed with this protocell model? These are important questions in the pre-life chemical origin scenario that have not been answered to date. EXPERIMENTS: The phase behavior and formation mechanism of the aggregates for SDP/IPN/H2O ternary system were characterized and studied by different electron microscopy, fluorescent probe technology, DLS, IR, ESI-MS, SAXS, etc. The stability (freeze-thaw and wet-dry treatments) and cell-like behavior (chemical signaling communication) were tested via simulating particular scenarios. FINDINGS: Vesicles, microtubules and asters phases resembling the morphology and structure of modern cells/organelles were obtained. The intermolecular hydrogen bonding is the main driving force for the emergence of the aggregates. The protocell models not only display remarkable stabilities by simulating the primordial Earth's diurnal temperature differences and ocean tides but also are able to exhibit cell-like behavior of chemical signaling transition.


Assuntos
Microtúbulos , Microtúbulos/química , Microtúbulos/metabolismo , Células Artificiais/química , Tamanho da Partícula , Modelos Biológicos
13.
Acta Biomater ; 185: 85-97, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39025394

RESUMO

MgGa alloys are considered highly potential biodegradable materials, owing to its good mechanical properties and appropriate corrosion resistance. However, it is still far from application due to the lack of biological evaluation. In the present study, biocompatibility, osteogenesis and antibacterial activity of extruded Mg-xGa (x = 1 and 5 wt%) alloys were investigated by in vitro cell culture experiments and in vivo implantation. The cell adhesion and proliferation of osteoblast precursor cells (MC3T3-E1) showed the excellent cytocompatibility of Mg-1Ga and poor cytocompatibility of Mg-5Ga. The osteogenic activity was evaluated and revealed that Ga3+ in the Mg-1Ga extract had the ability to enhance osteogenic differentiation through the facilitation of its early stages. In vivo studies in a rat femoral condyle model revealed that both Mg-1Ga and Mg-5Ga significantly promoted new bone formation without causing any adverse effects. Mg-5Ga exhibited a much higher corrosion rate in vivo than Mg-1Ga. Its osteogenic activity was better due to the rapid release of Mg2+ and Ga3+, but this caused premature structural integrity loss. Mg-1Ga and Mg-5Ga released Ga3+ to inhibit E. coli and S. aureus, with antibacterial rate increasing with Ga content. Our studies demonstrate that Mg-Ga alloys have the potential to be used as osteogenic and antibacterial implant materials. STATEMENT OF SIGNIFICANCE: This study evaluates the biocompatibility, osteogenesis, and antibacterial activity of Mg-Ga alloys, which are promising biodegradable materials for medical applications. The study finds that Mg-1Ga exhibits excellent cytocompatibility and promotes osteogenic differentiation, facilitating the early stages of osteoblast precursor cell development. In vivo studies in a rat femoral condyle model reveal that Mg-1Ga and Mg-5Ga significantly promote new bone formation without causing any adverse effects. The antibacterial activity of both alloys is evaluated against E. coli and S. aureus, with the inhibition rate increasing with Ga content. These findings suggest that Mg-Ga alloys have the potential to serve as osteogenic and antibacterial implant materials, providing significant insights into the development of novel biomedical implants.


Assuntos
Ligas , Antibacterianos , Gálio , Magnésio , Osteogênese , Animais , Osteogênese/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Ligas/farmacologia , Ligas/química , Camundongos , Gálio/química , Gálio/farmacologia , Magnésio/farmacologia , Magnésio/química , Ratos , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Masculino , Teste de Materiais , Linhagem Celular , Corrosão , Proliferação de Células/efeitos dos fármacos
14.
Invest Ophthalmol Vis Sci ; 65(8): 4, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38953845

RESUMO

Purpose: The purpose of this study was to investigate the role and mechanism of microtubule-associated protein light chain-3 (LC3)-associated phagocytosis (LAP) in the immune response to Aspergillus fumigatus (A. fumigatus) keratitis. Methods: The formation of single-membrane phagosomes was visualized in the corneas of healthy or A. fumigatus-infected humans and C57BL/6 mice using transmission electron microscopy (TEM). Rubicon siRNA (si-Rubicon) was used to block Rubicon expression. RAW 264.7 cells or mice corneas were infected with A. fumigatus with or without pretreatment of si-Rubicon and scrambled siRNA. RAW 264.7 cells were pretreated with Dectin-1 antibody or Dectin-1 overexpressed plasmid and then stimulated with A. fumigatus. Flow cytometry was used to label macrophages in normal and infected corneas of mice. In mice with A. fumigatus keratitis, the severity of the disease was assessed using clinical scores. We used lentiviral technology to transfer GV348-Ubi-GFP-LC3-II-SV40-Puro Lentivirus into the mouse cornea. The GFP-LC3 fusion protein was visualized in corneal slices using a fluorescence microscope. We detected the mRNA and protein expressions of the inflammatory factors IL-6, IL-1ß, and IL-10 using real-time PCR (RT-PCR) and ELISA. We detected the expression of LAP-related proteins Rubicon, ATG-7, Beclin-1, and LC3-II using Western blot or immunofluorescence. Results: Accumulation of single-membrane phagosomes within macrophages was observed in the corneas of patients and mice with A. fumigatus keratitis using TEM. Flow cytometry (FCM) analysis results show that the number of macrophages in the cornea of mice significantly increases after infection with A. fumigatus. LAP-related proteins were significantly elevated in the corneas of mice and RAW 264.7 cells after infection with A. fumigatus. The si-Rubicon treatment elevated the clinical score of mice. In A. fumigatus keratitis mice, the si-Rubicon treated group showed significantly higher expression of IL-6 and IL-1ß and lower expression of IL-10 and LC3-II compared to the control group. In RAW 264.7 cells, treatment with the Dectin-1 overexpressed plasmid upregulated the expression of LAP-related proteins, a process that was significantly inhibited by the Dectin-1 antibody. Conclusions: LAP participates in the anti-inflammatory immune process of fungal keratitis (FK) and exerts an anti-inflammatory effect. LAP is regulated through the Dectin-1 signaling pathway in A. fumigatus keratitis.


Assuntos
Aspergilose , Aspergillus fumigatus , Infecções Oculares Fúngicas , Ceratite , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos , Fagocitose , Animais , Feminino , Humanos , Camundongos , Aspergilose/microbiologia , Aspergilose/metabolismo , Aspergilose/imunologia , Córnea/metabolismo , Córnea/microbiologia , Córnea/patologia , Modelos Animais de Doenças , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/metabolismo , Citometria de Fluxo , Ceratite/microbiologia , Ceratite/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Microscopia Eletrônica de Transmissão , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética
15.
Sci Rep ; 14(1): 13896, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886500

RESUMO

The etiology and pathophysiology of heart failure are still unknown. Increasing evidence suggests that abnormal microRNAs (miRNAs) and transcription factors (TFs) expression may be associated with the development of heart failure. Therefore, this study aims to explore key miRNAs, TFs, and related genes in heart failure to gain a greater understanding of the pathogenesis of heart failure. To search and download the dataset of mRNA chips related to heart failure from the GEO database (GSE59867, GSE9128, and GSE134766), we analyzed differential genes and screened the common differentially expressed genes on two chips using R language software. The binary interactions and circuits among miRNAs, TFs, and corresponding genes were determined by Pearson correlation coefficient. A regulatory network of miRNAs, TFs, and target genes was constructed based on bioinformatics. By comparing the sequences of patients with and without heart failure, five downregulated genes with hypermethylated mRNA and three upregulated genes with hypomethylated mRNA were identified. The miRNA-TF gene regulatory network consisted of 26 miRNAs, 22 TFs and six genes. GO and KEGG analysis results revealed that BP terms like cellular response to organic substance, cellular response to cytokine stimulus, and KEGG pathways like osteoclast differentiation, MAPK signaling pathway, and legionellosis were enriched of the DEGs. TMEM87A, PPP2R2A, DUSP1, and miR-92a have great potential as biomarkers for heart failure. The integrated analysis of the mRNA expression spectrum and microRNA-transcription factor-gene revealed the regulatory network of heart failure, which may provide clues to its alternative treatment.


Assuntos
Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Insuficiência Cardíaca , MicroRNAs , Fatores de Transcrição , MicroRNAs/genética , Insuficiência Cardíaca/genética , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Biologia Computacional/métodos , Regulação da Expressão Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Bases de Dados Genéticas
16.
ACS Appl Mater Interfaces ; 16(24): 30776-30792, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38848491

RESUMO

Wound infections are an escalating clinical challenge with continuous inflammatory response and the threat of drug-resistant bacteria. Herein, a series of self-healing conductive hydrogels were designed based on carboxymethyl chitosan/oxidized sodium alginate/polymerized gallic acid/Fe3+ (CMC/OSA/pGA/Fe3+, COGFe) for promoting infected wound healing. The Schiff base and catechol-Fe3+ chelation in the dynamical dual network structure of the hydrogels endowed dressings with good toughness, conductivity, adhesion, and self-healing properties, thus flexibly adapting to the deformation of skin wounds. In terms of ultraviolet (UV) resistance and scavenging of reactive oxygen species (ROS), the hydrogels significantly reduced oxidative stress at the wound site. Additionally, the hydrogels with photothermal therapy (PTT) achieved a 95% bactericidal rate in 5 min of near-infrared (NIR) light radiation by disrupting the bacterial cell membrane structure through elevated temperature. Meanwhile, the inherent antimicrobial properties of GA could reduce healthy tissue damage caused by excessive heat. The composite hydrogels could effectively promote the proliferation and migration of fibroblasts and possess good biocompatibility and hemostatic effect. In full-thickness infected wound repair experiments in rats, the COGFe5 hydrogel combined with NIR effectively killed bacteria, modulated macrophage polarization (M1 to M2 phenotype) to improve the immune microenvironment of the wound, and shortened the repair time by accelerating the expression of collagen deposition (TGF-ß) and vascular factors (CD31). This combined therapy might provide a prospective strategy for infectious wound treatment.


Assuntos
Antibacterianos , Quitosana , Hidrogéis , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Ratos , Quitosana/química , Quitosana/farmacologia , Quitosana/análogos & derivados , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Terapia Fototérmica , Staphylococcus aureus/efeitos dos fármacos , Alginatos/química , Alginatos/farmacologia , Ratos Sprague-Dawley , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino
17.
Molecules ; 29(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38893538

RESUMO

Protocell models play a pivotal role in the exploration of the origin of life. Vesicles are one type of protocell model that have attracted much attention. Simple single-chain amphiphiles (SACs) and organic small molecules (OSMs) possess primitive relevance and were most likely the building blocks of protocells on the early Earth. OSM@SAC vesicles have been considered to be plausible protocell models. Pyrite (FeS2), a mineral with primitive relevance, is ubiquitous in nature and plays a crucial role in the exploration of the origin of life in the mineral-water interface scenario. "How do protocell models based on OSM@SAC vesicles interact with a mineral-water interface scenario that simulates a primitive Earth environment" remains an unresolved question. Hence, we select primitive relevant sodium monododecyl phosphate (SDP), isopentenol (IPN) and pyrite (FeS2) mineral particles to build a protocell model. The model investigates the basic physical and chemical properties of FeS2 particles and reveals the effects of the size, content and duration of interaction of FeS2 particles on IPN@SDP vesicles. This deepens the understanding of protocell growth mechanisms in scenarios of mineral-water interfaces in primitive Earth environments and provides new information for the exploration of the origin of life.

18.
Materials (Basel) ; 17(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38893983

RESUMO

This study delves into the formation, transformation, and impact on coating performance of MgZn2 and Mg2Zn11 phases in low-aluminum Zn-Al-Mg alloy coatings, combining thermodynamic simulation calculations with experimental verification methods. A thermodynamic database for the Zn-Al-Mg ternary system was established using the CALPHAD method, and this alloy's non-equilibrium solidification process was simulated using the Scheil model to predict phase compositions under varying cooling rates and coating thicknesses. The simulation results suggest that the Mg2Zn11 phase might predominate in coatings under simulated production-line conditions. However, experimental results characterized using XRD phase analysis show that the MgZn2 phase is the main phase existing in actual coatings, highlighting the complexity of the non-equilibrium solidification process and the decisive effect of experimental conditions on the final phase composition. Further experiments confirmed that cooling rate and coating thickness significantly influence phase composition, with faster cooling and thinner coatings favoring the formation of the metastable phase MgZn2.

19.
Microsyst Nanoeng ; 10: 76, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863795

RESUMO

Silicon interposers embedded with ultra-deep through-silicon vias (TSVs) are in great demand for the heterogeneous integration and packaging of opto-electronic chiplets and microelectromechanical systems (MEMS) devices. Considering the cost-effective and reliable manufacturing of ultra-deep TSVs, the formation of continuous barrier and seed layers remains a crucial challenge to solve. Herein, we present a novel dual catalysis-based electroless plating (ELP) technique by tailoring polyimide (PI) liner surfaces to fabricate dense combined Ni barrier/seed layers in ultra-deep TSVs. In additional to the conventional acid catalysis procedure, a prior catalytic step in an alkaline environment is proposed to hydrolyze the PI surface into a polyamide acid (PAA) interfacial layer, resulting in additional catalysts and the formation of a dense Ni layer that can function as both a barrier layer and a seed layer, particularly at the bottom of the deep TSV. TSVs with depths larger than 500 µm and no voids are successfully fabricated in this study. The fabrication process involves low costs and temperatures. For a fabricated 530-µm-deep TSV with a diameter of 70 µm, the measured depletion capacitance and leakage current are approximately 1.3 pF and 1.7 pA at 20 V, respectively, indicating good electrical properties. The proposed fabrication strategy can provide a cost-effective and feasible solution to the challenge of manufacturing ultra-deep TSVs for modern 3D heterogeneous integration and packaging applications.

20.
Opt Lett ; 49(9): 2377-2380, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691723

RESUMO

We demonstrate a multichannel entropy loading mechanism in an optical frequency comb-based coherent communication system. In high-capacity wavelength division multiplexing communications, the individual laser sources can be replaced by an optical frequency comb, thus reducing the complexity and energy consumption of the transmitter. However, the power variation among different comb lines will lead to performance discrepancies. Spectral flattening filters can be adopted to suppress the variation at the expense of an additional system loss. Alternatively, by applying probabilistic shaping, we have implemented multichannel entropy loading to facilitate a continuous adaptation of the source entropy. The data rate can be dynamically allocated according to the performance of each channel. Through the loading scheme, the non-uniform performances across the channels are effectively mitigated, achieving a capacity enhancement of 34.91 Gbit/s.

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