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1.
EMBO J ; 43(12): 2397-2423, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38760575

RESUMO

The nucleoside analogue decitabine (or 5-aza-dC) is used to treat several haematological cancers. Upon its triphosphorylation and incorporation into DNA, 5-aza-dC induces covalent DNA methyltransferase 1 DNA-protein crosslinks (DNMT1-DPCs), leading to DNA hypomethylation. However, 5-aza-dC's clinical outcomes vary, and relapse is common. Using genome-scale CRISPR/Cas9 screens, we map factors determining 5-aza-dC sensitivity. Unexpectedly, we find that loss of the dCMP deaminase DCTD causes 5-aza-dC resistance, suggesting that 5-aza-dUMP generation is cytotoxic. Combining results from a subsequent genetic screen in DCTD-deficient cells with the identification of the DNMT1-DPC-proximal proteome, we uncover the ubiquitin and SUMO1 E3 ligase, TOPORS, as a new DPC repair factor. TOPORS is recruited to SUMOylated DNMT1-DPCs and promotes their degradation. Our study suggests that 5-aza-dC-induced DPCs cause cytotoxicity when DPC repair is compromised, while cytotoxicity in wild-type cells arises from perturbed nucleotide metabolism, potentially laying the foundations for future identification of predictive biomarkers for decitabine treatment.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , Decitabina , Ubiquitina-Proteína Ligases , Decitabina/farmacologia , Humanos , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Metilação de DNA/efeitos dos fármacos , Antimetabólitos Antineoplásicos/farmacologia , Animais , Sumoilação/efeitos dos fármacos
2.
J Biol Chem ; 300(3): 105773, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38382671

RESUMO

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1). Knocking down ZNF692 resulted in the nucleolar redistribution of NPM1 in ring-like structures and reduced protein synthesis. Purified NPM1 forms spherical condensates in vitro but mixing it with ZNF692 produces irregular condensates more closely resembling living cell nucleoli. Our findings indicate that ZNF692, by interacting with NPM1, plays a critical role in regulating nucleolar architecture and function in living cells.


Assuntos
Nucléolo Celular , Proteínas de Ligação a DNA , Nucleofosmina , Fatores de Transcrição , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , Proteínas Nucleares/metabolismo , Ligação Proteica , RNA Ribossômico/metabolismo , Humanos , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo
3.
Anal Chem ; 96(13): 5150-5159, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38502727

RESUMO

Hexavalent chromium [Cr(VI)] is considered a serious environmental pollutant that possesses a hazardous effect on humans even at low concentrations. Thus, the development of a bifunctional material for ultratrace-selective detection and effective elimination of Cr(VI) from the environment remains highly desirable and scarcely reported. In this work, we explore an imidazolium-appended polyfluorene derivative PF-DBT-Im as a highly sensitive/selective optical probe and a smart adsorbent for Cr(VI) ions with an ultralow detection limit of 1.77 nM and removal efficiency up to 93.7%. In an aqueous medium, PF-DBT-Im displays obvious transformation in its emission color from blue to magenta on exclusively introducing Cr(VI), facilitating naked-eye colorimetric detection. Consequently, a portable sensory device integrated with a smartphone is fabricated for realizing real-time and on-site visual detection of Cr(VI). Besides, the imidazolium groups attached onto side chains of PF-DBT-Im are found to be highly beneficial for achieving selective and efficient elimination of Cr(VI) with capacity as high as 128.71 mg g-1. More interestingly, PF-DBT-Im could be easily regenerated following treatment with KBr and can be recycled at least five times in a row. The main factor behind ultrasensitive response and excellent removal efficiency is found to be anion-exchange-induced formation of a unique ground-state complex between PF-DBT-Im and Cr(VI), as evident by FT-IR, XPS, and simulation studies. Thus, taking advantage of the excellent signal amplification property and rich ion-exchange sites, a dual-functional-conjugated polymer PF-DBT-Im is presented for the concurrent recognition and elimination of Cr(VI) ions proficiently and promptly with great prospects in environmental monitoring and water decontamination.

4.
Small ; : e2401701, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38705844

RESUMO

Enhancing the intrinsic stability of perovskite and through encapsulation to isolate water, oxygen, and UV-induced decomposition are currently common and most effective strategies in perovskite solar cells. Here, the atomic layer deposition process is employed to deposit a nanoscale (≈100 nm), uniform, and dense Al2O3 film on the front side of perovskite devices, effectively isolating them from the erosion caused by water and oxygen in the humid air. Simultaneously, nanoscale (≈100 nm) TiO2 films are also deposited on the glass surface to efficiently filter out the ultraviolet (UV) light in the light source, which induces degradation in perovskite. Ultimately, throughthe collaborative effects of both aspects, the stability of the devices is significantly improved under conditions of humid air and illumination. As a result, after storing the devices in ambient air for 1000 h, the efficiency only declines to 95%, and even after 662 h of UV exposure, the efficiency remains at 88%, far surpassing the performance of comparison devices. These results strongly indicate that the adopted Al2O3 and TiO2 thin films play a significant role in enhancing the stability of perovskite solar cells, demonstrating substantial potential for widespread industrial applications.

5.
New Phytol ; 243(2): 720-737, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38812277

RESUMO

During arbuscular mycorrhizal (AM) symbiosis, plant innate immunity is modulated to a prime state to allow for fungal colonization. The underlying mechanisms remain to be further explored. In this study, two rice genes encoding LysM extracellular (LysMe) proteins were investigated. By obtaining OsLysMepro:GUS transgenic plants and generating oslysme1, oslysme2 and oslysme1oslysme2 mutants via CRISPR/Cas9 technique, OsLysMe genes were revealed to be specifically induced in the arbusculated cells and mutations in either gene caused significantly reduced root colonization rate by AM fungus Rhizophagus irregularis. Overexpression of OsLysMe1 or OsLysMe2 dramatically increased the colonization rates in rice and Medicago truncatula. The electrophoretic mobility shift assay and dual-luciferase reporter assay supported that OsLysMe genes are regulated by OsWRI5a. Either OsLysMe1 or OsLysMe2 can efficiently rescue the impaired AM phenotype of the mtlysme2 mutant, supporting a conserved function of LysMe across monocotyledonous and dicotyledonous plants. The co-localization of OsLysMe proteins with the apoplast marker SP-OsRAmy3A implies their probable localization to the periarbuscular space (PAS) during symbiosis. Relative to the fungal biomass marker RiTEF, some defense-related genes showed disproportionately high expression levels in the oslysme mutants. These data support that rice plants deploy two OsLysMe proteins to facilitate AM symbiosis, likely by diminishing plant defense responses.


Assuntos
Regulação da Expressão Gênica de Plantas , Mutação , Micorrizas , Oryza , Proteínas de Plantas , Simbiose , Micorrizas/fisiologia , Oryza/microbiologia , Oryza/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Mutação/genética , Plantas Geneticamente Modificadas , Medicago truncatula/microbiologia , Medicago truncatula/genética , Motivos de Aminoácidos , Espaço Extracelular/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Fungos
6.
Plant Cell Environ ; 47(6): 2011-2026, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38392921

RESUMO

Crispr/CAS9-enabled homologous recombination to insert a tag in frame with an endogenous gene can circumvent difficulties such as context-dependent promoter activity that complicate analysis of gene expression and protein accumulation patterns. However, there have been few reports examining whether such gene targeting/gene tagging (GT) can alter expression of the target gene. The enzyme encoded by Δ1-pyrroline-5-carboxylate synthetase 1 (P5CS1) is key for stress-induced proline synthesis and drought resistance, yet its expression pattern and protein localisation have been difficult to assay. We used GT to insert YFP in frame with the 5' or 3' ends of the endogenous P5CS1 and At14a-Like 1 (AFL1) coding regions. Insertion at the 3' end of either gene generated homozygous lines with expression of the gene-YFP fusion indistinguishable from the wild type allele. However, for P5CS1 this occurred only after selfing and advancement to the T5 generation allowed initial homozygous lethality of the insertion to be overcome. Once this was done, the GT-generated P5CS1-YFP plants revealed new information about P5CS1 localisation and tissue-specific expression. In contrast, insertion of YFP at the 5' end of either gene blocked expression. The results demonstrate that GT can be useful for functional analyses of genes that are problematic to properly express by other means but also show that, in some cases, GT can disrupt expression of the target gene.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Plantas Geneticamente Modificadas , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , Mutagênese Insercional/genética , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
7.
Opt Lett ; 49(11): 3267-3270, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824380

RESUMO

We present a spectral-scanning frequency-modulated continuous wave (FMCW) 3D imaging system capable of producing high-resolution depth maps with an extended field of view (FOV). By employing a multipass configuration with an echelle grating, the system achieves an FOV of 5.5° along the grating axis. The resulting depth maps have a resolution of 70 × 40 pixels, with a depth resolution of 5.1 mm. The system employs an echelle grating for beam steering and leverages the multipass configuration for angular FOV magnification. Quantitative depth measurements and 3D imaging results of a static 3D-printed depth variation target are demonstrated. The proposed approach offers a promising solution for enhancing the FOV of spectral-scanning FMCW LiDAR systems within a limited wavelength-swept range, thereby reducing system complexity and cost, paving the way for improved 3D imaging applications.

8.
Inorg Chem ; 63(1): 593-601, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38103019

RESUMO

In nature, biological nitrogen fixation is accomplished through the π-back-bonding mechanism of nitrogenase, which poses significant challenges for mimic artificial systems, thanks to the activation barrier associated with the N≡N bond. Consequently, this motivates us to develop efficient and reusable photocatalysts for artificial nitrogen fixation under mild conditions. We employ a charge-assisted self-assembly process toward encapsulating one polyoxometalate (POM) within a dehydrated Zr-based metal-organic framework (d-UiO-66) exhibiting nitrogen photofixation activities, thereby constructing an enzyme-mimicking photocatalyst. The dehydration of d-UiO-66 is favorable for facilitating nitrogen chemisorption and activation via the unpaired d-orbital electron at the [Zr6O6] cluster. The incorporation of POM guests enhanced the charge separation in the composites, thereby facilitating the transfer of photoexcited electrons into the π* antibonding orbital of chemisorbed N2 for efficient nitrogen fixation. Simultaneously, the catalytic efficiency of SiW9Fe3@d-UiO-66 is enhanced by 9.0 times compared to that of d-UiO-66. Moreover, SiW9Fe3@d-UiO-66 exhibits an apparent quantum efficiency (AQE) of 0.254% at 550 nm. The tactics of "working-in-tandem" achieved by POMs and d-UiO-66 are extremely vital for enhancing artificial ammonia synthesis. This study presents a paradigm for the development of an efficient artificial catalyst for nitrogen photofixation, aiming to mimic the process of biological nitrogen fixation.

9.
Environ Sci Technol ; 58(9): 4193-4203, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38393778

RESUMO

Sulfur disproportionation (S0DP) poses a challenge to the robust application of sulfur autotrophic denitrification due to unpredictable sulfide production, which risks the safety of downstream ecosystems. This study explored the S0DP occurrence boundaries with nitrate loading and temperature effects. The boundary values increased with the increase in temperature, exhibiting below 0.15 and 0.53 kg-N/m3/d of nitrate loading at 20 and 30 °C, respectively. A pilot-scale sulfur-siderite packed bioreactor (150 m3/d treatment capacity) was optimally designed with multiple subunits to dynamically distribute the loading of sulfur-heterologous electron acceptors. Operating two active and one standby subunit achieved an effective denitrification rate of 0.31 kg-N/m3/d at 20 °C. For the standby subunit, involving oxygen by aeration effectively transformed the facultative S0DP functional community from S0DP metabolism to aerobic respiration, but with enormous sulfur consumption resulting in ongoing sulfate production of over 3000 mg/L. Meanwhile, acidification by the sulfur oxidation process could reduce the pH to as low as 2.5, which evaluated the Gibbs free energy (ΔG) of the S0DP reaction to +2.56 kJ, thermodynamically suppressing the S0DP occurrence. Therefore, a multisubunit design along with S0DP inhibition strategies of short-term aeration and long-term acidification is suggested for managing S0DP in various practical sulfur-packed bioreactors.


Assuntos
Carbonatos , Ecossistema , Compostos Férricos , Nitratos , Nitratos/metabolismo , Processos Autotróficos , Temperatura , Enxofre/metabolismo , Reatores Biológicos , Desnitrificação , Nitrogênio
10.
Chem Biodivers ; 21(8): e202400963, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38778509

RESUMO

The Sterculia genus is comprised of approximately 300 species, which have been widely used as traditional medicines to treat inflammation, snake bites, gastrointestinal diseases, skin diseases, microbial infections and many other diseases. To gain a comprehensive understanding of the therapeutic potential of Sterculia plants, an extensive literature search was conducted in CNKI, Bing, Wanfang Database, Springer Database, Elsevier Database, Google Scholar, Baidu Scholar, PubMed, and other similar websites from January 1971 to March 2024. The research indicated that Sterculia species predominantly contain flavonoids, terpenoids, phenylpropanoids, fatty acids, alkaloids and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, antioxidant, antibacterial and other biological activities have been reported. Nevertheless, there isn't much scholarly research on the therapeutic material basis of the genus Sterculia. This review reports the ethnobotany, phytochemicals, and biological activities of the plants in the Sterculia genus as herbal remedies.


Assuntos
Compostos Fitoquímicos , Sterculia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Humanos , Sterculia/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação
11.
Chem Biodivers ; 21(2): e202301958, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38130145

RESUMO

Three novel diterpenoid alkaloids, comprising two C19 -diterpenoid alkaloids (1 and 2) and one C20 -diterpenoid alkaloid (3), were isolated from Delphinium ajacis, alongside the six known compounds (4-9). Their structures were elucidated by spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and chemical properties. Simultaneously, the anti-inflammatory properties of all compounds (1-9) was conducted, focusing on nitric oxide (NO) production in LPS-induced BV-2 cells. The results indicated compounds 1-3, 7, and 8 have potential anti-inflammatory activity.


Assuntos
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Espectroscopia de Ressonância Magnética , Alcaloides/farmacologia , Alcaloides/química , Diterpenos/farmacologia , Diterpenos/química , Anti-Inflamatórios/farmacologia , Estrutura Molecular
12.
Alzheimers Dement ; 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39129310

RESUMO

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

13.
Compr Rev Food Sci Food Saf ; 23(3): e13343, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38629458

RESUMO

Innovations in food packaging systems could meet the evolving needs of the market; emerging concepts of non-migrating technologies reduce the negative migration of preservatives from packaging materials, extend shelf life, and improve food quality and safety. Non-migratory packaging activates the surface of inert materials through pretreatment to generate different active groups. The preservative is covalently grafted with the resin of the pretreated packaging substrate through the graft polymerization of the monomer and the coupling reaction of the polymer chain. The covalent link not only provides the required surface properties of the material for a long time but also retains the inherent properties of the polymer. This technique is applied to the processing for durable, stable, and easily controllable packaging widely. This article reviews the principles of various techniques for packaging materials, surface graft modification, and performance characterization of materials after grafting modification. Potential applications in the food industry and future research trends are also discussed.


Assuntos
Embalagem de Alimentos , Armazenamento de Alimentos , Embalagem de Alimentos/métodos , Polímeros/química , Qualidade dos Alimentos
14.
Int Wound J ; 21(1): e14635, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38272805

RESUMO

This study compared the ankle-brachial index (ABI) with transcutaneous oxygen pressure (TcPO2 ) in assessing peripheral vascular disease (PVD) prevalence in 100 diabetic foot ulcer (DFU) patients. Patients were categorized into vascular or nonvascular reconstruction groups and underwent both ABI and TcPO2 measurements four times over 6 months. Predictive validity for PVD diagnosis was analysed using the area under the receiver-operating characteristic curve (AUC). The study found TcPO2 to be a superior predictor of PVD than ABI. Among the DFU patients, 51 with abnormal TcPO2 values underwent vascular reconstruction. Only TcPO2 values showed significant pretreatment differences between the groups and increased post-reconstruction. These values declined over a 6-month follow-up, whereas ABI values rose. For those with end-stage renal disease (ESRD), TcPO2 values saw a sharp decrease within 3 months. Pre-reconstruction TcPO2 was notably lower in amputation patients versus limb salvage surgery patients. In conclusion, TcPO2 is more effective than ABI for evaluating ischemic limb perfusion and revascularization necessity. It should be prioritized as the primary follow-up tool, especially for ESRD patients.


Assuntos
Diabetes Mellitus , Pé Diabético , Falência Renal Crônica , Doenças Vasculares Periféricas , Humanos , Monitorização Transcutânea dos Gases Sanguíneos , Pé Diabético/cirurgia , Pé Diabético/complicações , Isquemia/diagnóstico , Isquemia/cirurgia , Oxigênio/uso terapêutico
15.
Angew Chem Int Ed Engl ; 63(29): e202405382, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38682252

RESUMO

Isotactic polythioesters (PTEs) that are thioester analogs to natural polyhydroxyalkanoates (PHAs) have attracted growing attention due to their distinct properties. However, the development of chemically synthetic methods for preparing isotactic PTEs has long been an intricate endeavour. Herein, we report the successful synthesis of perfectly isotactic PTEs via stereocontrolled ring-opening polymerization. This binaphthalene-salen aluminium (SalBinam-Al) catalyst promoted a robust polymerization of rac-α-substituted-ß-propiothiolactones (rac-BTL and rac-PTL) with highly kinetic resolution, affording perfectly isotactic P(BTL) and P(PTL) with Mn up to 276 kDa. Impressively, the isotactic P(BTL) formed a supramolecular stereocomplex with improved thermal property (Tm=204 °C). Ultimately, this kinetic resolution polymerization enabled the facile isolation of enantiopure (S)-BTL, which could efficiently convert to an important pharmaceutical building block (S)-2-benzyl-3-mercapto-propanoic acid. Isotactic P(PTL) served as a tough and ductile material comparable to the commercialized polyolefins. This synthetic system allowed to access of isotactic PTEs, establishing a powerful platform for the discovery of sustainable plastics.

16.
Microb Biotechnol ; 17(5): e14470, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38683675

RESUMO

Avermectins (AVEs), a family of macrocyclic polyketides produced by Streptomyces avermitilis, have eight components, among which B1a is noted for its strong insecticidal activity. Biosynthesis of AVE "a" components requires 2-methylbutyryl-CoA (MBCoA) as starter unit, and malonyl-CoA (MalCoA) and methylmalonyl-CoA (MMCoA) as extender units. We describe here a novel strategy for increasing B1a production by enhancing acyl-CoA precursor supply. First, we engineered meilingmycin (MEI) polyketide synthase (PKS) for increasing MBCoA precursor supply. The loading module (using acetyl-CoA as substrate), extension module 7 (using MMCoA as substrate) and TE domain of MEI PKS were assembled to produce 2-methylbutyrate, providing the starter unit for B1a production. Heterologous expression of the newly designed PKS (termed Mei-PKS) in S. avermitilis wild-type (WT) strain increased MBCoA level, leading to B1a titer 262.2 µg/mL - 4.36-fold higher than WT value (48.9 µg/mL). Next, we separately inhibited three key nodes in essential pathways using CRISPRi to increase MalCoA and MMCoA levels in WT. The resulting strains all showed increased B1a titer. Combined inhibition of these key nodes in Mei-PKS expression strain increased B1a titer to 341.9 µg/mL. Overexpression of fatty acid ß-oxidation pathway genes in the strain further increased B1a titer to 452.8 µg/mL - 8.25-fold higher than WT value. Finally, we applied our precursor supply strategies to high-yield industrial strain A229. The strategies, in combination, led to B1a titer 8836.4 µg/mL - 37.8% higher than parental A229 value. These findings provide an effective combination strategy for increasing AVE B1a production in WT and industrial S. avermitilis strains, and our precursor supply strategies can be readily adapted for overproduction of other polyketides.


Assuntos
Acil Coenzima A , Ivermectina , Ivermectina/análogos & derivados , Engenharia Metabólica , Redes e Vias Metabólicas , Policetídeo Sintases , Streptomyces , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Acil Coenzima A/metabolismo , Acil Coenzima A/genética , Streptomyces/genética , Streptomyces/metabolismo , Streptomyces/enzimologia , Redes e Vias Metabólicas/genética , Ivermectina/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
17.
Int Immunopharmacol ; 131: 111807, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38471362

RESUMO

CD28null T cells, an atypical subset characterized by the loss of CD28 costimulatory molecule expression, exhibit functional variants and progressively expand with age. Moreover, T cells with these phenotypes are found in both typical and atypical humoral immune responses. Consequently, they accumulate during infectious diseases, autoimmune disorders, cardiovascular conditions, and neurodegenerative ailments. To provide an in-depth review of the current knowledge regarding CD28null T cells, we specifically focus on their phenotypic and functional characteristics as well as their physiological roles in aging and diseases. While uncertainties regarding the clinical utility remains, we will review the following two crucial research perspectives to explore clinical translational applications of the research on this specific T cell subset: 1) addressing the potential utility of CD28null T cells as immunological markers for prognosis and adverse outcomes in both aging and disease, and 2) speculating on the potential of targeting CD28null T cells as an interventional strategy for preventing or delaying immune aging processes and disease progression.


Assuntos
Doenças Autoimunes , Antígenos CD28 , Humanos , Antígenos CD28/metabolismo , Envelhecimento , Subpopulações de Linfócitos T , Doenças Autoimunes/metabolismo , Biologia , Linfócitos T CD4-Positivos
18.
J Colloid Interface Sci ; 656: 376-388, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38000250

RESUMO

Achieving rapid hemostasis and highly effective antibacterial holds significant importance in the early-stage treatment of wounds. In this study, a hybrid aerogel patch comprising carbon quantum dots (CQDs) modified 2-dimensional (2D) porphyrinic metal-organic framework (MOF) nanosheets was designed by incorporating gelatin methacrylate (GelMA) and polyacrylamide (PAM) based matrix. On one hand, CQDs were stably doped onto the surface of the 2D MOF nanosheets, thereby enhancing the photodynamic activity through fluorescence resonance energy transfer (FRET) process. After the preparation of hybrid aerogel patch, the patch loaded with CQDs-doped 2D MOF exhibited excellent photodynamic bactericidal activity against Gram-positive Staphylococcus aureus (>99.99 %) and Gram-negative Escherichia coli (>99.99 %). On the other hand, the hybrid patch with highly porous and absorbent structure can rapidly absorb blood to aggregate clotting components and form a hydration barrier covering the wound to enhance hemostasis. Besides, the hemolysis and cytotoxicity assays demonstrated a good biocompatibility of this designed patch. In summary, this 2D MOF-loaded aerogel patch holds a potential to achieve rapid hemostasis and effective anti-infection in the early-stage treatment of traumatic wounds.


Assuntos
Hemostáticos , Estruturas Metalorgânicas , Estruturas Metalorgânicas/farmacologia , Coagulação Sanguínea , Gelatina , Antibacterianos/farmacologia , Carbono
19.
Front Med (Lausanne) ; 11: 1362588, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523908

RESUMO

Background: Accurately differentiating between ovarian endometrioma and ovarian dermoid cyst is of clinical significance. However, the ultrasound appearance of these two diseases is variable, occasionally causing confusion and overlap with each other. This study aimed to develop a diagnostic classification model based on ultrasound radiomics to intelligently distinguish and diagnose the two diseases. Methods: We collected ovarian ultrasound images from participants diagnosed as patients with ovarian endometrioma or ovarian dermoid cyst. Feature extraction and selection were performed using the Mann-Whitney U-test, Spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO) regression. We then input the final features into the machine learning classifiers for model construction. A nomogram was established by combining the radiomic signature and clinical signature. Results: A total of 407 participants with 407 lesions were included and categorized into the ovarian endometriomas group (n = 200) and the dermoid cyst group (n = 207). In the test cohort, Logistic Regression (LR) achieved the highest area under curve (AUC) value (0.981, 95% CI: 0.963-1.000), the highest accuracy (94.8%), and the highest sensitivity (95.5%), while LightGBM achieved the highest specificity (97.1%). A nomogram incorporating both clinical features and radiomic features achieved the highest level of performance (AUC: 0.987, 95% CI: 0.967-1.000, accuracy: 95.1%, sensitivity: 88.0%, specificity: 100.0%, PPV: 100.0%, NPV: 88.0%, precision: 93.6%). No statistical difference in diagnostic performance was observed between the radiomic model and the nomogram (P > 0.05). The diagnostic indexes of radiomic model were comparable to that of senior radiologists and superior to that of junior radiologist. The diagnostic performance of junior radiologists significantly improved with the assistance of the model. Conclusion: This ultrasound radiomics-based model demonstrated superior diagnostic performance compared to those of junior radiologists and comparable diagnostic performance to those of senior radiologists, and it has the potential to enhance the diagnostic performance of junior radiologists.

20.
Int J Biol Macromol ; 272(Pt 2): 132910, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38844276

RESUMO

The development of high-efficiency molecularly imprinted photocatalysts is still challenging due to the lack of hydrophilic and suitable functional monomers. In this work, the bio-sourced lysozyme was developed as the hydrophilic functional monomer, and Cu-doped BiOBr was used as the photocatalysts, to prepare a novel hydrophilic molecularly imprinted lysozyme-BiOBr composite (BiOBr-Cu/LyzMIP) with enhanced visible light utilization. Lysozyme could form a transparent layer to mitigate the light transmission obstruction caused by the surface imprinting layer, making it an ideal functional monomer. The prepared BiOBr-Cu/LyzMIP possessed red-shifted visible-light absorption edge and minor reduction of light absorbance, indicating the enhanced utilization of visible light. Accordingly, BiOBr-Cu/LyzMIP demonstrated excellent degradation rate (99.4 % in 20 min), exceptional degradation efficiency (0.211 min-1), and superior reusability. Moreover, BiOBr-Cu/LyzMIP exhibited rapid adsorption equilibrium (20 min), good imprinting factor (2.67), and favourable degradation selectivity (>1.75), indicating the good imprinting effect resulting from abundant functional groups of lysozyme. Versatility experiments on different templates suggested that the proposed approach allowed flexibility in selecting a wide range of hazardous contaminants according to practical requirements. The present work expands the application of lysozyme-based composites in the environmental field, and provides a new one-stop pathway for efficient and sustainable treatment of contaminated water.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Luz , Impressão Molecular , Muramidase , Poluentes Químicos da Água , Purificação da Água , Muramidase/química , Poluentes Químicos da Água/química , Impressão Molecular/métodos , Purificação da Água/métodos , Adsorção , Cobre/química , Catálise
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