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1.
Nano Lett ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046144

RESUMO

In this contribution, we report on the visualization of 12-crown-4 molecular diffusion behavior within a single-crystal particle of covalent organic framework-300 (COF-300) using operando dark-field optical microscopy. The diffusion area and front of 12-crown-4 are directly tracked in real time, offering key information for quantifying the diffusion coefficient (D). The direction of the diffusion and variation of D reveal intraparticle and interparticle heterogeneity. Notably, an unexpected hydration-accelerated diffusion process of 12-crown-4 within the pore channels of COF-300 is captured, in which a relatively low concentration of 12-crown-4 aqueous solution induces a fast diffusion, whereas the pure 12-crown-4 liquid cannot access the framework. The observed acceleration diffusion is demonstrated to arise from the hydrogen-bonding interactions between surface water molecules of hydrated 12-crown-4 and the imine groups of COF-300. These findings expand the mechanistic understanding of the noncovalent interactions between COFs and crown ethers (CEs), which will help to design and prepare CE-based COFs with improved performance.

2.
Elife ; 122024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046447

RESUMO

The Arabidopsis thaliana FLAGELLIN-SENSITIVE2 (FLS2), a typical receptor kinase, recognizes the conserved 22 amino acid sequence in the N-terminal region of flagellin (flg22) to initiate plant defense pathways, which was intensively studied in the past decades. However, the dynamic regulation of FLS2 phosphorylation at the plasma membrane after flg22 recognition needs further elucidation. Through single-particle tracking, we demonstrated that upon flg22 treatment the phosphorylation of Ser-938 in FLS2 impacts its spatiotemporal dynamics and lifetime. Following Förster resonance energy transfer-fluorescence lifetime imaging microscopy and protein proximity indexes assays revealed that flg22 treatment increased the co-localization of GFP-tagged FLS2/FLS2S938D but not FLS2S938A with AtRem1.3-mCherry, a sterol-rich lipid marker, indicating that the phosphorylation of FLS2S938 affects FLS2 sorting efficiency to AtRem1.3-associated nanodomains. Importantly, we found that the phosphorylation of Ser-938 enhanced flg22-induced FLS2 internalization and immune responses, demonstrating that the phosphorylation may activate flg22-triggered immunity through partitioning FLS2 into functional AtRem1.3-associated nanodomains, which fills the gap between the FLS2S938 phosphorylation and FLS2-mediated immunity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Flagelina , Proteínas Quinases , Imagem Individual de Molécula , Fosforilação , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Flagelina/metabolismo , Flagelina/farmacologia , Imunidade Vegetal , Transferência Ressonante de Energia de Fluorescência , Membrana Celular/metabolismo
3.
BMC Ophthalmol ; 24(1): 293, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026209

RESUMO

OBJECTIVE: This study aimed to evaluate and explore the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling and gas tamponade in treating myopic foveoschisis (MF) through a meta-analysis. METHODS: Systematic searches were conducted on the PubMed, Web of Science and National Library of Medicine (NLM) English-language databases and the China National Knowledge Infrastructure (CNKI) and Wanfang Chinese-language databases. The primary outcome measures were postoperative best-corrected visual acuity (BCVA) and central foveal thickness (CFT), with the secondary outcome being the postoperative complication rate. Data analysis was performed using RevMan5.3 software. RESULTS: A total of 10 studies involving 234 eyes were included. The meta-analysis results showed the following: (1) The average postoperative BCVA improved compared with preoperative levels, with an average improvement in the logarithm of the minimum angle of resolution of 0.40, a statistically significant difference (95% CI: -0.44, - 0.20, p < 0.001); (2) the rate of postoperative BCVA improvement was 77% (95% CI: 65%, 90%, p < 0.001); (3) the postoperative CFT significantly decreased by an average of 385.92 µm, a statistically significant difference (95% CI: -437.85, - 333.98, p < 0.001); (4) the postoperative macular retinal complete reattachment rate was 90% (95% CI: 83%, 97%, p < 0.001); (5) the most common postoperative complication was a cataract, with an incidence of 55.9%. CONCLUSION: Using PPV combined with ILM peeling and gas tamponade to treat MF is reliable.


Assuntos
Membrana Basal , Tamponamento Interno , Retinosquise , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Retinosquise/cirurgia , Tamponamento Interno/métodos , Acuidade Visual/fisiologia , Membrana Basal/cirurgia , Miopia Degenerativa/cirurgia , Miopia Degenerativa/complicações , Miopia Degenerativa/fisiopatologia , Miopia/cirurgia , Miopia/fisiopatologia
4.
Skeletal Radiol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980364

RESUMO

Articular cartilage damage and degeneration are among hallmark manifestations of joint injuries and arthritis, classically osteoarthritis. Cartilage compositional MRI (Cart-C MRI), a quantitative technique, which aims to detect early-stage cartilage matrix changes that precede macroscopic alterations, began development in the 1990s. However, despite the significant advancements over the past three decades, Cart-C MRI remains predominantly a research tool, hindered by various technical and clinical hurdles. This paper will review the technical evolution of Cart-C MRI, delve into its clinical applications, and conclude by identifying the existing gaps and challenges that need to be addressed to enable even broader clinical application of Cart-C MRI.

5.
Chaos ; 34(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38885069

RESUMO

In the phenomenon of mixed-mode oscillations, transitions between large-amplitude and small-amplitude oscillations may lead to anomalous jitter in the probe of a tapping mode atomic force microscope (TM-AFM) during the scanning process, thereby affecting the accuracy and clarity of the topographical images of the tested sample's surface. This work delves deeply into various mixed-mode oscillations and the corresponding formation mechanisms in TM-AFM under low-frequency resonant excitation. Through a detailed analysis of bifurcation sets of the fast subsystem, we found that the system's mixed-mode oscillations encompass the typical two coexisting branches and the novel three coexisting branches of equilibrium point attractors. In the stable case, a certain transition pattern in phase trajectory can be observed involving two jumps and four jumps, switching between quiescent and spiking states. In the bi-stable case, the trajectory undergoes distinct transitions decided by whether to pass through or crossover the middle branch of attractors when bifurcation occurs. By applying basin of attraction and fast-slow analysis methods, we unfold the dynamic mechanism of mixed-mode oscillations with distinct switching patterns. Our research contributes to a better understanding of complex oscillations of TM-AFM and provides valuable insights for improving image quality and measurement precision while mitigating detrimental oscillations.

6.
Sci Total Environ ; 945: 174076, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38908583

RESUMO

Chlorophyll-a (Chl-a) is a crucial pigment in algae and macrophytes, which makes the concentration of total Chl-a in the water column (total Chl-a) an essential indicator for estimating the primary productivity and carbon cycle of the ocean. Integrating the Chl-a concentration at different depths (Chl-a profile) is an important way to obtain the total Chl-a. However, due to limited cost and technology, it is difficult to measure Chl-a profiles directly in a spatially continuous and high-resolution way. In this study, we proposed an integrated strategy model that combines three different machine learning methods (PSO-BP, random forest and gradient boosting) to predict the Chl-a profile in the Mediterranean by using several sea surface variables (photosynthetically active radiation, spectral irradiance, sea surface temperature, wind speed, euphotic depth and KD490) and subsurface variables (mixed layer depth) observed by or estimated from satellite and BGC-Argo float observations. After accuracy estimation, the integrated model was utilized to generate the time series total Chl-a in the Mediterranean from 2003 to 2021. By analysing the time series results, it was found that seasonal fluctuation contributed the most to the variation in total Chl-a. In addition, there was an overall decreasing trend in the Mediterranean phytoplankton biomass, with the total Chl- decreasing at a rate of 0.048 mg/m2 per year, which was inferred to be related to global warming and precipitation reduction based on comprehensive analysis with sea surface temperature and precipitation data.


Assuntos
Clorofila A , Monitoramento Ambiental , Fitoplâncton , Monitoramento Ambiental/métodos , Clorofila A/análise , Mar Mediterrâneo , Clorofila/análise , Imagens de Satélites , Água do Mar/química , Estações do Ano , Região do Mediterrâneo , Aprendizado de Máquina
7.
Bioengineering (Basel) ; 11(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38927762

RESUMO

Bone marrow edema-like lesions (BMEL) in the knee have been linked to the symptoms and progression of osteoarthritis (OA), a highly prevalent disease with profound public health implications. Manual and semi-automatic segmentations of BMELs in magnetic resonance images (MRI) have been used to quantify the significance of BMELs. However, their utilization is hampered by the labor-intensive and time-consuming nature of the process as well as by annotator bias, especially since BMELs exhibit various sizes and irregular shapes with diffuse signal that lead to poor intra- and inter-rater reliability. In this study, we propose a novel unsupervised method for fully automated segmentation of BMELs that leverages conditional diffusion models, multiple MRI sequences that have different contrast of BMELs, and anomaly detection that do not rely on costly and error-prone annotations. We also analyze BMEL segmentation annotations from multiple experts, reporting intra-/inter-rater variability and setting better benchmarks for BMEL segmentation performance.

8.
Chin J Integr Med ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900227

RESUMO

The hippocampus is one of the most commonly studied brain regions in the context of depression. The volume of the hippocampus is significantly reduced in patients with depression, which severely disrupts hippocampal neuroplasticity. However, antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet. Chinese medicine (CM) can slow the progression of depression, potentially by modulating hippocampal neuroplasticity. Xiaoyaosan (XYS) is a CM formula that has been clinically used for the treatment of depression. It is known to protect Gan (Liver) and Pi (Spleen) function, and may exert its antidepressant effects by regulating hippocampal neuroplasticity. In this review, we have summarized the association between depression and aberrant hippocampal neuroplasticity. Furthermore, we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression. The results of this review can aid future research on XYS for the treatment of depression.

9.
Appl Microbiol Biotechnol ; 108(1): 386, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896257

RESUMO

Bacterial biofilms commonly cause chronic and persistent infections in humans. Bacterial biofilms consist of an inner layer of bacteria and an autocrine extracellular polymeric substance (EPS). Biofilm dispersants (abbreviated as dispersants) have proven effective in removing the bacterial physical protection barrier EPS. Dispersants are generally weak or have no bactericidal effect. Bacteria dispersed from within biofilms (abbreviated as dispersed bacteria) may be more invasive, adhesive, and motile than planktonic bacteria, characteristics that increase the probability that dispersed bacteria will recolonize and cause reinfection. The dispersants should be combined with antimicrobials to avoid the risk of severe reinfection. Dispersant-based nanoparticles have the advantage of specific release and intense penetration, providing the prerequisite for further antibacterial agent efficacy and achieving the eradication of biofilms. Dispersant-based nanoparticles delivered antimicrobial agents for the treatment of diseases associated with bacterial biofilm infections are expected to be an effective measure to prevent reinfection caused by dispersed bacteria. KEY POINTS: • Dispersed bacteria harm and the dispersant's dispersion mechanisms are discussed. • The advantages of dispersant-based nanoparticles in bacteria biofilms are discussed. • Dispersant-based nanoparticles for cutting off reinfection in vivo are highlighted.


Assuntos
Antibacterianos , Biofilmes , Nanopartículas , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Nanopartículas/química , Antibacterianos/farmacologia , Humanos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Reinfecção/prevenção & controle , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Matriz Extracelular de Substâncias Poliméricas/química , Matriz Extracelular de Substâncias Poliméricas/efeitos dos fármacos
10.
Front Oncol ; 14: 1322090, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863621

RESUMO

Background: As one of the most prevalent primary lung tumors, non-small cell lung cancer (NSCLC) has garnered considerable research interest due to its high metastasis rates and poor prognosis outcomes. Across different cancer types, metabolic processes are required for tumors progression and growth, thus interfering with such processes in NSCLC may therapeutically viable for limiting/halting disease progression. Therefore, comprehending how metabolic processes contribute to growth and survival mechanisms in cancers, including NSCLC, may elucidate key functions underpinning tumor cell metabolism. However, no bibliometric analyses have been published in this field, therefore we address this knowledge gap here. Methods: Between 2013 and 2023 (December 28th), articles related to the NSCLC and metabolism (NSCLC-Met) field were retrieved from the Web of Science Core Collection (WoSCC). To fully dissect NSCLC-Met research directions and articles, we used the Bibliometrix package in R, VOSviewer and CiteSpace software to visually represent global trends and hotspots. Results: Between 2013 and 2023, 2,246 NSCLC-Met articles were retrieved, with a continuous upward trend and rapid development observed year on year. Cancers published the most articles, with Cancer Research recording the highest average citation numbers. Zhang Li from China was the most prolific author, but the highest number of authors came from the USA. China, USA, and Italy were the top three countries with the highest number of published articles, with close cooperation identified between countries. Recent hotspots and research directions were reflected by "lung adenocarcinoma", "immunotherapy", "nivolumab", "checkpoint inhibitors", "blockade", and "pembrolizumab", while "gut microbiome", "egfr" and "dose painting" were important topics for researchers. Conclusion: From our analyses, scientists can now explore new hotspots and research directions in the NSCLC-Met field. Further in-depth research in this field will undoubtedly provide more new insights on disease diagnostics, treatment, and prognostics.

11.
Adv Mater ; : e2406256, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38897184

RESUMO

Synthesizing uniform functional covalent organic framework (COF) microspheres is the prerequisite of applying COFs as novel stationary phases for liquid chromatography. However, the synthesis of functionalized COF microspheres is challenging due to the difficulty in maintaining microspheric morphology when conferring functions. Here, a facile and universal "self-limited dynamic linker exchange" strategy is developed to achieve surface functionalization of uniform COF microspheres. Six different types of COF microspheres are constructed, showing the universality and superiority of the strategy. The library of COF microspheres' stationary phases can be further enriched on demand by varying different functional building blocks. The "self-limited dynamic linker exchange" is attributed to the result of a delicate balance of reaction thermodynamics and molecular diffusion energy barrier. As a demonstration, the chiral functional COF microspheres are used as stationary phases of chiral chromatography and realized effective enantioseparation.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38896348

RESUMO

Metamizole easily decomposes in the body and has a short action time and low bioavailability. Hence, frequent injection administrations are needed to maintain its plasma concentration. This study aimed to design and develop an in-situ gel based on poloxamer 407 and 188 to assess its long-acting antipyretic effects. The in-situ gel-forming systep00m with optimum sol-gel transition temperature of 35.9 °C to 36.3 °C could be formed using a combination of P407 at a ratio of 21-23% (w/v) and P188 at a ratio of 2-4% (w/v). In vitro erosion test showed that the in-situ gel's erosion curve and the metamizole release rate both reached about 90% at 6 h, revealing a good linear relationship between the in-situ gel erosion and the drug release. In vitro release test with dialysis tube showed that the release of metamizole from the in-situ gel was remarkably slower than that from the metamizole solution. Approximately 85% of metamizole was released in the dialysis tube within 7 h, implying a good sustained release effect. Pharmacodynamic study showed that the in-situ gel injection extended the action time of metamizole relative to that when using the metamizole solution. Pharmacokinetic study revealed that the in-situ gel significantly increased the blood serum half-life and area under the curve), contributing to a sustained release and improved bioavailability. This study demonstrated that in-situ gel injection could prolong the action of metamizole in the body to reduce the number of administration times and has good clinical application.

13.
Environ Sci Pollut Res Int ; 31(25): 36761-36777, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38753235

RESUMO

Developing the Co-based catalysts with high reactivity for the sulfate radical (SO4-·)-based advanced oxidation processes (SR-AOPs) has been attracting numerous attentions. To improve the peroxymonosulfate (PMS) activation process, a novel Co-based catalyst simultaneously modified by bamboo carbon (BC) and vanadium (V@CoO-BC) was fabricated through a simple solvothermal method. The atenolol (ATL) degradation experiments in V@CoO-BC/PMS system showed that the obtained V@CoO-BC exhibited much higher performance on PMS activation than pure CoO, and the V@CoO-BC/PMS system could fully degrade ATL within 5 min via the destruction of both radicals (SO4-· and O2-··) and non-radicals (1O2). The quenching experiments and electrochemical tests revealed that the enhancing mechanism of bamboo carbon and V modification involved four aspects: (i) promoting the PMS and Co ion adsorption on the surface of V@CoO-BC; (ii) enhancing the electron transfer efficiency between V@CoO-BC and PMS; (iii) activating PMS with V3+ species; (iv) accelerating the circulation of Co2+ and Co3+, leading to the enhanced yield of reactive oxygen species (ROS). Furthermore, the V@CoO-BC/PMS system also exhibited satisfactory stability under broad pH (3-9) and good efficiency in the presence of co-existing components (HCO3-, NO3-, Cl-, and HA) in water. This study provides new insights to designing high-performance, environment-friendly bimetal catalysts and some basis for the remediation of antibiotic contaminants with SR-AOPs.


Assuntos
Atenolol , Carbono , Atenolol/química , Catálise , Carbono/química , Peróxidos/química , Vanádio/química , Oxirredução , Poluentes Químicos da Água/química
14.
Phytomedicine ; 130: 155660, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38815407

RESUMO

BACKGROUND: Xiaoyao pills (XYP) is a commercial Chinese patent medicine used in the treatment of depression. However, the mechanisms underlying its therapeutic effects, as well as the patients who can benefit from XYP, have not been evaluated so far. OBJECTIVES: To this end, we conducted a double-blinded, random, and placebo-controlled clinical trial of orally administered XYP in patients with depression. METHODS: The 17-item Hamilton Depression Rating Scale (HAMD-17) scores were recorded at baseline, and every 2 weeks after the start of treatment. To further elucidate the epigenetic mechanism of XYP, we performed mRNA sequencing and genome-wide DNA methylation sequencing using peripheral blood leukocytes of patients and healthy. RESULTS: XYP effectively alleviated the symptoms in patients with mild or moderate depressive disorders, particularly that of psychomotor retardation. XYP restored aberrant gene expression and DNA methylation patterns associated with depression, and the normalization of DNA methylation correlated with downregulation of several genes. In addition, altered DNA methylation levels in the XYP-treated samples were attributed to increased expression of the DNA methyltransferase DNMT1. CONCLUSIONS: Our study provides new insights into the epigenetic mechanism underlying depression and the therapeutic effects of XYP, along with an experimental basis for using XYP in the treatment of depression. TRIAL REGISTRATION INFORMATION: The name of the registry and number: U.S. CLINICAL TRIALS REGISTRY: The link to the registration: ClinicalTrials.gov ISRCTN12746343 (https://www.isrctn.com/ISRCTN12746343). The name of the trial register is "Efficacy and safety of the Xiaoyao pill for improving the clinical symptoms of stagnation of liver qi (chi) and spleen deficiency". The clinical trial registration number is ISRCTN12746343.


Assuntos
Metilação de DNA , Depressão , Medicamentos de Ervas Chinesas , Humanos , Metilação de DNA/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Método Duplo-Cego , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Depressão/tratamento farmacológico , DNA (Citosina-5-)-Metiltransferase 1/genética , Epigênese Genética/efeitos dos fármacos , Antidepressivos/uso terapêutico , Antidepressivos/farmacologia
15.
Phytomedicine ; 129: 155688, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38728920

RESUMO

BACKGROUND: Malignant breast cancer cells trigger the over-activation of osteoclast precursor cells, leading to bone loss and severe pain. Targeted inhibition of osteoclast differentiation has emerged as an important strategy for treating bone syndromes induced by breast cancer. PURPOSE: The objective is to discover natural osteoclast inhibitor to treat osteoclastogenesis and bone destruction induced by breast cancer, and clarify the specific mechanisms. METHODS: Recepteur d'origine Nantais (RON) protein was employed to search the natural osteoclast inhibitor for breast cancer-induced osteoclastogenesis by molecular docking, molecular dynamics simulation and cellular thermal shift assay (CETSA). In the in vitro experiment, breast cancer MDA-MB-231 cell-conditioned medium (MDA-MB-231 CM) was used to induce osteoclastogenesis in murine bone marrow-derived macrophages (BMMs), aiming to elucidate the effects and mechanisms of the natural osteoclast inhibitor. In the in vivo model, MDA-MB-231 cells was injected into the mouse tibia to evaluate the therapeutic effect of drug on breast cancer-induced bone destruction. RESULTS: We discovered a significant increase in the expression of RON during MDA-MB-231 CM-induced osteoclast differentiation in vitro. Molecular docking analysis found that oroxylin A (OA), a flavonoid derived from the Chinese medicine Scutellaria baicalensis Georgi, showed binding ability with RON, while its impact and mechanism on breast cancer-induced osteoclastogenesis and osteolysis remains unclear. Molecular dynamics simulation and CETSA further revealed that OA bound directly to the RON protein, and it also decreased RON expression in breast cancer CM-induced osteoclastogenesis. Correspondingly, OA suppressed the MDA-MB-231 CM-induced osteoclastogenesis and bone resorption in vitro. The downstream signals of RON including Src and NFATc1, as well as the osteoclast-specific genes, were downregulated by OA. Of interesting, the suppressive effect of OA on osteoclastogenesis induced by MDA-MB-231 CM was abolished after RON was knocked down by the specific RON-siRNA, this further confirmed that OA showed inhibitory effects on osteoclasts through targeting RON. In addition, we found that OA attenuated MDA-MB-231 cell-induced osteolysis and reduced the number of osteoclasts in vivo. CONCLUSION: Our results indicate that OA acts as a natural RON inhibitor to suppress breast cancer-induced osteoclastogenesis and osteolysis. This provides new strategy for treating breast cancer-induced bone destruction and related syndromes.


Assuntos
Neoplasias da Mama , Flavonoides , Simulação de Acoplamento Molecular , Osteoclastos , Osteogênese , Osteólise , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Flavonoides/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteólise/tratamento farmacológico , Receptores Proteína Tirosina Quinases , Camundongos Nus
16.
Genome Biol ; 25(1): 117, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715110

RESUMO

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.


Assuntos
Pré-Eclâmpsia , Trofoblastos , Remodelação Vascular , Pré-Eclâmpsia/genética , Gravidez , Feminino , Humanos , Trofoblastos/metabolismo , Remodelação Vascular/genética , Placenta/metabolismo , Metilação de DNA , Epigênese Genética , Células Endoteliais/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Impressão Genômica , Fator de Crescimento Transformador beta/metabolismo , Retardo do Crescimento Fetal/genética , Placentação/genética , Proteínas de Ligação a RNA , Proteínas Reguladoras de Apoptose
17.
Orphanet J Rare Dis ; 19(1): 205, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764027

RESUMO

BACKGROUND: Trio-based whole-exome sequencing (trio-WES) enables identification of pathogenic variants, including copy-number variants (CNVs), in children with unexplained neurodevelopmental delay (NDD) and neurodevelopmental comorbidities (NDCs), including autism spectrum disorder (ASD), epilepsy, and attention deficit hyperactivity disorder. Further phenotypic and genetic analysis on trio-WES-tested NDD-NDCs cases may help to identify key phenotypic factors related to higher diagnostic yield of using trio-WES and novel risk genes associated with NDCs in clinical settings. METHODS: In this study, we retrospectively performed phenotypic analysis on 163 trio-WES-tested NDD-NDCs children to determine the phenotypic differences between genetically diagnosed and non-genetically diagnosed groups. Additionally, we conducted genetic analysis of ASD genes with the help of Simons Foundation for Autism Research Institute (SFARI) Gene database to identify novel possible ASD-risk genes underlying genetic NDD conditions. RESULTS: Among these 163 patients, pathogenic variants were identified in 82 cases (82/163, 50.3%), including 20 cases with CNVs. By comparing phenotypic variables between genetically diagnosed group (82 cases) and non-genetically diagnosed group (81 cases) with multivariate binary logistic regression analysis, we revealed that NDD-NDCs cases presenting with severe-profound NDD [53/82 vs 17/81, adjusted-OR (95%CI): 4.865 (2.213 - 10.694), adjusted-P < 0.001] or having multiple NDCs [26/82 vs 8/81, adjusted-OR (95%CI): 3.731 (1.399 - 9.950), adjusted-P = 0.009] or accompanying ASD [64/82 vs 35/81, adjusted-OR (95%CI): 3.256 (1.479 - 7.168), adjusted-P = 0.003] and head circumference abnormality [33/82 vs 11/81, adjusted-OR (95%CI): 2.788 (1.148 - 6.774), adjusted-P = 0.024] were more likely to have a genetic diagnosis using trio-WES. Moreover, 37 genes with monogenetic variants were identified in 48 patients genetically diagnosed with NDD-ASD, and 15 dosage-sensitive genes were identified in 16 individuals with NDD-ASD carrying CNVs. Most of those genes had been proven to be ASD-related genes. However, some of them (9 genes) were not proven sufficiently to correlate with ASD. By literature review and constructing protein-protein interaction networks among these 9 candidate ASD-risk genes and 102 established ASD genes obtained from the SFARI Gene database, we identified CUL4B, KCNH1, and PLA2G6 as novel possible ASD-risk genes underlying genetic NDD conditions. CONCLUSIONS: Trio-WES testing is recommended for patients with unexplained NDD-NDCs that have severe-profound NDD or multiple NDCs, particularly those with accompanying ASD and head circumference abnormality, as these independent factors may increase the likelihood of genetic diagnosis using trio-WES. Moreover, NDD patients with pathogenic variants in CUL4B, KCNH1 and PLA2G6 should be aware of potential risks of developing ASD during their disease courses.


Assuntos
Transtorno do Espectro Autista , Sequenciamento do Exoma , Transtornos do Neurodesenvolvimento , Humanos , Sequenciamento do Exoma/métodos , Feminino , Masculino , Criança , Pré-Escolar , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/epidemiologia , Transtorno do Espectro Autista/genética , Estudos Retrospectivos , Variações do Número de Cópias de DNA/genética , Fenótipo , Adolescente , Lactente , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/epidemiologia , População do Leste Asiático
19.
Molecules ; 29(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38792219

RESUMO

Most traditional synthetic dyes and functional reagents used in silk fabrics are not biodegradable and lack green environmental protection. Natural dyes have attracted more and more attention because of their coloring, functionalization effects, and environmental benefits. In this study, natural dyes were extracted from lac and used for coloring and functionalization in silk fabrics without any other harmful dyes. The extraction conditions were studied and analyzed by the univariate method. The optimal extraction process was that the volume ratio of ethanol to water was 60:40 with a solid-liquid ratio of 1:10, and reacting under the neutrality condition for 1 h at 70 °C. Silk fabric can be dyed dark owing to the certain lifting property of lac. After being dyed by Al3+ post-medium, the levels of the washing fastness, light fastness, and friction fastness of silk fabric are all above four with excellent fastness. The results show that the dyed silk fabrics have good UV protection, antioxidation, and antibacterial properties. The UV protection coefficient UPF is 42.68, the antioxidant property is 98.57%, and the antibacterial property can reach more than 80%. Therefore, the dyeing and functionalization of silk fabrics by utilizing naturally lac dyes show broad prospects in terms of the application of green sustainable dyeing and functionalization.


Assuntos
Corantes , Seda , Têxteis , Corantes/química , Seda/química , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química
20.
J Nanobiotechnology ; 22(1): 272, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773580

RESUMO

BACKGROUND: Transdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity. RESULTS: We fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility. CONCLUSIONS: The present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.


Assuntos
Administração Cutânea , Micelas , Absorção Cutânea , Solubilidade , Solventes , Animais , Solventes/química , Pele/metabolismo , Pele/efeitos dos fármacos , Camundongos , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Relação Quantitativa Estrutura-Atividade , Masculino , Simulação de Dinâmica Molecular , Portadores de Fármacos/química
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