Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 966
Filtrar
1.
Front Immunol ; 15: 1340702, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690275

RESUMO

The extracellular matrix (ECM) is a complex three-dimensional structure composed of proteins, glycans, and proteoglycans, constituting a critical component of the tumor microenvironment. Complex interactions among immune cells, extracellular matrix, and tumor cells promote tumor development and metastasis, consequently influencing therapeutic efficacy. Hence, elucidating these interaction mechanisms is pivotal for precision cancer therapy. T lymphocytes are an important component of the immune system, exerting direct anti-tumor effects by attacking tumor cells or releasing lymphokines to enhance immune effects. The ECM significantly influences T cells function and infiltration within the tumor microenvironment, thereby impacting the behavior and biological characteristics of tumor cells. T cells are involved in regulating the synthesis, degradation, and remodeling of the extracellular matrix through the secretion of cytokines and enzymes. As a result, it affects the proliferation and invasive ability of tumor cells as well as the efficacy of immunotherapy. This review discusses the mechanisms underlying T lymphocyte-ECM interactions in the tumor immune microenvironment and their potential application in immunotherapy. It provides novel insights for the development of innovative tumor therapeutic strategies and drug.


Assuntos
Matriz Extracelular , Neoplasias , Linfócitos T , Microambiente Tumoral , Microambiente Tumoral/imunologia , Humanos , Matriz Extracelular/metabolismo , Matriz Extracelular/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/terapia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Comunicação Celular/imunologia , Imunoterapia/métodos
2.
Nat Prod Rep ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712365

RESUMO

Covering: Up to 2024Due to the widespread distribution of protoberberine alkaloids (PBs) and tetrahydroberberine alkaloids (THPBs) in nature, coupled with their myriad unique physiological activities, they have garnered considerable attention from medical practitioners. Over the past few decades, synthetic chemists have devised various total synthesis methods to attain these structures, continually expanding reaction pathways to achieve more efficient synthetic strategies. Simultaneously, the chiral construction of THPBs has become a focal point. In this comprehensive review, we categorically summarized the developmental trajectory of the total synthesis of these alkaloids based on the core closure strategies of protoberberine and tetrahydroberberine.

3.
Chemosphere ; 358: 142192, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38701862

RESUMO

Current human health risk assessments of soil arsenic (As) contamination rarely consider bioaccessibility (IVBA), which may overestimate the health risks of soil As. The IVBA of As (As-IVBA) may differ among various soil types. This investigation of As-IVBA focused As from geological origin in a typical subtropical soil, lateritic red soil, and its risk control values. The study used the SBRC gastric phase in vitro digestion method and As speciation sequential extraction based upon phosphorus speciation extraction method. Two construction land sites (CH and HD sites) in the Pearl River Delta region were surveyed. The results revealed a high content of residual As (including scorodite, mansfieldite, orpiment, realgar, and aluminum arsenite) in the lateritic red soils at both sites (CH: 84.9%, HD: 91.7%). The content of adsorbed aluminum arsenate (CH: 3.24%, HD: 0.228%), adsorbed ferrum arsenate (CH: 8.55%, HD: 5.01%), and calcium arsenate (CH: 7.33%, HD: 3.01%) were found to be low. The bioaccessible As content was significantly positively correlated with the As content in adsorbed aluminum arsenate, adsorbed ferrum arsenate, and calcium arsenate. A small portion of these sequential extractable As speciation could be absorbed by the human body (CH: 14.9%, HD: 3.16%), posing a certain health risk. Adsorbed aluminum arsenate had the highest IVBA, followed by calcium arsenate, and adsorbed ferrum arsenate had the lowest IVBA. The aforementioned speciation characteristics of As from geological origin in lateritic red soil contributed to its lower IVBA compared to other soils. The oxidation state of As did not significantly affect As-IVBA. Based on As-IVBA, the carcinogenic and non-carcinogenic risks of soil As in the CH and HD sites decreased greatly in human health risk assessment. The results suggest that As-IVBA in lateritic red soil should be considered when assessing human health risks on construction land.

4.
BMC Med Res Methodol ; 24(1): 112, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734644

RESUMO

Orphan diseases, exemplified by T-cell prolymphocytic leukemia, present inherent challenges due to limited data availability and complexities in effective care. This study delves into harnessing the potential of machine learning to enhance care strategies for orphan diseases, specifically focusing on allogeneic hematopoietic cell transplantation (allo-HCT) in T-cell prolymphocytic leukemia. The investigation evaluates how varying numbers of variables impact model performance, considering the rarity of the disease. Utilizing data from the Center for International Blood and Marrow Transplant Research, the study scrutinizes outcomes following allo-HCT for T-cell prolymphocytic leukemia. Diverse machine learning models were developed to forecast acute graft-versus-host disease (aGvHD) occurrence and its distinct grades post-allo-HCT. Assessment of model performance relied on balanced accuracy, F1 score, and ROC AUC metrics. The findings highlight the Linear Discriminant Analysis (LDA) classifier achieving the highest testing balanced accuracy of 0.58 in predicting aGvHD. However, challenges arose in its performance during multi-class classification tasks. While affirming the potential of machine learning in enhancing care for orphan diseases, the study underscores the impact of limited data and disease rarity on model performance.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Prolinfocítica de Células T , Aprendizado de Máquina , Transplante Homólogo , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Homólogo/métodos , Leucemia Prolinfocítica de Células T/terapia , Leucemia Prolinfocítica de Células T/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Doença Aguda
5.
Phys Med Biol ; 69(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604186

RESUMO

Objective. Recently, deep learning models have been used to reconstruct parallel magnetic resonance (MR) images from undersampled k-space data. However, most existing approaches depend on large databases of fully sampled MR data for training, which can be challenging or sometimes infeasible to acquire in certain scenarios. The goal is to develop an effective alternative for improved reconstruction quality that does not rely on external training datasets.Approach. We introduce a novel zero-shot dual-domain fusion unsupervised neural network (DFUSNN) for parallel MR imaging reconstruction without any external training datasets. We employ the Noise2Noise (N2N) network for the reconstruction in the k-space domain, integrate phase and coil sensitivity smoothness priors into the k-space N2N network, and use an early stopping criterion to prevent overfitting. Additionally, we propose a dual-domain fusion method based on Bayesian optimization to enhance reconstruction quality efficiently.Results. Simulation experiments conducted on three datasets with different undersampling patterns showed that the DFUSNN outperforms all other competing unsupervised methods and the one-shot Hankel-k-space generative model (HKGM). The DFUSNN also achieves comparable results to the supervised Deep-SLR method.Significance. The novel DFUSNN model offers a viable solution for reconstructing high-quality MR images without the need for external training datasets, thereby overcoming a major hurdle in scenarios where acquiring fully sampled MR data is difficult.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina não Supervisionado , Humanos
6.
Food Funct ; 15(9): 5000-5011, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38618651

RESUMO

The anti-obesity effect of conjugated linoleic acid (CLA) has been well elucidated, but whether CLA affects fat deposition by regulating intestinal dietary fat absorption remains largely unknown. Thus, this study aimed to investigate the effects of CLA on intestinal fatty acid uptake and chylomicron formation and explore the possible underlying mechanisms. We found that CLA supplementation reduced the intestinal fat absorption in HFD (high fat diet)-fed mice accompanied by the decreased serum TG level, increased fecal lipids and decreased intestinal expression of ApoB48 and MTTP. Correspondingly, c9, t11-CLA, but not t10, c12-CLA induced the reduction of fatty acid uptake and TG content in PA (palmitic acid)-treated MODE-K cells. In the mechanism of fatty acid uptake, c9, t11-CLA inhibited the binding of CD36 with palmitoyltransferase DHHC7, thus leading to the decreases of CD36 palmitoylation level and localization on the cell membrane of the PA-treated MODE-K cells. In the mechanism of chylomicron formation, c9, t11-CLA inhibited the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the PA-treated MODE-K cells. In in vivo verification, CLA supplementation reduced the DHHC7-mediated total and cell membrane CD36 palmitoylation and suppressed the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the jejunum of HFD-fed mice. Altogether, these data showed that CLA reduced intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.


Assuntos
Antígenos CD36 , Quilomícrons , Dieta Hiperlipídica , Ácidos Linoleicos Conjugados , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos C57BL , Animais , Antígenos CD36/metabolismo , Antígenos CD36/genética , Ácidos Linoleicos Conjugados/farmacologia , Camundongos , Masculino , Quilomícrons/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Aciltransferases/metabolismo , Aciltransferases/genética , Absorção Intestinal/efeitos dos fármacos
7.
Eur J Med Chem ; 271: 116395, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38626523

RESUMO

The transforming growth factor ß1 (TGFß1)/SMAD signaling pathway regulates many vital physiological processes. The development of potent inhibitors targeting activin receptor-like kinase 5 (ALK5) would provide potential treatment reagents for various diseases. A significant number of ALK5 inhibitors have been discovered, and they are currently undergoing clinical evaluation at various stages. However, the clinical demands were far from being met. In this study, we utilized an alternative conformation-similarity-based virtual screening (CSVS) combined with a fragment-based drug designing (FBDD) strategy to efficiently discover a potent and active hit with a novel chemical scaffold. After structural optimization in the principle of group replacement, compound 57 was identified as the most promising ALK5 inhibitor. Compound 57 demonstrated significant inhibitory effects against the TGF-ß1/SMAD signaling pathway. It could markedly attenuate the production of extracellular matrix (ECM) and deposition of collagen. Also, the lead compound showed adequate pharmacokinetic (PK) properties and good in vivo tolerance. Moreover, treatment with compound 57 in two different xerograph models showed significant inhibitory effects on the growth of pancreatic cancer cells. These results suggested that lead compound 57 refers as a promising ALK5 inhibitor both in vitro and in vivo, which merits further validation.


Assuntos
Desenho de Fármacos , Inibidores de Proteínas Quinases , Pirazóis , Pirimidinas , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Humanos , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Animais , Estrutura Molecular , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/metabolismo
8.
Molecules ; 29(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38611934

RESUMO

Spirotryprostatin alkaloids, a class of alkaloids with a unique spirocyclic indoledionepiperazine structure, were first extracted from the fermentation broth of Aspergillus fumigatus and have garnered significant attention in the fields of biology and pharmacology. The investigation into the pharmacological potential of this class of alkaloids has unveiled promising applications in drug discovery and development. Notably, certain spirotryprostatin alkaloids have demonstrated remarkable anti-cancer activity, positioning them as potential candidates for anti-tumor drug development. In recent years, organic synthetic chemists have dedicated efforts to devise efficient and viable strategies for the total synthesis of spirotryprostatin alkaloids, aiming to meet the demands within the pharmaceutical domain. The construction of the spiro-C atom within the spirotryprostatin scaffold and the chirality control at the spiro atomic center emerge as pivotal aspects in the synthesis of these compounds. This review categorically delineates the synthesis of spirotryprostatin alkaloids based on the formation mechanism of the spiro-C atom.


Assuntos
Alcaloides , Fermentação , Aspergillus fumigatus , Descoberta de Drogas
9.
J Pharm Anal ; 14(4): 100903, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38655400

RESUMO

A two-photon near infrared (NIR) fluorescence turn-on sensor with high selectivity and sensitivity for Zn2+ detection has been developed. This sensor exhibits a large Stokes' shift (∼300 nm) and can be excited from 900 to 1000 nm, with an emission wavelength of ∼785 nm, making it ideal for imaging in biological tissues. The sensor's high selectivity for Zn2+ over other structurally similar cations, such as Cd2+, makes it a promising tool for monitoring zinc ion levels in biological systems. Given the high concentration of zinc in thrombi, this sensor could provide a useful tool for in vivo thrombus imaging.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38671264

RESUMO

The high cost and low adsorption capacity of primary metal-organic frameworks (ZIF-8) limit their application in heavy metal removal. In this paper, Co/Zn bimetallic MOF materials were synthesized with excellent adsorption performance for As5+. The adsorption reached equilibrium after 180 min and the maximum adsorption was 250.088 mg/g. In addition, Co-ZIF-8 showed strong selective adsorption of As5+. The adsorption process model of Co-ZIF-8 fits well with the pseudo-second-order kinetic model (R2=0.997) and Langmuir isotherm model (R2=0.994), and it is demonstrated that the adsorption behavior of the adsorbent is a single layer of chemical adsorption. In addition, when the adsorbent enters the arsenic-containing solution, the surface of Co-ZIF-8 is hydrolyzed to produce a large number of Co-OH active sites, and As5+ arrives at the surface of Co-ZIF-8 by electrostatic adsorption and combines with the active sites to generate the arsenic-containing complex As-O-Co. After four cycles, Co-ZIF-8 showed 80% adsorption of As5+. This study not only provides a new method to capture As5+ in water by preparing MOF with partial replacement of the central metal, but also has great significance for the harmless disposal of polluted water.

11.
Nat Commun ; 15(1): 3495, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664399

RESUMO

Quantum annealing, which involves quantum tunnelling among possible solutions, has state-of-the-art applications not only in quickly finding the lowest-energy configuration of a complex system, but also in quantum computing. Here we report a single-crystal study of the frustrated magnet α-CoV2O6, consisting of a triangular arrangement of ferromagnetic Ising spin chains without evident structural disorder. We observe quantum annealing phenomena resulting from time-reversal symmetry breaking in a tiny transverse field. Below ~ 1 K, the system exhibits no indication of approaching the lowest-energy state for at least 15 hours in zero transverse field, but quickly converges towards that configuration with a nearly temperature-independent relaxation time of ~ 10 seconds in a transverse field of ~ 3.5 mK. Our many-body simulations show qualitative agreement with the experimental results, and suggest that a tiny transverse field can profoundly enhance quantum spin fluctuations, triggering rapid quantum annealing process from topological metastable Kosterlitz-Thouless phases, at low temperatures.

12.
Nano Lett ; 24(15): 4454-4461, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38572779

RESUMO

Colloidal quantum well (CQW) based light emitting diodes (LEDs) possess extra-high theoretical efficiency, but their performance still lags far behind conventional LEDs due to severe exciton quenching and unbalanced charge injection. Herein, we devised a gradient composition CdxZn1-xS shell to address these issues. The epitaxial shell with gradient composition was achieved through controlling competition between Cd2+ and Zn2+ cations to preferentially bind to the anions S2-. Thus, exciton quenching was suppressed greatly by passivating defects and reducing nonradiative recombination, thereby achieving near-unity photoluminescence quantum yield (PLQY). The gradient energy level of the shell reduced the hole injection barriers and increased the hole injection efficiency to balance the charge injection of LEDs. As a result, the LEDs achieved a high external quantum efficiency (EQE) of 22.83%, luminance of 111,319 cd/m2 and a long operational lifetime (T95@100 cd/m2) over 6,500 h, demonstrating the state-of-the-art performance for the CQW based LEDs.

13.
IEEE Trans Biomed Eng ; PP2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38683702

RESUMO

OBJECTIVE: Intraoperative liver deformation poses a considerable challenge during liver surgery, causing significant errors in image-guided surgical navigation systems. This study addresses a critical non-rigid registration problem in liver surgery: the alignment of intrahepatic vascular trees. The goal is to deform the complete vascular shape extracted from preoperative Computed Tomography (CT) volume, aligning it with sparse vascular contour points obtained from intraoperative ultrasound (iUS) images. Challenges arise due to the intricate nature of slender vascular branches, causing existing methods to struggle with accuracy and vascular self-intersection. METHODS: We present a novel non-rigid sparse-dense registration pipeline structured in a coarse-to-fine fashion. In the initial coarse registration stage, we introduce a parametrization deformation graph and a Welsch function-based error metric to enhance convergence and robustness of non-rigid registration. For the fine registration stage, we propose an automatic curvature-based algorithm to detect and eliminate overlapping regions. Subsequently, we generate the complete vascular shape using posterior computation of a Gaussian Process Shape Model. RESULTS: Experimental results using simulated data demonstrate the accuracy and robustness of our proposed method. Evaluation results on the target registration error of tumors highlight the clinical significance of our method in tumor location computation. Comparative analysis against related methods reveals superior accuracy and competitive efficiency of our approach. Moreover, Ex vivo swine liver experiments and clinical experiments were conducted to evaluate the method's performance. CONCLUSION: The experimental results itasize the accurate and robust performance of our proposed method. SIGNIFICANCE: Our proposed non-rigid registration method holds significant application potential in clinical practice.

14.
Nano Lett ; 24(17): 5238-5245, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629707

RESUMO

ZnTe colloidal semiconductor nanocrystals (NCs) have shown promise for light-emitting diodes (LEDs) and displays, because they are free from toxic heavy metals (Cd). However, so far, their low photoluminescence (PL) efficiency (∼30%) has hindered their applications. Herein, we devised a novel structure of ZnTe NCs with the configuration of ZnSe (core)/ZnTe (spherical quantum well, SQW)/ZnSe (shell). The inner layer ZnTe was grown at the surface of ZnSe core with avoiding using highly active and high-risk Zn sources. Due to the formation of coherently strained heterostructure which reduced the lattice mismatch, and the thermodynamic growth of ZnTe, the surface or interface defects were suppressed. A high PL efficiency of >60% was obtained for the green light-emitting ZnSe/ZnTe/ZnSe SQWs after ZnS outer layer passivation, which is the highest value for colloidal ZnTe-based NCs. This work paves the way for the development of novel semiconductor NCs for luminescent and display applications.

15.
Pharmacoeconomics ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613660

RESUMO

BACKGROUND: The current use of health economic decision models in HTA is mostly confined to single use cases, which may be inefficient and result in little consistency over different treatment comparisons, and consequently inconsistent health policy decisions, for the same disorder. Multi-use disease models (MUDMs) (other terms: generic models, whole disease models, disease models) may offer a solution. However, much is uncertain about their definition and application. The current research aimed to develop a blueprint for the application of MUDMs. METHODS: We elicited expert opinion using a two-round modified Delphi process. The panel consisted of experts and stakeholders in health economic modelling from various professional backgrounds. The first questionnaire concerned definition, terminology, potential applications, issues and recommendations for MUDMs and was based on an exploratory scoping review. In the second round, the panel members were asked to reconsider their input, based on feedback regarding first-round results, and to score issues and recommendations for priority. Finally, adding input from external advisors and policy makers in a structured way, an overview of issues and challenges was developed during two team consensus meetings. RESULTS: In total, 54 respondents contributed to the panel results. The term 'multi-use disease models' was proposed and agreed upon, and a definition was provided. The panel prioritized 10 potential applications (with comparing alternative policies and supporting resource allocation decisions as the top 2), while 20 issues (with model transparency and stakeholders' roles as the top 2) were identified as challenges. Opinions on potential features concerning operationalization of multi-use models were given, with 11 of these subsequently receiving high priority scores (regular updates and revalidation after updates were the top 2). CONCLUSIONS: MUDMs would improve on current decision support regarding cost-effectiveness information. Given feasibility challenges, this would be most relevant for diseases with multiple treatments, large burden of disease and requiring more complex models. The current overview offers policy makers a starting point to organize the development, use, and maintenance of MUDMs and to support choices concerning which diseases and policy decisions they will be helpful for.

16.
Materials (Basel) ; 17(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38591630

RESUMO

Investigations regarding the preparation and durability of cement-based materials applied in specific coastal acid rain environments are scarce, particularly those involving the addition of four auxiliary cementitious materials (ACMs) to cement for modification. To improve the durability of concrete structures in coastal acid rain areas, a systematic study was conducted regarding the preparation of high-strength and corrosion-resistant cement-based materials using ACM systems composed of fly ash (FA), granulated blast furnace slag (GBFS), silica fume (SF), and desulfurization gypsum (DG) instead of partial cement. Through an orthogonal experimental design, the effect of the water-binder ratio, cementitious ratio, and replacement cement ratio on the compressive strength, corrosion resistance coefficient, and chloride ion permeability coefficient of the materials were analyzed and the mix proportions of the materials were evaluated and optimized using the comprehensive scoring method. The results show that implementing a FA:GBFS:SF:DG ratio of 2:6:1:1 to replace 60% of cement allows the consumption of calcium hydroxide crystals generated through cement hydration, promotes the formation of ettringite, optimizes the pore structures of cementitious materials, and improves the compressive strength, acid corrosion resistance, and chloride ion permeability of the materials. This study provides a reference for selecting concrete materials for buildings in coastal acid rain environments.

17.
FEBS Lett ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589226

RESUMO

Overactivation of the epidermal growth factor receptor (EGFR) is critical for the development of multiple cancers. Previous studies have shown that the cell membrane is a key regulator of EGFR kinase activity through its interaction with the EGFR juxtamembrane domain (JM). However, the lipid recognition specificity of EGFR-JM and its interaction details remain unclear. Using lipid strip and liposome pulldown assays, we showed that EGFR-JM could specifically interact with PI(4,5)P2-or phosphatidylserine-containing membranes. We further characterized the JM-membrane interaction using NMR-titration-based chemical shift perturbation and paramagnetic relaxation enhancement analyses, and found that residues I649 - L659 comprised the membrane-binding site. Furthermore, the membrane-binding region contains the predicted dimerization motif of JM, 655LRRLL659, suggesting that membrane binding may affect JM dimerization and, therefore, regulate kinase activation.

18.
Environ Pollut ; 349: 123927, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38582184

RESUMO

The recovery phase of mangrove seedlings in coastal wetland ecosystems can be negatively affected by exposure to external pollutants. This study aimed to investigate the impact of microplastics (MPs) influx, specifically polystyrene (PS) and polymethyl methacrylate (PMMA), on the growth of Aegiceras corniculatum seedlings and their accumulation of heavy metals (HMs). PS and PMMA significantly increased HMs accumulation (up to 21.0-548%), particularly in the roots of seedlings, compared to the control treatment (CK). Additionally, elevated activities of malondialdehyde and catalase enzymes were observed in the leaves of seedlings, while peroxidase enzyme activity decreased. Topological analysis of the root sediment microbiota coexistence network revealed that the modularization data increased from 0.69 (CK treatment) to 1.07 (PS treatment) and 5.11 (PMMA treatment) under the combined stress of MPs and HMs. This suggests that the introduction of MPs intensifies microbial modularization. The primary cause of increased HMs accumulation in plants is the MPs input, which influences the secretion of organic acids by plants and facilitates the shift of HMs in sediment to bioavailable states. Furthermore, changes in microbial clustering may also contribute to the elevated HMs accumulation in plants. This study provides valuable insights into the effects of external pollutants on mangrove seedlings and offers new perspectives for the preservation and restoration of mangrove coastal wetlands.


Assuntos
Metais Pesados , Microplásticos , Plântula , Poluentes Químicos da Água , Áreas Alagadas , Metais Pesados/metabolismo , Poluentes Químicos da Água/metabolismo , Plântula/metabolismo , Microplásticos/metabolismo , Monitoramento Ambiental/métodos , Primulaceae/metabolismo , Sedimentos Geológicos/química
19.
J Nat Prod ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687877

RESUMO

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1 and 2) and four known (3-6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH3 to a carboxyl group to produce 4 from 3. Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6 from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aß treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.

20.
J Mater Chem B ; 12(17): 4080-4096, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38577851

RESUMO

Gene silencing through RNA interference (RNAi), particularly using small double-stranded RNA (siRNA), has been identified as a potent strategy for targeted cancer treatment. Yet, its application faces challenges such as nuclease degradation, inefficient cellular uptake, endosomal entrapment, off-target effects, and immune responses, which have hindered its effective delivery. In the past few years, these challenges have been addressed significantly by using camouflaged metal-organic framework (MOF) nanocarriers. These nanocarriers protect siRNA from degradation, enhance cellular uptake, and reduce unintended side effects by effectively targeting desired cells while evading immune detection. By combining the properties of biomimetic membranes and MOFs, these nanocarriers offer superior benefits such as extended circulation times, enhanced stability, and reduced immune responses. Moreover, through ligand-receptor interactions, biomimetic membrane-coated MOFs achieve homologous targeting, minimizing off-target adverse effects. The MOFs, acting as the core, efficiently encapsulate and protect siRNA molecules, while the biomimetic membrane-coated surface provides homologous targeting, further increasing the precision of siRNA delivery to cancer cells. In particular, the biomimetic membranes help to shield the MOFs from the immune system, avoiding unwanted immune responses and improving their biocompatibility. The combination of siRNA with innovative nanocarriers, such as camouflaged-MOFs, presents a significant advancement in cancer therapy. The ability to deliver siRNA with precision and effectiveness using these camouflaged nanocarriers holds great promise for achieving more personalized and efficient cancer treatments in the future. This review article discusses the significant progress made in the development of siRNA therapeutics for cancer, focusing on their effective delivery through novel nanocarriers, with a particular emphasis on the role of metal-organic frameworks (MOFs) as camouflaged nanocarriers.


Assuntos
Materiais Biomiméticos , Estruturas Metalorgânicas , Neoplasias , RNA Interferente Pequeno , Estruturas Metalorgânicas/química , RNA Interferente Pequeno/química , Humanos , Materiais Biomiméticos/química , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Animais , Portadores de Fármacos/química , Biomimética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...