文献检索
检索与阿拉丁产品相关的同行评审论文、DOI、PubMed 编号、期刊、作者、CAS 号及研究领域。
科研影响力快照
在搜索之前,这些指标可帮助访客快速了解产品关联科研的规模与质量。
参考指标 指标基于阿拉丁文献引用数据库及期刊影响因子记录。文献关联仅供科研参考,请以原始文献为准。
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are regarded as ‘incretins’ working closely to regulate glucose homeostasis. Unimolecular dual and triple agonists of GLP-1R and GIPR have shown remarkable clinical benefits in treating type 2 diabetes. However, their pharmacological characterization is usually carried out in a single receptor-expressing system. In the present study we constructed a co-expression system of both GLP-1R and GIPR to study the signaling profiles elicited by mono, dual and triple agonists. We show that when the two receptors were co-expressed in HEK 293T cells with comparable receptor ratio to pancreatic cancer cells, GIP predominately induced cAMP accumulation while GLP-1 was biased towards β-arrestin 2 recruitment. The presence of GIPR negatively impacted GLP-1R-mediated cAMP and β-arrestin 2 responses. While sharing some common modulating features, dual agonists (peptide 19 and LY3298176) and a triple agonist displayed differentiated signaling profiles as well as negative impact on the heteromerization that may help interpret their superior clinical efficacies.
Overcoming barriers in solid tumor immunotherapy remains challenging, with adoptive T cell therapies limited by antigen loss, poor tumor infiltration, and T cell exhaustion. Here, we present a nanoengineered tumor-infiltrating lymphocyte (TIL) therapy using anti-PD-1 antibody (αPD-1)-conjugated ZIF-8 nanoparticles to effectively suppress pancreatic tumor growth. These nanoparticles release hyaluronidase (HAase) and decitabine (DEC) in acidic tumor microenvironments, promoting stroma degradation and C–C motif chemokine ligand 5 (CCL5) secretion, while retaining αPD-1 on TILs to prevent exhaustion. CCL5 recruits additional nanodrug-loaded TILs for further release of HAase and DEC, establishing a self-reinforcing infiltration loop. This approach increases TIL infiltration by 12-fold in immunodeficient mice and, in immunocompetent settings, mobilizes both exogenous TILs and endogenous CD8 + T cells, enabling tumor eradication and metastasis suppression with 10-fold lower TIL doses than conventional therapies. Collectively, this nanoengineered TIL therapy offers a potential strategy for addressing immune-resistant tumors, showing distinct benefits in stromal-rich settings.
Both of chemical sunscreen 2,4-dihydroxyl benzophenone (BP-1) and physical UV-blocker titanium dioxide (TiO 2 ) nanocomposites are frequently found in aquatic environment, their environmental fates and potential risks should be concerned. The toxicity variation of the composite sunscreen BP-1-TiO 2 during UV-chlorine combined treatment was investigated in this study. It was found that the reaction mixtures exhibited dramatically increased acute toxicity after UV-chlorine treatment of BP-1-TiO 2 , implying the formation of toxic products. Totally, 21 transformation products were tentatively identified, including chlorinated/hydroxylated benzophenones (BPs), hydroxylated benzoyl benzoquinones, phenols, and benzoic acids. We proposed the plausible transformation pathways of BP-1, mainly including hydroxylation, oxidation, chlorination, decarboxylation and ring closing via electrophilic substitution, and Norrish I cleavage. Notably, cosmetic-grade TiO 2 (CG-TiO 2 ) nanocomposites promoted BP-1 transformation and toxic products formation during UV-chlorine combined treatment. The present results highlight that the coatings of CG-TiO 2 nanocomposites are not stable during UV-chlorine combined treatment, the naked TiO 2 would act as photocatalyst to promote BP-1 transformation and generate toxic products. These findings provide valuable insights for assessing potential environmental risks of sunscreen products.
Plants have evolved sophisticated mechanisms to balance growth and defense. The evolutionarily conserved polymerase-associated factor 1 complex (PAF1C) plays multiple roles in transcription. Here, we show that PAF1C regulates the growth-defense tradeoff by repressing defense genes expression in Arabidopsis . Loss of PAF1C leads to increased expression of defense genes, enhanced disease resistance, but compromised growth. Mechanistically, PAF1C binds to defense genes, where it interacts with histone deacetylases, such as HDA6, to promote histone deacetylation, thereby repressing defense genes expression. The plant immune hormone salicylic acid (SA) promotes the interaction between PAF1 and the SA receptor NPR1, which functions as an E3 ubiquitin ligase to mediate the polyubiquitination and degradation of PAF1. Genetically, loss of PAF1 suppresses the immune defects of the npr1 mutant, supporting the notion that PAF1 functions downstream of NPR1. Collectively, this study identifies the NPR1-PAF1C-HDA6 module that regulates the growth-defense tradeoff.
Mucus layer coating the vaginal epithelium represents a barrier for intravaginally delivered recombined adenoviral (rAd) vectors, but it could be overcome by proper polyethylene glycol (PEG) modification. Here we synthesized two cationic PEG derivatives, amino-(EO) n /(AGE) m -Cyss (APCs). The polymers contained neutral linear PEG (2–5 kDa) to provide a hydrophilic surface and amine pendants to provide positive charge for coating negatively charged rAd by physical adsorption. Given proper molecular composition, the polymer (5k-APC) could coat rAd without causing aggregation, facilitating its mucus penetrating ability and enhancing gene expression both in vitro and in vivo . With HIVgag as the model antigen, the polymer-rAd complexes were administered intravaginally to elicit both systemic and mucosal immune responses. 5k-APC-rAd immunization elicited robust HIVgag-specific cellular responses and also induced higher antigen-specific serum IgG. More importantly, mice immunized with 5k-APC-rAd showed higher level of IgA in vaginal lavage fluid. These findings suggest that 5k-APC-rAd is a promising system for intravaginal immunization against infectious diseases such as HIV within the vaginal tract.
Microwave dielectric ceramics of Sr 2 SiO 4 incorporated with different contents of Ba 0.5 Sr 0.5 TiO 3 were prepared using a solid-phase reaction. Their phase composition, micro-structure evolution and dielectric properties were investigated systematically. The results reveal that increasing the x content to 50 wt% leads to greater lattice distortion and defects formation caused by ion substitution within the composite ceramics, resulting in an increase in the dielectric permittivity while a degradation in the Q value. As the x content continues to increase, the enhanced connectivity and ferroelectric properties caused by Ba 0.5 Sr 0.5 TiO 3 within the composite ceramics trigger a sharp increase in the dielectric permittivity. However, the deterioration in Q value is suppressed by the composite effect, and its value gradually increases. At the same time, structural transformations occur within the composites, possessing relaxation properties. Optimal microwave dielectric performance is achieved at x = 25 wt%, indicating balanced properties with ε r = 26.41, Q = 1578 (4.658 GHz), and tanδ = 0.001581.
Developing high-performance H 2 /CH 4 separation membranes is of great potential for H 2 production in the petroleum industry. Incorporating nanofillers into a polymer matrix to form mixed matrix membranes (MMMs) can elevate selectivity and permeability, but poor polymer-filler interfacial compatibility and filler aggregation are formidable problems. Targeting this, we propose a novel approach by incorporating a metal–organic framework (MOF) gel, ZIF-8 gel, as the versatile filler to a high free volume polymer PIM-1 and investigate the H 2 /CH 4 separation capabilities of the MMMs. Benefiting from the gel network morphology of ZIF-8, they were dispersed evenly in the PIM-1 matrix. The interconnected gel network structure of ZIF-8 gel helped to construct continuous gas transport pathways in the polymer. As a result, the H 2 /CH 4 separation performance was notably improved, demonstrating a substantial increase in H 2 permeability by 78.9% (exceeding 6800 Barrer) and a 38.0% enhancement in H 2 /CH 4 selectivity at a ZIF-8 gel loading of 31.0 wt%. These improvements surpassed the upper bound established in 2008. The Maxwell and Lewis-Nielsen models were developed to clarify gas transport mechanisms across membranes, and the experimental data of ZIF-8 gel/PIM-1 was well-matched with the calculated results of the Lewis-Nielsen models. Adopting MOF gel as fillers may pave a new approach to design high-performance MMMs with interconnected transport pathways.
The addition-esterification reaction of fatty acids and alkenes is an important method for replacing the Fischer-Speier esterification due to its 100 % atomic utilization. In this study, sec -hexyl acetate was synthesized through the addition-esterification of 1-hexene. At the same time, five different zinc-exchanged phosphotungstic acid catalysts were prepared using the ion exchange method, and their catalytic activities in the addition-esterification were tested and compared. Results indicate that the Zn 0.5 H 2.0 PW- I catalyst exhibits the best performance in six different catalysts, which is attributed to the synergistic effect of Brönsted and Lewis acids. The activity of catalysts is determined by the equilibrium relationship between Brönsted and Lewis acidity. In the addition-esterification of alkenes, the main activity center is the Brönsted acid site, while the Lewis acid site can improve the adsorption capacity of the catalyst for acetic acid molecules. Moreover, the preparation methods have a significant impact on the activity of catalysts. In addition, the in-situ FT-IR spectrum experiment confirms that the reaction rate of alkene isomerization is greater than that of addition-esterification, and a higher temperature is not conducive to the generation of acetate.
Metal-organic frameworks (MOFs) have shown potential as nanofillers for the selective capture of specific gases in mixed matrix membranes (MMMs). This study introduces an efficient method, utilizing a mild (100 °C) reaction condition and a short reaction time (20 min), for the synthesis of MOF-808(Ce) nanocrystals. The MOF-808(Ce) that is obtained exhibits porous characteristics, a notable affinity for CO 2 , and robust intermolecular interactions with PIM-1. Furthermore, this study pioneers the incorporation of MOF-808(Ce) as a filler into PIM-1, with varying loadings, to create PIM/MOF-808 MMMs for the purpose of CO 2 separation. Consequently, the MMMs containing 2 wt% MOF-808(Ce) demonstrate high CO 2 permeability of 6854 Barrer and CO 2 /N 2 selectivity of 23.2, which is far surpasses 2008 upper bound from Robeson and approaches the refined 2019 upper bound from MeKenow. A comparative analysis demonstrates the efficacy of MOF-808(Ce) as a filler in PIM-1 for the purpose of CO 2 separation.
Bioactive peptides have attracted significant attention for their potential health benefits; however, their oral administration is challenged by degradation from digestive proteases and limited intestinal absorption. In this study, we demonstrated the exceptional gastrointestinal stability of ferritin nanocages, which remained largely intact after 30 min of simulated gastric digestion and were highly resistant to intestinal proteolysis. Consistent with in vitro findings, orally administered ferritin successfully reached the intestinal tract without significant degradation in mice. We engineered a fusion protein by linking a glucagon-like peptide-1 (GLP-1) motif to the C-terminus of heteropolymer ferritin, generating HLG. Through Caco-2 monolayer assays, we confirmed that HLG absorption occurs primarily via TfR1-mediated endocytosis, followed by lysosomal trafficking and subsequent release of bioactive GLP-1. Oral administration of HLG significantly reduced blood glucose levels and food intake in type 2 diabetic mice, whereas the GLP-1 analog exenatide alone showed no such effects. These findings highlight the potential of ferritin-based nanocages as an effective oral delivery platform for bioactive peptides.
Immune checkpoint inhibitor (ICI) therapies increase the risk of metabolic syndrome; the underlying mechanisms remain elusive. We show that an anti-PD-1 antibody targets macrophage PD-1 to reduce energy expenditure without affecting food intake, augmenting the susceptibility of mice to high-fat diet (HFD)-induced obesity and systemic metabolic disorders. Mechanistically, lipopolysaccharide (LPS) activates Unc-51-like autophagy activating kinase 1 (ULK1) in a mammalian target of rapamycin (mTOR)-dependent manner. Activated ULK1 phosphorylates PD-1 at Thr250 to inhibit FBXO38-mediated PD-1 ubiquitination and degradation by disrupting FBXO38-PD-1 binding. Phosphorylated PD-1 interacts with inositol-requiring enzyme 1α (IRE1α) and attenuates IRE1α autophosphorylation to suppress endoplasmic reticulum (ER) stress-mediated inflammatory responses. Suppressing IRE1α alleviates HFD-induced metabolic disorders in macrophage-specific PD-1 knockout mice by rescuing the reduced energy expenditure. Our findings highlight the critical role of macrophage PD-1 at the intersection of immune checkpoint blockade, energy expenditure, and metabolic dysfunction. The underscored moonlighting function of macrophage PD-1 may provide a new rationale for combating ICI therapy- and HFD-induced metabolic diseases.
文献关联基于可获得的产品、CAS、DOI 及引用记录。收录不代表作者或出版方对阿拉丁产品的背书,请以原始文献为准。
危险品化学品经营许可证（带存储）