Organic anion transporting polypeptide (OATP)1A2 and OATP2B1 have potential N-glycosylation sites, but their influence remains unclear. This study aimed to identify the N-glycosylation sites of OATP1A2/2B1 and investi...
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Organic anion transporting polypeptide (OATP)1A2 and OATP2B1 have potential N-glycosylation sites, but their influence remains unclear. This study aimed to identify the N-glycosylation sites of OATP1A2/2B1 and investigate their impact on the expression and function of OATP1A2/2B1. Human embryonic kidney cells expressing OATP1A2 or OATP2B1 (HEK293-OATP1A2/2B1) were exposed to tunicamycin, an N-glycosylation inhibitor, and a plasma membrane fraction (PMF) Western blot assay and an estrone 3-sulfate (E3S) uptake study were conducted. HEK293-OATP1A2/OATP2B1 cell lines with mutation (s) at potential N-glycosylation sites were established, and the Western blotting and uptake study were repeated. Tunicamycin reduced the PMF levels and E3S uptake of OATP1A2/OATP2B1. The Asn124Gln, Asn135Gln, and Asn492Gln mutations in OATP1A2 and Asn176Gln and Asn538Gln mutations in OATP2B1 reduced the molecular weights of the OATP molecules and their PMF levels. The PMF levels of OATP1A2 Asn124/135Gln, OATP1A2 Asn124/135/492Gln, and OATP2B1 Asn176/538Gln were further reduced. The maximum transport velocities of OATP1A2 Asn124Gln, OATP1A2 Asn135Gln, and OATP2B1 Asn176/538Gln were markedly reduced to 10 %, 4 %, and 10 % of the wild-type level, respectively. In conclusion, the N-glycans at Asn124 and Asn135 of OATP1A2 and those at Asn176 and Asn538 of OATP2B1 are essential for the plasma membrane expression of these molecules and also affect their transport function. (c) 2024 Published by Elsevier Inc. on behalf of American Pharmacists Association.
Background: Macrophages constitute the main part of infiltrating immune cells in Malignant pleural mesothelioma (MPM) and abnormally high ratios of M2 macrophages are present in both pleural effusion and tissue sample...
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Background: Macrophages constitute the main part of infiltrating immune cells in Malignant pleural mesothelioma (MPM) and abnormally high ratios of M2 macrophages are present in both pleural effusion and tissue samples of MPM patients. Whether MPM cells affect formation of M2 macrophages is poorly understood. In this study, we focused on identification of MPM-cells-derived soluble factors with M2-promoting effects. Methods: Media of malignant pleural mesothelioma cells were collected and soluble factors affecting macrophages were analyzed by mass spectrometry. TGF-beta receptor inhibitor SB431542 was used as the entry point to explore the downstream mechanism of action by qRT-PCR, WB and immunofluorescence. Results: The serum-free culture media collected from the human MPM cells Meso1 and Meso2 significantly enhanced expression of the M2 signature molecules including IL-10, TGF-beta and CD206 in the human macrophages THP-1, while the culture medium of the human MPM cells H2452 did not show such M2-promoting effects. Analysis of proteins by mass spectrometry and ELISA suggested that Leucine rich alpha 2 glycoprotein 1(LRG1) was a potential candidate. LRG1 time- and dose-dependently increased expression of the M2 signature molecules, confirming its M2-promoting effects. Furthermore, LRG1's M2-promoting effects were reduced by the TGF-beta receptor inhibitor SB431542, and LRG1 increased phosphorylation of Smad2, indicating that M2-promoting effects of LRG1 were via the TGF-beta receptor/Smad2 signaling pathway. Conclusions: Our results provide a potential M2-promoting new member, LRG1, which contributes to the immune escape of MPM via the TGF-beta receptor/Smad2 signaling pathway.
In the realm of lower-dimensional accelerating spacetimes, it is well-established that the presence of domain walls, which are co-dimension one topological defects, is a necessary condition for their construction. We ...
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In the realm of lower-dimensional accelerating spacetimes, it is well-established that the presence of domain walls, which are co-dimension one topological defects, is a necessary condition for their construction. We expand upon the geometric framework employed in the generation of such spacetime solutions by incorporating a conformally coupled scalar field within the matter sector. This endeavor leads to the identification of several new families of three-dimensional accelerating spacetimes with asymptotically locally anti-de Sitter (AdS) behavior. Notably, one of these solutions showcases a hairy generalization of the accelerating BTZ black hole. This solution is constructed at both slow and rapid phases of acceleration, and its connection with established vacuum spacetime models is explicitly elucidated. The inclusion of the scalar field imparts a non-constant Ricci curvature to the domain wall, thereby rendering these configurations particularly suitable for the construction of two-dimensional quantum black holes. To establish a well-posed variational principle in the presence of the domain wall, two essential steps are undertaken. First, we extend the conventional renormalized AdS3 action to accommodate the presence of the scalar field. Second, we explicitly incorporate the Gibbons-Hawking-York term associated with the internal boundaries of our geometries and account for the tension of the domain wall in the action. This dual step process enables us to derive the domain wall field equations via the variational principle. Consequently, the action furnishes the appropriate quantum statistical relation. We engage in holographic computations, thereby determining the explicit form of the holographic stress tensor. In this context, the stress tensor can be expressed as that of a perfect fluid situated on a curved background. Additionally, it paves the road to ascertain the spacetime mass. Finally, we close by demonstrating the existence of three-dimensional accelera
We construct coloured lattice models whose partition functions represent symplectic and odd orthogonal Demazure characters and atoms. We show that our lattice models are not solvable, but we are able to show the exist...
We construct coloured lattice models whose partition functions represent symplectic and odd orthogonal Demazure characters and atoms. We show that our lattice models are not solvable, but we are able to show the existence of sufficiently many solutions of the Yang-Baxter equation that allow us to compute functional equations for the corresponding partition functions. From these functional equations, we determine that the partition function of our models are the Demazure atoms and characters for the symplectic and odd orthogonal Lie groups. We coin our lattice models as quasi-solvable. We use the natural bijection of admissible states in our models with Proctor patterns to give a right key algorithm for reverse King tableaux and Sundaram tableaux.
BackgroundChronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males and loss of sperm quality. Current therapeutic options have failed to achieve satisfactory results. Sodium b...
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BackgroundChronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males and loss of sperm quality. Current therapeutic options have failed to achieve satisfactory results. Sodium butyrate (NaB) plays a beneficial role in reducing inflammation, increasing antioxidant capacities, and improving organ dysfunction;additionally NaB has good safety prospects and great potential for clinical application. The purpose of the current research was to study the effect of NaB on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) *** EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. Then, EAP mice received daily intraperitoneal injections of NaB (100, 200, or 400 mg/kg/day) for 16 days, from Days 26 to 42. We then explored anti-inflammatory potential mechanisms of NaB by studying the effects of Nrf2 inhibitor ML385 and HO-1 inhibitor zinc protoporphyrin on prostate inflammation and pelvic pain using this model. On Day 42, hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying Von Frey filaments to the lower abdomen. The levels of inflammation-related cytokines, such as interleukin (IL)-1 beta, IL-6, and tumor necrosis factor were detected by enzyme-linked immunosorbent assay. The regulation of Nrf2/HO-1 signaling pathway and the expression of NLRP3 inflammasome-related protein in EAP mice were detected by western blot analysis *** with the EAP group, chronic pain development, histological manifestations, and cytokine levels showed that NaB reduced the severity of EAP. NaB treatment could inhibit NLRP3 inflammasome activation. Mechanism studies showed that NaB intervention could alleviate oxidative stress in EAP mice through Nrf2/HO-1 signal
A stable diareno[a, f]pentalene, dinaphtho[2,1-a:2,3-f]pentalene 6, was synthesized and characterized. The nonsymmetrical dinaphtho-fused structure of 6 highly localized the pi-electrons on the pentalene core, creatin...
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A stable diareno[a, f]pentalene, dinaphtho[2,1-a:2,3-f]pentalene 6, was synthesized and characterized. The nonsymmetrical dinaphtho-fused structure of 6 highly localized the pi-electrons on the pentalene core, creating a quinoidal closed-shell singlet state with a weakened antiaromatic nature. Due to the relatively high HOMO level and the presence of CH-pi contacts, the mesityl derivative 6b exhibited a hole mobility of 4.37 x 10(14) cm(2)V(-1) s(-1), as measured by a space-charge-limited current (SCLC) method.
We develop an effective metric description of 2+1 dimensional black holes describing deviations from the classical Banados–Teitelboim–Zanelli (BTZ) black hole. The latter is a classical 2+1 dimensional rotating blac...
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AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), whi...
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AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic beta-amyloid peptide (A beta). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and A beta in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and A beta, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.
Context: Endometriosis (EMs) is a gynecological disorder. Ligustrazine has been reported to exert an anti-inflammatory effect on EMs. However, the underlying mechanisms are not completely understood. Objective: To inv...
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Context: Endometriosis (EMs) is a gynecological disorder. Ligustrazine has been reported to exert an anti-inflammatory effect on EMs. However, the underlying mechanisms are not completely understood. Objective: To investigate the effects of ligustrazine on the progression of EMs and the underlying regulatory mechanisms. Materials and methods: Human endometrial stromal cells (HESCs) were isolated from patients with EMs or control subjects. HESCs were treated with 25, 50, 100, or 200 mu M ligustrazine for 1, 3, 6, or 12 h. Western blot and enzyme-linked immunosorbent assays were performed to determine the levels of proteins and inflammatory cytokines, respectively. The binding between STAT3 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by chromatin immunoprecipitation and dual-luciferase reporter assays. The relationship between IGF2BP1 and RELA was assessed by RNA immunoprecipitation and RNA pull-down assay. Results: Phosphorylated STAT3, IGF2BP1, RELA, TNF-alpha, IL-6, and IL-1 beta were upregulated in EMs tissues compared with control tissues (by 1.79-, 2.55-, 1.58-, 3.01-, 2.55-, and 3.34-fold, respectively). Ligustrazine inhibited the expression of p-STAT3, IGF2BP1, RELA, IL-6, TNF alpha, and IL-1 beta. Overexpression of STAT3 promoted RELA-mediated inflammatory responses, while ligustrazine (100 mu M) notably reversed this phenomenon. Ligustrazine also alleviated RELA-induced inflammation via downregulating IGF2BP1. STAT3 bound to the promoter of IGF2BP1, and IGF2BP1 bound to the RELA mRNA. Discussion and conclusion: Ligustrazine inhibited inflammation in EMs via regulating the STAT3/IGF2BP1/RELA axis. These findings propose a new agent against EMs and support the development of ligustrazine-based treatment strategies for EMs.
Lead toxicity and poor stability under operating conditions are major drawbacks that impede the widespread commercialization of metal-halide perovskite solar cells. Ti(IV) has been considered as an alternative species...
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Lead toxicity and poor stability under operating conditions are major drawbacks that impede the widespread commercialization of metal-halide perovskite solar cells. Ti(IV) has been considered as an alternative species to replace Pb(II) because it is relatively nontoxic and abundant and its perovskite-like compounds have demonstrated promising performance when applied in solar cells (eta > 3%), photocatalysts, and nonlinear optical applications. Yet, Ti(IV) perovskites show instability in air, hindering their use. On the other hand, Sn(IV) has a similar cationic radius to Ti(IV), adopting the same vacancy-ordered double perovskite (VODP) structure and showing good stability in ambient conditions. We report here a combined experimental and computational study on mixed titanium-tin bromide and iodide VODPs, motivated by the hypothesis that these mixtures may show a stability higher than that of the pure titanium compositions. Thermodynamic analysis shows that the cations are highly miscible in these vacancy-ordered structures. Experimentally, we synthesized mixed titanium-tin VODPs as nanocrystals across the entire mixing range x (Cs2Ti1-x Sn (x) X-6;X = I or Br), using a colloidal synthetic approach. Analysis of the experimental and computed absorption spectra reveals weak hybridization and interactions between Sn and Ti octahedra with the alloy absorption being essentially a linear combination of the pure Sn and Ti compositions. These compounds are stabilized at high percentages of Sn (x of similar to 60%), as expected, with bromide compositions demonstrating greater stability compared to the iodides. Overall, we find that these materials behave akin to molecular aggregates, with the thermodynamic and optoelectronic properties governed by the intraoctahedral interactions.
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