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关键词： 1, 3-Medium chain-2-long chain triacylglycerols   Acyltransferase   Sodium laurate   Acyl-CoA synthetase   italic>Saccharomyces cerevisiae  

摘要： The Management of Myelomeningocele Study (MOMS) trial established the benefit of in-utero repair of myelomeningocele, with a decreased need for ventriculoperitoneal shunt placement. However, although there was some improvement of motor function, over half of the patients were unable to ambulate independently. Live placenta-derived mesenchymal stem cells (PMSCs) seeded on an extracellular matrix have shown promise in rescuing neurological function in the fetal ovine model of myelomeningocele. We aimed to evaluate the safety of this novel, living, stem cell product to augment the prenatal repair of myelomeningocele.

关键词： Endo-1,4-beta-xylanase   Homology modeling   In silico analysis   Glycoside hydrolase family 10   Gonocephalum sp. gut bacteria  

摘要： Xylanases are one of the most important hydrolytic enzymes involved in plant hemicellulose degradation with potential industrial as well as ecological significance. This study presents a comprehensive characterization of an endo-1,4-beta-xylanase enzyme from Agrobacterium sp. Strain DKPNP3 isolated from the beetle gut of Gonocephalum sp. (Coleoptera: Tenebrionidae). Bioinformatics analyses were performed, including physicochemical characterization, phylogenetic assessment, conserved domain identification, secondary and tertiary structure prediction, subcellular localization prediction, homology modeling, structural validation, molecular docking and molecular dynamics simulation to assess the stability of this protein. The enzyme belongs to the glycoside hydrolase family 10 (GH10) with 339 amino acids, molecular weight of 37.8 kDa, and acidic in nature (pi 5.8). The homology model demonstrated high structural reliability, with an ERRAT score of 96.364% and a QMEAN Z-score of 0.59. Molecular dynamics simulations demonstrated that the enzyme is structurally stable in both its apo and ligand-bound forms. The apo form showed stability comparable to a well-characterized synthetic construct xylanase from Bacillus halodurans (GenBank accession number: MW311490), which was used as a positive control. Furthermore, simulations performed at multiple temperatures indicated retention of conformational integrity under different thermal conditions, suggesting potential thermostability. The intracellular nature of the enzyme, as predicted by in silico analysis, was confirmed by experimental validation using Congo Red-xylan agar assay and quantification with di nitro salicylic acid (DNSA).

关键词： systemic lupus erythematosus   lupus nephritis   glycomics   glycosylation   repeat kidney biopsy   outcomes  

摘要： Background: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterised by unpredictable outcomes due to the absence of reliable biomarkers. This hypothesis-generating study aimed to evaluate whether changes in the N-glycosylation of IgG, C3, AGP, and the serum proteins over one year of treatment correlate with clinical and histological features of LN and predict renal outcomes. Methods: Serum samples from 19 treatment-na & iuml;ve patients with LN were collected at baseline and 12 months post-treatment, in conjunction with per-protocol repeat kidney biopsy. IgG (Fc, Fab, and total), C3, AGP, and total serum glycoproteins were isolated and analysed as either released N-glycans or N-glycopeptides using high-throughput glycomic approaches. Clinical and histological data were obtained at both time points, along with assessments of clinical and histological response at 12 months and long-term renal function. Results: In total, we identified 24/243 increased N-glycosylation traits (2 total IgG, 5 IgG Fc, 7 IgG Fab, 5 serum glycoproteins, 4 AGP, and 1 C3) and 10/243 decreased N-glycosylation traits (7 total IgG, 2 IgG Fc, 1 IgG Fab) following treatment. Baseline AGP IORMIF1N5H6S2F1 showed a positive correlation with eGFR both at baseline (r = 0.64, p = 0.005) and at 12 months (r = 0.51, p = 0.032). Among AGP N-glycosylation traits, IVORMI1N7H8S3 (r = 0.66, p = 0.002;r = 0.48, p = 0.041, respectively), VORMI1N8H9S4 (r = 0.51, p = 0.029;r = 0.49, p = 0.038, respectively), and VORMI1N8H9S4F1 (r = 0.48, p = 0.039;r = 0.49, p = 0.034, respectively) significantly correlated with activity index (AI) at baseline and at 12 months. Presence of cellular crescents at baseline positively correlated with three AGP N-glycosylation traits: IORMISORMIIA1N4H5S2 (r = 0.49, p = 0.036), VORMII1N5H6S3F1 (r = 0.63, p = 0.006), and VORMII1N4H5S2 (r = 0.48, p = 0.046). Total serum N-glycan (structure) N5H4F1 at 12 months was associated with both clinical an

关键词： Immunotherapy   Tumor microenvironment   Adenosine   Single cell sequencing  

摘要： BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, their low response rates and poor 5-year survivals indicate a need for improvement. One key factor in this resistance may be molecules that mediate immunosuppression within the tumor microenvironment (TME), such as adenosine. Combining therapies that mitigate the effects of adenosine with ICIs could potentially overcome these *** utilized the Lewis lung carcinoma (LLC) and CMT167 murine lung carcinoma models to investigate the combined use of the A2B receptor antagonist PBF1129 and anti-PD-1 ICI. The mechanisms underlying the efficacy of this combination therapy were explored using single-cell RNA sequencing (scRNA-seq).ResultsIn both models, combination therapy improved tumor control. Our scRNA-seq analysis characterized alterations in malignant cells, macrophages, cancer-associated fibroblasts (CAFs), T cells, and endothelial cells in the tumor after treatment. Malignant cells treated with combination therapy exhibited reduced inflammatory, epithelial-to-mesenchymal transition (EMT) and angiogenic signatures. Malignant cells and M2-like macrophages showed high expression of TGF beta pathway genes, which were significantly reduced in the combination therapy group. We also observed decreased interactions between M2-like macrophages and CAFs as well as T cells, and dramatically increased Gzmb expression in M1-like macrophages with combination therapy. Combination therapy modulated TGF beta-mediated cellular crosstalk and extracellular matrix (ECM) *** findings suggest that inhibition of adenosine activity by blocking the A2B receptor reduces TGF beta signaling and enhances the efficacy of ICI therapy in NSCLC.

关键词： Time-fractional chiral nonlinear Schr & ouml   dinger equation   generalized projective Riccati equation method   solitons   nonlinear wave dynamics   bifurcation analysis   chaos   sensitivity analysis  

摘要： In this paper, we use the modified Riemann-Liouville derivative to study the dynamical behaviors of the time-fractional (3+1)-dimensional chiral nonlinear Schr & ouml;dinger equation. In many scientific domains, such as quantum mechanics, nonlinear optics, and hydrodynamics, the given equation is a fundamental idea in the theory of nonlinear wave processes. To obtain analytical solutions, we apply the generalized projective Riccati equation method, which enables the construction of various exact traveling wave solutions. These solutions range from bell-shaped solitons, one soliton, and dark solitons, and demonstrate the richness of the wave structures inherent within the fractional-order system. To obtain some understanding of the qualitative nature of the resulting solutions, we conduct a careful bifurcation analysis of the governing equation. By employing phase portraits and classification of equilibrium points, we study how modifications to system parameters affect the stability and dynamical transition of the nonlinear waves. We determine threshold values of our system at which it displays qualitative changes, i.e. periodic to quasi-periodic to chaotic transitions. We then proceed to the study of chaotic and quasi-periodic oscillations in fractional-order systems, demonstrating their sensitivity to initial conditions and external perturbations. Numerical simulations, such as time series analysis, Poincar & eacute;sections, and phase space orbits, capture the complexity and unpredictability of the system under the small perturbation. These results underscore the importance of fractional-order derivatives in regulating wave evolution and nonlinear dynamic behavior. Ultimately, by revealing new analytical solutions and providing a thorough dynamical analysis of stability, bifurcations, and chaotic behaviors, our findings advance our understanding of fractional nonlinear wave equations on a global scale. Wave dynamics are a significant concern in nonlinear optics, p

关键词： Autophagy   C-X-C motif chemokine receptor   Epilepsy   TWIK-related K+ channel 1  

摘要： Objective: Epilepsy is a neurological disease whose onset causes a variety of sequelae, reducing the standard of living. TWIK-related K+ channel 1 (TREK-1) has been linked to epilepsy. C-X-C motif chemokine receptor (CXCR2) is a potential target for the treatment of epilepsy inflammation. This work aims to observe the effect of CXCR2 expression on neuron autophagy and TREK-1 expression in the hippocampus of epileptic mice. Material and Methods: An animal model of epilepsy was established, and the CXCR2 gene was silenced. The expression of TREK-1, interleukin (IL)-1b, tumor necrosis factor-a, and IL-6 in the hippocampus of mice was detected by quantitative real-time polymerase chain reaction. Autophagy-related proteins beclin-1 and microtubule-associated protein light chain 3 (LC3) were examined by Western blot. Cell proliferation and activity were analyzed using cell counting kit-8 and 5-Bromodeoxyuridine assays. Results: Compared with that in the normal group, TREK-1 expression decreased and CXCR2 expression increased significantly in the hippocampus of epileptic model mice (P < 0.01). Two autophagy markers, beclin-1 and LC3 II/LC3 I, showed an increased expression in the hippocampal regions of the epileptic model group (P < 0.01). In addition, B-cell lymphoma 2 (Bcl-2)-associated X protein levels increased and Bcl-2 levels decreased in the epileptic mice (P < 0.01). After CXCR2 silencing, the expression of proinflammatory factor in the hippocampus of epileptic mice significantly decreased (P < 0.01). In vitro, cell viability and proliferation increased significantly after silencing CXCR2 (P < 0.05). Meanwhile, the expression levels of TREK-1 and Bcl-2 significantly increased (P < 0.001) and the levels of autophagy markers decreased in vivo and in vitro (P < 0.01). In vivo, CXCR2 expression did not change significantly after silencing TREK-1. After silencing TREK-1 and overexpressing CXCR2, the proliferation ability of HT22 cells decreased significantly (P < 0.001)

摘要： GLP-1 receptor agonists were initially developed to treat type 2 diabetes and have had a transformative effect on its therapy, and are highly effective for glycaemic control, with the added benefit of bodyweight reduction and a low risk of causing hypoglycaemia. GLP-1 receptor agonists reduce risks for major adverse cardiovascular events (eg, non-fatal myocardial infarction, stroke, and cardiovascular death), and the risk of admission to or treatment within hospital for heart failure. These drugs reduce albuminuria and slow the decline in estimated glomerular filtration rate over time, therefore delaying or preventing kidney failure. Furthermore, GLP-1 receptor agonists (eg, liraglutide and semaglutide) and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor co-agonist tirzepatide have been approved for treatment of obesity, with clinical trials establishing benefits for various obesity-related conditions: prevention of type 2 diabetes; risk for major adverse cardiovascular events; heart failure, especially with preserved ejection fraction; regression of steatosis and prevention of fibrosis in steatotic liver disease; and symptomatic improvements in obstructive sleep apnoea and knee osteoarthritis. Current developments include the exploration of novel indications (eg, neurodegenerative diseases and substance use disorders) with suggestive evidence of efficacy, and the development of small-molecule GLP-1 receptor agonists for oral treatment to improve convenience. Dual (ie, GLP-1–glucagon and GLP-1–amylin) and triple (ie, GIP–GLP-1–glucagon) receptor agonists activating multiple receptors promise greater efficacy than mono-agonists, especially for weight loss. However, some clinical development programmes have a high burden of adverse gastrointestinal events, and dose-escalation regimens should be optimised to reach acceptable tolerability.

关键词： Electrostatic interaction   Photocatalytic hydrogen evolution   Protonated g-C3N4   ZnxCd1-xS  

摘要： To tackle the pressing dual challenges of the energy crisis and environmental pollution, it is urgent to develop low-cost, high-activity photocatalysts for solar-driven hydrogen production. In this work, a Zn_xCd_1-xS/protonated g-C₃N₄ S-scheme heterojunction photocatalyst is successfully constructed using an electrostatic interaction-driven assembly strategy. The optimized composite photocatalyst exhibits a hydrogen evolution rate of 17.64 mmol g⁻¹ h⁻¹, which is approximately 4.14 times and 28.45 times higher than that of pure Zn_xCd_1-xS and protonated g-C₃N₄. The apparent quantum efficiency (AQE) of ZCSCN-20 reaches 12.3 % at 420 nm. The electrostatic interaction drives the assembly of the heterojunction, leading to an intimate interfacial contact. This close connection, in turn, significantly shortens the migration distance and transfer time of photogenerated charges. The established S-scheme charge transfer pathway enables the efficient separation of photogenerated charge carriers while preserving the strong redox capability inherent in the constituent semiconductors. Furthermore, the use of sacrificial agents to deplete photogenerated holes further suppresses charge carrier recombination, synergistically enhancing the overall catalytic activity. This work provides an efficient strategy for preparing and optimizing sulfide-based S-scheme heterojunction photocatalysts, laying a foundation for developing stable, high-performance solar-driven hydrogen production systems.