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关键词： Continuous optimization   Convex optimization  

摘要：

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  NSA achieves a strict o(1/k²) rate in function value and ensures monotonic descent for smooth convex optimization.
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  The method is extended to handle zeroth-order and composite problems, maintaining o(1/k²) convergence.
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  A continuous-time analysis connects the algorithm to high-resolution ODEs underlying acceleration phenomena.

关键词： Bis-triazole Schiff bases   Corrosion inhibitors   Q235 steel   Quantum chemical calculations  

摘要： Q235 steel is susceptible to severe corrosion during the pickling process, especially in hydrochloric acid media, which not only shortens the service life of the equipment, but also may cause safety hazards and environmental pollution.

关键词： Hepatotoxicity   Cyclophosphamide   Cell death   Myricetin   Nrf2   Oxidative stress   Sirt1  

摘要：

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  Myricetin Mitigates Cyclophosphamide-Induced Hepatotoxicity
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  Myricetin Attenuates Oxidative Stress, Inflammation, and Apoptosis
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  Myricetin Modulates Sirt1 and Nrf2/HO-1 Signaling Pathway

摘要： This study provides a systematic thermophysical investigation of 1,2-propanediol–alcohol binary mixtures, focusing on intermolecular interactions, structural features, and hydrogen-bonded networks. Permittivity and refractive index were measured over the full composition range at 298.15, 308.15, and 318.15 K and 101.3 kPa to elucidate intermolecular interactions and structural effects. The constituent components exhibit small negative temperature coefficients of permittivity. Analysis of excess permittivity and excess refractive index reveals the formation of hydrogen-bonded multimeric structures with antiparallel dipolar alignment and weakened effective dispersion interactions relative to the pure components. 1,2-propanediol acts as the primary hydrogen-bond network former due to its bifunctional hydroxyl groups, while the long-chain alcohols participate in hydrogen bonding but mainly perturb the network structure and dipolar alignment through steric and dispersion interactions. Despite the close structural similarity of the selected alcohols, their inherent differences in structure, polarity, and alkyl chain length influence the overall mixture behavior. The 1,2-propanediol–alcohol mixtures are stable, low-toxicity, and environmentally compatible, highlighting their potential as sustainable solvents and model hydrogen-bonded systems.

关键词： Pterocarpus soyauxii   Pterocarpus mildbraedii   HIV-1   SARS-CoV-2   molecular docking   network pharmacology  

摘要： This research explored the therapeutic efficacy of bioactive substances derived from Pterocarpus soyauxii and Pterocarpus mildbraedii against HIV-1 and SARS-CoV-2 co-infection. Pharmacokinetic characteristics were evaluated with ADMETlab 3.0. Network pharmacology analyses were conducted using Swiss Target Prediction, GeneCards, STRING, Cytoscape and Metascape, along with pathway mapping in Srplot. The protein structures of EGFR, MMP9 and SARS-CoV-2 polyprotein 1ab were assessed through the SwissModel and ProSA-web databases. Molecular docking and binding sites determination were performed through 1-Click Docking and BC-Dock2 web servers. Inhibitory activity of the compounds on the CDK2 and HIV-1 proteins was carried out in the kinCSM way2drug databases. Results show that Khrinone A and E exhibited positive absorption and distribution profiles. Network pharmacology revealed essential molecular targets and enriched KEGG pathways associated with viral replication. MolProbity scores ranged from 0.77 to 2.28, with over 92% of residues located in Ramachandran preferred regions. Molecular docking revealed significant binding affinities, especially Pterocarpin (-9.9 kcal/mol) with MMP9 and Khrinone A (-8.9 kcal/mol) with NOS2, surpassing reference inhibitors. In comparison to EGFR, the affinities of natural ligands (-7.7 kcal/mol to -7.0 kcal/mol) were similar to Gefitinib, whereas Claussequinone and Khrinone E demonstrated compelling interactions with HIV-1 reverse transcriptase (-7.4 kcal/mol to -7.2 kcal/mol), resembling those of Lawsone (-8.3 kcal/mol). Additionally, Khrinone A and E can serve as potent CDK2 inhibitors (IC50 < 10 mu M), exhibiting pKi values (5.902-5.929) comparable to those of Palbociclib (6.029). These results indicate that compounds derived from Pterocarpus have multitarget antiviral and host-modulating abilities, reinforcing their potential as valuable candidates for therapeutic intervention in HIV/SARS-CoV-2 co-infection.

关键词： metabolic myopathy   mouse model   purine metabolism   adenylosuccinate synthetase   ADSS1  

摘要： ADSS1 myopathy is an ultrarare congenital myopathy characterized by progressive cardiac and skeletal muscle degeneration with childhood to adolescent onset. This autosomal recessive disease is caused by mutations in the ADSS1 gene, encoding the enzyme adenylosuccinate synthetase (AdSS1). AdSS1 plays a critical role in the adenine nucleotide cycle, which is important for energy metabolism in muscle cells. Enzymatic defects, engendered by loss-of-function mutations in ADSS1, lead to a bottleneck in the adenine nucleotide cycle, causing metabolic dysfunction that ultimately results in progressive muscle weakness, mobility impairment, and respiratory and cardiac dysfunction, often requiring the use of a ventilator. Despite its debilitating nature, there are currently no cures or targeted treatments available, and little research into possible therapeutic strategies has been done. With a limited patient profile encompassing fewer than 200 known patients worldwide, establishing a mouse model for ADSS1 myopathy is critical to understanding its pathogenesis and for developing future therapies. Here, we present and characterize the first mouse model of ADSS1 myopathy-a constitutive Adss1 knockout model-by (1) defining its natural history 2) exploring its metabolic pathomechanisms, and (3) characterizing its histopathological features. We find that Adss1KO/KO mice have subtle motor deficits and present with histopathological features consistent with patient phenotypes. Overall, we show that despite a relatively mild phenotype, this novel mouse model has quantifiable pathological features that can be used to develop therapies for, and further probe pathophysiology of, ADSS1 myopathy.

关键词： HIV integrase   LEDGF/p75   LEDGINs   natural products   molecular dynamics simulation   thermodynamics profile  

摘要： HIV integrase is an essential enzyme responsible for incorporating viral DNA into the host's genome, a vital phase in the HIV replication process. The host protein, Lens Epithelium-Derived Growth Factor p75 (LEDGF/p75), connects with the HIV Integrase (IN) Catalytic Core Domain (CCD) via its Integrase Binding Domain (IBD) and anchors the pre-integration complex, aiding in the integration of HIV into regions of chromatin that are transcriptionally active. This interaction underscores the importance of the integrase-LEDGF/p75 complex as a target for therapeutic intervention. Interrupting this interaction with allosteric inhibitors of the LEDGF/p75-IN interaction, known as LEDGINs, has become a promising method to curb HIV replication. Although LEDGINs are still being studied for clinical application, they may be too costly for developing countries if approved, emphasizing the necessity for ongoing research into alternative methods. Natural substances like terpenes and flavonoids show antiviral properties. Consequently, utilizing natural compound libraries to target the HIV integrase-LEDGF/p75 interaction offers a new strategy for creating effective antiviral medications. This research assessed a collection of compounds derived from natural sources. To refine a library of over 76,000 compounds, Lipinski's rule of five was applied. Molecular docking and 300 ns Molecular Dynamics (MD) simulations were conducted to pinpoint compounds with strong binding affinity and stability to the CCD-IBD interface, using LEDGIN6 as a benchmark inhibitor. Through molecular docking studies, Guanipiperazine B, CHEBI:211233 and Okaramine T were identified as promising inhibitors of the HIV-1 integrase-LEDGF/p75 complex, showing stronger binding affinities compared to the reference drug LEDGIN6. Among these, Guanipiperazine B exhibited the most stable binding, as evidenced by the lowest Root Mean Square Deviation (RMSD) and RMSF values in MD simulations, indicating robust and stable interac

关键词： 2,3-dihydro-1,3,4-thiadiazole-benzenesulfonamide   triple inhibitors   EGFR   carbonic anhydrase   breast cancer  

摘要： A novel 2,3-dihydro-1,3,4-thiadiazole-benzenesulfonamide hybrid, N-(4- E )-1- Z )-5-acetyl-3-(4-sulfamoylphenyl)-1,3,4-thiadiazol-2(3H)-ylidene)hydrazono)ethyl)phenyl)-4-chloro benzamide (N-ASTPC was rationally designed as a triple inhibitor targeting carbonic anhydrase IX (CAIX carbonic anhydrase XII (CAXII and the epidermal growth factor receptor (EGFR) - key targets overexpressed in cancer. Molecular docking and 200-ns molecular dynamics (MD) simulations confirmed stable and high-affinity interactions of N-ASTPC with the active sites of all three targets. MM-GBSA binding free energy calculations and ProLIF interaction profiling further supported these findings, while principal component analysis (PCA) revealed limited conformational drift, indicating robust complex formation. Additionally, density functional theory (DFT) assessments affirmed N-ASTPC's electronic stability and favorable reactivity. Biological assays demonstrated potent inhibitory activity with IC50 values of 0.039 mu M, 0.04 mu M, and 0.05 mu M for CAIX, CAXII, and EGFR, respectively, comparable or superior to standard inhibitors (acetazolamide and erlotinib). Regarding in vitro cytotoxicity, N-ASTPC displayed selective toxicity toward cancer cells over normal fibroblasts, with notable effects in MDA-MB-231 and MCF-7 breast cancer lines compared to doxorubicin. Flow cytometry showed that N-ASTPC induces significant S-phase arrest and robust early apoptosis, confirmed by a similar to 5.7-fold increase in Bax, similar to 4.5-fold increase in caspase-3, and similar to 2-fold decrease in Bcl-2 expression - consistent with mitochondrial apoptotic pathway activation. Collectively, these findings establish N-ASTPC as a promising multifunctional anti-cancer lead compound capable of simultaneously disrupting tumor cell metabolism and signaling via CAIX, CAXII, and EGFR inhibition. Its multi-modal mechanism and selective apoptotic induction underscore its potential for further preclinical development, parti

关键词： Type 1 diabetes   children   smoking   pregnancy   risk factor  

摘要： Childhood-onset type 1 diabetes (T1D) is a chronic autoimmune disease characterized by a steadily increasing global incidence and significant public health implications. The relationship between maternal smoking during pregnancy and T1D risk remains uncertain. To clarify this association, we conducted a meta-analysis of prospective cohort studies to enhance methodological reliability. We systematically searched PubMed, Embase, and Web of Science from their inception to May 2025 for prospective cohort studies examining the link between maternal smoking during pregnancy and the incidence of T1D in offspring. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model, accounting for heterogeneity. Twelve prospective cohort datasets from ten studies, encompassing over 5.9 million children, were included. Maternal smoking during pregnancy was significantly associated with a reduced risk of childhood-onset T1D (RR: 0.74, 95% CI: 0.72-0.76, p < 0.001 with no evidence of statistical heterogeneity (I2 = 0%, p = 0.48). This association remained robust across sensitivity analyses that excluded one dataset at a time. Subgroup analyses demonstrated consistent results across various categories, including cohort size, prevalence of maternal smoking, method of T1D diagnosis, and adjustments for maternal age, diabetes, and delivery mode. Notably, the inverse association was significantly weaker in studies that did not adjust for maternal diabetes (RR: 0.79 vs. 0.72, p for subgroup difference = 0.01). We found no substantial evidence of publication bias (Egger's test, p = 0.55). In conclusion, this meta-analysis identified an inverse association between maternal smoking during pregnancy and the incidence of childhood-onset T1D. However, this finding should be interpreted cautiously, as residual confounding cannot be ruled out, and maternal smoking is associated with numerous serious adverse health consequences.

关键词： after surgery   sepsis   sTREM1   diagnosis and prognosis  

摘要： Introduction Sepsis represents a critical response to infection;it is characterized by systemic inflammation, shock, and potential organ failure. Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) has been identified as a crucial marker in sepsis, connecting the activation of innate immunity to systemic inflammation. Methods This prospective nested case control study was carried out in the intensive care unit and surgery department from March 2018 to June 2019. Adults undergoing abdominal surgery, with and without sepsis, were included in the study, and sTREM-1 and cytokine levels were measured. Results A total of 120 patients were included in the study, comprising 31 noninfected individuals, 37 with sepsis, and 52 with septic shock. sTREM-1 levels were statistically significantly elevated in patients with sepsis and septic shock compared with noninfected individuals (P < .001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.722 for sTREM-1 in the prediction of septic shock. Discussion Elevated sTREM-1 levels are associated with the severity of sepsis and may function as a prognostic biomarker. Additional research is required to confirm these findings and investigate therapeutic interventions aimed at the sTREM-1 pathway.