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关键词： AP-1   Huanglian Jiedu Decoction   Hypertensive Nephropathy   Network pharmacology   Renal fibrosis   UPLC-Q-Exactive MS/MS Analysis  

摘要： Hypertensive Nephropathy (HN) is a severe complication of hypertension characterized by progressive renal fibrosis, which current treatments fail to halt. Huanglian Jiedu Decoction (HLJDD), a classic traditional Chinese medicine (TCM) renowned for its “heat-clearing, detoxifying” and anti-inflammatory properties, is widely used against hypertension and associated target organ damage. Thus, its potential therapeutic mechanisms against HN warrant in-depth investigation.

摘要： Heterocyclic scaffolds, particularly 1,3,4-thiadiazole and s-triazine cores, are increasingly recognized as privileged motifs in anticancer drug discovery, attributable to their broad-spectrum pharmacological activities and favorable physicochemical characteristics that support drug-likeness and target engagement. This study evaluates the biological potential of a previously reported series of 1,3,4-thiadiazole-s-triazine hybrids across a panel of human cancer models, focusing on their cytotoxic efficacy and tumor selectivity. In vitro screening identified compounds 4, 9, 11, and 14 as the most active hybrids, exhibiting micromolar cytotoxicity, particularly against triple-negative breast cancer (MDA-MB-231) cells. Among them, compound 11 showed the most potent and broad-spectrum activity (IC₅₀ = 1.93–4.73 μM), approaching that of doxorubicin; however, its comparable toxicity toward HaCaT cells indicated limited selectivity. In contrast, compounds 4, 9, and 14 demonstrated favorable therapeutic indices. Notably, compound 4 achieved a remarkable selectivity index (SI = 90.41), substantially outperforming doxorubicin (SI < 0.5). Compound 9 exhibited potent and relatively selective activity, particularly against MDA-MB-231 cells (IC₅₀ = 4.92 μM, SI > 26), while showing markedly reduced toxicity toward normal keratinocytes. Similarly, compound 14 displayed selective inhibition of MDA-MB-231 cells with minimal cytotoxicity to HaCaT cells. Taken together, these hybrids, especially compounds 4 and 9, demonstrated promising anticancer activity with improved cancer selectivity, supporting their potential for further mechanistic and preclinical investigation. Structure-activity relationship (SAR) analysis scientifically substantiated that the integration

关键词： Rheumatoid arthritis   Zhiwang decoction   Inflammatory response   Macrophage polarization   PI3K/AKT pathway  

摘要： Zhiwang Decoction (ZWD) is a classical traditional Chinese medicine formulation with documented efficacy in alleviating the clinical manifestations of RA, yet its precise molecular mechanisms are not fully defined.

关键词： OME   POMDME   MBMS   Flow reactor   Low-temperature oxidation   Kinetic modeling   NTC  

摘要： This study investigates the oxidation of three oxymethylene ethers (OME_1–3) in a new elevated-pressure laminar plug-flow reactor, utilizing electron-ionization molecular-beam mass spectrometry. Experiments were conducted at an absolute pressure of 5 bar to mimic conditions more relevant to combustion systems but still allowing for the exploration of reaction kinetics and pathways in a controlled environment. The experimental work is supported by kinetic modeling using our in-house DLR Concise mechanism to gain deeper insights into OME_1-3 combustion chemistry and highlight the controlling pathways. Kinetic modeling with two additional literature mechanisms was also employed to complement the findings. The measurements at constant carbon flow and similar conditions enable a systematic analogy among the three studied OMEs. The results reveal preferred formation of small C₁–C₂ hydrocarbons and oxygenates such as formaldehyde and methyl formate as combustion intermediates. Formation of methanol and formic acid was also observed during oxidation of all three OMEs, but the latter in significantly higher concentrations for both longer-chain OMEs. OME₁ shows only low reactivity in the low-temperature chemistry (LTC) regime, while the two larger OMEs have a higher reactivity in the LTC regime and also show a negative temperature coefficient behavior at the studied conditions. In line with previous reactor studies at atmospheric pressure, the reactivity of OME₂ and OME₃ is also similar at 5 bar, but is clearly distinguishable from OME₁. This work not only enhances our understanding of the fundamental chemistry underlying the oxidation mechanisms of OMEs, but also underscores their potential as cleaner fuel alternatives.

关键词： 1,2-pentanediol   Catalytic hydrocracking   Furfural   Membrane dispersed microreactor  

摘要： The conventional production of 1,2-pentanediol (1,2-PeD) from fossil fuels suffers from high energy consumption and significant environmental pressure. Therefore, developing efficient catalysts to enable the hydrolytic hydrogenation of biomass-derived furfural (FF) is an urgent requirement for obtaining a green alternative. In this work, a membrane dispersion microreactor was successfully employed to incorporate Ce into a Cu-based catalyst for the catalytic hydro conversion of FF to 1,2-PeD. The optimum process conditions were determined by orthogonal reaction: 170 ℃, 6 MPa, 5.5 h. Under these conditions, FF was completely converted with the selectivity increased to 44%, resulting in a yield 2.2 times higher than that obtained with the undoped Ce catalyst. Furthermore, the catalyst exhibited excellent stability with no significant activity loss after five cycles of use. The characterization results show that the introduction of Ce significantly improved the dispersion of the active components, effectively suppressed the agglomeration of Cu particles, and increased the specific surface area of the catalysts; the calcination temperature changes the number of basic sites on the surface of the catalyst and affects the mode of adsorption of the intermediate furfuryl alcohol (FFA), thus affecting the catalyst performance.

摘要： For a non-decreasing positive integer sequence $S=(s_1,\dots ,s_k)$, an $S$-packing edge-coloring of a graph $G$ is a decomposition of edges of $G$ into disjoint sets $E_1$, $\dots ,$ $E_k$ such that for each $1\le i\le k$ the distance between any two distinct edges $e_1$, $e_2\in E_i$

摘要： In the present work, indole-functionalized 1,2,3-triazole derivatives (8a-8l) were efficiently synthesized via N-propargylation of indole scaffolds followed by Cu(I)-catalyzed azide-alkyne cycloaddition (click chemistry) using a green and benign reaction protocol. The synthesized indole-triazole hybrids were characterized by FT-IR, ¹H and ¹³C NMR spectroscopy, and mass spectrometry. All indole-triazole hybrids were screened for their in vitro antibacterial activity against S. marcescens and S. aureus, and antifungal activity against C. albicans and A. niger using the Kirby–Bauer disc diffusion method. Most of the indole-triazole derivatives exhibited moderate to promising antimicrobial activity, among which compounds 8g and 8h emerged as promising candidates. Molecular docking studies revealed strong binding affinities of the most active compounds with key microbial targets. Density functional theory (DFT) calculations at the B3LYP/6–31G(d,p) level provided insights into the electronic properties, reactivity descriptors, and charge distribution of the synthesized molecules. Furthermore, in silico ADME analysis suggested acceptable pharmacokinetic properties and drug-likeness profiles. This integrated experimental and computational investigation highlights indole–triazole hybrid scaffolds as promising compounds for the development of new antimicrobial agents.

摘要： The global fight to prevent tuberculosis remains a great challenge, particularly with the prolonged treatment regimen, increased drug-resistant strains, and a lack of funding to support the development of new treatments. A critical unmet clinical need to combat the global tuberculosis epidemic is the development of new drug regimens capable of reducing the time of tuberculosis therapy. Previously, Imidazo[1,2-a]pyridine-3-carboxamides have demonstrated low minimal inhibitory concentration (MIC) values against M. tuberculosis in vitro. This potent anti-tuberculosis activity and the novel target (QcrB) of imidazo[1,2-a]pyridine-3-carboxamides encouraged extended structure-activity relationship studies of additional scaffolds. We, herein, report the optimization of the clinical candidate Q203, an imidazo[1,2 a]pyridine amide, by replacing the amide functionality with 1,3,4-oxadiazoles to design and synthesis a series of novel imidazo[1,2-a]pyridine-1,3,4-oxadiazole hybrids bearing different side chains. The present study reports the molecular docking studies of 42 imidazo[1,2-a]pyridine-1,3,4-oxadiazole hybrids, along with the synthesis and in-vitro biological evaluation of 35 novel imidazo[1,2-a]pyridine-1,3,4-oxadiazole hybrids, as a promising new class of antitubercular agents. These compounds exhibited micromolar inhibitory activity against Mycobacterium tuberculosis H37Rv (MIC < 10 μM) and low cytotoxicity toward HepG2 cells (IC₅₀ > 100 μM).

关键词： Benzophenanthridine   Benzophenanthridinone   Cancer resistance   DNA damage   Radiosensitivity   Tyrosyl-DNA phosphodiesterase  

摘要： Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a potential radiotherapeutic target for cancer treatment. Herein, two series of analogues, benzophenanthridinone derivatives and benzophenanthridine derivatives, were designed and synthesized based on the reported TDP1 inhibitor NTD119B showing strong radiosensitization in vitro and in vivo. The structural modification gave seventeen analogues with stronger TDP1 inhibitory activity than NTD119B (IC₅₀ = 6.9 μM). B11 showed the most potent TDP1 inhibition (IC₅₀ = 1.2 ± 0.7 μM), 5.8-fold greater than NTD119B. Colony formation assays showed four TDP1 inhibitors A6, A26, B1, B7 showing stronger radiosensitizing activity than NTD119B in HCT116 cells. Further studies demonstrate that A6 targets TDP1 in cells and suppresses NHEJ repair activity, enhancing ionizing radiation-induced DNA damage resulting in a strong radiosensitizing activity both in HCT116 cells and xenografts animal model. The structure-activity relationship for TDP1 inhibition is also analyzed.