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关键词： Cascade activation   Immunogenic cell death   Precision immunotherapy   STING pathway   Tumor microenvironment  

摘要： Immunotherapy represents a pioneering approach in clinical cancer treatment, but its application is often limited by insufficient immune stimulation and off-target side effects. Therefore, developing novel nanomaterials capable of precisely reshaping the tumor microenvironment (TME) is crucial for enhancing the efficacy of tumor immunotherapy. Herein, we constructed a “precision immune bomb” DOX@MZIF-P3 embodying a “PD-L1-targeted, on-site unlocking, local detonation” strategy. It actively targets and blocks highly expressed programmed death ligand 1 (PD-L1) on tumor cells, achieving tumor accumulation while attenuating immune evasion. In response to the TME, it depletes glutathione (GSH) and releases effector substances including doxorubicin (DOX), Mn²⁺, and Zn²⁺. Specifically, DOX induces apoptosis via DNA damage and elevates intratumoral H₂O₂ levels. Mn²⁺ generates reactive oxygen species (ROS) through Fenton-like reactions to trigger ferroptosis, while simultaneously sensitizing and augmenting the stimulator of interferon genes (STING) pathway. Zn²⁺ overload induces tumor cell pyroptosis and further promotes immunogenic cell death (ICD). Additionally, synergy between activated STING pathway and ICD enhances immune cell infiltration in tumor tissue and increases the levels of related inflammatory factors in the TME, ultimately promoting immunotherapy. This strategy precisely activates tumor immunity while significantly reducing off-target toxicity, effectively inhibiting primary tumor growth and blocking metastasis, providing a new paradigm for precision tumor immunotherapy.

关键词： Aminoindanol   Docking   α-glucosidase   Herbicidal   iso(thio)cyanates  

摘要：

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  A series of novel trans-1-amino-2-indanol derivatives were synthesized.
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  Structures were confirmed by advanced spectroscopic techniques.
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  Compounds 2a–2f and 2 g–2i showed strong phytotoxic activity.
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  Docking at acetohydroxyacid synthase supported herbicidal potential.
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  Compounds 2a, 2c, 2 g, and 2h inhibited α-glucosidase effectively.

摘要： Triple-negative breast cancer (TNBC) lacks targeted therapies due to the absence of hormone receptors. The oncogenic crosstalk between STAT3 and NF-κB pathways drives tumor proliferation, epithelial-mesenchymal transition (EMT), metastasis, and therapeutic resistance, underscoring a critical need for novel dual inhibitors. Here, we report the rational design and synthesis of new 1-phenyl-2-thioaryl-4-benzyl-5-methylimidazole derivatives targeting this dual pathway axis. Optimized, metal-free S-alkylation reactions of imidazole-2-thione afforded twelve new analogs (5a,b, 6, 7a–g, 8a,b) in excellent yields. Their antiproliferative activity was evaluated in 4 T1 and MDA-MB-231 cells, while the mechanistic leads (5a,b and 8a,b) were assessed for specific STAT3/NF-κB inhibition using luciferase reporter assays together with migration and invasion assays. Structure-activity relationship (SAR) analysis identified the difluorobenzylthio derivative 5b as the optimal lead candidate. At a sub-cytotoxic concentration (10 μM), 5b exhibited potent and specific targeted blockade, suppressing NF-κB and STAT3 transcriptional activities by ∼80% and ∼ 60%, respectively. In contrast, structurally related analogs (5a, 8a, 8b) only exhibited inhibitory effects that were inextricably linked to severe cytotoxicity. Furthermore, 5b demonstrated robust antimetastatic efficacy at non-toxic doses, maintaining >91% wound persistence in 4 T1 cells at 24 h and markedly blocking Matrigel invasion. Molecular docking studies at the STAT3-SH2 domain corroborated the biological data, confirming that the flexibility of the thioether linkage in the 5a and 5b provided optimal binding energies compared to the more rigid or bulkier inactive analogs. This newly

关键词： and MEP   DFT   FMO   FT-IR   FT-Raman   NBO   NLO   NMR   UV–Visible  

摘要： A combined experimental (FT-IR, FT-Raman, NMR and UV–Visible) and density functional theory (DFT) study was performed to investigate the structural, spectroscopic, electronic and nonlinear optical properties of 2-(2-bromophenyl)-1,3-dioxolane (2BPD), 2-(3-bromophenyl)-1,3-dioxolane (3BPD) and 2-(4-bromophenyl)-1,3-dioxolane (4BPD). Geometry optimization and torsional potential energy surface analysis at the B3LYP/6–311++G(d,p) level confirmed stable minimum-energy conformations. The computed vibrational frequencies and GIAO-based ¹H and ¹³C NMR chemical shifts showed good agreement with experimental results, validating the molecular structures. TD-DFT simulations successfully reproduced the UV–Visible absorption maxima, attributing the bands to n → π* and π → π* transitions. Frontier molecular orbital analysis revealed moderate HOMO–LUMO energy gaps (∼4.37–4.42 eV), indicating effective conjugation and charge transfer. Global reactivity descriptors suggest favorable kinetic stability with moderate reactivity. The enhanced first-order hyperpolarizability values, exceeding that of urea, indicate strong nonlinear optical (NLO) potential. NBO and MEP analyses further confirm significant π-electron delocalization, intramolecular charge transfer and well-defined reactive sites. Overall, these results highlight the suitability of the studied molecules for optoelectronic and NLO applications.

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.

关键词： Nuclear receptor corepressor 1 (NCoR1)   Silencing mediator for retinoic acid and thyroid hormone receptors (SMRT)   Neurodevelopmental disorders (NDD)   Autism spectrum disorder (ASD)   Attention-deficit/hyperactivity disorder (ADHD)  

摘要：

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  Neuronal specific deletion of NCoR1 or SMRT caused hypoactivity, social deficits, and mild anxiety in adult mice.
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  NCoR1 KO mice displayed higher learning abilities.
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  449 genes were upregulated in amygdala of SMRT KO mice at postnatal day 21.
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  8 genes were upregulated in amygdala of NCoR1 KO mice at postnatal day 21.
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  NCoR1 and SMRT have separate functions in the central nervous system.

关键词： Myotonic dystrophy type 1 (DM1)   Nanopore sequencing   Long-read sequencing   Somatic mosaicism   Sequence interruptions   Molecular diagnostics   Adaptive sampling   Repeat expansion  

摘要：

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  ONT adaptive sampling sized DMPK CTG expansions in a pilot DM1 cohort.
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  Coriell, EMQN, and clinical samples supported feasibility for DM1 testing.
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  Expanded alleles showed read-level size distributions consistent with mosaicism.
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  Candidate interruption-like patterns required strand-aware interpretation.
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  Low and uneven expanded-allele coverage remains a key implementation challenge.

关键词： Fluorescence probe   Fluorescence quenching   Förster resonance energy transfer   Machine learning   PFAS detection   Smart monitoring  

摘要： Perfluorocarboxylic acids (PFCAs) exist as mixtures in aquatic environments. However, routine PFCA monitoring remains instrument-intensive and often reports concentrations rather than mixture toxicity for water risk management. Herein, we developed a machine-learning-assisted fluorescence framework that estimates the perfluorooctanoic acid (PFOA)-equivalent toxicity (PFOAe) for aqueous PFCA mixtures. The method used a simple bovine serum albumin/1-anilinonaphthalene-8-sulfonate (BSA/ANS) probe. The machine learning framework was developed by utilizing a stacked ensemble model, including XGBoost and CatBoost base-learners with a Ridge meta-learner to decipher the nonlinear relationships between excitation emission matrices and PFOAe. On the log₁₀(PFOAe) scale, the model achieved a root mean squared error (RMSE) of 0.286 on a held-out test set, and an RMSE of 0.280 for spiked tap-water samples. Five authentic electroplating wastewater samples further provided a limited real sample feasibility validation. The limit of detection was 0.126 µmol l^-1 PFOAe (52.2 µg l^-1 as PFOA), enabling rapid screening and prioritization of moderately-to-highly contaminated waters rather than trace-level analysis. Moreover, the reconciliation between chemical fluorescence phenomena and data-driven mechanistic interpretation suggests that the model behavior is consistent with the underlying chemical mechanism. Our method provides a lower complexity and risk-relevant screening tool to prioritize water samples for further confirmatory instrumental analysis and support monitoring-based risk management for PFCA mixtures.

关键词： 1,3,4-oxadiazole   MCF-7 cell line   pyrrolidin-2-one   single-crystal X-ray diffraction   STAT3 inhibition  

摘要：

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  Fourteen novel pyrrolidin-2-one/1,3,4-oxadiazole hybrids (5a-n) were synthesized and characterized.
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  Crystal structure of compound 5d confirmed by single-crystal X-ray diffraction.
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  Compound 5i showed highest cytotoxicity against MCF-7 (IC₅₀ = 5.703 µM).
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  Molecular docking revealed strong binding of 5i to STAT3 SH2 domain active site.
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  Compound 5i is a promising lead for further STAT3 inhibitor development.

关键词： Plasmodium falciparum   Naphthoquinone   Endoperoxide   Mn(acac)3   Hybrid molecules  

摘要：

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  First naphthoquinone-endoperoxide dual-pharmacophore antimalarial hybrids.
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  Mn(III)-mediated peroxycyclization enabled access to stereoisomeric series.
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  Full stereoisomer resolution was achieved by preparative chiral HPLC.
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  Stereochemistry significantly influenced potency (3-fold) and selectivity (9-fold).
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  Lead exhibited IC₅₀ 0.49 μM against MDR P. falciparum W2 with SI > 250 on CHO.