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A novel and efficient strategy for the direct synthesis of 3-arylthioquinoline derivatives via radical induced tandem cyclization of propargylamines with diaryl disulfides was developed. This protocol undergoes a cascade sulfuration/ cyclization/ oxidation/ aromatization pathway to afford the desired products in a broad substrate scope using readily available starting materials under mild conditions. Based on this strategy, we further modified 3-arylquinolines to obtain two novel deep blue fluorescent molecules, QLSCz and QLSTCz, with good optical properties through two-step synthesis by oxidation and electron donor modification., (© 2025 Wiley-VCH GmbH.)

Layered transition metal oxides (LTMOs) are attractive cathode candidates for rechargeable secondary batteries because of their high theoretical capacity. Unfortunately, LTMOs suffer from severe capacity attenuation, voltage decay, and sluggish kinetics, resulting from irreversible lattice oxygen evolution and unstable cathode-electrolyte interface. Besides, LTMOs accumulate surface residual alkali species, like hydroxides and carbonates, during synthesis, limiting their practical application. Herein, a universal strategy is suggested to in situ convert surface residual alkali into a stable polymer coating layer for LTMOs, thus turning wastes into treasure. The formation process of polymer coating involves NH 4 F treatment to consume residual alkali, then utilizing generated fluorides to induce the ring-opening polymerization of tetrahydrofuran. Implementing this strategy to Li-rich Mn-based cathode materials (LRM) results in a notable reduction in voltage hysteresis, along with enhanced kinetics and cycling stability in lithium-ion batteries. With this layer of encapsulation, surface lattice oxygen release and layered-to-spinel phase transition of LRM are significantly alleviated with minimal mechanical degradation and surface parasitic reactions. Such strategy can also be applied to air-sensitive sodium-rich LTMOs in sodium-ion batteries, which showcases superior universality. This work might provide a promising solution to overcome residual alkali and interfacial instability issues for LTMOs in practical application., (© 2025 Wiley‐VCH GmbH.)

Cancer heterogeneity, characterized by diverse populations of tumorigenic cells, involves the occurrence of differential phenotypes with variable expressions of receptor tyrosine kinases. Aberrant expressions of mesenchymal-epithelial transition (MET) and recepteur d'origine nantais (RON) receptors contribute to the phenotypic heterogeneity of cancer cells, which poses a major therapeutic challenge. This study aims to develop a dual-targeting antibody-drug conjugate (ADC) that can act against both MET and RON for treating cancers with high phenotypic heterogeneity. Through immunohistochemical staining, we show that MET and RON expressions are highly heterogeneous with differential combinations in more than 40% of pancreatic and triple-negative breast cancer cases. This expressional heterogeneity provides the rationale to target both receptors for cancer therapy. A humanized bispecific monoclonal antibody specific to both MET and RON (PCMbs-MR) is generated through IgG recombination using monoclonal antibody sequences specific to MET and RON, respectively. Monomethyl auristatin E is conjugated to PCMbs-MR to generate a dual-targeting ADC (PCMdt-MMAE), with a drug-to-antibody ratio of 4:1. Various cancer cell lines were used to determine PCMdt-MMAE-mediated biological activities. The efficacy of PCMdt-MMAE in vivo is evaluated using multiple xenograft tumor models. PCMdt-MMAE shows a favorable pharmacokinetic profile, with a maximum tolerated dose of ~30 mg/kg in mice. Toxicological studies using Sprague-Dawley rats reveal that PCMdt-MMAE is relatively safe with slight-to-moderate, temporary, and reversible adverse events. Functionally, PCMdt-MMAE induces a robust internalization of both MET and RON and causes a large-scale cell death in cancer cell lines exhibiting MET and RON heterogeneous co-expressions. Both in vitro and in vivo studies demonstrate that the dual-targeting approach in the form of an ADC is highly effective with a long-lasting effect against tumors exhibiting MET/RON heterogeneous phenotypes. Hence, we can suggest that a dual-targeting ADC specific to both MET and RON can be employed as a novel therapeutic strategy for tumors with expressional phenotypic heterogeneity., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: The use of clinical samples was approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang University (registration numbers: 2017-427-1), with all participants signing informed consent forms. Animal procedures were approved by the same ethics committee (registration numbers: 2017-400-1) and performed in accordance with the Guide for the Care and Use of Laboratory Animals of Zhejiang Province., (© 2025. The Author(s).)

Background: The fat mass and obesity-associated protein (FTO) has been showed to be involved in the pathogenesis and progression of coronary artery disease (CAD). However, the effects of FTO variants on CAD risk remain poorly understood. We herein genotyped three SNPs (rs1121980, rs72803657, and rs4783818) in FTO to investigate the influence of FTO polymorphisms on individual susceptibility to CAD., Methods: Genotyping for the three SNPs (rs1121980, rs72803657, and rs4783818) was conducted in a cohort of 712 CAD cases with 349 myocardial infarction (MI) cases and 701 control participants, utilizing the polymerase chain reaction-ligation detection reaction (PCR-LDR) technique. The associations of these SNPs with CAD were analyzed using multivariate logistic regression, and the associations with lipid profiles were assessed by the Kruskal-Wallis or Wilcoxon-Mann-Whitney tests., Results: The A allele (OR = 1.26, 95% CI = 1.01-1.57, and P = 0.044) and the AA genotype (OR = 3.13, 95% CI = 1.53-6.38, and P = 0.002) of FTO rs1121980 were significantly associated with an elevated risk of CAD. Similarly, the A allele (OR = 1.54, 95% CI = 1.18-2.02, and P = 0.002) and the AA genotype (OR = 5.61, 95% CI = 2.57-12.27, and P < 0.001) of rs1121980 exhibited increased MI risk. This SNP also showed significant associations under recessive genetic models for both CAD and MI (OR = 3.09, 95% CI = 1.52-6.27, P = 0.002 for CAD; OR = 5.40, 95% CI = 2.49-11.71, P < 0.001 for MI). However, the other two SNPs did not show significant associations with CAD or MI risks under any genetic model tested. Stratified analyses indicated a more pronounced association of the A allele with increased CAD/MI risk among younger participants, non-smokers, and non-drinkers. Interestingly, A allele carriers in younger subjects exhibited higher triglyceride (TG) levels and lower high-density lipoprotein cholesterol (HDL-C) levels compared to non-carriers (P < 0.05)., Conclusions: Our data provides the first evidence that the FTO rs1121980 polymorphism is associated with an increased risk of CAD in the Chinese population. This association is more significant in younger subjects, likely due to the elevated TG levels and reduced HDL-C levels., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)