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As the most common form of epigenetic regulation by RNA, N6 methyladenosine (m6A) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis, drug resistance, immunity and prognosis. This close association between m6A and cancers has garnered substantial attention in recent years. An increasing number of small molecules have emerged as potential agents to target m6A regulators for cancer treatment. These molecules target the epigenetic level, enabling precise intervention in RNA modifications and efficiently disrupting the survival mechanisms of tumor cells, thus paving the way for novel approaches in cancer treatment. However, there is currently a lack of a comprehensive review on small molecules targeting m6A regulators for anti-tumor. Here, we have comprehensively summarized the classification and functions of m6A regulators, elucidating their interactions with the proliferation, metastasis, drug resistance, and immune responses in common cancers. Furthermore, we have provided a comprehensive overview on the development, mode of action, pharmacology and structure–activity relationships of small molecules targeting m6A regulators. Our aim is to offer insights for subsequent drug design and optimization, while also providing an outlook on future prospects for small molecule development targeting m6A. [ABSTRACT FROM AUTHOR]

Summary: Non‐small‐cell lung cancer (NSCLC), which has a high rate of metastatic spread and drug resistance, is the most common subtype of lung cancer. Therefore, NSCLC patients have a very poor prognosis and a very low chance of survival. Human cancers are closely linked to regulated cell death (RCD), such as apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. Currently, small‐molecule compounds targeting various types of RCD have shown potential as anticancer treatments. Moreover, RCD appears to be a specific part of the antitumor immune response; hence, the combination of RCD and immunotherapy might increase the inhibitory effect of therapy on tumor growth. In this review, we summarize small‐molecule compounds used for the treatment of NSCLC by focusing on RCD and pharmacological systems. In addition, we describe the current research status of an immunotherapy combined with an RCD‐based regimen for NSCLC, providing new ideas for targeting RCD pathways in combination with immunotherapy for patients with NSCLC in the future. [ABSTRACT FROM AUTHOR]

As a new type of nanomaterials, nickel nanoparticles (Ni NPs) have been widely used by human beings, whose exposure probability was greatly increasing. Many studies have shown that Ni NPs can induce apoptosis, oxidative stress and DNA damage. Nowadays, male reproductive health is an important public health problem, which is a hot topic in toxicological research. In the present study, to protect reproductive health, the effect of Ni NPs exposure on spermatogenesis injury was assessed, understanding the toxicity and safety of Ni NPs. Sixty ICR male mice with 20 ± 2 g were randomly divided into five groups. The experimental groups were treated with 5 mg/kg, 15 mg/kg and 45 mg/kg Ni NPs. The reproductive toxicity of Ni NPs on male mice was evaluated by the indexes of testicular organ coefficient, testicular marker enzyme, sperm motility and histopathology. As a result, the somatic index of testis and epididymis increased in each group. Compared with the control group, the activity of testicular markers increased and the sperm motility index decreased in the low-, middle- and high-dose groups. Pathological results indicated that various cell apoptosis and disordered arrangement of cells occurred in the seminiferous tubules of the exposed groups. In conclusion, the findings of this study suggest that Ni NPs have certain damage to spermatogenesis in mice. [ABSTRACT FROM AUTHOR]