Population ageing amplifies future heat-related excess deaths 2.3- to 5.8-fold under different SSPs, particularly for the northeast region. Our findings can help guide public health responses to ameliorate the risk of climate change.This study aimed to investigate the mechanism of SChLAP1 (second chromosome locus associated with prostate-1) on microRNA expression in prostate cancer. Differential expression of lncRNAs and microRNA prostate cancer cells were predicted by informatics and confirmed by qRT-PCR. SChLAP1-interacting proteins were characterized by RNA pull-down combined with western blotting, which was verified using RIP and qPCR analysis. Then ChIP assay and DNA pull-down were used to validate the binding of DNMT3a and HEK27me3 with miRNA gene promoters. Target genes of miRNAs were bioinformatically predicted and validated by dual-luciferase reporter assays. The tumorigenicity of prostate cancer cells was assessed using the cancer cell line-based xenograft (CDX) model. We found that SChLAP1 expression was significantly elevated in prostate cancer tissues and cell lines, which was negatively correlated with miR-340 expression. SChLAP1 directly binds with EZH2 and repressed multiple miRNA expression on chromosome 5 including the miR-340-3p in prostate cancer cells through recruiting H3K27me3 to mediate promoter methylation modification of miR-340-5p/miR-143-3p/miR-145-5p to suppress gene transcription. Moreover, DNMT3a was one of the common target genes of miR-340-5p/miR-143-3p/miR-145-5p in prostate cancer cells. And SChLAP1/EZH2 could also promote prostate cancer tumor development via the interaction of microRNA-DNMT3a signaling pathways in xenograft nude mice. Altogether, our results suggest that SChLAP1 enhanced the proliferation, migration, and tumorigenicity of prostate cancer cells through interacting with EZH2 to recruit H2K27me3 and mediate promoter methylation modification of miR-340-5p/miR-143-3p/miR-145-5p with a DNMT3a-feedback loop.As the crucial powerhouse for cell metabolism and tissue survival, the mitochondrion frequently undergoes morphological or positional changes when responding to various stresses and energy demands. In addition to intracellular changes, mitochondria can also be transferred intercellularly. Besides restoring stressed cells and damaged tissues due to mitochondrial dysfunction, the intercellular mitochondrial transfer also occurs under physiological conditions. SM102 In this review, the phenomenon of mitochondrial transfer is described according to its function under both physiological and pathological conditions, including tissue homeostasis, damaged tissue repair, tumor progression, and immunoregulation. Then, the mechanisms that contribute to this process are summarized, such as the trigger factors and transfer routes. Furthermore, various perspectives are explored to better understand the mysteries of cell-cell mitochondrial trafficking. In addition, potential therapeutic strategies for mitochondria-targeted application to rescue tissue damage and degeneration, as well as the inhibition of tumor progression, are discussed.Genomic sequencing analysis of tumors provides potential molecular therapeutic targets for precision medicine. However, identifying a key driver gene or mutation that can be used for hepatocellular carcinoma (HCC) treatment remains difficult. Here, we performed whole-exome sequencing on genomic DNA obtained from six pairs of HCC and adjacent tissues and identified two novel somatic mutations of UBE2S (p. Gly57Ala and p. Lys63Asn). Predictions of the functional effects of the mutations showed that two amino-acid substitutions were potentially deleterious. Further, we observed that wild-type UBE2S, especially in the nucleus, was significantly higher in HCC tissues than that in adjacent tissues and closely related to the clinicopathological features of patients with HCC. Functional assays revealed that overexpression of UBE2S promoted the proliferation, invasion, metastasis, and G1/S phase transition of HCC cells in vitro, and promoted the tumor growth significantly in vivo. Mechanistically, UBE2S interacted with TRIM28 in the nucleus, both together enhanced the ubiquitination of p27 to facilitate its degradation and cell cycle progression. Most importantly, the small-molecule cephalomannine was found by a luciferase-based sensitive high-throughput screen (HTS) to inhibit UBE2S expression and significantly attenuate HCC progression in vitro and in vivo, which may represent a promising strategy for HCC therapy.Chemotherapy drug-induced nephrotoxicity limits clinical applications for treating cancers. Pyroptosis, a newly discovered programmed cell death, was recently reported to be associated with kidney diseases. However, the role of pyroptosis in chemotherapeutic drug-induced nephrotoxicity has not been fully clarified. Herein, we demonstrate that the chemotherapeutic drug cisplatin or doxorubicin, induces the cleavage of gasdermin E (GSDME) in cultured human renal tubular epithelial cells, in a time- and concentration-dependent manner. Morphologically, cisplatin- or doxorubicin-treated renal tubular epithelial cells exhibit large bubbles emerging from the cell membrane. Furthermore, activation of caspase 3, not caspase 9, is associated with GSDME cleavage in cisplatin- or doxorubicin-treated renal tubular epithelial cells. Meanwhile, silencing GSDME alleviates cisplatin- or doxorubicin-induced HK-2 cell pyroptosis by increasing cell viability and decreasing LDH release. In addition, treatment with Ac-DMLD-CMK, a polypeptide targeting mouse caspase 3-Gsdme signaling, inhibits caspase 3 and Gsdme activation, alleviates the deterioration of kidney function, attenuates renal tubular epithelial cell injury, and reduces inflammatory cytokine secretion in vivo. Specifically, GSDME cleavage depends on ERK and JNK signaling. NAC, a reactive oxygen species (ROS) inhibitor, reduces GSDME cleavage through JNK signaling in human renal tubular epithelial cells. Thus, we speculate that renal tubular epithelial cell pyroptosis induced by chemotherapy drugs is mediated by ROS-JNK-caspase 3-GSDME signaling, implying that therapies targeting GSDME may prove efficacious in overcoming chemotherapeutic drug-induced nephrotoxicity.