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Photodynamic therapy (PDT) is a promising and innovative approach for treating tumors. The synergistic effect of PDT and chemotherapy can enhance the anti-tumor efficacy by leveraging their complementing benefits. In this study, we created lipid vesicles to deliver a photosensitizer (chlorin e6, Ce6) and Regorafenib into tumors for the purpose of examining the effectiveness and mechanism of Lipo-Ce6@Rego-PDT (LCR-P) on Hepatocellular carcinoma (HCC) both in vitro and in vivo. We found that the cytotoxicity on HCC caused by LCR-P was significantly stronger than that caused by Lipo-Ce6-PDT (LC-P). Cellular ROS production in the LCR-P group was approximately higher than that in the LC-P group, and Regorafenib significantly inhibited the phosphorylation of JNK, ERK, and P38 of Lipo-Ce6-PDT group in vitro and in vivo. Furthermore, Regorafenib significantly downregulated the expression of Bcl-2 and upregulated the expression of Bax and cleaved caspase-3 of LC-P group in vitro and in vivo. Compared with LC-P, LCR-P significantly increased cell apoptosis rate. The body weight and HE staining of normal organs primarily indicated the safety of this combined strategy. These results indicate that the combination of Regorafenib and Lipo-Ce6 can significantly enhance the anti-tumor efficiency of PDT for HCC and exhibits good biosafety.

The knowledge of gut microbial information helps evaluate the nutrition and health of the host and can be used as an important tool for improving wildlife conservation and management. Guizhou golden monkey (Rhinopithecus brelichi) is on the International Union for Conservation of Nature (IUCN 2023) Red List. The purpose of the current study was to investigate the difference of gut microbiome and resistome among three different groups of Guizhou golden monkeys using a metagenome approach, thus providing valuable insights and tools for management of captive golden monkeys. Fecal samples of Guizhou golden monkeys were collected from three places including Fanjingshan National Nature Reserve in Guizhou (n =3, Wild), Panxi wildlife rescue center in Guizhou (n=3, CapGZ), and Beijing Zoo (n=3, CapBJ). Fecal DNA was extracted and libraries were prepared and then were sequenced on Illumina PE150 platform with 2 × 150 bp paired reads. The results showed that wild Guizhou golden monkeys had lower abundance of Firmicutes, Uroviricota, Spirochaetes, Fibrobacterota, Campylobacterota, and Candidatus Melainabacteria and higher abundance Proteobacteria, Bacteroidetes and Actinobacteria than the two groups of captive monkeys. PCoA analysis showed that fecal samples from three groups could be distinctly separated. Wild monkeys had significantly higher abundance of genes associated with metabolic function, including carbohydrate metabolism, amino acid metabolism, energy metabolism, and metabolism of cofactors and vitamins. Among the top 20 ARGs analyzed, more ARGs were detected in the wild monkeys than the rest two groups. Overall, this study provides a comprehensive analysis of microbiomes and resistome in wild and captive Guizhou golden monkeys. The data is important for improving the health, management, and conservation of Guizhou golden monkeys based on the deviations in gut microbiome. It also establishes the scientific foundation for future comparative studies on the gut microbiome and resistome of Guizhou golden monkeys and other closely related Rhinopithecus species.

Myricetin(MYR) is a flavonoid compound widely found in many natural plants including bayberry. So far, MYR has been proven to have multiple biological functions and it is a natural compound with promising research and development prospects. This review comprehensively retrieved and collected the latest pharmacological abstracts on MYR, and discussed the potential molecular mechanisms of its effects. The results of our review indicated that MYR has a therapeutic effect on many diseases, including tumors of different types, inflammatory diseases, atherosclerosis, thrombosis, cerebral ischemia, diabetes, Alzheimer's disease and pathogenic microbial infections. Furthermore, it regulates the expression of Hippo, MAPK, GSK-3β, PI3K/AKT/mTOR, STAT3, TLR, IκB/NF-κB, Nrf2/HO-1, ACE, eNOS / NO, AChE and BrdU/NeuN. MYR also enhances the immunomodulatory functions, suppresses cytokine storms, improves cardiac dysfunction, possesses an antiviral potential, can be used as an adjuvant treatment against cancer, cardiovascular injury and nervous system diseases, and it may be a potential drug against COVID-19 and other viral infections. Generally, this article provides a theoretical basis for the clinical application of MYR and a reference for its further use.

Cantharidin (CTD) is the main bioactive component of Cantharides, which is called Banmao in Traditional Chinese Medicine (TCM). Norcantharidin (NCTD) is a structural modifier of CTD. To compare with CTD, NCTD has lighter side effects and stronger bioactivity in anti-cancer through inhibiting cell proliferation, causing apoptosis and autophagy, overwhelming migration and metastasis, affecting immunity as well as lymphangiogenesis. Examples of these effects include suppressing Protein Phosphatase 2A and modulating Wnt/beta catenin signal, with Caspase family proteins, AMPK pathway and c-Met/EGFR pathway involving respectively. Moreover, NCTD has the effects of immune enhancement, anti-platelet aggregation and inhibition of renal interstitial fibrosis with distinct signaling pathways. The immunological effects induced by NCTD are related to the regulation of macrophage polarization and LPS-mediated immune response. The antiplatelet activity that NCTD induced is relevant to the inhibition of platelet signaling and the downregulation of α2 integrin. Furthermore, some of novel derivatives designed and synthesized artificially show stronger biological activities (e.g., anticancer effect, enzyme inhibition effect, antioxidant effect) and lower toxicity than NCTD itself. Plenty of literatures have reported various pharmacological effects of NCTD, particularly the anticancer effect, which has been widely concerned in clinical application and laboratory research. In this review, the pharmaceutical activities and derivatives of NCTD are discussed, which can be reference for further study.