CRC is one of the leading causes of cancer mortality worldwide. Chemotherapy is widely used for the treatment of CRC, but its efficacy remains unsatisfactory, mainly due to drug resistance. Therefore, it is urgent to develop new strategies to overcome drug resistance. Combination therapy that aims to achieve additive or synergistic therapeutic effects is an effective approach to tackle the development of drug resistance. Given its established roles in tumor development, progression and metastasis, IGF-1R is a promising drug target for combination therapy against CRC. In this study, we revealed that the novel IGF-1R inhibitor PB-020 can act synergistically with mebendazole (MBZ) to reduce the viability of CRC cells and block xenograft CRC progression. Moreover, the PB-020/anti-PD-1 combination synergistically blocked CRC propagation in the MC38 murine colon carcinoma model. Both combination therapies potently suppressed the PI3K/AKT signaling pathway genes in CRC that may be associated with the development of drug resistance. Our findings establish a preclinical proof-of-concept for combating CRC using combined multi-target treatment with PB-020 and clinical anticancer drugs, which may provide useful clues for clinical trials to evaluate the efficacy and safety of these drug combinations in CRC patients.
In this paper, Sedum simingshanensesp. nov. is described as a new species based on morphological and molecular analyses, and its taxonomic relationships are discussed. Morphological analysis indicates S. simingshanense should be classified in the genus Sedum sect. Sedum and is distinct from the related species S. xunvense and S. formosanum in the morphology of its solitary, light green and smooth stems, flattened leaves, larger, obovate and spurless sepals, yellow anthers, 22–30 ovules per carpel, oblique follicles, and its habitat on shaded slopes or rocks. Phylogenetic analysis of sequences of the nuclear ribosomal internal transcribed spacer (ITS) also demonstrates that S. simingshanense has a highest similarity of only 97.22% with any known species and S. formosanum is the closest extant relative of the new species.
In this study, we sequenced and characterized the complete mitochondrial genome of Acorssocheilus spinifer, an endemic stream-dwelling cyprinid species from South China first described in 2006. The mitogenome is 16,591 bp in length and contains the standard set of 37 genes (13 protein-coding genes, 22 tRNA genes, 2 rRNA genes) plus a control region. The genome exhibits typical cyprinid characteristics, with most genes encoded on the H-strand and a nucleotide composition biased toward A + T (55.9%). All tRNA genes display the typical cloverleaf secondary structure, except for tRNASer (GCU), which lacks the dihydrouridine (DHU) arm. Phylogenetic analysis using complete mitogenomes from 14 Acrossocheilus species revealed that 12 species form a monophyletic assemblage with three distinct clades. Within this framework, A. spinifer clusters closely with A. beijiangensis, supporting previous morphological observations. Our findings provide valuable genetic data for further taxonomic refinement and conservation efforts for Chinese barred species of Cyprinidae.
In this paper, Sedum yongkangense is described as a new species based on morphological and molecular analyses, and its taxonomic relationships are discussed. Morphological analysis indicates S. yongkangense should be classified in the genus Sedum L. sect. Sedum and is distinct from the related species S. ryukyuense, S. mukojimense and S. boninense in having the morphology of a biennial life form; spreading cymes with numerous flowers; unequal, linear, terete sepals; horizontally spreading follicles; and an inland habitat. Molecular analysis of sequences of the nuclear ribosomal internal transcribed spacer (ITS) also demonstrates that S. yongkangense has a highest similarity of only 87.21% with any known species. Phylogenetic analyses indicate that S. yongkangense should be closely related to S. bulbiferum, but the latter differs in having the morphology of a perennial life form; a congested fertile stem; axillary bulbils of leaves; a spatulate-oblanceolate and flat leaf blade; lanceolate to oblanceolate and flat sepals; and deep yellow anthers and spreading follicles.
In this paper, Sedum zhenghaianum sp. nov. is described as a new species based on morphological and molecular analyses, and its taxonomic relationships are discussed. Morphological analysis indicates that S. zhenghaianum should be classified in the genus Sedum sect. Sedum and is distinct from the related species S. tosaense in morphology, e.g. by lacking sterile stems, rosulate leaves 4‐whorled, leaf blade and sepal apices retuse or obtuse, flowers pedicellate, ventral suture of follicles with a wing‐like membranous structure, and seeds with auricled protrusions. Phylogenetic analysis of sequences of the nuclear ribosomal internal transcribed spacer (ITS) further demonstrates that S. tosaense is the closest extant relative of the new species.
Sedum taishunense X.X. Chen, X. Liu & Y.L. Xu (Crassulaceae) is described as a new species from Taishun County, Zhejiang Province, China. Based on morphology, S. taishunense should be placed in sect. Sedum due to the presence of adaxially gibbous carpels. It is morphologically similar to S. lipingense, S. kawaraense and S. shunhuangense, but differs from them by having larger rosulate leaves, fertile stem leaves and primary bracts; inflorescence with multiple flowers; spatulate sepals; ovules 16–24 per carpel; and seed surface with narrow elliptical or scale-like tuberculae. The systematic position of S. taishunense was assessed using the internal transcribed spacer (ITS) region of nuclear ribosomal DNA. Phylogenetic analysis supported S. taishunense as sister to S. makinoi with high support values (UFBS/ PP/ SH-aLRT) 98.5/1/99.