Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no useful drugs that target FMOD for CRC treatment in clinics. Here, we first used public whole-genome expression datasets to analyze the expression level of FMOD in CRC and found that FMOD was upregulated in CRC and associated with poor patient prognosis. We then used the Ph.D.-12 phage display peptide library to obtain a novel FMOD antagonist peptide, named RP4, and tested its anti-cancer effects of RP4 in vitro and in vivo. These results showed that RP4 inhibited CRC cell growth and metastasis, and promoted apoptosis both in vitro and in vivo by binding to FMOD. In addition, RP4 treatment affected the CRC-associated immune microenvironment in a tumor model by promoting cytotoxic CD8+ T and NKT (natural killer T) cells and inhibiting CD25+ Foxp3+ Treg cells. Mechanistically, RP4 exerted anti-tumor effects by blocking the Akt and Wnt/β-catenin signaling pathways. This study implies that FMOD is a potential target for CRC treatment, and the novel FMOD antagonist peptide RP4 can be developed as a clinical drug for CRC treatment.
Human papillomavirus type 16 (HPV16) E7 is a viral oncoprotein believed to play a major role in cervical cancer. In this study, an antagonist peptide against HPV16E7 protein was first identified from screening the c7c phage display peptide library. The binding specificity and affinity of the selected peptide to HPV16E7 were tested by competitive enzyme-linked immunosorbent assay (ELISA). The antagonist peptide showed obvious anti-tumor efficacy both in cell lines and animal tumor models. Significant cell proliferation inhibition with high specificity was noted when HPV16-positive cells were treated with the peptide. This anti-tumor efficacy was resulted from overriding the activities of HPV16E7 and reactivating the pRb/E2F pathway, as shown by a series of experiments. Flow cytometry analysis revealed that the selected peptide induced G1 arrest in a dose-dependent manner. Competitive ELISA, pull down, and Co-IP experiments indicated that the selected peptide disrupted the interaction between HPV16E7 and pRb proteins both in vitro and in vivo. Luciferase reporter assay verified that transcription activities of E2F were suppressed by the peptide through restoration of pRb. RT-PCR and Western blot revealed that it reduced cyclins A, D1, and E1 expression, and led to HPV16E7 protein degradation, but pRb protein stabilization. The current study suggests that this specific peptide may serve as a potential therapeutic agent for HPV16-positive cervical cancer.
In recent years, there has been a rapid rise in the development of engineered bamboo materials, which have the potential to play an important role as alternatives to conventional building materials. Despite the growing diversity of bamboo products available on the market, the international standardization of both bamboo products and their constituent elements is limited, and a lack of universal nomenclature is recognized as one of the main constraints on developing standards. Similar or identical terminology is used interchangeably to describe different bamboo elements, processes, or products across sectors and continents. In some cases, translated colloquial names are misleading and scientifically inaccurate, which forms a barrier to global collaboration and research, creates ambiguity, and potentially limits trade. The present work aims to address this gap by proposing a set of appropriate terms in English that accurately describe and differentiate between currently produced engineered bamboo products and their constituent elements, accompanied by parallel terms in Chinese and Spanish. From these, new categories of engineered bamboo building materials are proposed for the Harmonized System of product codes. This paper highlights current ambiguities and provides terminology together with clear definitions of the main primary elements, processing steps, and products.
Abstract Lysosome‐targeting chimeras (LYTACs) are an emerging therapeutic modality that effectively degrade cancer cell membranes and extracellular target proteins. In this study, a nanosphere‐based LYTAC degradation system is developed. The amphiphilic peptide‐modified N ‐acetylgalactosamine (GalNAc) can self‐assemble into nanospheres with a strong affinity for asialoglycoprotein receptor targets. They can degrade different membranes and extracellular proteins by linking with the relevant antibodies. CD24, a heavily glycosylated glycosylphosphatidylinositol‐anchored surface protein, interacts with Siglec‐10 to modulate the tumor immune response. The novel Nanosphere‐AntiCD24, synthesized by linking nanospheres with CD24 antibody, accurately regulates the degradation of CD24 protein and partially restores the phagocytic function of macrophages toward tumor cells by blocking the CD24/Siglec‐10 signaling pathway. When Nanosphere‐AntiCD24 is combined with glucose oxidase, an enzyme promoting the oxidative decomposition of glucose, the combination not only effectively restores the function of macrophages in vitro but also suppresses tumor growth in xenograft mouse models without detectable toxicity to normal tissues. The results indicate that GalNAc‐modified nanospheres, as a part of LYTACs, can be successfully internalized and are an effective drug‐loading platform and a modular degradation strategy for the lysosomal degradation of cell membrane and extracellular proteins, which can be broadly applied in the fields of biochemistry and tumor therapeutics.
Spatiotemporal mode locking is a nonlinear process of multimode soliton self-organization. Here the real-time buildup dynamics of the multiple solitons in a spatiotemporal mode-locked multimode fiber laser are investigated, assisted by the time-stretch technique. We find that the buildup processes are transverse mode dependent, especially during the stages of relaxation oscillation and Q -switching prior to multiple soliton formation. Furthermore, we observe that the transverse modal composition of these generated pulses among the multiple solitons can be different from each other, indicating the spatiotemporal structure of the multiple soliton. A simplified theoretical model based on pulse energy evolution is put forward to interpret the role of 3D saturable absorber on spatiotemporal structures of spatiotemporal mode-locking multiple solitons. Our work has presented the spatiotemporal nonlinear dynamics in multimode fiber lasers, which are novel to those inside the single transverse mode fiber lasers.
The 2022 International Conference—Bamboo: A Very Sustainable Construction Material & the 3rd World Symposium on Sustainable Bio-Composite Materials and Structures—was held from November 8 to December 13, 2022. This conference was led by INBAR and INBAR Bamboo Construction Task Force and co-organized by 37 other national and international institutions. More than 80 experts from over 20 countries delivered speeches or presentations to approximately 1400 participants from 81 countries and shared the latest research and development on bamboo and timber construction with them. The conference convened global architects, engineers, forestry experts, researchers, entrepreneurs, and policy makers to present the potential uses and suitability of bamboo, timber, and other biomaterials as conventional construction materials in modern society. This paper summarizes the key deliberations and findings of the diverse research, including the state-of-practice and the means of moving the state-of-the-art forward. Further actions on training, standardization, and research were urged to be taken to promote this industry.
Neuwiedia malipoensis Z. J. Liu, L. J. Chen & Ke Wei Liu (Orchidaceae, Apostasioideae), from southeastern Yunnan Province in China, is described, illustrated, and photographed. The new species is characterized by a true corolla lip, which is widely obovate and concave, with a subterete claw at the base and a fleshy linear callus extending from its claw to the upper portion. By these features it can be easily distinguished from its allied N. veratrifolia Blume, N. balansae Baill. ex Gagnep., and other species of this genus.
Abstract To improve our understanding of the origin and evolution of mycoheterotrophic plants, we here present the chromosome-scale genome assemblies of two sibling orchid species: partially mycoheterotrophic Platanthera zijinensis and holomycoheterotrophic Platanthera guangdongensis . Comparative analysis shows that mycoheterotrophy is associated with increased substitution rates and gene loss, and the deletion of most photoreceptor genes and auxin transporter genes might be linked to the unique phenotypes of fully mycoheterotrophic orchids. Conversely, trehalase genes that catalyse the conversion of trehalose into glucose have expanded in most sequenced orchids, in line with the fact that the germination of orchid non-endosperm seeds needs carbohydrates from fungi during the protocorm stage. We further show that the mature plant of P. guangdongensis , different from photosynthetic orchids, keeps expressing trehalase genes to hijack trehalose from fungi. Therefore, we propose that mycoheterotrophy in mature orchids is a continuation of the protocorm stage by sustaining the expression of trehalase genes. Our results shed light on the molecular mechanism underlying initial, partial and full mycoheterotrophy.
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