Mesoscopic-Functionalization of Silk Fibroin with Gold Nanoclusters Mediated by Keratin and Bioinspired Silk Synapse

2017年9月，厦门大学物理科学与技术学院刘向阳教授团队与河北大学闫小兵副教授团队合作, 在Small上发表此论文，第一次将功能化蚕丝用于制造阻变存储/神经元突触电子元件。这种蚕丝基生物仿生元器件, 可制成生物相容/可植入/可降解生物电子芯片, 在人工智领域以及生物医药方面，具有重要的应用前景。【Abstract】Silk fibroin (SF) offers great opportunities in manufacturing biocompatible/partially biodegradable devices with environmental benignity and biomedical applications. To obtain active SF devices of next generation, this work is to demonstrate a new functionalization strategy of the mesoscopic functionalization for soft materials. Unlike the atomic functionalization of solid materials, the meso-functionalization is to incorporate meso-dopants, i.e., functional molecules or nanomaterials, quantum dots, into the mesoscopic networks of soft materials. In this work, wool keratin (WK) molecules were adopted as mediating molecules to incorporate gold nanoclusters (AuNCs), into the mesoscopic networks of SF. It follows from our analyses that the β-crystallites between WK and SF molecules establish the binding between WK@AuNCs and the SF networks. The incorporated WK@AuNCs are electron rich and serve as electronically charged nano particles to bridge the growth of Ag filaments in bio-degradable WK@AuNCs–SF memristors. The meso-functionalization can greatly enhance the performance of SF materials and endows them with new functionalities. This can be highlighted by biocompatible/partly degradable WK@AuNCs functionalized SF resistive random-access memories, having the enhanced resistive switching memory performance, and the unique synapse characteristics and the capability of synapse learning compared with neat SF devices, and of great importance in nonvolatile memory, analog circuits, and neuromorphic applications.The work was supported by NUS tear 1 funding (WBS: R-144-000-367-112), the 111 Project (Grant No. B16029), National Natural Science Foundation of China (Grant Nos. 21404087 and 61674050, U1405226), Fujian Provincial Department of Science & Technology (Grant Nos. 2014H6022, 2015J05109), Natural Science Foundation of Guangdong Province (Grant No. 2015A030310007), 1000 Talents Program, and President Foundation from Xiamen University (Grant No. 20720160088), Ph. D. Programs Foundation of Ministry of Education of China (Grant No. 20130121110018). One of the authors, the primary affiliation of X.Y.L. is the Department of Physics, National University of Singapore. The authors are grateful to the China Scholarship Council (CSC) for the scholarship (Grant No. 201506630067) provided to one of the authors (Xing)

A Pilot Study: Changes of Gut Microbiota in Post-surgery Colorectal Cancer Patients

Colorectal cancer (CRC) is a growing health problem throughout the world. Strong evidences have supported that gut microbiota can influence tumorigenesis; however, little is known about what happens to gut microbiota following surgical resection. Here, we examined the changes of gut microbiota in CRC patients after the surgical resection. Using the PCoA analysis and dissimilarity tests, the microbial taxonomic compositions and diversities of gut microbiota in post-surgery CRC patients (A1) were significantly different from those in pre-surgery CRC patients (A0) and healthy individuals (H). Compared with A0 and H, the Shannon diversity and Simpson diversity were significantly decreased in A1 (P < 0.05). Based on the LEfSe analysis, the relative abundance of phylum Proteobacteria in A1 was significantly increased than that in A0 and H. The genus Klebsiella in A1 had higher proportions than that in A0 (P < 0.05). Individual variation was distinct; however, 90% of CRC patients in A1 had more abundances of Klebsiella than A0. The Klebsiella in A1 was significantly associated with infectious diseases (P < 0.05), revealed by the correlation analysis between differentiated genera and metabolic pathway. The Klebsiella (Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae) in A1 was significantly linked with lymphatic invasion (P < 0.05). Furthermore, the PCA of KEGG pathways indicated that gut microbiota with a more scattered distribution in A1 was noticeably different from that in A0 and H. The nodes, the links, and the kinds of phylum in each module in A1 were less than those in A0 and H, indicating that gut microbiota in A1 had a relatively looser ecologcial interaction network. To sum up, this pilot study identified the changes of gut microbiota in post-surgery CRC patients, and highlights future avenues in which the gut microbiota is likely to be of increasing importance in the care of surgical patients

Chemotherapy Alters the Phylogenetic Molecular Ecological Networks of Intestinal Microbial Communities

Intestinal microbiota is now widely known to play key roles in nutritional uptake, metabolism, and regulation of human immune responses. There are multiple studies assessing intestinal microbiota changes in response to chemotherapy. In this study, microbial phylogenetic molecular ecological networks (pMENs) were firstly used to study the effects of chemotherapy on the intestinal microbiota of colorectal cancer (CRC) patients. Based on the random network model, we demonstrated that overall network structures and properties were significantly changed by chemotherapy, especially in average path length, average clustering coefficient, average harmonic geodesic distance and modularity (P < 0.05). The taxa in the module tended to co-exclude rather than co-occur in CRC patient networks, indicating probably competition relationships. The co-exclude correlations were decreased by 37.3% from T0 to T5 in response to chemotherapy. Significantly negative correlations were observed in positive/negative OTU degree and tumor markers (P < 0.05). Furthermore, the topological roles of the OTUs (module hubs and connectors) were changed with the chemotherapy. For example, the OTU167, OTU8, and OTU9 from the genera Fusobacterium, Bacteroides, and Faecalibacterium, respectively, were identified as keystone taxa, which were defined as either “hubs” or OTUs with highest connectivity in the network. These OTUs were significantly correlated with tumor markers (P < 0.05), suggesting that they probably were influenced by chemotherapy. The pMENs constructed in this study predicted the potential effects of chemotherapy on intestinal microbial community co-occurrence interactions. The changes may have an effect on the therapeutic effects. However, larger clinical samples are required to identify the conclusion

Comprehensive analyses of molecular features, prognostic values, and regulatory functionalities of m6A-modified long non-coding RNAs in lung adenocarcinoma

Abstract Background Lung adenocarcinoma (LUAD) has a high incidence and recurrence rate. N6-methyladenosine (m6A) modification of RNA has become a promising epigenetic marker in tumors. The dysregulation of both RNA m6A levels and m6A regulator expression levels reportedly affects essential biological processes in various tumors. Long non-coding RNAs (lncRNAs), a subgroup of RNAs over 200 nucleotides in length that do not code for protein, can be modified and regulated by m6A, but the relevant profile in LUAD remains unclear. Results The m6A levels of total RNA were decreased in LUAD tumor tissues and cells. Multiple m6A regulators were abnormally expressed at both the RNA and protein levels, and were related in expression patterns and functionally synergistic. Our microarray revealed 2846 m6A-modified lncRNA transcripts as well as its molecular features, 143 of which were differentially m6A-modified and manifested a negative correlation between expression levels and m6A modification levels. More than half of the differentially m6A-modified lncRNAs associated with dysregulated expression. The 6-MRlncRNA risk signature was a reliable indicator for assessing survival time of LUAD patients. The competitive endogenous regulatory network suggested a potential m6A-induced pathogenicity in LUAD. Conclusions These data have demonstrated that differential RNA m6A modification and m6A regulator expression levels were identified in LUAD patients. In addition, this study provides evidence increasing the understanding of molecular features, prognostic values, and regulatory functionalities of m6A-modified lncRNAs in LUAD

Table8_PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer.XLSX

Background: The polypyrimidine tract-binding protein (PTBP) nuclear ribonucleoprotein family of proteins, including PTBP1, PTBP2 and PTBP3, regulate the process of cell proliferation, differentiation, apoptosis and carcinogenesis. PTBPs exhibit oncogenic effects in certain tumors. However, the role of PTBPs in pan-cancer remains unclear. Our study examined the clinical significance and mechanism of PTBPs in pan-cancer.Methods: We compared the expression of PTBPs in paired and unpaired tissue samples from the Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression, Kaplan–Meier curves, and time-dependent receiver operating characteristic (ROC) curves were used to assess the prognostic significance of PTBPs in pan-cancer. The cBioPortal database also identified genomic abnormalities in PTBPs. TISIDB, TCGA, and Cellminer were used to investigate the relationship between PTBP expression and immune subtypes, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), tumor-infiltrating immune cells, and chemosensitivity. cBioPortal was used to search for PTBP co-expressing genes in pan-cancer, and GO and KEGG enrichment analyses were performed to search for PTBP-related signaling pathways.Results:PTBPs were shown to be widely upregulated in human tumor tissues. PTBP1 showed good prognostic value in ACC, KIRP, and LGG; PTBP2 in ACC and KICH; and PTBP3 in ACC, LGG, and PAAD, with AUC >0.7. PTBPs were differentially expressed in tumor immune subtypes and had a strong correlation with tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME). In addition, PTBP expressions were related to ICP, TMB, and MSI, suggesting that these three PTBPs may be potential tumor immunotherapeutic targets and predict the efficacy of immunotherapy. Enrichment analysis of co-expressed genes of PTBPs showed that they may be involved in alternative splicing, cell cycle, cellular senescence, and protein modification.Conclusion: PTBPs are involved in the malignant progression of tumors. PTBP1, PTBP2 and PTBP3 may be potential biomarkers for prognosis and immunotherapy in pan-cancer and may be novel immunotherapeutic targets.</p

Table1_PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer.docx

Background: The polypyrimidine tract-binding protein (PTBP) nuclear ribonucleoprotein family of proteins, including PTBP1, PTBP2 and PTBP3, regulate the process of cell proliferation, differentiation, apoptosis and carcinogenesis. PTBPs exhibit oncogenic effects in certain tumors. However, the role of PTBPs in pan-cancer remains unclear. Our study examined the clinical significance and mechanism of PTBPs in pan-cancer.Methods: We compared the expression of PTBPs in paired and unpaired tissue samples from the Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression, Kaplan–Meier curves, and time-dependent receiver operating characteristic (ROC) curves were used to assess the prognostic significance of PTBPs in pan-cancer. The cBioPortal database also identified genomic abnormalities in PTBPs. TISIDB, TCGA, and Cellminer were used to investigate the relationship between PTBP expression and immune subtypes, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), tumor-infiltrating immune cells, and chemosensitivity. cBioPortal was used to search for PTBP co-expressing genes in pan-cancer, and GO and KEGG enrichment analyses were performed to search for PTBP-related signaling pathways.Results:PTBPs were shown to be widely upregulated in human tumor tissues. PTBP1 showed good prognostic value in ACC, KIRP, and LGG; PTBP2 in ACC and KICH; and PTBP3 in ACC, LGG, and PAAD, with AUC >0.7. PTBPs were differentially expressed in tumor immune subtypes and had a strong correlation with tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME). In addition, PTBP expressions were related to ICP, TMB, and MSI, suggesting that these three PTBPs may be potential tumor immunotherapeutic targets and predict the efficacy of immunotherapy. Enrichment analysis of co-expressed genes of PTBPs showed that they may be involved in alternative splicing, cell cycle, cellular senescence, and protein modification.Conclusion: PTBPs are involved in the malignant progression of tumors. PTBP1, PTBP2 and PTBP3 may be potential biomarkers for prognosis and immunotherapy in pan-cancer and may be novel immunotherapeutic targets.</p

Table11_PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer.XLSX

Background: The polypyrimidine tract-binding protein (PTBP) nuclear ribonucleoprotein family of proteins, including PTBP1, PTBP2 and PTBP3, regulate the process of cell proliferation, differentiation, apoptosis and carcinogenesis. PTBPs exhibit oncogenic effects in certain tumors. However, the role of PTBPs in pan-cancer remains unclear. Our study examined the clinical significance and mechanism of PTBPs in pan-cancer.Methods: We compared the expression of PTBPs in paired and unpaired tissue samples from the Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression, Kaplan–Meier curves, and time-dependent receiver operating characteristic (ROC) curves were used to assess the prognostic significance of PTBPs in pan-cancer. The cBioPortal database also identified genomic abnormalities in PTBPs. TISIDB, TCGA, and Cellminer were used to investigate the relationship between PTBP expression and immune subtypes, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), tumor-infiltrating immune cells, and chemosensitivity. cBioPortal was used to search for PTBP co-expressing genes in pan-cancer, and GO and KEGG enrichment analyses were performed to search for PTBP-related signaling pathways.Results:PTBPs were shown to be widely upregulated in human tumor tissues. PTBP1 showed good prognostic value in ACC, KIRP, and LGG; PTBP2 in ACC and KICH; and PTBP3 in ACC, LGG, and PAAD, with AUC >0.7. PTBPs were differentially expressed in tumor immune subtypes and had a strong correlation with tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME). In addition, PTBP expressions were related to ICP, TMB, and MSI, suggesting that these three PTBPs may be potential tumor immunotherapeutic targets and predict the efficacy of immunotherapy. Enrichment analysis of co-expressed genes of PTBPs showed that they may be involved in alternative splicing, cell cycle, cellular senescence, and protein modification.Conclusion: PTBPs are involved in the malignant progression of tumors. PTBP1, PTBP2 and PTBP3 may be potential biomarkers for prognosis and immunotherapy in pan-cancer and may be novel immunotherapeutic targets.</p