Prostate-specific antigen (PSA), a serine protease, is a promising target for the development of prodrugs in prostate cancer treatment. In this study, we designed a novel fusion peptide, BSD352, containing three functional domains: a protein transduction domain from HIV transactivating regulatory protein (TAT) followed by the BH3 domain of the p53 upregulated modulator of apoptosis (TAT-BH3), an anti-vascular endothelial growth factor peptide (SP5.2), and an anti-basic fibroblast growth factor peptide (DG2). These different domains in BSD352 were linked together by a linker sequence corresponding to a PSA hydrolytic substrate peptide. The BSD352 fusion peptide could be selectively cleaved by PSA in PSA-producing LNCaP prostate cancer cells. Furthermore, the BSD352 fusion peptide was efficiently transduced into tumor cells both in vitro and in vivo, and the BH3 domain was found to induce tumor cell apoptosis by elevating the expression of Bax, cytochrome C release, and caspase-9 cleavage. Moreover, the SP5.2 and DG2 domains in the BSD352 fusion peptide also exhibited in-vitro endothelial cell growth inhibition and in-vivo antiangiogenic activities. Direct injection of BSD352 into an established LNCaP xenograft tumor in mice inhibited tumor growth, whereas a synergistic effect was observed with the combined use of wild-type BH3, SP5.2, and DG2 functional domains. These results suggest that BSD352 could be beneficial for the treatment of accessible prostate tumors and may provide a complementary strategy for prostate cancer therapy.
The recent observed anomalous Hall effect in magic angle twisted bilayer graphene (TBG) aligned to hexagonal boron nitride (hBN) and unconventional ferroelectricity in Bernal bilayer graphene sandwiched by hBN present a new platform to tune the correlated properties in graphene systems. In these graphene-based moiré superlattices, the aligned hBN substrate plays an important role. In this paper, we analyze the effects of hBN substrate on the band structure of the TBG. By means of an atomistic tight-binding model we calculate the electronic properties of TBG suspended and encapsulated with hBN. Interestingly, we found that the physical properties of TBG are extremely sensitive to the presence of hBN and they may be completely different if TBG is suspended or encapsulated. We quantify these differences by analysing their electronic properties, optical conductivity and band topology. We found that the narrow bandwidth, band gap, local density of states and optical conductivity are significantly modified by the aligned hBN substrates. Interestingly, these electronic properties can be used as a signature of the alignment in experiment. Moreover, the TBG/hBN superlattices in the presence or absence of the two-fold rotation symmetry response differently to the external electric field. For the TBG suspended in the hBN, application of an electric field results in the charge unevenly distributed between graphene layers, which can be used to tune the strength of the valley Hall effect or the anomalous Hall effect. Such rich topological phase diagram in these systems may be useful for experiments.
Abstract Many control algorithms for formation of robot swarms are often inspired from animal swarms. However, these algorithms are derived by simply imitating the behaviors of animal swarms instead of directly applying intrinsic principles because of the capability gaps between animals and robots. Here we experimentally proved that the principle of differential adhesion hypothesis in cell biology can be directly applied to the formation of robot swarms. Like cell collectives, swarms of sensor-less robots aggregated and sorted in a self-organized manner. Based on this finding, we programmed robot swarms to form functional morphologies via tuning their adhesion. This work advances swarm robotics in forming functional morphologies and enables us to quantitatively investigate morphogenesis in cell collectives using robot swarms.
Background: Previous studies have confirmed that ibeA is a key virulence gene of E.coli K1 which plays an important role in the pathogenesis of E.coli K1. The adhesion of E.coli K1 to human brain microvascular endothelial cells is one of the key issues in the pathogenesis of bacterial neonatal meningitis. Biofilm is associated with bacterial adhesion. In this study, the biofilm formation was observed in the IbeA gene deletion mutant, confirming that IbeA is involved in biofilm formation. Methods and materials: The bacteria were divided into four groups: (1) DH5α, (2) E. coli K1, the IbeA knockout strain and the IbeA complemented strain. The biofilm formation was detected by crystal violet staining. The adhesion was measured specifically due to IbeA by comparing the adhesive properties of the IbeA complemented strain to those of the IbeA knockout mutant strain. Results: The formation of biofilm in the wildtype E. coli K1 group was significantly higher than that in the knockout group and in the negative group (p < 0.05). The biofilm formation of the IbeA complemented group was significantly higher than that in IbeA knockout group (p < 0.05). Besides, the adhesion of E. coli K1 was significantly higher than that in the knockout group and the negative group (p < 0.05). The adhesion rate of the IbeA complemented group was significantly higher than that of the IbeA knockout group (p < 0.05). Conclusion: The biofilm formation of E. coli K1 strain is induced by ibeA which is a key virulence gene in the pathogenesis, and ibeA-mediated virulence enhances biofilm-associated adhesion to human brain microvascular endothelial cells in vitro. (Acknowledgements: *Corresponding author: Hong Cao, The study was supported by Undergraduate Training Program for Innovation and Entrepreneurship of SMU, China, No. 201912121275 and Scientific Research Enlightenment Plan of SMU, China,2019)
Abstract Emerging adsorption technology shows great potential for Pb 2+ removal in the human body because of its high adsorption efficiency and easy operation. However, biosafety concerns in the human body limit the development of adsorbents in integrated lead removal for acute poisoning in humans from the gastrointestinal tract and even the blood. In this work, highly bio‐safe and natural saccharomyces cerevisiae cells are immobilized on the interworking natural regenerated cellulose nanofibers network for integrated lead removal in the human body. High intrinsic biosafety of the aerogel is guaranteed due to the biocompatibility of aerogel composition and the absence of cross‐linking substances. Attributing to the porous structure of cellulose nanofibrous scaffolds, saccharomyces cerevisiae cells are protected from shedding, and considerable loading sites for saccharomyces cerevisiae cells are ensured. Simultaneously, abundant functional groups on the saccharomyces cerevisiae cells exhibit superior adsorption ability with a saturated adsorption capacity of lead ions as high as 107 mg g −1 in the aquatic environment. After adsorption, Pb 2+ concentration decreases from 879.70 to 248.53 µg L −1 in the intestinal phase and from 400 to 186.29 µg L −1 (within a safe level) in blood, providing an attractive strategy for detoxification of integrated lead in the human body.
Immunomodulatory drugs (IMiDs) including lenalidomide and pomalidomide bind cereblon (CRBN) and activate the CRL4CRBN ubiquitin ligase to trigger proteasomal degradation of the essential transcription factors IKZF1 and IKZF3 and multiple myeloma (MM) cytotoxicity. To have a comprehensive understanding of mechanism underlying sensitivity of MM cells to IMiDs, we performed genome-wide CRISPR-Cas9 screening in three MM cell lines: MM.1S, NCI-H929 and OPM2, which showed resistance to IMiDs at different extent. In the published screening in MM.1S cell, we found that CSN9 signalosome complex, a deactivator of Cullin-RING ubiquitin ligase, regulates MM sensitivity to IMiDs by modulating CRBN expression via SCFFbxo7 ubiquitin ligase. With the newly outcome from H929 and OPM2 cells, we identified 5 top ranking genes with more than 2 sgRNAs ranking in the top 5% sgRNAs in all the three cell lines. CRBN was the top ranking gene with all CRBN-targeting sgRNAs ranking in the top 1% enriched sgRNAs. UbE2G1, reported as an E2 of CRL4-CRBN E3 ligase recently, was another top ranking gene in all the three cell lines. DEPDC5, a component of the GATOR1 complex which inhibits mTORC1 pathway, and SLC35G2, classified as a member of nucleotide sugars transporters (NSTs), were also identified in the top list of all the three cell lines, indicating that mTOR pathway as well as Glycosylation may play an important role in the MM cytotoxicity induced by IMiDs. We also identified 76 top genes shared in two of the three cell lines with more than 2 sgRNAs. Taken together, these results provide a research framework leading to distinguish the cancer patients who become resistant to IMiDs therapy.Citation Format: Wenrong Zhou, Tianyu Song, Min Long, Jiye Liu, Qunsheng Ji, Yong Cang. Comprehensive CRISPR screening unravel the different mechanisms of IMiDs resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2088.
The prevalence of subclinical hypothyroidism (SCH) is high among patients with diabetes, although the relationship between SCH and diabetic vascular complications is unknown. This study aimed to determine the relationship between SCH and vascular complications in patients with Type 2 diabetes.In this cross sectional study, 991 patients with Type 2 diabetes were screened for thyroid function at their admission to the Second Affiliated Hospital of Chongqing Medical University. We compared the prevalence of coronary heart disease (CHD), ischaemic stroke and chronic kidney disease (CKD) with the prevalence of euthyroidism and SCH.Among the 991 patients, 126 (12.7%) patients had SCH. The prevalence of CHD was significantly higher in the SCH group than in the euthyroid group (22.2% and 15.0%, respectively; P = 0.039). In the logistic regression analyses, SCH was associated with CHD [odds ratio (OR): 1.993; 95% confidence interval (CI): 1.135-3.497; P = 0.016]. This association was stronger in patients aged ≥ 65 years than in younger patients [2.474 (1.173-5.220); P = 0.017]. No significant association was found between SCH and ischaemic stroke. Patients with severe SCH had a high risk of CKD [1.842 (1.120-3.029); P = 0.016].This study provides evidence that SCH in patients with Type 2 diabetes is associated with a high prevalence of CHD (and CKD in severe SCH), although not with ischaemic stroke.
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