Eun-Jin Go  Hannah Yang  Wooram Park  Seung Joon Lee  Jun-Hyeok Han  So Jung Kong  Won Suk Lee  Dong Keun Han  Hong Jae Chon  Chan Kim 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(43):2300544

Although stimulator of interferon genes (STING) agonists has shown great promise in preclinical studies, the clinical development of STING agonist therapy is challenged by its limited systemic delivery. Here, positively charged fusogenic liposomes loaded with a STING agonist (PoSTING) are designed for systemic delivery and to preferentially target the tumor microenvironment. When PoSTING is administered intravenously, it selectively targets not only tumor cells but also immune and tumor endothelial cells (ECs). In particular, delivery of STING agonists to tumor ECs normalizes abnormal tumor vasculatures, induces intratumoral STING activation, and elicits robust anti-tumor T cell immunity within the tumor microenvironment. Therefore, PoSTING can be used as a systemic delivery platform to overcome the limitations of using STING agonists in clinical trials.  相似文献   

    

Yang Zhou  Yang Guo  Yuanhe Wang 《IET systems biology》2022,16(2):72

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《Journal of dairy science》2019,102(11):9651-9662

Streptococcus thermophilus is an important bacterium used in the production of fermented dairy products. Yogurt with good flavor is preferred by consumers; thus, variation in flavor-formation characteristics among isolates is attracting attention. Here, acetaldehyde production characteristics of 30 isolates were evaluated in parallel with genotyping and multilocus sequence typing of key functional genes involved in acetaldehyde production. The results showed that isolates could be divided into 3 phenotypically distinct groups: high-acetaldehyde-yielding isolates (>10 mg/L), medium-acetaldehyde-yielding isolates (5–10 mg/L) and low-acetaldehyde-yielding (<5 mg/L) based on evaluation of acetaldehyde production during yogurt storage. These groups, distinguishable by phenotypic characteristics, were clustered in corresponding groups based on functional gene multilocus sequence typing analysis. Combining functional gene sequence analysis of 30 Strep. thermophilus isolates with phenotypic evaluation of their flavor-related characteristics (specifically acetaldehyde production) demonstrated that groups of isolates established using genotype data analysis corresponded with groups identified based on their phenotypic traits. Interestingly, the 30 isolates of Strep. thermophilus showed significant phylogenetic clustering in acetaldehyde content by functional gene and acetaldehyde content analysis. A corresponding relationship exists between functional gene phylogenetic clustering and acetaldehyde content variation.  相似文献   

    

Huiling Guo  Lin Pan  Lina Li  Jie Lu  Laiyu Kwok  Bilige Menghe  Heping Zhang  Wenyi Zhang 《Journal of food science》2017,82(3):724-730

Lactobacilli are widely used as starter cultures or probiotics in yoghurt, cheese, beer, wine, pickles, preserved food, and silage. They are generally recognized as safe (GRAS). However, recent studies have shown that some lactic acid bacteria (LAB) strains carry antibiotic resistance genes and are resistant to antibiotics. Some of them may even transfer their intrinsic antibiotic resistance genes to other LAB or pathogens via horizontal gene transfer, thus threatening human health. A total of 33 Lactobacillus strains was isolated from fermented milk collected from different areas of China. We analyzed (1) their levels of antibiotic resistance using a standardized dilution method, (2) their antibiotic resistance gene profiles by polymerase chain reaction (PCR) using gene‐specific primers, and (3) the transferability of some of the detected resistance markers by a filter mating assay. All Lactobacillus strains were found to be resistant to vancomycin, but susceptible to gentamicin, linezolid, neomycin, erythromycin, and clindamycin. Their susceptibilities to tetracycline, kanamycin, ciprofloxacin, streptomycin, quinupristin/dalfopristin, trimethoprim, ampicillin, rifampicin, and chloramphenicol was different. Results from our PCR analysis revealed 19 vancomycin, 10 ciprofloxacin, and 1 tetracycline‐resistant bacteria that carried the van(X), van(E), gyr(A), and tet(M) genes, respectively. Finally, no transferal of the monitored antibiotic resistance genes was observed in the filter mating assay. Taken together, our study generated the antibiotic resistance profiles of some milk‐originated lactobacilli isolates and preliminarily assessed their risk of transferring antibiotic gene to other bacteria. The study may provide important data concerning the safe use of LAB.  相似文献   

    

Didem Akpınar Kankaya  Yasin Tuncer 《Journal of Food Processing and Preservation》2020,44(6):e14468

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Vikas Pathak  Satyasai Jagannath Nanda  Amit Mahesh Joshi  Sitanshu Sekhar Sahu 《International Journal of Circuit Theory and Applications》2020,48(12):2242-2256

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Qiang Li  Meng Dang  Jun Tao  Xiaoye Li  Weijun Xiu  Zhuo Dai  Ao He  Meng Ding  Yu Zhang  Zhi-fa Wen  Xiaodan Su  Aaron James Elbourne  Lei Bao  Lin Chen  Yongbin Mou  Zhaogang Teng  Heng Dong 《Advanced functional materials》2024,34(26):2311480

In situ tumor vaccines (ISTVs) hold great potential in tumor immunotherapy, however, three major obstacles, including inadequate endogenous antigen uptake by dendritic cells (DCs), weak T-cell immune responses, and stubborn immunosuppressive tumor microenvironment (TME), still need to be fully addressed. Herein, a trifecta nanovaccine (TriNV) with TME-responsive transformable ability is developed to tri-boost antitumor immunity. First, sufficient endogenous tumor-associated antigens (TAAs) are liberated in situ after immunogenic cell death is induced via TriNV-based photoimmunotherapy. In the TME, soft-transformed TriNV improves the uptake of TAAs by DCs to enhance acquired immunity. Second, the self-adjuvating TriNV and the TME-responsive released Mn²⁺ synergistically promote DC maturation and macrophage M1 polarization by augmenting the stimulator of interferon genes activation to further amplify T-cell immune responses. Moreover, the decomposition of MnO₂ within the core of TriNV exhausts glutathione and facilitates O₂ release to alleviate hypoxia in the TME, thereby overcoming the chemical obstacles of the TME to further mitigate immunosuppression. Thus, TriNV remarkably eradicates primary tumors and inhibits distant metastasis, thus demonstrating great potential as a feasible and effective ISTV nanoplatform for combating poorly immunogenic solid tumors.  相似文献   

    

《Applied Soft Computing》2019

The improvement of protein expression levels represents one of the most important goals in synthetic biology. In order to accomplish it, a promising and widely-used strategy lies on integrating multiple genes that encode the subject protein into an organism genome. This important task, however, is affected by several challenging issues. Firstly, the integration of highly similar sequences can potentially induce homologous recombination, a negative effect that implies a reduction in the number of genes effectively integrated. This is the reason why it is important to design multiple protein-coding sequences (also named CDSs) that are as different as possible, between both different CDSs and different subsequences within the same CDS. Additionally, codon usage frequencies in these CDSs should be as highly adapted to the organism as possible. Therefore, this task involves different and conflicting objectives that must be optimized, thus being suitable to be tackled as a multi-objective optimization problem. In this work, we design and implement the algorithm MOABC (Multi-Objective Artificial Bee Colony) to solve the problem of designing multiple CDSs that encode the same protein, considering three objectives to be optimized. The experimental evaluation herein performed suggests that MOABC is able to obtain relevant results, showing statistically significant improvements over the ones found in the literature.  相似文献   

    

Junjie Zhu  Yanfeng Zhao  Ming Liu  Diego Gonzalez‐Rivas  Xinnan Xu  Weijing Cai  Huiwei Qi  Lei Dai  Zijian Wang  Xiao Song  Gening Jiang  Yang Yang 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(9)

An accurate genotyping analysis is one of the critical prerequisites for lung cancer targeted therapy. Here, a quantitative polymerase chain reaction (qPCR)‐based mutation detection system, mutation‐selected amplification‐specific system PCR (MASS‐PCR), is developed. The specific primers and probes used in MASS‐PCR exactly match with the mutant sequence that only allows mutant gene to emit the fluorescence peak. To determine the sensitivity of MASS‐PCR, 717 lung cancer specimens, 61 formalin‐fixed paraffin‐embedded (FFPE) tissues, and 656 fresh reaction tissues are collected and undergo mutation detection of lung cancer driver genes (EGFR, KRAS, BRAF, HER2, MET, ALK, and ROS1). These samples are divided into two groups. Mutations in Group I, which has 631 fresh reaction tissues, are analyzed by MASS‐PCR and the amplification refractory mutation system PCR (ARMS‐PCR). While group II samples, 25 fresh reaction tissues and 61 FFPE tissues, are screened through MASS‐PCR and next‐generation sequencing (NGS). All results are verified by direct sequencing. MASS‐PCR shows high consistency with ARMS‐PCR (kappa value > 0.733) and NGS (kappa value = 0.79) (P < 0.001). For the samples with inconsistent MASS‐PCR and ARMS‐PCR results, DS results more likely support the MASS‐PCR results. These data suggest that MASS‐PCR is a convenient, accurate, and economical method for the detection of lung cancer driver gene mutations in clinical practice.  相似文献   

    

Meiling Han  Ai Li  Ting Shen  Jiaxin Meng  Yongqin Lei  Xian Zhang  Pengyuan Liu  Linxin Gan  Lei Ao  Houhua Li 《Journal of Food Biochemistry》2019,43(11)

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