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981.
982.
《药学学报(英文版)》2020,10(10):1966-1976
Inflammatory bowel diseases (IBD) are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs. In this study, patchouli alcohol, a main active compound of traditional Chinese herb patchouli, was developed into biomimetic liposomes for macrophage-targeting delivery for IBD treatment. The developed lactoferrin-modified liposomes (LF-lipo) can specifically bind to LRP-1 expressed on the activated colonic macrophages and achieve cell-targeting anti-inflammatory therapy. LF-lipo reduced the levels of inflammatory cytokines and ROS and suppressed the MAPK/NF-κB pathway. LF-lipo also suppressed the formation of NLRP3 inflammasome and the consequent IL-1β activation. LF-lipo showed improved therapeutic efficacy in a DSS-induced colitis murine model, evidenced by the reduced disease activity index, the improved colon functions, and the downregulated inflammatory cytokines in the colon. LF-lipo provided an effective and safe macrophage-targeting delivery and therapeutic strategy for addressing the unmet medical need in IBD management. 相似文献
983.
With the advent of high density SNP arrays and the progress of next generation sequencing, demands for new methods to handle the subsequent data analysis have exploded. Forensic laboratories are generally hesitant to implement new methods in casework unless they are thoroughly tested and validated. This is particularly true when a third party contractor is involved in the analysis. In this paper we explore data from dense sets of SNP markers and study how different errors could potentially affect the results. Particularly, we study the effects of genotyping errors, linkage disequilibrium as well as the use of inappropriate population frequencies. We demonstrate that ignoring these concepts may lead to false conclusions for some different relationship cases and outline solutions to mitigate these problems. 相似文献
984.
Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors (ICIs) have been successfully developed to treat various cancers by motivating the adaptive anti-tumor immunity. Particularly, the checkpoint blockade approach has achieved great clinic success as evidenced by several U.S. Food and Drug Administration (FDA)-approved anti-programmed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 antibodies. However, the majority of cancers have low clinical response rates to these ICIs due to poor tumor immunogenicity. Indeed, the cyclic guanosine monophosphate-adenosine monophosphate synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS‒STING‒TBK1) axis is now appreciated as the major signaling pathway in innate immune response across different species. Aberrant signaling of this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection and cancers. In this perspective, we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS‒STING‒TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory therapy. Meanwhile, highlights on the clinical candidates, limitations and challenges, as well as future directions in this field are also discussed. Further, small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well. 相似文献
985.
986.
This work revealed the drug resistance and population structure of Moraxella catarrhalis strains isolated from children less than three years old with pneumonia. Forty-four independent M. catarrhalis strains were analyzed using broth dilution antimicrobial susceptibility testing and multilocus sequence typing (MLST). The highest non-susceptibility rate was observed for amoxicillin (AMX), which reached 95.5%, followed by clindamycin (CLI) (n = 33; 75.0%), azithromycin (AZM) (61.4%), cefaclor (CEC) (25.0%), trimethoprim-sulfamethoxazole (SXT) (15.9%), cefuroxime (CXM) (4.5%), tetracycline (TE) (2.3%), and doxycycline (DOX) (2.3%). There was no strain showing non-susceptibility to other six antimicrobials. Using MLST, the 44 M. catarrhalis strains were divided into 33 sequence types (STs). Based on their allelic profiles, the 33 STs were divided into one CC (CC363) and 28 singletons. CC363 contained five STs and ST363 was the founder ST. CC363 contained 63.6%, 33.3%, and 40.7% of CEC non-susceptible, CLI non-susceptible and AZM non-susceptible strains, respectively. The proportions of CEC non-susceptible, CLI non-susceptible and AZM non-susceptible strains in CC363 were higher than that of singletons; these differences were significant for CEC (p = 0.002) and AZM (p = 0.011). Furthermore, CC363 contained more AMX-CLI-AZM co-non-susceptible and AMX-CEC-CLI-AZM co-non-susceptible strains than the singletons (p = 0.007 and p < 0.001, respectively). CC363 is a drug-resistant clone of clinical M. catarrhalis strains in China. Expansion of this clone under selective pressure of antibiotics should be noted and long-term monitoring should be established. 相似文献
987.
Laura Eme Laila J. Reigstad Anja Spang Anders Lanzén Thomas Weinmaier Thomas Rattei Christa Schleper Céline Brochier-Armanet 《Research in microbiology》2013,164(5):425-438
Based on phylogenetic analyses and gene distribution patterns of a few complete genomes, a new distinct phylum within the Archaea, the Thaumarchaeota, has recently been proposed. Here we present analyses of six archaeal fosmid sequences derived from a microbial hot spring community in Kamchatka. The phylogenetic analysis of informational components (ribosomal RNAs and proteins) reveals two major (hyper-)thermophilic clades (“Hot Thaumarchaeota-related Clade” 1 and 2, HTC1 and HTC2) related to Thaumarchaeota, representing either deep branches of this phylum or a new archaeal phylum and provides information regarding the ancient evolution of Archaea and their evolutionary links with Eukaryotes. 相似文献
988.
A revision is presented of the peak-valley method for the in situ determination of low-level concentrations of 137Cs in soils in which its vertical distribution is uniform or quasi-exponential, and relaxation coefficients within the range 3.5–15 g/cm2. In tests of soils that satisfied these conditions, the revised method was found to reproduce the real 137Cs concentrations to at least within the same order of magnitude, and with uncertainties of less than 40%. Finally a protocol is proposed to improve in so far as possible the precision of assays of this radionuclide in soils in which its presence is relatively low—of the order of a few kBq/m2. 相似文献
989.
Takahiro Hashimoto Yu-Long Sun Kai-Nan An Peter C. Amadio Chunfeng Zhao 《Medical engineering & physics》2012,34(10):1387-1393
For both tendon allografts and autografts, the surface, initially optimized for gliding, may not be ideal to facilitate tissue integration for graft healing to host tendon or bone. As a prelude to studying tendon–bone integration, we investigated the effect of surface treatments with trypsin or mechanical abrasion on cell attachment to the tendon surface in a canine ex vivo intrasynovial tendon tissue culture model. Intrasynovial tendon allograft surfaces were seeded with cells after the following treatments: (1) no treatment, (2) mechanical abrasion, (3) trypsin, and (4) abrasion and trypsin. The area covered by cells was determined using confocal laser microscopy at one and two weeks. Results were compared to untreated extrasynovial tendon. Additional tendons were characterized with scanning electron microscopy. Tendons with trypsin treatment had significantly more surface coverage with cells than the other groups, after both one and two weeks of culture. In terms of the cellular shape and size, cells on tendons with trypsin treatment spread more and were more polygonal in shape, whereas tendons with mechanical abrasion with/without trypsin treatment contained smaller, more spindle-like cells. Surface roughening can affect cell behavior with topographical stimulation. Trypsin surface digestion exposes a mesh-like structure on the tendon surface, which could enhance cell adherence and, possibly, tendon/bone healing. 相似文献
990.
本文介绍了小波基函数的定义、构造和小波提升。并将小波变换和小波提升应用于胃电(EGG)信号处理中。通过对信息熵、信号能量和联合熵等滤波后的信号特征进行分析,介绍了小波基函数的一般评价选择方法。为了验证评价方法的合理性,实验中采用了不同的小波基函数进行实验数据处理和信号滤波。通过小波变换和小波提升对EGG信号进行了滤波,分离了EGG快、慢波频段信号。并通过实验数据验证了小波变换和小波提升方案的合理性和EGG滤波算法的有效性。为胃的疾病诊断和测量提供了一个有效的解决工具和测量方法。 相似文献