Matrix Metalloproteinase Inhibitors (MMPIs) from Marine Natural Products: the Current Situation and Future Prospects

Matrix metalloproteinases (MMPs) are a family of more than twenty five secreted and membrane-bound zinc-endopeptidases which can degrade extracellular matrix (ECM) components. They also play important roles in a variety of biological and pathological processes. Matrix metalloproteinase inhibitors (MMPIs) have been identified as potential therapeutic candidates for metastasis, arthritis, chronic inflammation and wrinkle formation. Up to present, more than 20,000 new compounds have been isolated from marine organisms, where considerable numbers of these naturally occurring derivatives are developed as potential candidates for pharmaceutical application. Eventhough the quantity of marine derived MMPIs is less when compare with the MMPIs derived from terrestrial materials, huge potential for bioactivity of these marine derived MMPIs has lead to large number of researches. Saccharoids, flavonoids and polyphones, fatty acids are the most important groups of MMPIs derived from marine natural products. In this review we focus on the progress of MMPIs from marine natural products

Testing Operating Performance of Chinese Listed Firms before and after Cross-border M&As: The Role of Entrepreneurial Orientation

t a time when China encourages its firms to go overseas, especially to countries and regions involved in its “Belt and Road Initiative”, and sets up a favorable domestic environment for innovation and entrepreneurship, this paper is a first trial looking along both the two dimensions to test whether Chinese firms' operating performance changes after cross-border merger and acquisition (CBM&A) activities, using entrepreneurial orientation (EO) as a moderating factor. The paper combines data from Chinese listed firms’ annual reports, Chinese stock market financial statements database and the Zephyr database from 2001 to 2015 to examine how acquirers’ operating performance changes after CBM&A activities using EO as a moderating factor. In order to test whether the results are affected by the stock market, this paper also defines abnormal return on equity (ROE) to detect abnormal operating performance. After these, the paper divides the sample into separate industry groups to see whether results will change. The results obtained for the whole sample show that the performance of Chinese listed firms is fluctuant after CBM&As within the sample years. It increases one year after the acquisition but drops two years later and then follows an increasing trend again. The moderating factor of EO is not significant for the sample as a whole. However, after dividing the sample into separate industry groups, it becomes clear that different industries have their own characteristics. EO helps Chinese listed firms to adjust to the post-acquisition situation and even to improve their performance to some extent in the metal mining industry and the business services industry. When ROE is substituted with abnormal ROE, the results do not change much

Reproducibility, stability, and accuracy of microbial profiles by fecal sample collection method in three distinct populations.

The gut microbiome likely plays a role in the etiology of multiple health conditions, especially those affecting the gastrointestinal tract. Little consensus exists as to the best, standard methods to collect fecal samples for future microbiome analysis. We evaluated three distinct populations (N = 132 participants) using 16S rRNA gene amplicon sequencing data to investigate the reproducibility, stability, and accuracy of microbial profiles in fecal samples collected and stored via fecal occult blood test (FOBT) or Flinders Technology Associates (FTA) cards, fecal immunochemical tests (FIT) tubes, 70% and 95% ethanol, RNAlater, or with no solution. For each collection method, based on relative abundance of select phyla and genera, two alpha diversity metrics, and four beta diversity metrics, we calculated intraclass correlation coefficients (ICCs) to estimate reproducibility and stability, and Spearman correlation coefficients (SCCs) to estimate accuracy of the fecal microbial profile. Comparing duplicate samples, reproducibility ICCs for all collection methods were excellent (ICCs ≥75%). After 4-7 days at ambient temperature, ICCs for microbial profile stability were excellent (≥75%) for most collection methods, except those collected via no-solution and 70% ethanol. SCCs comparing each collection method to immediately-frozen no-solution samples ranged from fair to excellent for most methods; however, accuracy of genus-level relative abundances differed by collection method. Our findings, taken together with previous studies and feasibility considerations, indicated that FOBT/FTA cards, FIT tubes, 95% ethanol, and RNAlater are excellent choices for fecal sample collection methods in future microbiome studies. Furthermore, establishing standard collection methods across studies is highly desirable

SwinCross: Cross-modal Swin Transformer for Head-and-Neck Tumor Segmentation in PET/CT Images

Radiotherapy (RT) combined with cetuximab is the standard treatment for patients with inoperable head and neck cancers. Segmentation of head and neck (H&N) tumors is a prerequisite for radiotherapy planning but a time-consuming process. In recent years, deep convolutional neural networks have become the de facto standard for automated image segmentation. However, due to the expensive computational cost associated with enlarging the field of view in DCNNs, their ability to model long-range dependency is still limited, and this can result in sub-optimal segmentation performance for objects with background context spanning over long distances. On the other hand, Transformer models have demonstrated excellent capabilities in capturing such long-range information in several semantic segmentation tasks performed on medical images. Inspired by the recent success of Vision Transformers and advances in multi-modal image analysis, we propose a novel segmentation model, debuted, Cross-Modal Swin Transformer (SwinCross), with cross-modal attention (CMA) module to incorporate cross-modal feature extraction at multiple resolutions.To validate the effectiveness of the proposed method, we performed experiments on the HECKTOR 2021 challenge dataset and compared it with the nnU-Net (the backbone of the top-5 methods in HECKTOR 2021) and other state-of-the-art transformer-based methods such as UNETR, and Swin UNETR. The proposed method is experimentally shown to outperform these comparing methods thanks to the ability of the CMA module to capture better inter-modality complimentary feature representations between PET and CT, for the task of head-and-neck tumor segmentation.Comment: 9 pages, 3 figures. Med Phys. 202

Leukotriene B4 (LTB4) and its receptor in Experimental Autoimmune Uveitis (EAU) and in human retinal tissues: clinical severity and LTB4-dependence of retinal Th17 cells

Nomacopan, a drug originally derived from tick saliva, has dual functions of sequestering leukotriene B4 (LTB4) and inhibiting complement component 5 (C5) activation. It was demonstrated that nomacopan provides therapeutic benefit in experimental autoimmune uveitis (EAU). The longer-acting forms of nomacopan were more efficacious in mouse EAU models and the long-acting variant that inhibited only LTB4 was at least as effective as the long-acting variant that inhibited both C5 and LTB4, preventing structural damage to the retina and a significant reduction of effector Th17 cells and inflammatory macrophages. Increased levels of LTB4 and C5a (produced upon C5 activation) were detected during disease progression. Retinal activated lymphocytes were shown to express LTB4 receptors (R) in vitro and in inflamed draining lymph nodes (dLN). Levels of LTB4R-expressing retinal active/inflammatory macrophages were also increased. Within the dLN CD4+T cell population, 30% expressed LTB4R+ following activation in vitro, while retinal infiltrating cells expressed LTB4R and C5aR. Validation of expression of those receptors in human uveitis and healthy tissues suggests that infiltrating cells could be targeted by inhibitors of the LTB4-BLT1 pathway as a novel therapeutic approach. In conclusion, this study provides novel data on intraocular LTB4 and C5a in EAU, their associated receptor expression by retinal infiltrating cells in mouse and human tissues and in attenuating EAU via the dual inhibitor nomacopan

Possible egg masses from amphibians, gastropods, and insects in mid-Cretaceous Burmese amber

The eggs of fish, amphibians, and many invertebrates are soft, delicate structures that are only rarely preserved in the fossil record. Here we report egg masses preserved as inclusions in mid-Cretaceous amber deposits of Myanmar. Of five specimens recovered, three of the egg masses probably pertain to insects, but the other two appear different. One mass is composed of relatively stiff eggs that retain their shape throughout the mass and may be linked by mucoid strands. This morphology resembles that of some terrestrial molluscs. The second mass is composed of softer eggs that have compressed one another so that their shapes are strongly distorted within the mass. These eggs most closely resemble those of amphibians. Given the forest environment reconstructed for the amber locality, the eggs were presumably attached on or close to the resin producing tree