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DspI, a putative enoyl-coenzyme A (CoA) hydratase/isomerase, was proposed to be involved in the synthesis of cis -2-decenoic acid (CDA), a quorum sensing (QS) signal molecule in the pathogen Pseudomonas aeruginosa ( P . aeruginosa ). The present study provided a structural basis for the dehydration reaction mechanism of DspI during CDA synthesis. Structural analysis reveals that Glu126, Glu146, Cys127, Cys131 and Cys154 are important for its enzymatic function. Moreover, we show that the deletion of dspI results in a remarkable decreased in the pyoverdine production, flagella-dependent swarming motility, and biofilm dispersion as well as attenuated virulence in P . aeruginosa PA14. This study thus unravels the mechanism of DspI in diffusible signal factor (DSF) CDA biosynthesis, providing vital information for developing inhibitors that interfere with DSF associated pathogenicity in P . aeruginosa .

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse. The objective of this study was to construct a novel CPP modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG -MAL and CPP-PVGLIG-PEG , to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration. The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency. CPP modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.

Invasive species have impacted biodiversity all around the world. Among various ecosystems, islands are most vulnerable to these impacts due to their high ratio of endemism, highly specialized adaptation, and isolated and unique fauna. As with other subtropical islands, Taiwan faces constant risk of biological invasions and is currently ranked as one of the countries most affected by invasive amphibians and reptiles. In this paper, a comprehensive checklist of all known exotic amphibians and reptiles is provided, including twelve species which have successfully colonized Taiwan and six species with a controversial status. We provide an update on the knowledge of all these species including their distribution, colonization history, threats to native animals, and population trends based on literature records, fauna surveys, and data collected during invasive species eradication and control programs. A list of species with high invasive potentials is also provided. This study reports, for the first time, a comprehensive survey of invasive herpetofauna in Taiwan, which should provide a valuable reference to other regions which might suffer from similar invasion risk.

Sperm‐induced Ca 2+ rise is critical for driving oocyte activation and subsequent embryonic development, but little is known about how lasting Ca 2+ oscillations are regulated. Here it is shown that NLRP14, a maternal effect factor, is essential for keeping Ca 2+ oscillations and early embryonic development. Few embryos lacking maternal NLRP14 can develop beyond the 2‐cell stage. The impaired developmental potential of Nlrp14 ‐deficient oocytes is mainly caused by disrupted cytoplasmic function and calcium homeostasis due to altered mitochondrial distribution, morphology, and activity since the calcium oscillations and development of Nlrp14 ‐deficient oocytes can be rescued by substitution of whole cytoplasm by spindle transfer. Proteomics analysis reveal that cytoplasmic UHRF1 (ubiquitin‐like, containing PHD and RING finger domains 1) is significantly decreased in Nlrp14 ‐deficient oocytes, and Uhrf1 ‐deficient oocytes also show disrupted calcium homeostasis and developmental arrest. Strikingly, it is found that the mitochondrial Na + /Ca 2+ exchanger (NCLX) encoded by Slc8b1 is significantly decreased in the Nlrp14 mNull oocyte. Mechanistically, NLRP14 interacts with the NCLX intrinsically disordered regions (IDRs) domain and maintain its stability by regulating the K27‐linked ubiquitination. Thus, the study reveals NLRP14 as a crucial player in calcium homeostasis that is important for early embryonic development.

Kong L, Zhang S, Chu J, et al. Int J Nanomedicine. 2020;15:6451-6468. The authors have advised due to an error at the time of figure assembly, Figure 6A on page 6463 is incorrect. The correct Figure 6 is shown in Download Article. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Ubiquitin specific peptidase 39 (USP39) serves important roles in mRNA processing and is involved in tumorigenesis of multiple solid malignancies. However, the influence and underlying mechanism of USP39 on human renal cell carcinomas (RCC) remain to be elucidated. The current study investigated the functional roles of USP39 in human RCC cell lines. siRNA-mediated RNA interference was used to downregulate USP39 in RCC cells. CCK-8, wound healing and invasion assays were performed to assess the proliferative ability and metastatic potential. The cell cycle distribution and apoptosis were evaluated by flow cytometry. The activity of signaling pathways and the expression of cell cycle-related proteins were detected by western blot analysis. The siRNA-directed RNA interference targeting USP39 could effectively downregulate the expression level of USP39 in two RCC cell lines. Depletion of USP39 by siRNA significantly suppressed cell growth and decreased invasive capacity of RCC cells. Silencing of USP39 induced cell apoptosis and cell cycle arrest at G2/M phase. Additionally, the expression levels of apoptotic and G2/M phase-related proteins were notably decreased following depletion of USP39. Mechanistically, downregulation of USP39 blocked the activation of Akt and extracellular signal regulated kinase signaling pathways in RCC cells. These findings indicate that USP39 may serve as an oncogenic factor in RCC and could be a potential therapeutic candidate for human RCCs.

Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells' self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections.

Background Before 1986, scrub typhus was only found endemic in southern China. Because human infections typically occur in the summer, it is called \"summer type\". During the autumn-winter period of 1986, a new type of scrub typhus was identified in Shandong and northern Jiangsu province of northern China. This newly recognized scrub typhus was subsequently reported in many areas of northern China and was then called \"autumn-winter type\". However, clinical characteristics of associated cases have not been reported. Methods From 1995 to 2006, all suspected scrub typhus cases in five township hospitals of Feixian county, Shandong province were enrolled. Indirect immunofluorescent assay (IFA) was used as confirmatory serodiagnosis test. Polymerase chain reaction (PCR) connected with restriction fragment length polymorphism (RFLP) and sequence analyses were used for genotyping of O. tsutsugamushi DNAs. Clinical symptoms and demography of confirmed cases were analyzed. Results A total of 480 scrub typhus cases were confirmed. The cases occurred every year exclusively between September and December with a peak occurrence in October. The case numbers were relatively higher in 1995, 1996, 1997, and 2000 than in other years. 57.9% of cases were in the group aged 21–50. More cases occurred in male (56%) than in female (44%). The predominant occupational group of the cases was farmers (85.0%). Farm work was reported the primary exposure to infection in 67.7% of cases. Fever, rash, and eschar were observed in 100.0%, 90.4%, and 88.5% of cases, respectively. Eschars formed frequently on or around umbilicus, abdomen areas, and front and back of waist (34.1%) in both genders. Normal results were observed in 88.7% (WBC counts), 84.5% (PLT counts), and 89.7% (RBC counts) of cases, respectively. Observations from the five hospitals were compared and no significant differences were found. Conclusion The autumn-winter type scrub typhus in northern China occurred exclusively from September to December with a peak occurrence in October, which was different from the summer type in southern China. In comparison with the summer type, complications associated with autumn-winter type scrub typhus were less severe, and abnormalities of routine hematological parameters were less obvious.

To probe the detailed structure of dextran hydrogels, periodical models for three dextran hydrogel systems with different dextran contents have been constructed and compared using molecular dynamic simulations. The software packages of Amorphous and Discover in Material Studio with COMPASS force field were used for the simulation. Energy minimization and geometry optimization were used to refine the models. In particular, the structure and dynamic movement of dextran chains which impose on water in the dextran hydrogel systems have been studied. The results show that in the physically crosslinked dextran hydrogels, KCl served as the crosslinker and it interacted with dextran via the oxygen atoms of hydroxyl groups in dextran ring. With increasing dextran content, the free volumes of the hydrogels and the diffusion coefficients of water in the hydrogel decrease. By the radial distribution analysis, the water in the hydrogel networks was found to interact with dextran via hydrogen bond and there are at least three kinds of water in the physically crosslinked dextran hydrogels. These results have a great significance for understanding the structure and properties of the hydrogel.