Bacterial pathogens like Mycobacterium tuberculosis (Mtb) encounter acidic microenvironments in the host and must maintain their acid-base homeostasis to survive. A genetic screen identified two Mtb strains that cannot control intrabacterial pH (pHIB) in an acidic environment; infection with either strain led to severe attenuation in mice. To search for additional proteins that Mtb requires to survive at low pH, we introduced a whole-cell screen for compounds that disrupt pHIB, along with counter-screens that identify ionophores and membrane perturbors. Application of these methods to a natural product library identified four compounds of interest, one of which may inhibit novel pathway(s). This approach yields compounds that may lead to the identification of pathways that allow Mtb to survive in acidic environments, a setting in which Mtb is resistant to most of the drugs currently used to treat tuberculosis.

The incorporation of polymerizable cationic monomers has been attempted to generate dental resinous materials with antibacterial activity. This study tested the hypothesis that a dental adhesive containing a cationic monomer, methacryloxylethyl cetyl dimethyl ammonium chloride (DMAE-CB), would influence biofilm formation and gtf gene expression of Streptococcus mutans. The effect of the photo-polymerized DMAE-CB-incorporated adhesive on in vitro biofilm accumulation was investigated with spectrophotometry and scanning electron microscopy. The relative level of gtf gene expression by Streptococcus mutans in the biofilm was quantified by real-time reverse-transcription polymerase chain-reaction. The DMAE-CB-incorporated adhesive significantly decreased bio-film accumulation on its surface (P < 0.05), and suppressed the expression of gtfB and gtfC of Streptococcus mutans in the biofilm (P < 0.05). The results suggest that the cured DMAE-CB-incorporated adhesive may hamper biofilm accumulation via selective down-regulation of the expression of gtf genes in Streptococcus mutans.

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The black rockfish (Sebastes schlegelii) is a teleost in which eggs are fertilized internally and retained in the maternal reproductive system, where they undergo development until live birth (viviparity). In the present study, we report a chromosome‐level black rockfish genome assembly. High‐throughput transcriptome analysis (RNA‐seq and ATAC‐seq) coupled with in situ hybridization (ISH) and immunofluorescence reveal several candidate genes for maternal preparation, sperm storage and release, and hatching. We propose that zona pellucida (ZP) proteins retain sperm at the oocyte envelope, while genes in two distinct astacin metalloproteinase subfamilies serve to release sperm from the ZP and free the embryo from chorion at prehatching stage. We present a model of black rockfish reproduction, and propose that the rockfish ovarian wall has a similar function to the uterus of mammals. Together, these genomic data reveal unprecedented insights into the evolution of an unusual teleost life history strategy, and provide a sound foundation for studying viviparity in nonmammalian vertebrates and an invaluable resource for rockfish ecological and evolutionary research.

With the development of mobile Internet technology and the popularity of intelligent mobile terminals, the data traffic load of mobile client users on the smart campus network platform has surged. How to reduce the data traffic of the smart campus network platform is an urgent problem to be solved. First, this paper discussed the key technologies of smart campus network teaching platform under the background of the 5G network, expounded the critical technologies of the transport layer of the Internet of Things (IoT) technology, and analyzed from the development perspective of the IoT platform. Second, by investigating the online classroom data of five types of colleges and universities in China and comparing the advantages and disadvantages of online classroom teaching and traditional classroom teaching, it is found that the number of online courses in colleges and universities has exploded in the second half of 2017. Next, this paper analyzed the demand of smart campus online teaching platform under the background of the 5G network, thus established an online teaching platform based on the four initiatives operation model (government-led, college sponsor, teacher subject, and academic director). Finally, this paper adopted the improved VIRE localization algorithm to obtain the specific location information of the student users in the classroom and, then, compared with the error obtained by the VIRE algorithm, and the error of the improved VIRE algorithm is smaller. In the process of obtaining information, the 5G network technology is used for data transmission, which can shorten the check-in time and can improve the positioning accuracy. INDEX TERMS 5G network, smart campus, online teaching platform, improved VIRE location algorithm.

BackgroundAloperine, a natural alkaloid constituent isolated from the herb Sophora alopecuroides displays anti-inflammatory properties in vitro and in vivo. Our group previously demonstrated that aloperine significantly induced apoptosis in colon cancer SW480 and HCT116 cells. However, its specific target(s) remain to be discovered in multiple myeloma (MM) and have not been investigated.MethodsHuman myeloma cell lines (n = 8), primary myeloma cells (n = 12), drug-resistant myeloma cell lines (n = 2), and animal models were tested for their sensitivity to aloperine in terms of proliferation and apoptosis both in vitro and in vivo, respectively. We also examined the functional mechanisms underlying the apoptotic pathways triggered by aloperine.ResultsAloperine induced MM cell death in a dose- and time-dependent manner, even in the presence of the proliferative cytokines interleukin-6 and insulin-like growth factor I. Mechanistic studies revealed that aloperine not only activated caspase-8 and reduced the expression of FADD-like interleukin-1β-converting enzyme (FLICE)-like inhibitory protein long (FLIPL) and FLICE-inhibitory proteins (FLIPS) but also activated caspase-9 and decreased the expression of phosphorylated (p)-PTEN. Moreover, co-activation of the caspase-8/cellular FLICE-inhibitory protein (cFLIP)- and caspase-9/p-PTEN/p-AKT-dependent apoptotic pathways by aloperine caused irreversible inhibition of clonogenic survival. Aloperine induce more MM apoptosis with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or borterzomib. A U266 xenograft tumor model and 5T33 MM cells recapitulated the antitumor efficacy of aloperine, and the animals displayed excellent tolerance of the drug and few adverse effects.ConclusionsAloperine has multifaceted antitumor effects on MM cells. Our data support the clinical development of aloperine for MM therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0120-x) contains supplementary material, which is available to authorized users.

The form of (1-3)-beta-D glucan found in the cell walls of the anamorphic Trichocomaceae that grow on damp building materials is considered to have potent toxic and inflammatory effects on cells of the respiratory system. It is also considered to have a potential role in the development of non-allergenic respiratory health effects. While human studies involving experimental exposures all point to the inflammatory potential of pure curdlan, a linear (1-3)-beta-D glucan in a triple helix configuration, animal experiments result in conflicting conclusions concerning the inflammatory potency of this glucan. However, because mice appear to be a better model than guinea pigs for exploring the respiratory effects of curdlan and because molecular mechanisms associated with this glucan remain largely unknown, we conducted further work to clarify the role of curdlan on the inflammatory response using our mouse model of lung disease. This study used in situ hybridization (ISH) to probe dectin-1 mRNA transcription with a digoxigenin-labeled cDNA probe, with reverse transcription (RT)-PCR based arrays used to measure inflammation gene and receptor transcriptional responses. Also, immunohistochemistry (IHC) was used to probe dectin-1 as well as anti-mouse Ccl3, Il1-alpha, and TNF-alpha expression to evaluate dose and time-course (4 and 12 h) postexposure (PE) response patterns in the lungs of intratracheally instilled mice exposed to a single 50 mul dose of curdlan at 10(-7), 10(-8), 10(-9), and 10(-10) M/animal (=4 mug to 4 ng curdlan/kg lung wt). Dectin-1 mRNA transcription and expression was observed in bronchiolar epithelium, alveolar macrophages (AMs), and alveolar type II cells (ATIIs) of lungs exposed to 4 mug to 40 ng curdlan/kg lung wt, at both time points. Compared to controls, array analysis revealed that 54 of 83 genes assayed were significantly modulated by curdlan. mRNA transcription patterns showed both dose and time dependency, with highest transcription levels in 10(-7) and 10(-8) M treatment animals, especially at 4-h PE. Nine gene mRNA transcripts (Ccl3, Ccl11, Ccl17, Ifng, Il1alpha, Il-20, TNF-alpha, Tnfrsf1b, and CD40lg) were significantly expressed at all doses suggesting they may have a central role in immunomodulating curdlan exposures. IHC revealed Ccl3, Il1-alpha, and TNF-alpha expression in bronchiolar epithelium, AMs and ATIIs illustrate the important immunomodulatory role that these cells have in the recognition of, and response to glucan. Collectively, these results confirm the inflammatory nature of curdlan and demonstrate the complex of inflammation-associated gene responses induced by (1-3)-beta-D glucan in triple helical forms. These observations also provide a biological basis for the irritant and inflammatory response to curdlan observed in humans and animals in experimental studies.

Osthole, also known as osthol, is a coumarin derivative found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. It can be obtained via extraction and separation from plants or total synthesis. Plenty of experiments have suggested that osthole exhibited multiple biological activities covering antitumor, anti-inflammatory, neuroprotective, osteogenic, cardiovascular protective, antimicrobial, and antiparasitic activities. In addition, there has been some research done on the optimization and modification of osthole. This article summarizes the comprehensive information regarding the sources and modification progress of osthole. It also introduces the up-to-date biological activities of osthole, which could be of great value for its use in future research.