Virtual Screening and Biomolecular Interactions of CviR-Based Quorum Sensing Inhibitors Against Chromobacterium violaceum

The rise of bacterial multi drug resistance becomes a global threat to the mankind. Therefore it is essential to find out alternate strategies to fight against these “super bugs.” Quorum sensing (QS) is a cell-to-cell communication mechanism by which many bacteria regulate their biofilm and virulence factors expression to execute their pathogenesis. Hence, interfering the quorum sensing is an effective alternate strategy against various pathogens. In this study, we aimed to find out potential CviR-mediated quorum sensing inhibitors (QSIs) against Chromobacterium violaceum. Virtual screening from a natural products database, in vitro biofilm and violacein inhibition assays have been performed. Biofilm formation was investigated using confocal microscopy and gene expression studies were carried out using qRT-PCR. Further, to study the biomolecular interaction of QSIs with purified CviR Protein (a LuxR homologue), microscale thermophoresis (MST) analysis was performed. Results suggested that phytochemicals SPL, BN1, BN2, and C7X have potential GScore when compared to cognate ligand and reduced the biofilm formation and violacein production significantly. Especially, 100 μM of BN1 drastically reduced the biofilm formation about 82.61%. qRT-PCR studies revealed that cviI, cviR, vioB, vioC, vioD genes were significantly down regulated by QSIs. MST analysis confirmed the molecular interactions between QSIs and purified CviR protein which cohere with the docking results. Interestingly, we found that BN2 has better interaction with CviR (Kd = 45.07 ±1.90 nm). Overall results suggested that QSIs can potentially interact with CviR and inhibit the QS in a dose dependent manner. Since, LuxR homologs present in more than 100 bacterial species, these QSIs may be developed as broad spectrum anti-infective drugs in future

Specific two-photon imaging of live cellular and deep-tissue lipid droplets by lipophilic AIEgens at ultra-low concentration

Lipid droplets are highly associated with obesity, diabetes, inflammatory disorders and cancer. A reliable two-photon dye for specific lipid droplets imaging in live cells and live tissues at ultra-low concentration has rarely been reported. In this work, four new aggregation-induced emission luminogens (AIEgens) based on the naphthalene core were designed and synthesized for specific two-photon lipid droplets staining. The new molecules, namely NAP AIEgens, exhibit large Stokes shift (>110 nm), high solid-state fluorescence quantum yield (up to 30%), good two-photon absorption cross section (45–100 GM at 860 nm), high biocompatibility and good photostability. They could specifically stain lipid droplets at ultra-low concentration (50 nM) in a short time of 15 min. Such ultra-low concentration is the lowest value for lipid droplets staining in live cells reported so far. In vitro and ex vivo two-photon imaging of lipid droplets in live cells and live mice liver tissues were successfully demonstrated. In addition, selective visualization of lipid droplets in live mice liver tissues could be achieved at a depth of about 70 μm. These excellent properties render them as promising candidates for investigating lipid droplets-associated physiological and pathological processes in live biological samples

Evolution of Complex Thallus Alga: Genome Sequencing of Saccharina japonica

Saccharina, as one of the most important brown algae (Phaeophyceae) with multicellular thallus, has a very remarkable evolutionary history, and globally accounts for most of the economic marine aquaculture production worldwide. Here, we present the 580.5 million base pairs of genome sequence of Saccharina japonica, whose current assembly contains 35,725 protein-coding genes. In a comparative analysis with Ectocarpus siliculosus, the integrated virus sequence suggested the genome evolutionary footprints, which derived from their co-ancestry and experienced genomic arrangements. Furthermore, the gene expansion was found to be an important strategy for functional evolution, especially with regard to extracelluar components, stress-related genes, and vanadium-dependent haloperoxidases, and we proposed a hypothesis that gene duplication events were the main driving force for the evolution history from multicellular filamentous algae to thallus algae. The sequenced Saccharina genome paves the way for further molecular studies and is useful for genome-assisted breeding of S. japonica and other related algae species

Methylmercury Exposure and Health Effects from Rice and Fish Consumption: A Review

Methylmercury (MeHg) is highly toxic, and its principal target tissue in humans is the nervous system, which has made MeHg intoxication a public health concern for many decades. The general population is primarily exposed to MeHg through consumption of contaminated fish and marine mammals, but recent studies have reported high levels of MeHg in rice and confirmed that in China the main human exposure to MeHg is related to frequent rice consumption in mercury (Hg) polluted areas. This article reviews the progress in the research on MeHg accumulation in rice, human exposure and health effects, and nutrient and co-contaminant interactions. Compared with fish, rice is of poor nutritional quality and lacks specific micronutrients identified as having health benefits (e.g., n-3 long chain polyunsaturated fatty acid, selenium, essential amino acids). The effects of these nutrients on the toxicity of MeHg should be better addressed in future epidemiologic and clinical studies. More emphasis should be given to assessing the health effects of low level MeHg exposure in the long term, with appropriate recommendations, as needed, to reduce MeHg exposure in the rice-eating population

Aggregation-Induced Emission (AIE), Life and Health

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health

Identification, Molecular Characterization, and Tissue Expression Profiles of Three Smad Genes from Water Buffalo (Bubalus bubalis)

Smads are involved in a variety of biological activities by mediating bone morphogenetic protein (BMP) signals. The full-length coding sequences (CDSs) of buffalo Smads 1, 4, and 5 were isolated and identified through RT-PCR in this study. Their lengths are 1398 bp, 1662 bp, and 1398 bp, respectively. In silico analysis showed that their transcriptional region structures, as well as their amino acid sequences, physicochemical characteristics, motifs, conserved domains, and three-dimensional structures of their encoded proteins are highly consistent with their counterparts in the species of Bovidae. The three Smad proteins are all hydrophilic without the signal peptides and transmembrane regions. Each of them has an MH1 domain and an MH2 domain. A nuclear localization sequence was found in the MH1 domain of buffalo Smads 1 and 5. Prediction showed that the function of the three Smads is mainly protein binding, and they can interact with BMPs and their receptors. The three genes were expressed in all 10 buffalo tissues assayed, and their expression in the mammary gland, gonad, and spleen was relatively high. The results here indicate that the three buffalo Smads may be involved in the transcriptional regulation of genes in a variety of tissues.</jats:p

Single-Machine Scheduling Problems with a Sum-of-Processing-Time-Based Learning Function

Recently, learning scheduling problems have received increasing attention. However, the majority of the research assume that the actual job processing time is a function of its position. This paper deals with the single-machine scheduling problem with a sum-of-processing-time-based learning effect. By the effect of sum-of-processing-time-based learning, we mean that the processing time of a job is defined by total normal processing time of jobs in front of it in the sequence. We show that the single-machine makespan problem remains polynomially solvable under the proposed model. We show that the total completion time minimization problem for a≥1 remains polynomially solvable under the proposed model. For the case of 0<a<1, we show that an optimal schedule of the total completion time minimization problem is V-shaped with respect to normal job processing times