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This article focuses on the vibration reducing and angle tracking problems of a flexible unmanned spacecraft system subject to input nonlinearity, asymmetric output constraint, and system parameter uncertainties. Using the backstepping technique, a boundary control scheme is designed to suppress the vibration and regulate the angle of the spacecraft. A modified asymmetric barrier Lyapunov function is utilized to ensure that the output constraint is never transgressed. Considering the system robustness, neural networks are used to handle the system parameter uncertainties and compensate for the effect of input nonlinearity. With the proposed adaptive neural network control law, the stability of the closed-loop system is proved based on the Lyapunov analysis, and numerical simulations are carried out to show the validity of the developed control scheme.

Background. Ginsenoside Rg1 is a major component of ginseng with antioxidative and antiaging effects, which is a traditional Chinese medicine. In this study, we investigated the potential spillover and mechanism of action of Rg1 on LiCl-driven hematopoietic stem cell aging. Results. Collect the purified Sca-1+ hematopoietic cells for differentiation ability detection and biochemical and molecular labeling. The experiment found that Rg1 plays an antiaging role in reversing the SA-β-gal staining associated with LiCl-induced hematopoietic stem cell senescence, the increase in p53 and p21 proteins, and sustained DNA damage. At the same time, Rg1 protects hematopoietic cells from the reduced differentiation ability caused by LiCl. In addition, Rg1 increased the excessive inhibition of intracellular GSK-3β protein, resulting in the maintenance of β-catenin protein levels in hematopoietic cells after LiCl treatment. Then, the target gene level of β-catenin can be maintained. Conclusions. Rg1 exerts the pharmacological effect of maintaining the activity of GSK-3β in Sca-1+ hematopoietic cells, enhances the antioxidant potential of cells, improves the redox homeostasis, and thus protects cells from the decline in differentiation ability caused by aging. This study provides a potential therapeutic strategy to reduce stem cell pool failure caused by chronic oxidative damage to hematopoietic stem cells.

Microevolution studies can disclose more elaborate evolutionary mechanisms of genes, appearing especially important for genes with multifaceted function such as those encoding outer membrane proteins. However, in most cases, the gene is considered as a whole unit, and the evolutionary patterns are disclosed.

In this paper, we propose and experimentally demonstrate HyperSight, which is a precise image decoding algorithm for the mobile-phone camera based visible light communication (VLC) system. The conventional algorithms have to select an appropriate column matrix, and then decode the image according to the fitting curve. The selection of the column matrix and the fitting of the function are not only time-consuming but also error-prone, leading to low decoding efficiency and high bit error rate (BER). While HyperSight calculates characteristic grayscale matrix to avoid column matrix selection and uses critical grayscale to replace the function fitting to decode the image. As expected, our algorithm not only reduces the BER, but also improves the processing performance. The experimental results show that, the BER can be reduced by two orders of magnitude on average compared with the conventional scheme. For the $4.8\,$ kbps data rate, our algorithm can achieve the transmission distance of $50\,$ cm under the $7\%$ forward error correction (FEC) threshold with the low illuminance of $702\,$ lux.

In this article, a novel method for constructing a pre-equalizer by optimized filter synthesis with vector fitting is proposed to broaden the bandwidth of a visible light communication (VLC) system. By using the proposed method, an active-passive hybrid equalization circuit is constructed, and it is demonstrated that the 3-dB bandwidth of the VLC system with commercially available phosphorescent white LED is extended from 30 MHz to 600 MHz. A 1.35 Gb/s NRZ-OOK VLC transmission over 12 cm free space transmission distance is experimentally realized, achieving a bit error rate (BER) of $\text{8.8} \times \text{10}^{-\text{5}}$ . To the best of the authors knowledge, this is the largest reported 3-dB bandwidth and real-time data rate achieved in the VLC system with a single commercially phosphorescent white LED.

Bacterial porins serve as the interface interacting with extracellular environment, and are often found under positive selection to fit in different environmental stresses. Local recombination has been identified in a handful of porin genes to facilitate the rapid adaptation of bacterial cells. It remains unknown whether it is a common evolutionary mechanism in gram-negative bacteria for all or a majority of the outer membrane proteins. In this research, we investigated the β-barrel porin encoding genes inEscherichia colithat were reported under positive Darwinia selection. BesidesfhuAthat was found with ingenic local recombination predominantly previously, we identified four other genes, i.e.,lamB, ompA, ompCandompF, all showing the similar mosaic evolution patterns as infhuA. Comparative analysis of the protein sequences disclosed a list of highly variable regions in each protein family, which are mostly located in the convex of extracellular loops and coinciding with the binding sites of various bacteriophages. For each of the porin family, mosaic recombination leads to various combinations of the HVRs with different sequence patterns, generating diverse protein groups. Structure modeling further indicated the conserved global topology for various groups of each porin family, but the extracellular surface varies a lot that is formed by individual or combinatorial HVRs. The conservation of global tertiary structure ensures the channel activity while the wide diversity of HVRs may assist bacteria avoiding the invasion of phages, antibiotics or immune surveillance factors. In summary, the study identified multiple bacterial porin genes with mosaic evolution, a likely general strategy, by which outer membrane proteins could facilitate the host bacteria to both maintain normal life processes and evade the attack of unflavored environmental factors rapidly.ImportanceMicroevolution studies can disclose more elaborate evolutionary mechanisms of genes, appearing especially important for genes with multifaceted function such as those encoding outer membrane proteins. However, in most cases, the gene is considered as a whole unit and the evolutionary patterns are disclosed. In this research, we reported that multiple bacterial porin proteins follow mosaic evolution, with local ingenic recombination combined with spontaneous mutations based positive Darwinia selection, and conservation for most of the other regions. It could represent a common mechanism for bacterial outer membrane proteins. The study also provides insights on development of new anti-bacterial agent or vaccines.

Bufonis (VB), an animal drug called Chansu in China, is the product of the secretion of Bufo gargarizans Cantor or B. melanostictus Schneider. As a traditional Chinese medicine (TCM) for a long time, it has been widely used in the treatment of heart failure, ulcer, pain, and various cancers. Cinobufaginn (CNB), the cardiotonic steroid or bufalene lactone extracted from VB, has the effects of detoxification, detumescence, and analgesia.The present study aimed to define the effects of CNB on non-small-cell lung cancer (NSCLC) and identify the potential molecular mechanisms.A549 cells were treated with cinobufagin and cell viability, apoptosis, migration, and invasion were then evaluated using Cell Counting Kit-8 (CCK8) assays, flow cytometry, and Transwell assays, respectively. Moreover, the levels of proliferating cell nuclear antigen (PCNA), cytokeratin8 (CK8), poly ADP-ribose polymerase (PARP), Caspase3, Caspase8, B-cell lymphoma/lewkmia-2(Bcl-2), Bcl2-Associated X(Bax), forkhead box O1 (FOXO1), and euchromatic histone-lysine N-methyltransferase2 (G9a, EHMT2) in A549 cells were evaluated using qRT-PCR and/or Western blot analysis (WB), Co-IP, immunofluorescence, and immunohistochemistry. An in vivo imaging system, TUNEL, Immunofluorescence, and immunohistochemistry were also used to detect proliferating cell nuclear antigen(PCNA), Ki67, E-Cadherin(E-Cad), FOXO1, and G9a in mouse xenograft model experiments.CNB suppressed cell proliferation, migration, and invasion but promoted apoptosis in A549 cells in a dose- and time-dependent manner, while cinobufagin had no cytotoxic effect on BEAS-2B cells. In vivo, cinobufagin inhibited the proliferation, migration, and invasion of A549 cells and promoted their apoptosis. The occurrence of the above phenomena was accompanied by an increase in FOXO1 expression and a decrease in G9a expression. In A549 cells, CNB did not reverse the changes in the proliferation, migration, invasion, and apoptosis of A549 cells after FOXO1 was successfully silenced.Our study provides the first evidence that cinobufagin suppresses the malignant biological behaviours of NSCLC cells in vivo and in vitro and suggests that mechanistically, this effect may be achieved by inhibiting the expression of the histone methyltransferase G9a and activating the tumour suppressor gene FOXO1. Taken together, our findings provide important insights into the molecular mechanism underlying cinobufagin's anticancer activity, and suggest that cinobufagin could be a candidate for targeted cancer therapy.

Metabolic activity in pulmonary lesion is associated with disease severity and relapse risk in tuberculosis. However, the nature of the metabolic activity associated with tuberculosis in humans remains unclear. Previous works indicate that tuberculosis bears resemblance transcriptionally with systemic lupus erythematosus in peripheral blood, except that the plasma cell component was absent in tuberculosis. Here we reported that the missing transcriptional component was present within the metabolic active tissues in the lung of patients with sputum culture-negative tuberculosis, within which increased levels of circulating immune complexes and anti-dsDNA antibodies were found relative to nearby non-metabolic active tissues. Histological examination revealed specific vascular deposition of immune complexes, neutrophil extracellular traps, and vascular necrosis in the metabolic-active tissue. Thus, tuberculosis-initiated metabolic activity was associated with hyperactive antibody responses and vascular pathology, and shared features with systemic lupus erythematosus and other autoimmune diseases. We discussed these observations in the context of earlier literatures demonstrating that similar effects could be induced in humans and animal models by complete freund’s adjuvant, the most potent antibody response inducer ever reported. Our small case series, if verified in a larger size study, might help inform host-directed therapies to alleviate disease progression and augment treatment efficacy.IMPORTANCEIn patients with pulmonary tuberculosis, lung tissues were destroyed by a hyperactive inflammatory response towardsM. tuberculosis. The mechanisms underlying the inflammatory response are still poorly understood. Using 18F-FDG avidity as a surrogate marker of inflammation, we have identified that hyper-inflamed tissues possessed features associated with systemic lupus erythematosus: gene expression signatures of plasma cell and immunoglobulins and increased levels of anti-dsDNA antibodies, immune deposits, and vasculopathy. This observation might suggest an explanation to why patients with tuberculosis share more gene expression signatures with autoimmune diseases than infectious diseases and why they are more likely to develop autoimmune diseases. Defining the inflammatory responses at the lesion could help inform host-directed therapies to intervene disease progression or even accelerate cure.

The protective effect and mechanism of Ginsenoside Rg1 on aging mouse pancreas damaged by D-galactose (D-gal)-induced was studied. Two-month-old male C57BL/6J mice were randomly divided into three groups of 10 mice per group. The D-gal group of mice received hypodermic injection of D-gal (120 mg/kg/day) for 42 days; the Rg1+D-gal group of mice receiving D-gal + intraperitoneal injection Rg1 (40 mg/kg/day) for 27 days from the 16th day of D-gal replication; and the naïve group that constituted the normal control mice receiving the same dose of saline instead of the drug. The related indicators were tested on the second day after modeling and administration. Fasting blood glucose (FBG), oral glucose tolerance test (OGTT) and fasting insulin level were measured by taking peripheral blood. Samples of pancreas were weighed and visceral index was calculated. Paraffin sections were prepared. H&E staining sections were produced to observe pancreatic tissue morphology. Immunohistochemical staining was used to observe advanced glycation end products (AGEs) and integral optical density (IOD) of stained positive tissue in pancreas. Ultrathin slices were used to observe ultrastructural change of pancreatic tissue. Frozen sections were prepared to test the relative optical density of positive cells that were stained by senescence-associated β-galactosidase (SA-β-gal) in pancreatic tissue. Superoxide dismutase (SOD), malonaldehyde (MDA) and total antioxidant capacity (T-AOC) were detected by preparing pancreas tissue homogenates. Compared with the control group, Rg1+D-gal mice had significantly decreased pancreatic wet weight and visceral index and significantly lower FBG; OGTT for 30 and 120 min. There was no significant difference of the blood sugar level between the groups. The area under the curve and the number and size of the nucleated cells within islet were markedly reduced. In addition, SA-β-gal-positive particles in pancreas tissue intracytoplasmic cells significantly decreased and relative optical density also reduced. The IOD of AGEs in pancreas tissue and MDA content decreased. SOD and T-AOC activity significantly increased. Ginsenoside Rg1 can be effective antagonistic structure and function of the pancreas injury induced by D-gal. The mechanism may be associated with reducing oxidative damage.

Objective. To preliminary explore the senescent dynamic changes of the bone marrow mesenchymal stem cells (BMMSCs) by human ageing and its possible mechanism. Methods. The bone marrows were harvested from healthy volunteers, and according to volunteers’ age, these were divided into group A (≤25 years), group B (26-45 years), group C (46-65 years), and group D (>65 years). Totally, the bone marrows were extracted from the posterior superior iliac spine from volunteers under aseptic conditions. Diluted with isovolumic PBS, followed by centrifugation at 1×105/cm2, cells were cultured in a 5% CO2 incubator at 37°C. After three passages, surface marker identification of hBMMSCs was tested by flow cytometry (FCM), oil red O staining was used to observe the ability of osteogenic differentiation, alkaline phosphatase (ALP) staining and the levels of osteocalcin (OST) in the supernatants were used to observe the ability of adipogenic differentiation, senescence-associated β-galactosidase (SA-β-Gal) staining was used to detect the senescent BMSCs, the ability of BMSC proliferation was detected by cell counting kit-8 (CCK-8), the distribution of the cell cycle was analyzed by flow cytometry (FCM), and malondialdehyde (MDA) content, total glutathione peroxidase, total antioxidant capacity, and total superoxide dismutase (SOD) activity was analyzed using enzymatic assay. Results. The BMSCs highly expressed CD73 and CD90, but lowly expressed CD34 and CD19/CD14. With age, osteogenic differentiation was markedly increased and audiogenic differentiation was significantly decreased. The number of SA-β-gal-positive cells was significantly increased, the proliferation ability of hBMMSCs declined, the BMSCs were held in the G1 phase, the MDA level of BMSCs was significantly increased, and total glutathione peroxidase, total antioxidant capacity, and SOD activity significantly declined. Conclusions. With age, the aging BMSCs were intensified; the mechanism may be related to oxidative damage mediated aging-related pathways.

Nowadays the yellow emissive YAG:Ce phosphors play an important role in fabricating white light-emitting diodes (WLEDs). However, they are deficient in red emission so we proposed polymer dot phosphors to compensate this poor photometric property. The polymer dot phosphors exhibited broad emission bands under excitation of a blue LED chip with weak reabsorption. We demonstrated hybrid white light-emitting diodes with commendable color rendering index (85–95), widely variable color temperatures (3050–7295 K) and high luminous efficacy (72–80 lm W−1 operated at 20 mA) by combining green and red emitting polymer dots on YAG:Ce-based WLEDs. The optical properties suggest the polymer dot phosphors are the suitable color converting materials, which may enable their application in WLED lighting.

The fhuACDB operon, present in a number of Enterobacteriaceae, encodes components essential for the uptake of ferric hydroxamate type siderophores. FhuA acts not only as a transporter for physiologically important chelated ferric iron but also as a receptor for various bacteriophages, toxins, and antibiotics, which are pathogenic to bacterial cells. In this research, fhuA gene distribution and sequence diversity were investigated in Enterobacteriaceae, especially Salmonella and Escherichia. Comparative sequence analysis resulted in a fhuA phylogenetic tree that did not match the expected phylogeny of species or trees of the fhuCDB genes. The fhuA sequences showed a unique mosaic clustering pattern. On the other hand, the gene sequences showed high conservation for strains from the same serovar or serotype. In total, six clusters were identified from FhuA proteins in Salmonella and Escherichia, among which typical peptide fragment variations could be defined. Six fragmental insertions/deletions and two substitution fragments were discovered, for which the combination of polymorphism patterns could well classify the different clusters. Structural modeling demonstrated that all the six featured insertions/deletions and one substitution fragment are located at the apexes of the long loops present as part of the FhuA external pocket. These frequently mutated regions are likely under high selection pressure, with bacterial strains balancing escape from phage infection or toxin/antibiotics attack via fhuA gene mutations while maintaining the siderophore uptake activity essential for bacterial survival. The unusual fhuA clustering suggests that high-frequency exchange of fhuA genes has occurred between enterobacterial strains after distinctive species were established.

ThefhuACDBoperon, present in a number ofEnterobacteriaceae, encodes components essential for the uptake of ferric hydroxamate type siderophores. FhuA acts not only as transporter for physiologically important chelated ferric iron, but also as receptor for various bacteriophages, toxins and antibiotics, which are pathogenic to bacterial cells. In this research, thefhuAgene distribution and sequence diversity were investigated inEnterobacteriaceae, especiallySalmonellaandEscherichia. Comparative sequence analysis resulted in afhuAphylogenetic tree that did not match the expected phylogeny based on housekeeping sequence analysis or trees offhuCDBgenes. ThefhuAsequences showed a unique mosaic-clustering pattern. On the other hand, the gene sequences showed high conservation for strains from the same serovar or serotype. In total, six clusters were identified from FhuA proteins inSalmonellaandEscherichia, among which typical peptide fragment variations could be defined. Six fragmental insertions / deletions and two substitution fragments were discovered, which could well classify the different clusters. Structure modeling demonstrated that all the six featured insertions/deletions and one substitution fragment are located at the apexes of the long loops of FhuA external pocket. These frequently mutated regions are likely under high selection pressure, and bacterial strains could have escaped from phage infection or toxin / antibiotics attack viafhuAgene mutations while maintaining the siderophore uptake activity essential for bacterial survival. The unusualfhuAclustering suggests that high frequency exchange offhuAgenes has occurred between enterobacterial strains after distinctive species were established.IMPORTANCEThe enterobacterialfhuACDBoperon encodes proteins which mediate the uptake of siderophores to supply the cells with iron essential for bacterial survival. Here we show different evolutionary patterns for thefhugenes within the same operon. ThefhuAhas a phylogenetic tree that does not match the species phylogeny, whereas the rest of thefhugenes do. ThefhuAgenes showed inter-species sequence convergence and conservation within specific serovars and serotypes. Nearly all of the significant sequence differences among FhuA clusters are located in potential ligand-binding sites on the extracellular surface of fhuA-encoding receptors. The unusualfhuAclustering suggests the frequent recombination and exchange offhuAgenes between enterobacterial strains in the evolutionary state after distinctive species were established.Our findings suggested either a new evolutionary mechanism or local gene recombination infhuAthat is in contrast to previous evolutionary hypotheses that have formed under the assumption of no recombination.

Experimental mouse models of TB suggest that early events in the lung impact immunity. Early events in the human lung in response to TB are difficult to probe and their impact on disease outcome is unknown. We have shown in mouse that a secreted alternatively-spliced variant of IL-12Rβ1, lacking the transmembrane domain and termed ΔTM-IL-12Rβ1, promotes dendritic cell migration to the draining lymph node, augments T cell activation and limits dissemination ofM. tuberculosis(Mtb). We show here that CBA/J and C3H/HeJ mice (both highly susceptible to Mtb) express higher levels of ΔTM-IL-12Rβ1 than resistant C57BL6 mice and limit early dissemination of Mtb from the lungs. Both CD11c+ cells and T cells express ΔTM-IL-12Rβ1 in humans, and mice unable to make ΔTM-IL-12Rβ1 in either CD4 or CD11c expressing cells permit early dissemination from the lung. Analysis of publically available blood transcriptomes indicates that pulmonary TB is associated with high ΔTM-IL-12Rβ1 expression and that of all IL-12 related signals, the ΔTM-IL-12Rβ1 signal best predicts active disease. ΔTM-IL-12Rβ1 expression reflects the heterogeneity of latent TB infection and has the capacity to discriminate between latent and active disease. In a new Chinese TB patient cohort, ΔTM-IL-12Rβ1 effectively differentiates TB from latent TB, healthy controls and pneumonia patients. Finally, ΔTM-IL-12Rβ1 expression drops in drug-treated individuals in the UK and China where infection pressure is low. We propose that ΔTM-IL-12Rβ1 regulates early dissemination from the lung and that it has diagnostic potential and provides mechanistic insights into human TB.

Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1) ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs) marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

The bandwidth of white light emitting diodes (WLEDs) is an important factor that affects most of the system performances in visible light communication (VLC). It is mainly limited by the down-conversion phosphors. We propose in this paper to employ nanomaterial phosphors with short fluorescence lifetime and high quantum yield in VLC. The white-emitting device of bandwidth-based lifetime was fabricated by using several kinds of nanophosphors with different fluorescence lifetimes. Moreover, we proposed two theoretical models to analyze the factors that affect bandwidth. Compared with the commercial YAG-based WLEDs, the bandwidth of nanophosphor-based WLEDs can be improved over three times and close to the blue excitation sources. Our study indicates that nanophosphors can become promising fluorescent materials in VLC, and provides a new direction for developing wide-bandwidth VLC systems.

Quantum dot white light-emitting diodes (QD-WLEDs) were fabricated from green- and red-emitting AgInS2/ZnS core/shell QDs coated on GaN LEDs. Their electroluminescence (EL) spectra were measured at different currents, ranging from 50 mA to 400 mA, and showed good color stability. The modulation bandwidth of previously prepared QD-WLEDs was confirmed to be much wider than that of YAG:Ce phosphor-based WLEDs. These results indicate that the AgInS2/ZnS core/shell QDs are good color-converting materials for WLEDs and they are capable in visible light communication (VLC).

In this paper, we first experimentally demonstrate a 550 Mbit/s real-time visible light communication (VLC) system based on nonreturn-to-zero on-off keying (NRZ-OOK) modulation of a commercial phosphorescent white light LED. The 3-dB modulation bandwidth of such devices is only a few megahertz. We proposed an analog pre-emphasis circuit based on NPN transistors and an active post-equalization circuit based on an amplifier to enhance the 3-dB bandwidth of VLC link. Utilizing our proposed pre-emphasis and post-equalization circuits, the 3-dB bandwidth of VLC link could be extended from 3 to 233 MHz with blue-filter, to the best of our knowledge, which is the highest ever achieved in VLC systems reported. The achieved data rate was 550 Mbit/s at the distance of 60 cm and the resultant bit-error-ratio (BER) was 2.6 × 10(-9). When the VLC link operated at 160 cm, the data rate was 480 Mbit/s with 2.3 × 10(-7) of BER. Our proposed VLC system is a good solution for high-speed low-complexity application.