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As an extension of centralized cloud services in a space-air-ground integrated network, an unmanned aerial vehicle (UAV-)-enabled edge network brings computation as close ground terminals of need as possible. In this scenario, the UAV is considered a mobile base station (MBS) to achieve data forwarding and processing from cloud servers to terminals. Note that downlink signals from the MBS to ground terminals are vulnerable to passive wiretapping by a malicious node. We formulate an average secrecy rate maximization problem to tackle the wiretapping issue by simultaneously transmitting confidential information and artificial noise (AN). We decompose the problem into two subproblems, including the UAV transmit power allocation subproblem and the UAV trajectory subproblem. Then, we adopt the successive convex approximation scheme and the alternating optimization method to develop our iterative algorithm to achieve secure transmission. Simulation results demonstrate that the proposed scheme is significantly better than other benchmarks in UAV-enabled downlink communication secrecy performance.

Different oxygen functionalization processes occur for N-doped soft carbon (N-SC) and hard carbon (N-HC), and there may be a competitive relationship between the formation of pyridinic-N and CO groups. For N-SC, abundant CO groups and defects bring excellent Na

Five ruminally and duodenally cannulated Kazakh male lambs (30 ± 2.75 kg) maintained singly in a metabolic cage were used in a 5 × 5 Latin square experiment to investigate the effect of supplementing a ration with five different levels of distillers' grape residue (DGR) on ruminal degradability, whole tract digestibility and nitrogen (N) metabolism of growing lambs. The rations were isoenergetic and isonitrogenous and contained 0, 3.85, 7.70, 11.55 and 15.41% DGR (DM basis). Each experimental period lasted for 18 d: 10 d for adaptation to the dietary treatment and 8 d for faecal, urinary, ruminal and duodenal digesta sample collections. The outflow rate of ruminal digesta increased (

Background aims Chimeric antigen receptor T cells (CAR‐T cells) have been successfully used in treatments of hematological tumors, however, their anti‐tumor activity in solid tumor treatments was limited. As IL‐12 increases T‐cell immune functions, we designed carcinoembryonic antigen (CEA) specific CAR‐T (CEA‐CAR‐T) cells and, for the first time, used them in combination with recombinant human IL‐12 (rhIL‐12) to treat several types of solid tumors. Methods In vitro anti‐tumor activity of CEA‐CAR‐T cells in combination with rhIL‐12 was confirmed by evaluation of CEA‐CAR‐T cell activation, proliferation, and cytotoxicity after co‐incubation with CEA‐positive or CEA‐negative human tumor cells. In vivo anti‐tumor activity of CEA‐CAR‐T cells in combination with rhIL‐12 was confirmed in a xenograft model in nude mice for treatments of several types of solid tumors. Results In vitro experiments confirmed that rhIL‐12 significantly increased the activation, proliferation, and cytotoxicity of CEA‐CAR‐T cells. Similarly, in vivo experiments found that CEA‐CAR‐T cells in combination with rhIL‐12 had significantly enhanced anti‐tumor activity than CEA‐CAR‐T cells in growth inhibition of newly colonized colorectal cancer cell HT‐29, pancreatic cancer cell AsPC‐1, and gastric cancer cell MGC803. Conclusions These works confirmed that simultaneous use of cytokines, for example, rhIL‐12, can increase the anti‐tumor activity of CAR‐T cells, especially for treatments of several types of solid tumors.

Chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) therapy has an excellent efficacy in cancer treatment, especially its impressive results in hematological malignancies. Unfortunately, its application on solid tumors is challenged by the off-target effects caused by lacking of tumor specific antigens and the immunosuppression caused by the tumor microenvironment. We constructed a switchable dual receptor CAR-T cell (sdCAR-T) whose activity relied upon double antigens (mesothelin and fluorescein isothiocyanate) and was strictly controlled by a "switch" (FPBM) consisting of a PD-L1 blocking peptide conjugated to fluorescein isothiocyanate. SdCAR-T cells were activated only when FPBM and cognate tumor cells expressing both PD-L1 and mesothelin coexist. Importantly, long-term proliferation experiments in vitro and the pharmacodynamic study in vivo showed a stronger antitumor activity of this system compared to the second generation mesothelin CAR-T cells. In view of this novel treatment paradigm being safer and more effective than traditional CAR-T cells, it may become a new strategy for the treatment of solid tumors.

Angiogenesis is known to serve an important role in embryonic development, wound healing, tissue regeneration, and growth. Two new abietane-type diterpenoids (3, 5), a new lanosterol triterpenoid (8) and seven known compounds haven been isolated from the Euphorbia neriifolia Linn. The structures of all compounds were elucidated by spectroscopic analysis and comparing their NMR data with reported data. Furthermore, we found that compounds 6 and 9 had the antiangiogenic effects in vitro. They could inhibit HUVEC migration and microvessel sprouting in rat aortic rings. Moreover, compound 6 inhibited VEGFR and phosphorylation of Akt, but compound 9 only shown inhibitory effect on phosphorylation of Akt. Taken together, these results suggest that inhibition of VEGF signaling and downstream pathways may be responsible for the antiangiogenic activity of compounds 6 and 9.

A lack of specificity is restricting the further application of conotoxin from Conus bullatus (BuIA). In this study, an analogue library of BuIA was established and virtual screening was used, which identified high &alpha, 7 nicotinic acetylcholine receptor (nAChR)-selectivity analogues. The analogues were synthesized and tested for their affinity to functional human &alpha, 7 nAChR and for the regulation of intracellular calcium ion capacity in neurons. Immunofluorescence, flow cytometry, and patch clamp results showed that the analogues maintained their capacity for calcium regulation. The results of the hot-plate model and paclitaxel-induced peripheral neuropathy model indicated that, when compared with natural BuIA, the analgesia activities of the analogues in different models were maintained. To analyze the adverse effects and toxicity of BuIA and its analogues, the tail suspension test, forced swimming test, and open field test were used. The results showed that the safety and toxicity of the analogues were significantly better than BuIA. The analogues of BuIA with an appropriate and rational mutation showed high selectivity and maintained the regulation of Ca2+ capacity in neurons and activities of analgesia, whereas the analogues demonstrated that the adverse effects of natural &alpha, conotoxins could be reduced.

Melatonin-mediated osmotic tolerance was attributed to increased antioxidant capacity, energy metabolism, osmoregulation and autophagy in wheat (Triticum aestivum L.). Melatonin is known to play multiple roles in plant abiotic stress tolerance. However, its role in wheat has been rarely investigated. In this study, 25% polyethylene glycol 6000 (PEG 6000) was used to simulate osmotic stress, and wheat seeds and seedlings were treated with different concentrations of melatonin under PEG stress. Isobaric tag for relative and absolute quantification (iTRAQ)-based proteomic techniques were used to identify the differentially accumulated proteins from melatonin-treated and non-treated seedlings. Seeding priming with melatonin significantly increased the germination rate, coleoptile length, and primary root number of wheat under PEG stress, as well as the fresh weight, dry weight, and water content of wheat seedlings. Under PEG stress, melatonin significantly improved reactive oxygen species homeostasis, as revealed by lower H2O2 and O 2 · content; and the expression of antioxidant enzymes at the transcription and translation levels was increased. Melatonin maintained seedling growth by improving photosynthetic rates and instantaneous and intrinsic water use efficiencies, as well as carbon fixation and starch synthesis at the protein level. Melatonin treatment significantly affected the expression of glycolytic proteins, including fructose-1,6-bisphosphate aldolase, hexokinase, glyceraldehyde-3-phosphate dehydrogenase, and enolase, and remarkably increased the expression of the nicotinamide adenine dinucleotide transporter and nicotinamide adenine dinucleotide binding protein, thereby indirectly modulating electron transport in the respiratory chain. This indicated that melatonin improved energy production in PEG-stressed seedlings. Further, melatonin played a regulatory role in autophagy, protease expression, and ubiquitin-mediated protein degradation by significantly upregulating rab-related protein, fused signal recognition particle receptor, aspartyl protease, serine protease, ubiquitin-fold modifier 1, and ubiquitin at the mRNA or protein level. These findings suggested that melatonin might activate a metabolic cascade related to autophagy under PEG stress in wheat seedlings.