Smart nanocarriers are of particular interest for highly effective photodynamic therapy (PDT) in the field of precision nanomedicine. Nevertheless, a critical challenge still remains in the exploration of potent PDT treatment against hypoxic tumor. Herein, light‐triggered clustered polymeric vesicles for photoinduced hypoxic tumor ablation are demonstrated, which are able to deeply penetrate into the tumor and simultaneously afford oxygen supply upon light irradiation. Hydrogen peroxide (H2O2) and poly(amidoamine) dendrimer conjugating chlorin e6/cypate (CC‐PAMAM) are coassembled with reactive‐oxygen‐species‐responsive triblock copolymer into the polymeric vesicles. Upon 805 nm irradiation, the vesicles exhibit the light‐triggered thermal effect that is able to decompose H2O2 into O2, which distinctly ensures the alleviation of tumor hypoxia at tumor. Followed by 660 nm irradiation, the vesicles are rapidly destabilized through singlet oxygen‐mediated cleavage of copolymer under light irradiation and thus allow the release of photoactive CC‐PAMAM from the vesicular chambers, followed by their deep penetration in the poorly permeable tumor. Consequently, the light‐triggered vesicles with both self‐supplied oxygen and deep tissue penetrability achieve the total ablation of hypoxic hypopermeable pancreatic tumor through photodynamic damage. These findings represent a general and smart nanoplatform for effective photoinduced treatment against hypoxic tumor.

High transmission reliability, energy efficiency, and long lifetime are pivotal issues for wireless body area networks (WBANs). However, these performance metrics are not independent of each other, making it hard to obtain overall improvements through optimizing one single aspect. Therefore, a Cross Layer Design Optimal (CLDO) scheme is proposed to simultaneously optimize transmission reliability, energy efficiency, and lifetime of WBANs from several layers. Firstly, due to the fact that the transmission power of nodes directly influences the reliability of links, the optimized transmission power of different nodes is deduced, which is able to maximize energy efficiency in theory under the premise that requirements on delay and jitter are fulfilled. Secondly, a relay decision algorithm is proposed to choose optimized relay nodes. Using this algorithm, nodes will choose relay nodes that ensure a balance of network energy consumption, provided that all nodes transmit with optimized transmission power and the same packet size. Thirdly, the energy consumption of nodes is still unbalanced even with optimized transmission power because of their different locations in the topology of the network. In addition, packet size also has an impact on final performance metrics. Therefore, a synthesized cross layer method for optimization is proposed. With this method, the transmission power of nodes with more residual energy will be enhanced while suitable packet size is determined for different links in the network, leading to further improvements in the WBAN system. Both our comprehensive theoretical analysis and experimental results indicate that the performance of our proposed scheme is better than reported in previous studies. Relative to the relay selection and power control game (RSPCG) scheme, the CLDO scheme can enhance transmission reliability by more than 44.6% and prolong the lifetime by as much as 33.2%.

Previous studies show that 3β-hydroxysterol-Δ24 reductase (DHCR24) has a remarked decline in the brain of AD patients. In brain cholesterol synthetic metabolism, DHCR24 is known as the heavily key synthetase in cholesterol synthesis. Moreover, mutations of DHCR24 gene result in inhibition of the enzymatic activity of DHCR24, causing brain cholesterol deficiency and desmosterol accumulation. Furthermore, in vitro studies also demonstrated that DHCR24 knockdown lead to the inhibition of cholesterol synthesis, and the decrease of plasma membrane cholesterol and intracellular cholesterol level. Obviously, DHCR24 could play a crucial role in maintaining cholesterol homeostasis via the control of cholesterol synthesis. Over the past two decades, accumulating data suggests that DHCR24 activity is downregulated by major risk factors for AD, suggesting a potential link between DHCR24 downregulation and AD pathogenesis. Thus, the brain cholesterol loss seems to be induced by the major risk factors for AD, suggesting a possible causative link between brain cholesterol loss and AD. According to previous data and our study, we further found that the reduced cholesterol level in plasma membrane and intracellular compartments by the deficiency of DHCR24 activity obviously was involved in β-amyloid generation, tau hyperphosphorylation, apoptosis. Importantly, increasing evidences reveal that the brain cholesterol loss and lipid raft disorganization are obviously linked to neuropathological impairments which are associated with AD pathogenesis. Therefore, based on previous data and research on DHCR24, we suppose that the brain cholesterol deficiency/loss might be involved in the pathogenesis of AD.

Simple SummarySoybean meal is a major protein ingredient in ruminant diets. However, the swine and poultry industries are also competitors for soybean meal as their primary protein ingredient. Thus, soybean meal is expensive, and actually the most expensive gradient of ruminant diets. In this context, urea is used as a low-cost nitrogen source to replace up to 75% of the soybean meal typically fed to fattening lambs. Urea at 10 g could substitute 130 g soybean meal per kg feed dry matter without adverse effects on digestion, metabolism, or growth in fattening lambs when fed a high concentrate diet.AbstractThis study investigated the effects of partially substituting soybean meal (SBM) with incremental amount of urea on rumen fermentation, nutrient digestion, plasma metabolites, and growth performance in fattening lambs. Seventy fattening male lambs were sorted into two blocks according to body weight (BW) and assigned to one of five dietary treatments in a randomized block design: SBM at 170 g/kg dry matter (DM) or reduced SBM (40 g/kg DM) plus 0, 10, 20, or 30 g urea/kg DM. Compared with the lambs receiving the SBM diet, the lambs fed the reduced SBM diet plus urea had higher (p < 0.01) concentrations of ruminal ammonia, and the ruminal concentration of ammonia also increased linearly (p < 0.01) with the increasing urea supplementation. Linear and quadratic effects (p < 0.01) on the crude protein (CP) intake and digestibility were observed with the increasing urea addition to the diet. The concentrations of plasma ammonia and blood urea nitrogen (BUN) increased (linear, p < 0.01; quadratic, p < 0.01) with the increasing urea supplementation. The final BW, DM intake (DMI), average daily gain (ADG), and gain efficiency were similar (p ≥ 0.42) between the SBM group and the urea-supplemented groups. However, the DMI and ADG increased quadratically (p ≤ 0.03) with the increasing urea addition to the diet, with the 10 g urea/kg DM diet resulting in the highest DMI and ADG. The results of this study demonstrated that 10 g urea could substitute 130 g soybean meal per kg feed DM without any adverse effect on growth performance or health in fattening lambs when fed a high concentrate diet.

Using mobile vehicles as “data mules” to collect data generated by a huge number of sensing devices that are widely spread across smart city is considered to be an economical and effective way of obtaining data about smart cities. However, currently most research focuses on the feasibility of the proposed methods instead of their final performance. In this paper, a latency and coverage optimized data collection (LCODC) scheme is proposed to collect data on smart cities through opportunistic routing. Compared with other schemes, the efficiency of data collection is improved since the data flow in LCODC scheme consists of not only vehicle to device transmission (V2D), but also vehicle to vehicle transmission (V2V). Besides, through data mining on patterns hidden in the smart city, waste and redundancy in the utilization of public resources are mitigated, leading to the easy implementation of our scheme. In detail, no extra supporting device is needed in the LCODC scheme to facilitate data transmission. A large-scale and real-world dataset on Beijing is used to evaluate the LCODC scheme. Results indicate that with very limited costs, the LCODC scheme enables the average latency to decrease from several hours to around 12 min with respect to schemes where V2V transmission is disabled while the coverage rate is able to reach over 30%.