Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway.

OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS: Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

Copper(II)-infused porphyrin MOF: maximum scavenging GSH for enhanced photodynamic disruption of bacterial biofilm.

Bacterial biofilm infection is a serious obstacle to clinical therapeutics. Photodynamic therapy (PDT) plays a dynamic role in combating biofilm infection by utilizing reactive oxygen species (ROS)-induced bacterial oxidation injury, showing advantages of mild side effects, spatiotemporal controllability and little drug resistance. However, superfluous glutathione (GSH) present in biofilm and bacteria corporately reduces ROS levels and seriously affects PDT efficiency. Herein, we have constructed a Cu2+-infused porphyrin metal-organic framework (MOF@Cu2+) for the enhanced photodynamic combating of biofilm infection by the maximum depletion of GSH. Our results show that the released Cu2+ from porphyrin MOF@Cu2+ could not only oxidize GSH in biofilm but also consume GSH leaked from ROS-destroyed bacteria, thus greatly weakening the antioxidant system in biofilm and bacteria and dramatically improving the ROS levels. As expected, our dual-enhanced PDT nanoplatform exhibits a strong biofilm eradication ability both in vitro and in an in vivo biofilm-infected mouse model. In addition, Cu2+ can promote biofilm-infected wound closing by provoking cell immigration, collagen sediment and angiogenesis. Besides, no apparent toxicity was detected after treatment with MOF@Cu2+. Overall, our design offers a new paradigm for photodynamic combating biofilm infection.

A nanozyme-reinforced injectable photodynamic hydrogel for combating biofilm infection.

Bacterial biofilm-associated infectious diseases remain serious menaces to human health. Recently, photodynamic therapy (PDT) has become a prospective strategy for combating biofilm infection. However, anaerobic conditions in a biofilm greatly inhibit its therapeutic efficacy. Here, a nanozyme-reinforced injectable hydrogel is prepared using Ca2+-crosslinked sodium alginate incorporated with photosensitizer-loaded MnO2 nanosheets and CaO2 nanoparticles for O2 self-sufficient PDT to eradicate biofilm infection. In our design, CaO2 reacts with water to produce locally concentrated H2O2, which could be catalyzed by MnO2 nanosheets (catalase-mimic nanozymes) to generate O2 and greatly relieve the hypoxic conditions in the biofilm, thus significantly strengthening PDT efficacy. In vitro assays confirmed that the hybrid hydrogel not only exhibits high-performance bactericidal activity in combating both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli but also shows great efficacy in eliminating biofilm infection. Moreover, benefiting from its good syringeability, the hybrid hydrogel is prone to fit irregular wounds and exhibits high efficiency in promoting wound healing in a biofilm-infected mice model. Besides, no obvious toxicity is detected in the hybrid hydrogel. Overall, we envision that our designed hydrogel could provide a prospective solution for combating biofilm-associated infections.

Optimizing triangle mesh lenses for non-uniform illumination with an extended source.

Precise control of irradiance distribution is a complicated problem for freeform lens design, especially when the target is non-uniform. Realistic sources are often simplified as zero-etendue ones in cases designed for content-rich irradiance fields while the surfaces are usually assumed smooth everywhere. These practices can limit the performance of the designs. We developed an efficient proxy for Monte Carlo (MC) ray tracing under extended sources, with the linear property of our triangle mesh (TM) freeform surface. Our designs show finer irradiance control compared to their counterparts from the LightTools design feature. One of the lenses is fabricated and evaluated in an experiment, and performed as expected.

Investigating deep optics model representation in affecting resolved all-in-focus image quality and depth estimation fidelity.

The end-to-end (E2E) optimization of optics and image processing, dubbed deep optics, has renewed the state-of-the-art in various computer vision tasks. However, specifying the proper model representation or parameterization of the optical elements remains elusive. This article comprehensibly investigates three modeling hypotheses of the phase coded-aperture imaging under a representative context of deep optics, joint all-in-focus (AiF) imaging and monocular depth estimation (MDE). Specifically, we analyze the respective trade-off of these models and provide insights into relevant domain-specific requirements, explore the connection between the spatial feature of the point spread function (PSF) and the performance trade-off between the AiF and MDE tasks, and discuss the model sensitivity to possible fabrication errors. This study provides new prospects for future deep optics designs, particularly those aiming for AiF and/or MDE.

An Energy Efficient Design of Computation Offloading Enabled by UAV.

The data volume is exploding due to various newly-developing applications that call for stringent communication requirements towards 5th generation wireless systems. Fortunately, mobile edge computing makes it possible to relieve the heavy computation pressure of ground users and decrease the latency and energy consumption. What is more, the unmanned aerial vehicle has the advantages of agility and easy deployment, which gives the unmanned aerial vehicle enabled mobile edge computing system opportunities to fly towards areas with communication demand, such as hotspot areas. However, the limited endurance time of unmanned aerial vehicle affects the performance of mobile edge computing services, which results in the incomplete mobile edge computing services under the time limit. Consequently, this paper concerns the energy-efficient scheme design of the unmanned aerial vehicle while providing high-quality offloading services for ground users, particularly in the regions where the ground communication infrastructures are overloaded or damaged after natural disasters. Firstly, the model of energy-efficient design of the unmanned aerial vehicle is set up taking the constraints of the energy limitation of the unmanned aerial vehicle, the data causality, and the speed of the unmanned aerial vehicle into account. Subsequently, aiming at maximizing the energy efficiency of the unmanned aerial vehicle in the unmanned aerial vehicle enabled mobile edge computing system, the bits allocation in each time slot and the trajectory of the unmanned aerial vehicle are jointly optimized. Secondly, a successive convex approximation based alternating algorithm is brought forward to deal with the non-convex energy efficiency maximization problem. Finally, it is proved that the proposed energy efficient scheme design of the unmanned aerial vehicle is superior to other benchmark schemes by the simulation results. Besides, how the performance of proposed scheme design change under different parameters is discussed.

Energy-Efficient UAV-Enabled MEC System: Bits Allocation Optimization and Trajectory Design.

The unmanned aerial vehicle (UAV) enabled mobile edge computing (MEC) system is attracting a lot of attentions for the potential of low latency and low transmission energy consumption, due to the advantages of high mobility and easy deployment. It has been widely applied to provide communication and computing services, especially in Internet of Things (IoT). However, there are still some challenges in the UAV-enabled MEC system. Firstly, the endurance of the UAV is limited and further impacts the performance of the system. Secondly, mobile devices are battery-powered and the batteries of some devices are hard to change. Therefore, in this paper, a UAV-enabled MEC system in which the UAV is empowered to have computing capability and provides tasks offloading service is studied. The total energy consumption of the UAV-enabled system, which includes the energy consumption of the UAV and the energy consumption of the ground users, is minimized under the constraints of the UAV's energy budget, the number of each task's bits, the causality of the data and the velocity of the UAV. The bits allocation of uploading data, computing data, downloading data and the trajectory of the UAV are jointly optimized with the goal of minimizing the total energy consumption. Moreover, a two-stage alternating algorithm is proposed to solve the non-convex formulated problem. Finally, the simulation results show the superiority of the proposed scheme compared with other benchmark schemes. Finally, the performance of the proposed scheme is demonstrated under different settings.

Dynamic Speed Control of Unmanned Aerial Vehicles for Data Collection under Internet of Things.

With the new advancements in flight control and integrated circuit (IC) technology, unmanned aerial vehicles (UAVs) have been widely used in various applications. One of the typical application scenarios is data collection for large-scale and remote sensor devices in the Internet of things (IoT). However, due to the characteristics of massive connections, access collisions in the MAC layer lead to high power consumption for both sensor devices and UAVs, and low efficiency for the data collection. In this paper, a dynamic speed control algorithm for UAVs (DSC-UAV) is proposed to maximize the data collection efficiency, while alleviating the access congestion for the UAV-based base stations. With a cellular network considered for support of the communication between sensor devices and drones, the connection establishment process was analyzed and modeled in detail. In addition, the data collection efficiency is also defined and derived. Based on the analytical models, optimal speed under different sensor device densities is obtained and verified. UAVs can dynamically adjust the speed according to the sensor device density under their coverages to keep high data collection efficiency. Finally, simulation results are also conducted to verify the accuracy of the proposed analytical models and show that the DSC-UAV outperforms others with the highest data collection efficiency, while maintaining a high successful access probability, low average access delay, low block probability, and low collision probability.

N-Glycan Branching Affects the Subcellular Distribution of and Inhibition of Matriptase by HAI-2/Placental Bikunin.

The gene product of SPINT 2, that encodes a transmembrane, Kunitz-type serine protease inhibitor independently designated as HAI-2 or placenta bikunin (PB), is involved in regulation of sodium absorption in human gastrointestinal track. Here, we show that SPINT 2 is expressed as two species of different size (30-40- versus 25-kDa) due to different N-glycans on Asn-57. The N-glycan on 25-kDa HAI-2 appears to be of the oligomannose type and that on 30-40-kDa HAI-2 to be of complex type with extensive terminal N-acetylglucosamine branching. The two different types of N-glycan differentially mask two epitopes on HAI-2 polypeptide, recognized by two different HAI-2 mAbs. The 30-40-kDa form may be mature HAI-2, and is primarily localized in vesicles/granules. The 25-kDa form is likely immature HAI-2, that remains in the endoplasmic reticulum (ER) in the perinuclear regions of mammary epithelial cells. The two different N-glycans could, therefore, represent different maturation stages of N-glycosylation with the 25-kDa likely a precursor of the 30-40-kDa HAI-2, with the ratio of their levels roughly similar among a variety of cells. In breast cancer cells, a significant amount of the 30-40-kDa HAI-2 can translocate to and inhibit matriptase on the cell surface, followed by shedding of the matriptase-HAI-2 complex. The 25-kDa HAI-2 appears to have also exited the ER/Golgi, being localized at the cytoplasmic face of the plasma membrane of breast cancer cells. While the 25-kDa HAI-2 was also detected at the extracellular face of plasma membrane at very low levels it appears to have no role in matriptase inhibition probably due to its paucity on the cell surface. Our study reveals that N-glycan branching regulates HAI-2 through different subcellular distribution and subsequently access to different target proteases.