Saposin B Is a Human Coenzyme Q10-Binding/Transfer Protein

Coenzyme Q10 (CoQ10) is essential for ATP production in the mitochondria, and is an important antioxidant in every biomembrane and lipoprotein. Due to its hydrophobicity, a binding and transfer protein for CoQ10 is plausible, but none have yet been isolated and characterized. Here we purified a CoQ10-binding protein from human urine and identified it to be saposin B, a housekeeping protein necessary for sphingolipid hydrolysis in lysosomes. We confirmed that cellular saposin B binds CoQ10 in human sperm and the hepatoma cell line HepG2 by using saposin B monoclonal antibody. The molar ratios of CoQ10 to saposin B were estimated to be 0.22 in urine, 0.003 in HepG2, and 0.12 in sperm. We then confirmed that aqueous saposin B extracts CoQ10 from hexane to form a saposin B-CoQ10 complex. Lipid binding affinity to saposin B decreased in the following order: CoQ10>CoQ9>CoQ7>>α-tocopherol>>cholesterol (no binding). The CoQ10-binding affinity to saposin B increased with pH, with maximal binding seen at pH 7.4. On the other hand, the CoQ10-donating activity of the saposin B-CoQ10 complex to erythrocyte ghost membranes increased with decreasing pH. These results suggest that saposin B binds and transports CoQ10 in human cells

High-efficiency 100-W Kerr-lens mode-locked Yb:YAG thin-disk oscillator

We demonstrate a Kerr-lens mode-locked femtosecond Yb:YAG thin-disk oscillator and investigate the approach to increase the optical-to-optical efficiency based on the scheme of direct multiple passes of the laser beam through the thin-disk medium. With twelve passes through the thin disk, 266-fs pulses were delivered from the oscillator with an average power of 105.6 W at a repetition rate of 20 MHz. The corresponding optical-to-optical efficiency is 31.1%, which is, to the best of our knowledge, the highest efficiency of any mode-locked thin-disk oscillator with pulse duration below 300 fs. This demonstration paves the way to even more efficient mode-locked femtosecond thin-disk oscillators, and provides an excellent laser source for the applications such as non-linear frequency conversion and high-precision industrial processing

CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses

Multivariate Statistical Online Analysis for Self Protection against Network Attacks

Detection and self-protection against viruses, worms, and network attacks is urgently needed to protect network systems and their applications from catastrophic loss. Once a network component is infected by viruses, worms, or became a target of the network attacks, its operation state will shift from normal to abnormal. Online monitoring mechanism can be used to collect important aspects of network traffic and host data (CPU utilization, memory usage, etc.), that can effectively detect abnormal behaviors caused by attacks. In this paper, we develop an online multivariate analysis algorithm- MANA based on Hotelling’s T 2 multivariate statistical technique [6] to analyze the behaviors of system resources and network protocols in order to proactively detect network attacks. The new algorithm builds an adaptive behavior profile of normal operation for system resources. We have validated this algorithm and showed how it can proactively detect well-known attacks such a

The Efficacy of Jing Wan Hong Ointment for Nerve Injury Diabetic Foot Ulcer and Its Mechanisms

Jing Wan Hong ointment contains 30 kinds of Chinese herbs, with functions of activating blood circulation to disperse blood stasis, clearing heat, eliminating dampness, and reducing swelling by detoxification. Therefore, Jing Wan Hong ointment may facilitate the healing of ulcers. The aim of this study was to evaluate the efficacy and mechanisms of Jing Wan Hong ointment for healing diabetic foot ulceration in Wistar rats induced by streptozotocin and sciatic nerve damage. The results showed that Jing Wan Hong ointment had a marked effect on foot ulcers in diabetic rats induced by initial nerve injury. These effects were manifested by reducing the foot ulcer size and Wagner grade after seven days of treatment. The diabetic rats with foot ulcers were almost healed after 21 days of treatment. Moreover, the mechanisms of this effect seem to be dependent on increased expression of PDGF mRNA, but there was no influence on the expression of TGF-β, VEGF, and FLT-1 mRNA