There is a clinical need for new bronchodilator drugs in asthma, because more than half of asthmatic patients do not receive adequate control with current available treatments. We report that inhibition of metallothionein-2 protein expression in lung tissues causes the increase of pulmonary resistance. Conversely, metallothionein-2 protein is more effective than β-agonists in reducing pulmonary resistance in rodent asthma models, alleviating tension in tracheal spirals, and relaxing airway smooth muscle cells (ASMCs). Metallothionein-2 relaxes ASMCs via transgelin-2 (TG2) and induces dephosphorylation of myosin phosphatase target subunit 1 (MYPT1). We identify TSG12 as a nontoxic, specific TG2-agonist that relaxes ASMCs and reduces asthmatic pulmonary resistance. In vivo, TSG12 reduces pulmonary resistance in both ovalbumin- and house dust mite-induced asthma in mice. TSG12 induces RhoA phosphorylation, thereby inactivating the RhoA-ROCK-MYPT1-MLC pathway and causing ASMCs relaxation. TSG12 is more effective than β-agonists in relaxing human ASMCs and pulmonary resistance with potential clinical advantages. These results suggest that TSG12 could be a promising therapeutic approach for treating asthma.

Ultraviolet (UV)-absorbing chemicals (UV filters) are used in personal care products for the protection of human skin and hair from damage by UV radiation. Although these substances are released into the environment in the production and consumption processes, little is known about their ecotoxicology effects. The acute toxicity and potential ecological risk of UV filters benzophenone-3 (BP-3) and benzophenone-4 (BP-4) on Chlorella vulgaris, Daphnia magna, and Brachydanio rerio were analyzed in the present study. The EC50 values (96 h) of BP-3 and BP-4 on C. vulgaris were 2.98 and 201.00 mg/L, respectively. The 48 h-LC50 of BP-3 and BP-4 on D. magna were 1.09 and 47.47 mg/L, respectively. The 96 h-LC50 of BP-3 and BP-4 on B. rerio were 3.89 and 633.00 mg/L, respectively. The toxicity of a mixture of BP-3 and BP-4 on C. vulgaris, D. magna, and B. rerio all showed antagonistic effects. The induced predicted no-effect concentrations of BP-3 and BP-4 by the assessment factor method were 1.80 × 10−3 and 0.47 mg/L, respectively, by assessment factor (AF) method, which were both lower than the concentrations detected in the environment at present, verifying that BP-3 and BP-4 remain low-risk chemicals to the aquatic ecosystem.

As technology scaling down, power consumption of integrated circuits increases tremendously due to leakage current. Power gating is one of the most effective techniques to reduce leakage power by shutting off idle blocks from power supply. However, during a power-mode transition, an instantaneous charge current passes through the switch transistor, and creates current surge elsewhere. Because of the self-inductance of the off-chip bonding wires and parasitic inductance inherent to the on-chip power rails, these surges result in severe simultaneous switching noise (SSN), which results in function failure.Based on typical power delivery network, it is found that the magnitude of SSN would accumulate positively with Fcurrent = 1/(n + 1) Resonant, and the magnitude of SSN would accumulate negatively with Fcurrent = 1/(n + 1/2) Resonant. In this paper, a new method is proposed to suppress the power supply noise based on its periodic characteristic. By cutting power grid, partition of switch transistors and controlling their switching, smaller segmented charge current magnitude and controllable period can be provided into gated block for mitigating noise. The power supply noise produced by charge current can be suppressed through adjusting the delay of charge current and the magnitude of charge current which is verified by simulation. Compared to conventional power gating structures, this method can save decap area and is practical and flexible to embed in an optimization flow. A principle for controllable switch transistor chain is also given to simplify the high speed power delivery network design.