Improving Functionality of 2DOF Piezoelectric Cantilever for Broadband Vibration Energy Harvesting Using Magnets

This paper presents a 2DOF nonlinear piezoelectric energy harvester for improving the efficiency of energy harvesting in low frequency range.The device consisted of an L-shaped piezoelectric cantilever with a magnet at the tip of the first beam and two external magnets on the pedestal.The distance between the magnets which generated nonlinear magnetic attraction was adjusted such that the system can exhibit monostable or bistable characteristics.First,the model of this piezoelectric energy harvester was established and the dynamic equation was derived based on the magnetic attractive force.Then,the nonlinear dynamic responses of the system subject to harmonic excitation were explored by a numerical method and validated by experiments.At an excitation level of 4 m/s^(2)in reverse sweep test for the proposed nonlinear harvester,nearly 240%increase in frequency bandwidth was obtained compared to 2DOF linear one in the first two resonance regions under both monostable and bistable states.Moreover,the nonlinear device yielded a closer frequency band gap between the first two resonance regions.The findings provide insight for the design of a broadband energy harvester when there is nonlinearity using magnets.

EGFR TKIs impair lysosome-dependent degradation of SQSTM1 to compromise the effectiveness in lung cancer

Tyrosine kinase inhibitors for epidermal growth factor receptor(EGFR TKIs)greatly improved clinical outcomes of patients with non-small cell lung cancer(NSCLC).Unfortunately,primary and acquired resistance limits their clinical benefits.To overcome such resistance,new generations of EGFR TKIs have been developed by targeting newly identified mutations in EGFR.However,much less effort has been put into alternative strategies,such as targeting the intrinsic protective responses to EGFR TKIs.In this study,we found that EGFR TKIs,including gefitinib and AZD9291,impaired lysosome-dependent degradation of SQSTM1,thus compromising their anti-cancer efficiency.By accumulating in the lysosome lumen,gefitinib and AZD9291 attenuated lysosomal acidification and impaired autolysosomal degradation of SQSTM1 owing to their intrinsic alkalinity.As a result,SQSTM1 protein was stabilized in response to gefitinib and AZD9291 treatment and conferred EGFR TKI resistance.Depleting SQSTM1 significantly increased the sensitivity of NSCLC cells to gefitinib and AZD9291 both in vitro and in vivo.Furthermore,a chemically modified gefitinib analog lacking alkalinity displayed stronger inhibitory effects on NSCLC cells.Therefore,targeting accumulated SQSTM1 or chemically modified EGFR TKIs may represent new strategies to increase the effectiveness of EGFR targeted therapy.

Effect of environmental factors on the complexation of iron and humic acid

A method of size exclusion chromatography coupled with ultraviolet spectrophotometry and off-line graphite furnace atomic absorption spectrometry was developed to assess the complexation properties of iron（Fe） and humic acid（HA） in a water environment. The factors affecting the complexation of Fe and HA, such as ionic strength, pH, temperature and UV radiation, were investigated. The Fe–HA complex residence time was also studied. Experimental results showed that pH could influence the deprotonation of HA and hydrolysis of Fe, and thus affected the complexation of Fe and HA. The complexation was greatly disrupted by the presence of NaCl. Temperature had some influence on the complexation. The yield of Fe–HA complexes showed a small decrease at high levels of UV radiation, but the effect of UV radiation on Fe–HA complex formation at natural levels could be neglected. It took about 10 hr for the complexation to reach equilibrium, and the Fe–HA complex residence time was about 20 hr.Complexation of Fe and HA reached a maximum level under the conditions of pH 6, very low ionic strength, in the dark and at a water temperature of about 25°C, for 10 hr. It was suggested that the Fe–HA complex could form mainly in freshwater bodies and reach high levels in the warm season with mild sunlight radiation. With changing environmental parameters, such as at lower temperature in winter or higher pH and ionic strength in an estuary, the concentration of the Fe–HA complex would decrease.

Targeting nuclear acid-mediated immunity in cancer immune checkpoint inhibitor therapies

Cancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment.However,there are many patients who failed to benefit from these therapies,highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors.In this review,we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy.Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function,it seems that harnessing the nuclear acidmediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control.