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Macrophage‐mediated inflammatory responses including pyroptosis are involved in the pathogenesis of sepsis and acute lung injury (ALI), for which there are currently no effective therapeutic treatments. The natural product (+)‐Balasubramide is an eight‐membered lactam compound extracted from the leaves of the Sri Lanka plant Clausena Indica and has shown anti‐inflammatory activities, but its poor pharmacokinetic properties limit its further application for ALI. In this study, a compound (+)3C‐20 is discovered with improved both pharmacokinetic properties and anti‐inflammatory activity from a series of (+)‐Balasubramide derivatives. The compound (+)3C‐20 exhibits a markedly enhanced inhibitory effect against LPS‐induced expressions of pro‐inflammatory factors in mouse macrophages and human PBMCs from ALI patients and shows a preferable lung tissue distribution in mice. (+)3C‐20 remarkably attenuates LPS‐induced ALI through lung tissue‐specific anti‐inflammatory actions. Mechanistically, a chemical proteomics study shows that (+)3C‐20 directly binds to mitochondrial VDAC1 and inhibits VDAC1 oligomerization to block mtDNA release, further preventing NLRP3 inflammasome activation. These findings identify (+)3C‐20 as a novel VDAC1 inhibitor with promising therapeutic potential for ALI associated with inflammation. [ABSTRACT FROM AUTHOR]

A multilevel secure access control strategy for distributed system was proposed,which could guarantee the data confidentiality and security,through adding platform and middleware modules.The security policy was described in the XACML language,and the security and flexibility of the policy were analyzed.

Sarcolemmal ATP-sensitive potassium (KATP) channels play a vital role in cardioprotection. Cardiac KATP channels are enriched in caveolae and physically interact with the caveolae structural protein caveolin-3 (Cav3). Disrupting caveolae impairs the regulation of KATP channels through several signaling pathways. However, the direct functional effect of Cav3 on KATP channels is still poorly understood. Here, we used the cardiac KATP channel subtype, Kir6.2/SUR2A, and showed that Cav3 greatly reduced KATP channel surface density and current amplitude in a caveolae-independent manner. A screen of Cav3 functional domains revealed that a 25 amino acid region in the membrane attachment domain of Cav3 is the minimal effective segment (MAD1). The peptide corresponding to the MAD1 segment decreased KATP channel current in a concentration-dependent manner with an IC50 of ∼5 μM. The MAD1 segment prevented KATP channel recycling, thus decreasing KATP channel surface density and abolishing the cardioprotective effect of ischemic preconditioning. Our research identified the Cav3 MAD1 segment as a novel negative regulator of KATP channel recycling, providing pharmacological potential in the treatment of diseases with KATP channel trafficking defects. NEW & NOTEWORTHY Cardiac KATP channels physically interact with caveolin-3 in caveolae. In this study, we investigated the functional effect of caveolin-3 on KATP channel activity and identified a novel segment (MAD1) in the C-terminus domain of Caveolin-3 that negatively regulates KATP channel surface density and current amplitude by impairing KATP channel recycling. The peptide corresponding to the MAD1 segment abolished the cardioprotective effect of ischemic preconditioning. [ABSTRACT FROM AUTHOR]

[Objectives] To determine the optimal morphological characteristics for identifying nymphal instars of the yellow-spined bamboo locust, Ceracris kiangsu (Orthoptera: Arcypteridae), examine the applicability of Dyar and Crosby rules to this species, and provide a theoretical basis for determining the nymphal instars of Orthopterans based on the variability of morphological characteristics of different developmental stages. [Methods] Nymphs were reared in an insectary after hatching. Eight morphological variables, including body length, body weight, head length, head width, wing bud length, wing bud width, wing bud area and antennal length, were measured and analyzed statistically for each instar. [Results] Five instars were distinguished without gender differences. Five distribution peaks were apparent based on head length and head width, and three concentrated distribution areas for wing bud width and wing bud area were apparent after frequency analysis. The Brooks's ratio ranged from 1.09 to 3.86, and decreased with increasing instar. The Crosby's ratio was over 0.1. The growth dynamics of morphological variables were not consistent with Dyar and Crosby rules. The relationship between nymph instars and the eight measured morphological variables closely approximated a polynomial regression. The linear coefficient of determination of head width had the maximum value R² = 0.933 5, and the quadratic and cubic coefficients of determination of wing bud length had the maximum value R² = 0.978 9. [Conclusion] Head width is the optimal variable for distinguishing the nymphal instars of C. kiangsu, followed by head length and body length. All three variables can be used in pest monitoring and control. [ABSTRACT FROM AUTHOR]