siRNA Delivery against Myocardial Ischemia Reperfusion Injury Mediated by Reversibly Camouflaged Biomimetic Nanocomplexes.

siRNA-mediated management of myocardial ischemia reperfusion (IR) injury is greatly hampered by the inefficient myocardial enrichment and cardiomyocyte transfection. Herein, nanocomplexes (NCs) reversibly camouflaged with a platelet-macrophage hybrid membrane (HM) are developed to efficiently deliver Sav1 siRNA (siSav1) into cardiomyocytes, suppressing the Hippo pathway and inducing cardiomyocyte regeneration. The biomimetic BSPC@HM NCs consist of a cationic nanocore assembled from a membrane-penetrating helical polypeptide (P-Ben) and siSav1, a charge-reversal intermediate layer of poly(l-lysine)-cis-aconitic acid (PC), and an outer shell of HM. Due to HM-mediated inflammation homing and microthrombus targeting, intravenously injected BSPC@HM NCs can efficiently accumulate in the IR-injured myocardium, where the acidic inflammatory microenvironment triggers charge reversal of PC to shed off both HM and PC layers and allow the penetration of the exposed P-Ben/siSav1 NCs into cardiomyocytes. In rats and pigs, BSPC@HM NCs remarkably downregulates Sav1 in IR-injured myocardium, promotes myocardium regeneration, suppresses myocardial apoptosis, and recovers cardiac functions. This study reports a bioinspired strategy to overcome the multiple systemic barriers against myocardial siRNA delivery, and holds profound potential for gene therapy against cardiac injuries.

[Application of near infrared spectroscopy in screening Cordyceps militaris mutation strains and optimizing their fermentation process].

To fast screen high-yield Cordyceps militaris mutations strains and optimize their fermentation process, near infrared (NIR) spectroscopy technology combined with chemometrics has been applied to establishing models for simultaneous determination of adenosine, protein, polysaccharide and Cordyceps militaris acid contents in Cordyceps militaris powder samples. Fermentations were implemented in Erlenmeyer flask with 468 Cordyceps militaris mutations strains under various fermentation conditions and Cordyceps militaris powder samples were collected. Then their NIR spectra were obtained using UV-VIS-NIR spectrometer and their adenosine, protein, polysaccharide and Cordyceps militaris acid contents were determined using reference methods. Partial least squares (PLS) method was employed to model the relationships between NIR spectra and the above mentioned components' contents in Cordyceps militaris powder samples. Monte Carlo partial least square (MCPLS) was applied to identify the outliers and select suitable number of calibration samples. Moving window partial least square (MWPLS) was applied to select the characteristic wavelength of the components. The degree of the approaching (Da) was employed as criterion for selecting effective pretreatment methods investigated. The optimum models for determination of adenosine, protein, polysaccharide and Cordyceps militaris acid contents in Cordyceps militaris powder samples were obtained with the above mentioned optimization. Their correlation between actual and predictive values of calibration samples (Re) was 0.92943, 0.98479, 0.90785, and 0.85131, respectively. Their root mean square error of prediction set (RMSEP) was 0.66714, 0.02065, 0.01131, and 0.01159, respectively. The obtained results demonstrated that the fitting and the predictive accuracy were satisfactory. It is feasible to apply this method to screen the high yield Cordyceps militaris mutation strains and optimize their fermentation process.