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A novel STING agonist, CDGSF, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDGSF might be a site for covalent conjugation. Injection of CDGSF generated an immunogenic ("hot") tumor microenvironment to suppress melanoma, more efficiently than dithio CDG. In particular, immunization with SARS-CoV-2 spike protein using CDGSF as an adjuvant elicited an exceptionally high antibody titer and a robust T cell response, overcoming the drawbacks of aluminum hydroxide. These results highlighted the therapeutic potential of CDGSF for cancer immunotherapy and the adjuvant potential of the STING agonist in the SARS-CoV-2 vaccine for the first time.

We developed a host-guest ATP responsive strategy for efficient intracellular delivery of phosphopeptides, employing a pegylated arginine clustered calix[5]arene nanocarrier system that has great capability of recognizing the phosphate moieties on peptides and penetrating the cell membrane.

Biomimetic mineralization based on self-assembly has made great progress, providing bottom-up strategies for the construction of new organic-inorganic hybrid materials applied in the treatment of hard tissue defects. Herein, inspired by the cooperative effects of key components in biomineralization microenvironments, a new type of biocompatible peptide scaffold based on flexibly self-assembling low-complexity protein segments (LCPSs) containing phosphate or phosphonate groups is developed. These LCPSs can retard the transformation of amorphous calcium phosphate into hydroxyapatite (HAP), leading to merged mineralization structures. Moreover, the application of phosphonated LCPS over phosphorylated LCPS can prevent hydrolysis by phosphatases that are enriched in extracellular mineralization microenvironments. After being coated on the etched tooth enamel, these LCPSs facilitate the growth of HAP to generate new enamel layers comparable to the natural layers and mitigate the adhesion of Streptococcus mutans. In addition, they can effectively stimulate the differentiation pathways of osteoblasts. These results shed light on the potential biomedical applications of two LCPSs in hard tissue repair.

The solvothermal reaction of H3BO3, Li2B4O7, Na2B4O7·10H2O, 1,2-diaminopropane and pyridine led to a new open framework borate, Li2Na2[B12O19(OH)2] (1). Compound 1 crystallizes in the monoclinic space group C2/c. Its structure contains a large cyclic [B12O22(OH)2]10− cluster, which is connected to six neighboring ones via corner-sharing O atoms to give a 6-connected pcu network via B–O–B bonds. Notably, large shuttle-like pores are observed along the [001] direction as well as 8-ring channels along the [101] direction, leading to an intersecting channel system. UV/vis diffuse reflectance analysis indicates that the compound has a wide transparency range with a short-wavelength absorption edge below 200 nm.

Recent evidence suggests a link between cathepsin L (CTSL) and vascular diseases. However, its contribution to reactive oxygen species (ROS) homeostasis in the vasculature remains unknown. p66shc is a redox enzyme implicated in mitochondrial ROS generation and translation of oxidative signals. In this study, we explored the relationship between CTSL and oxidative damage in vasculature and whether the oxidative damage is mediated by p66shc.Carotid arteries from aged mice (24 months old) showed a reduction in CTSL expression compared with young wild-type mice (4 months old). Local knockdown of CTSL in carotid arteries of young mice by adenoviral vector encoding the short hairpin RNA targeting CTSL leading to premature vascular aging, as shown by mitochondrial disruption, increased β-galactosidase-positive cells, reduced telomerase activity, and up-regulation of p66shc. Knockdown of CTSL decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, III, and IV, leading to increased mitochondrial ROS and hyperpolarization of the mitochondrial membrane in vitro. Furthermore, knockdown of CTSL also stimulated ROS production and senescence in vascular cells, accompanied by the up-regulation of p66shc.However, p66shc knockdown blunted the alteration in ROS production, and senescence in CTSL knockdown vascular cells. This study suggests that CTSL knockdown partially induces vascular cells damage via increased ROS production and up-regulation of p66shc.

Intracellular protein delivery is of significance for cellular protein analysis and therapeutic development, but remains challenging technically. Herein, we report a general and highly potent strategy for intracellular protein delivery based on commercially available cationic lipids. In this strategy, a designed double branching poly-glutamate tag is site-specifically attached onto the C-terminal of protein cargos via expressed protein ligation (EPL), which mediates the entrapment of proteins into cationic liposomes driven by electrostatic interaction. The resultant protein-lipid complexes can enter into cytosol with a high efficiency even at the low protein concentration while maintaining protein's biological activity.

Kinetic energy rod (KE-rod) warheads are one of the most efficient types against tactical ballistic missile (TBM) that exist today, so the kill probability of KE-rod is extremely important. The paper firstly describes the necessity of KE-rod warhead, and then analyzes the separation velocity of KE-rod, the effective kill radius, static dispersal, dynamic kill zone, and the computational model of mathematical expectation for the hit rod number, and then presents the calculation method of kill probability for KE-rod. Finally, the kill probability of the KE-rod is simulated, the results show that the probability decreases rapidly with the increase of distance between the KE-rod warhead and the target, when the distance between the interceptor and target is less than 5 meters, the kill probability is up to 50%.

It is a new trend to control landslide by using anti-sliding composite structure of micro-piles combined with other engineering measures. At present, it is extensively applied to engineering practice for convenient construction, low cost, grouting pressure enhances the stability of landslide strikingly etc. Based on the analysis of the mechanism anti-sliding of micro-pile, characteristics of micro-piles under horizontal supporting force are studied by modest test. Finally, checking the sheer stability of micro-pile and combining with engineering example proves the feasibility and reliability of micro-pile on landslide control.

Isoquercitrin is a rare, natural ingredient with several biological activities that is a key precursor for the synthesis of enzymatically modified isoquercitrin (EMIQ). The enzymatic production of isoquercitrin from rutin catalyzed by hesperidinase is feasible; however, the bioprocess is hindered by low substrate concentration and a long reaction time. Thus, a novel biphase system consisting of [Bmim][BF4]:glycine-sodium hydroxide (pH 9) (10:90, v/v) and glyceryl triacetate (1:1, v/v) was initially established for isoquercitrin production. The biotransformation product was identified using liquid chromatography-mass spectrometry and the bonding mechanism of the enzyme and substrate was inferred using circular dichroism spectra and kinetic parameters. The highest rutin conversion of 99.5% and isoquercitrin yield of 93.9% were obtained after 3 h. The reaction route is environmentally benign and mild and the biphase system could be reused. The substrate concentration was increased 2.6-fold, the reaction time was reduced to three tenths the original time. The three-dimensional structure of hesperidinase was changed in the biphase system, which α-helix and random content were reduced and β-sheet content was increased. Thus, the developed biphase system can effectively strengthen the hesperidinase-catalyzed synthesis of isoquercitrin with high yield.

Lipoid proteinosis is caused by loss-of-function mutations in the glycoprotein extracellular matrix protein 1 (ECM1). We report here mutation analysis of the ECM1 gene in a Chinese family with lipoid proteinosis. A 10-year-old boy presented with a hoarse voice, acneiform scars and yellow skin nodules, as well as beaded eyelid papules and a thickened sublingual frenulum. Skin biopsy showed widespread deposition of hyaline material in the dermis and thickened basement membrane. His elder sister had the same clinical manifestations. The coding region of ECM1 was amplified and sequenced and both affected siblings were shown to have a novel homozygous single nucleotide substitution, c.658T>G, in exon 6, which converts cysteine to glycine, designated p.C220G. Both parents were heterozygous for this mutation which was not detected in 100 control chromosomes. Missense mutations in the ECM1 gene are an unusual finding in lipoid proteinosis, but this case adds to the spectrum of disease-associated mutations in this rare genodermatosis.

Pemphigus is an autoimmune blistering disease of skin and mucous membranes. Pemphigus vulgaris (PV) is a major subtype of pemphigus, which is histologically characterized by suprabasal acantholysis. The major antigen in PV is desmosomal glycoproteins desmoglein (Dsg) 3. The autoantibodies against Dsg3 cause loss of adhesion between keratinocytes. Some PV patients also have circulating anti-Dsg1 autoantibodies. Enzyme-linked immunosorbent assays (ELISAs) with recombinant Dsg3 and Dsg1 are highly sensitive and specific for detecting anti-Dsg3 and anti-Dsg1 autoantibodies in PV patients. To evaluate the role of desmosomal glycoproteins desmoglein (Dsg3) ELISA and Dsg1 ELISA for detecting anti-Dsg3 and anti-Dsg1 autoantibodies in monitoring disease activity in Pemphigus vulgaris patients.Twenty PV patients with long-term follow-up were included. We tested their serial sera with modified Dsg3 ELISA (MESACUP Desmoglein TEST "Dsg3", MedicalBiological Laboratories Co. LTD.), Dsg1 ELISA(MESACUP Desmoglein TEST "Dsg1", MedicalBiological Laboratories Co. LTD.) and indirect immunofluorescence (IIF). Then we analyzed the correlation between Dsg3 ELISA index values, Dsg1 ELISA index values, IIF titres and disease activity scores (ABSIS) along the time course.There were significant correlations between Dsg3 ELISA index values, Dsg1 ELISA index values, IIF titres and disease activity scores (both skin scores and oral scores) (P0.01) along the time course. Significant differences of Dsg3 ELISA index values, Dsg1 ELISA index values and IIF titres between active time-point group and clinical remission time-point group were also observed (P0.01). We found that Dsg3 ELISA index values, Dsg1 ELISA index values and IIF titres fluctuated in parallel with disease activity, and ELISA index values were superior to IIF titres.Dsg3 ELISA index values fluctuating in parallel with disease activity are useful to monitor disease activity, predict flares or relapses and plan the schedules for tapering the drugs.

Referring to the random and nonlinear interference and the slow change of parameters of launcher servo-system, a new algorithm was put forward to identify launcher servo-system model by combining the characteristics of the genetic algorithm and improved BP algorithm. The principle was expounded, and the algorithm flow and formulas were presented. It overcomes the shortcoming of BP NN, such as the slow learning rate, and easy to converge to the local minima. The result of simulation shows that the algorithm has greatly improved the convergent accuracy and speed of NN, and gets a good identification result.

In order to improve tracking accuracy of the servo system, an adaptive inverse controller with PID feedforward is designed. It is based on the time-delay characteristic of the adaptive inverse control when training. The controller can realize accurately tracking of the servo, so as to meet the working need of the system. Finally, the tracking simulation is carried out on the digital servo experimental platform, results show that the controller can satisfy the tracking requirement of the system.

Coronary flow velocity pattern (CFVP) recorded within 3 days of percutaneous coronary intervention (PCI) has been reported to be useful in predicting left ventricular (LV) function. The aim of this prospective study was to investigate, via transthoracic Doppler echocardiography, whether the relationship between CFVP and recovery of LV function persists. Our study group comprised 37 patients with 1st anterior-wall acute myocardial infarction who underwent successful PCI for lesions in the left anterior descending coronary artery (LAD). The CFVP in the LAD was recorded at 24-48 hours, 7 days, and 4 weeks after PCI. Myocardial contrast echocardiography was performed at 24-48 hours after PCI. The diastolic deceleration time (DDT) at each stage correlated significantly with the regional LV wall-motion score index at 6-month follow-up (r=-0.58 at 24-48 hr, -0.57 at day 7, and -0.50 at week 4; P0.01 for all). The mean DDT increased over time. Optimal cutoff values for DDT to predict regional LV wall-motion score indices of2.0 were 327 ms at 24-48 hours (sensitivity, 0.78; specificity, 0.64), 495 ms at day 7 (sensitivity, 0.75; specificity, 0.69), and 525 ms at week 4 (sensitivity, 0.83; specificity, 0.69). The DDT at 24-48 hours significantly correlated, better than the peak creatine kinase value, with reperfusion (r=0.68, P0.01) as defined by myocardial contrast echocardiography. In conclusion, CFVP in the LAD can be used, within 4 weeks after PCI, to predict the recovery of regional LV function in patients with reperfused anterior-wall acute myocardial infarction.