LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery

Circuit application of chaotic systems: modeling, dynamical analysis and control

This special issue selects some interesting contributions of recent scientific achievements in circuit application of chaotic systems, focusing on showing the new methods and technologies of the modeling, dynamical analysis and control of chaotic systems. This presented letter summarizes the work of the special issue and discusses some thoughts on the future directions of chaotic circuits and systems

Association between axial length and HDL in children: a hospital-based cross-sectional study

Abstract Background To analyze the relationship between axial length and levels of high-density lipoprotein (HDL) cholesterol in children. Methods A retrospective, hospital-based cross-sectional research with 69 right eyes from 69 children who underwent health examination by Zhejiang Provincial People’s Hospital was carried out. The participants were split into three groups: Group A (axial length  24 mm). Demographic epidemiological information, blood biochemical parameters and ophthalmic characteristics including refractive status and ocular geometric parameters were obtained and analyzed. Results 69 right eyes from 69 patients (25 males and 44 females) with a median age of 10.00 years old (IQR: 8.00–11.00 years) were included in the study. Within Group A, there were a total of 17 individuals; Group B consisted of 22 individuals; Group C included 30 individuals. The mean axial length of three groups was 22.148(0.360), 23.503(0.342) and 24.770(0.556) mm, respectively (p < 0.0001). The mean HDL levels were significantly different in three groups are 1.824(0.307), 1.485(0.253) and 1.507 (0.265) mmol/L, respectively. By applying a Pearson Coefficient, we evaluated the association between axial length and HDL and discovered that there was a statistically significant (p = 0.00025) and adverse (R = -0.43) association between axial length and HDL. Conclusions We concluded from our study that there was a significantly inverse relationship between axial length and the levels of HDL in children

Unveiling the synergistic effect of precursor stoichiometry and interfacial reactions for perovskite light-emitting diodes

Metal halide perovskites are emerging as promising semiconductors for cost-effective and high-performance light-emitting diodes (LEDs). Previous investigations have focused on the optimisation of the emissive perovskite layer, for example, through quantum confinement to enhance the radiative recombination or through defect passivation to decrease non-radiative recombination. However, an in-depth understanding of how the buried charge transport layers affect the perovskite crystallisation, though of critical importance, is currently missing for perovskite LEDs. Here, we reveal synergistic effect of precursor stoichiometry and interfacial reactions for perovskite LEDs, and establish useful guidelines for rational device optimization. We reveal that efficient deprotonation of the undesirable organic cations by a metal oxide interlayer with a high isoelectric point is critical to promote the transition of intermediate phases to highly emissive perovskite films. Combining our findings with effective defect passivation of the active layer, we achieve high-efficiency perovskite LEDs with a maximum external quantum efficiency of 19.6%.Funding Agencies|ERC Starting Grant [717026]; European Commission Marie Sklodowska-Curie Actions [691210]; National Key Research and Development Program of China [2016YFA0202402]; Jiangsu High Educational Natural Science Foundation [18KJA430012]; Priority Academic Program Development of Jiangsu Higher Education Institutions; 111 program; Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC); China Scholarship Council; National Natural Science Foundation of China [61704077]; Natural Science Foundation of Jiangsu Province [BK20171007]</p

Neutrophil-mediated delivery of pixantrone-loaded liposomes decorated with poly(sialic acid)–octadecylamine conjugate for lung cancer treatment

Poly(sialic acid) (PSA) is a natural hydrophilic biodegradable and non-immunogenic biopolymer, receptors for its monomer are expressed on peripheral blood neutrophils (PBNs), which plays important roles in the progression and invasion of tumors. A poly(sialic acid)–octadecylamine conjugate (PSA–ODA) was synthesized and then anchor it on the surface of liposomal pixantrone (Pix-PSL), to achieve an improved anticancer effect. The liposomes were prepared using a remote loading method via a pH gradient, and then assessed for particle size, zeta potential encapsulation efficiency, in vitro release, and in vitro cytotoxicity. Simultaneously, in vitro and in vivo cellular uptake studies confirmed that PSA-decorated liposomes provided an enhanced accumulation of liposomes in PBNs. An in vivo study presented that the anti-tumor activity of Pix-PSL was superior to that of other Pix formulations, probably due to the efficient targeting of PBNs by Pix-PSL, after which PBN containing Pix-PSL (Pix-PSL/PBNs) in the blood circulation are recruited by the tumor microenvironment. These findings suggest that PSA-decorated liposomal Pix may provide a neutrophil-mediated drug delivery system (DDS) for the eradication of tumors, which represents a promising approach for the tumor targeting of chemotherapeutic treatments

Resveratrol Improves the Digestive Ability and the Intestinal Health of Siberian Sturgeon

The lack of detailed information on nutritional requirement results in limited feeding in Siberian sturgeon. In this study, resveratrol, a versatile natural extract, was supplemented in the daily diet, and the digestive ability and microbiome were evaluated in the duodena and valvular intestines of Siberian sturgeon. The results showed that resveratrol increased the activity of pepsin, α-amylase, and lipase, which was positively associated with an increase in the digestive ability, but it did not influence the final body weight. Resveratrol improved the digestive ability probably by distinctly enhancing intestinal villus height. Microbiome analysis revealed that resveratrol changed the abundance and composition of the microbial community in the intestine, principally in the duodenum. Random forests analysis found that resveratrol significantly downregulated the abundance of potential pathogens (Citrobacter freundii, Vibrio rumoiensis, and Brucella melitensis), suggesting that resveratrol may also improve intestinal health. In summary, our study revealed that resveratrol improved digestive ability and intestinal health, which can contribute to the development of functional feed in Siberian sturgeon

Neutrophil-mediated delivery of pixantrone-loaded liposomes decorated with poly(sialic acid)–octadecylamine conjugate for lung cancer treatment

<p>Poly(sialic acid) (PSA) is a natural hydrophilic biodegradable and non-immunogenic biopolymer, receptors for its monomer are expressed on peripheral blood neutrophils (PBNs), which plays important roles in the progression and invasion of tumors. A poly(sialic acid)–octadecylamine conjugate (PSA–ODA) was synthesized and then anchor it on the surface of liposomal pixantrone (Pix-PSL), to achieve an improved anticancer effect. The liposomes were prepared using a remote loading method via a pH gradient, and then assessed for particle size, zeta potential encapsulation efficiency, <i>in vitro</i> release, and <i>in vitro</i> cytotoxicity. Simultaneously, <i>in vitro</i> and <i>in vivo</i> cellular uptake studies confirmed that PSA-decorated liposomes provided an enhanced accumulation of liposomes in PBNs. An <i>in vivo</i> study presented that the anti-tumor activity of Pix-PSL was superior to that of other Pix formulations, probably due to the efficient targeting of PBNs by Pix-PSL, after which PBN containing Pix-PSL (Pix-PSL/PBNs) in the blood circulation are recruited by the tumor microenvironment. These findings suggest that PSA-decorated liposomal Pix may provide a neutrophil-mediated drug delivery system (DDS) for the eradication of tumors, which represents a promising approach for the tumor targeting of chemotherapeutic treatments.</p