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Background Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits. Methods PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration. Results In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1. Conclusion PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

The effect of the grain orientation on corrosion behavior of rolled AZ31 magnesium alloy is investigated in this study. The test samples have a similar surface roughness to the Mg alloy in practical application. The immersion test and electrochemical impedance spectroscopy show that the TD-ND planes dominated by （101-0）, （1120） and （1011） oriented grains show a higher corrosion resistance compared with these of the RD-TD planes which consist mainly of （0001） oriented grains. Here, RD, ND and TD represent the rolling direction, the normal direction and the transverse direction of the alloy sheet, respectively. The surface morphologies of the alloys at various immersion stages are observed by scanning electron microscopy, and the surface topography of the alloy substitutes is also observed by laser scanning confocal microscopy. The TD-ND planes show a regular corrosion along the TD direction, but the RD-TD plane shows an irregular corrosion.

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel–Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

Based on the 3 factors and 3 levels orthogonal experiment method, compositional effects of Mg, Si, and Ti addition on the microstructures, tensile properties, and fracture behaviors of the high-pressure die-casting Al- x Mg- y Si- z Ti alloys have been investigated. The analysis of variance shows that both Mg and Si apparently influence the tensile properties of the alloys, while Ti does not. The tensile mechanical properties are comprehensively influenced by the amount of eutectic phase (α-Al + Mg 2 Si), the average grain size, and the content of Mg dissolved into α-Al matrix. The optimized alloy is Al-7.49 Mg-3.08Si-0.01Ti (wt%), which exhibits tensile yield strength of 219 MPa, ultimate tensile strength of 401 MPa, and elongation of 10.5%. Furthermore, contour maps, showing the relationship among compositions, microstructure characteristics, and the tensile properties are constructed, which provide guidelines for developing high strength and toughness Al–Mg–Si–Ti alloys for high-pressure die-casting.

Iron is an essential nutrient for bacterial survival and thus higher iron levels may precipitate bacterial infections. We investigated the association between the serum iron level and prognosis in patients with sepsis by using the single-centre Medical Information Mart for Intensive Care III (MIMIC-III) database. Sepsis patients with iron parameters measured on ICU admission were included and stratified according to quartiles of serum iron levels. A total of 1,891 patients diagnosed with sepsis according to the Sepsis-3 criteria were included in this study, 324 of whom were septic shock. After adjusting for confounding variables, higher iron quartile was associated with an increase in 90-day mortality in the Cox regression analysis. Moreover, a stepwise increase in the risk of 90-day mortality was observed as the quartiles of serum iron levels increased in the patients with sepsis. In conclusion, higher serum iron levels were independently associated with increased 90-day mortality in this large cohort of patients with sepsis.

Administration of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) has been demonstrated to alleviate infarction following ischemic stroke. Reportedly, the main effect of AUDA is exerting anti-inflammation and neovascularization via the inhibition of soluble epoxide hydrolase. However, the major contribution of this anti-inflammation and neovascularization effect in the acute phase of stroke is not completely elucidated. To investigate the neuroprotective effects of AUDA in acute ischemic stroke, we combined laser speckle contrast imaging and optical intrinsic signal imaging techniques with the implantation of a lab-designed cranial window. Forepaw stimulation was applied to assess the functional changes via measuring cerebral metabolic rate of oxygen (CMRO 2 ) that accompany neural activity. The rats that received AUDA in the acute phase of photothrombotic ischemia stroke showed a 30.5 ± 8.1% reduction in the ischemic core, 42.3 ± 15.1% reduction in the ischemic penumbra ( p < 0.05), and 42.1 ± 4.6% increase of CMRO 2 in response to forepaw stimulation at post-stroke day 1 ( p < 0.05) compared with the control group ( N = 10 for each group). Moreover, at post-stroke day 3, increased functional vascular density was observed in AUDA-treated rats (35.9 ± 1.9% higher than that in the control group, p < 0.05). At post-stroke day 7, a 105.4% ± 16.4% increase of astrocytes ( p < 0.01), 30.0 ± 10.9% increase of neurons ( p < 0.01), and 65.5 ± 15.0% decrease of microglia ( p < 0.01) were observed in the penumbra region in AUDA-treated rats ( N = 5 for each group). These results suggested that AUDA affects the anti-inflammation at the beginning of ischemic injury and restores neuronal metabolic rate of O 2 and tissue viability. The neovascularization triggered by AUDA restored CBF and may contribute to ischemic infarction reduction at post-stroke day 3. Moreover, for long-term neuroprotection, astrocytes in the penumbra region may play an important role in protecting neurons from apoptotic injury.

Dear Editor Human pluripotent stem cells including human embryonic stem cells （ESCs） and induced pluripotent stem cells （iPSCs） are cells displaying abilities of unlimited self-renewal and differentiation into any somatic cell type. These unique properties make them increasingly attractive for novel applications in disease modeling, drug discovery, and cell therapy （Buganim et al., 2014; Liu et al., 2011; Liu et al., 2012; Sanchez Alvarado and Yamanaka, 2014）. Moreover, iPSCs hold great potential for personalized cell therapy as they avoid some of the ethical concerns as well as the immunological rejection issues ascribed to ESCs.

Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning.

With continuous development of pesticide dosage forms, emulsifiable concentrates using large amounts of organic solvents are gradually obsoleted. Nanoemulsions with high water content have been developed and the preparation processes also evolved, but these processes still exist some problems, such as poor controllability and high energy consumption. Microfluidic is a controllable nanoemulsion preparation system which mainly applied to pharmaceutical synthesis. In this study, the pesticide phoxim nanoemulsion was prepared by microfluidic technology. The optimized formulation of phoxim nanoemulsion was composed of Tween 80 and pesticide emulsifier 500 as surfactant, hexyl acetate as oil, and n -propanol as co-surfactant. Moreover, when the flow rates of water and oil in the microfluidic system were adjusted to 5 μL/min and 20 μL/min, phoxim nanoemulsion was obtained with a cloud point/boiling point of 109 °C, a particle size of 21.5 ± 0.8 nm and a potential value of − 18.7 ± 0.6 mV. Furthermore, the nanoemulsion had a rapid release effect in vitro which could be fitted by the Ritger-Peppas model. The feeding toxicity of the phoxim nanoemulsion was higher than that of commercial formulation while the contact killing effect was higher than that of the active ingredient. Therefore, pesticide dosage was reduced and the insecticidal effect was enhanced by using phoxim nanoemulsions. These results also confirm the potential of microfluidics as a green process to produce pesticide nanoemulsions. Graphical abstract

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.