[Biological role and related mechanism of autophagy in acute lung injury of hemorrhagic shock mice].

OBJECTIVE: To study the biological role and related mechanism of autophagy in acute lung injury (ALI) of hemorrhagic shock mice. METHODS: According to random number table method, wild-type male C57BL/6 mice were divided into control group, ALI group, rapamycin group and 3-methyladenine (3-MA) group, with 8 mice in each group. Light chain 3 (LC3) gene knockout mice with C57BL/6 background were divided into LC3 knockout group and LC3 knockout+ALI group, with 8 mice in each group. Control group, ALI group, LC3 knockout group, LC3 knockout+ALI group were intraperitoneally injected with 2 mL/kg normal saline, rapamycin group was intraperitoneally injected with 3 mg/kg autophagy activator rapamycin, 3-MA group was intraperitoneally injected with 15 mg/kg autophagy inhibitor 3-MA, all of which were given for 3 consecutive days. 2 hours after the last administration, the hemorrhagic shock induced ALI model was established. 24 hours after modeling, the lung index was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissue and lung injury score was performed. The expressions of autophagy genes LC3- II/LC3- I and Beclin-1 in lung tissue were detected by Western blotting. The contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in lung tissue were detected according to the steps of the kit. RESULTS: Compared with the control group, the lung tissue structure was destroyed and exudation increased, lung index, lung injury score, the expressions of LC3- II/LC3- I, Beclin-1, and the contents of TNF-α, IL-6 and MDA in lung tissue significantly increased in the ALI group. Compared with the ALI group, the structural damage and exudation of lung tissue were reduced in the rapamycin group, lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue decreased, while the expressions of LC3- II/LC3- I and Beclin-1 in lung tissue increased [lung index: (7.56±0.39)% vs. (9.12±0.59)%, lung injury score: 3.04±0.58 vs. 9.32±2.14, TNF-α (ng/mg): 1.85±0.32 vs. 3.51±0.62, IL-6 (ng/mg): 1.61±0.32 vs. 2.52±0.44, MDA (nmol/mg): 1.03±0.16 vs. 1.88±0.24, LC3- II/LC3- I: 1.21±0.12 vs. 0.39±0.05, Beclin-1/ß-actin: 1.10±0.12 vs. 0.58±0.06, all P < 0.05], while lung tissue structure damage was aggravated and exudation was further increased in the 3-MA group, lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue increased, the expressions of LC3- II/LC3- I and Beclin-1 in lung tissue decreased [lung index: (10.44±0.62)% vs. (9.12±0.59)%, lung injury score: 11.59±2.28 vs. 9.32±2.14, TNF-α (ng/mg): 4.77±0.71 vs. 3.51±0.62, IL-6 (ng/mg): 3.44±0.52 vs. 2.52±0.44, MDA (nmol/mg): 2.71±0.42 vs. 1.88±0.24, LC3- II/LC3- I: 0.25±0.04 vs. 0.39±0.05, Beclin-1/ß-actin: 0.21±0.03 vs. 0.58±0.06, all P < 0.05]. Lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue of LC3 knockout ALI mice were higher than those of wild-type ALI mice [lung index: (10.44±0.75)% vs. (9.12±0.59)%, lung injury score: 12.41±2.86 vs. 9.32±2.14, TNF-α (ng/mg): 4.85±0.72 vs. 3.51±0.62, IL-6 (ng/mg): 3.28±0.51 vs. 2.52±0.44, MDA (nmol/mg): 2.75±0.41 vs. 1.88±0.24, all P < 0.05]. CONCLUSIONS: Autophagy plays a protective role in ALI of hemorrhagic shock mice, and the related molecular mechanism is the inhibition of inflammatory response and oxidative stress response.

Stepwise Solution-Interfacial Nanoarchitectonics for Assembled Film with Full-Color and White-Light Circularly Polarized Luminescence.

The fabrication of chiral thin films with tunable circularly polarized luminescence (CPL) colors is important in developing chiroptical materials but remains challenging due to the lack of assembly-initiated chiral film formation methodology. Here, by adopting a combined solution aggregation and interfacial assembly strategy, we report the fabrication of chiral film materials with full-color and white-light CPL. A biquinoline glutamic acid ester (abbreviated as BQGE) shows a typical aggregation-induced emission property with blue CPL after solution aggregation. Subsequent interfacial assembly of these solution aggregates on a solid substrate leads to the formation of a CPL active film consisting of nanobelt structures. Since the BQGE molecule has a coordination site, the CPL emission of an individual BQGE film can be extended from blue to green emission upon coordination with a zinc ion, accompanied by morphology transition from nanobelts to nanofibers. Further extension to red-color CPL is successfully achieved by coassembly with an achiral acceptor dye. Interestingly, the proper combination of coordination ratio and acceptor loading ratio provides bright white-light CPL emission from the BQGE/Zn2+/PDA triad composite film. This work provides a new approach to fabricating chiroptical film materials with controlled microscopic morphology and tunable CPL properties.

Self-Assembled Charge-Transfer Chiral π-Materials: Stimuli-Responsive Circularly Polarized Luminescence and Chiroptical Photothermic Effects.

Despite significant achievements in the field of chiroptical organic materials, the full utilization of both the excited state and ground state chiroptical properties in a single supramolecular system is still rarely disclosed. Here, we report that the rational combination of the charge-transfer (CT) interaction with the spacer effect and controlled protonation of π-histidine leads to chiroptical organic π-materials with both circularly polarized luminescence (CPL) and the supramolecular chirality-directed chiroptical photothermic effect. Three pyrene-conjugated histidine derivatives with varied acyl linkers (PyHis, PyC1His, and PyC3His) were designed to coassemble with electron-deficient 1,2,4,5-tetracyanobenzene (TCNB), leading to the formation of supramolecular CT complexes with intense orange to red CPL depending on the linker length. The linker length also affected the protonation-induced CPL responsiveness of the corresponding CT assemblies. Upon protonation of the histidine moiety, PyC3His/TCNB CT assemblies exhibited an inverted CPL signal, while PyHis/TCNB pairs gave quenched CPL due to the disassembly. The protonation-controlled PyC3His/TCNB CT assemblies at varied pH values showed different chiroptical photothermic effects (CPEs) for the same incident chiral light despite the molecular chirality of PyC3His remaining unchanged, supporting an interesting supramolecular chirality-directed photothermic effect.

Blockade of Stellate Ganglion Remediates Hemorrhagic Shock-Induced Intestinal Barrier Dysfunction.

BACKGROUND: Acute hemorrhage-induced excessive excitation of sympathetic-adrenal-medullary system (SAS) leads to gut hypoperfusion and barrier dysfunction, which is a critical event during hemorrhagic shock-induced multiple organ injury. Stellate ganglion blockade (SGB) has been widely used for suppression of sympathetic-adrenal-medullary system in the clinical practice. However, whether SGB improves intestinal barrier function after hemorrhagic shock remains unclear. Here, we hypothesized that the implementation of SGB restores intestinal barrier function and reduces gut injury. MATERIALS AND METHODS: Male rats received the SGB pretreatment and underwent hemorrhagic shock followed by resuscitation. The 96-h survival rate, intestinal permeability and morphology, D-lactic acid concentration and diamine oxidase activity in plasma, and expressions of F-actin, Claudin-1, and E-cadherin in intestinal tissues were observed. RESULTS: Pretreatment with SGB significantly enhances the 96-h survival rate in rats subjected to hemorrhagic shock (from 8.3% to 66.7%). Hemorrhagic shock reduced the coverage scale of intestinal mucus and intestinal villus width and height, enhanced the intestinal permeability to fluorescein isothiocyanate-dextran 4 and D-lactic acid concentration in plasma, and decreased the expressions of F-actin, Claudin-1, and E-Cadherin in intestinal tissue. These hemorrhagic shock-induced adverse effects were abolished by SGB treatment. CONCLUSIONS: SGB treatment has a beneficial effect during hemorrhagic shock, which is associated with the improvement of intestine barrier function. SGB may be considered as a new therapeutic strategy for treatment of hemorrhagic shock.