Mitochondrial Uncouplers Confer Protection by Activating AMP-Activated Protein Kinase to Inhibit Neuroinflammation Following Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a disease with high disability and mortality rates. Currently, the efficacy of therapies available for ICH is limited. Microglia-mediated neuroinflammation substantially exacerbates brain damage following ICH. Here, we investigated whether mitochondrial uncouplers conferred protection by suppressing neuroinflammation following ICH. To mimic ICH-induced neuroinflammation in vitro, we treated microglia with red blood cell (RBC) lysate. RBC lysate enhanced the expression of pro-inflammatory cytokines in microglia. A clinically used uncoupler, niclosamide (Nic), reduced the RBC lysate-induced expression of pro-inflammatory cytokines in microglia. Moreover, Nic ameliorated brain edema, decreased neuroinflammation, and improved neurological deficits in a well-established mouse model of ICH. Like niclosamide, the structurally unrelated uncoupler carbonyl cyanide p-triflouromethoxyphenylhydrazone (FCCP) reduced brain edema, decreased neuroinflammation, and improved neurological deficits following ICH. It has been reported that mitochondrial uncouplers activate AMP-activated protein kinase (AMPK). Mechanistically, Nic enhanced AMPK activation following ICH, and AMPK knockdown abolished the beneficial effects of Nic following ICH. In conclusion, mitochondrial uncouplers conferred protection by activating AMPK to inhibit microglial neuroinflammation following ICH.

Selecting reasonable soil moisture-maintaining measures to improve the soil physicochemical properties and achieve high yield and quality of purple garlic in the China Hexi Corridor oasis agricultural area.

Agricultural plastic film, as an important agricultural production material in the China Hexi Corridor oasis agricultural area, is widely used in the intensive production process of purple garlic, which plays an important role in increasing yield, improving quality, ensuring supply, etc. However, the difference in decomposition characteristics between ordinary plastic film and degradable plastic film may affect soil moisture and temperature, thereby affecting soil biochemical properties. Therefore, we conducted a study to solve this problem. Specifically, in the Minle area of the Hexi Corridor, we selected 10 moisture-maintaining measures of ordinary transparent plastic film, transparent oxo-biodegradable plastic film (50-, 80-, and 110-day induction period), ordinary black plastic film, black oxo-biodegradable plastic film (50-, 80-, and 110-day induction period), wheat straw, and aubergine-super absorbent polymers and used the traditional open field without super absorbent polymers as a control. To analyze the effects of different moisture-maintaining measures on soil quality, garlic yield and quality, and water-fertilizer productivity in purple garlic farmland, and conduct a comprehensive evaluation of moisture-maintaining measures using principal component analysis. The results showed that all the moisture-maintaining measures could increase garlic yield, improve bulb quality and water-fertilizer productivity, improve the soil hydrothermal conditions, maintain soil fertility, increase the microbial quantity, and improve enzyme activity. Overall, transparent plastic film mulching was superior to black plastic film mulching, straw mulching, and A-SAP, with 110-day transparent oxo-biodegradable plastic film mulching being the most effective, and was not significantly different from the ordinary transparent plastic film. Compared with other moisture-maintaining measures, the yield, water productivity, irrigation water productivity, and nitrogen fertilizer partial factor productivity of purple garlic were significantly increased by 13.33% to 119.77%, 13.81% to 126.77%, 13.41% to 119.95%, and 13.33% to 119.76%, respectively. Meanwhile, the contents of allicin, soluble sugar, soluble protein, crude fiber, and amino acid content were increased by 1.44% to 14.66%, 4.64% to 36.46%, 0.38% to 28.27%, 1.89% to 26.29%, and 0.38% to 3.74%, and, due to the prolongation of oxo-biodegradable plastic film induction period, the soil microbial community changes from "fungi type" to "bacterium type," reducing the occurrence of soil diseases and improving soil quality. On the basis of the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method, the soil quality was evaluated, and the yield, quality, and water productivity of garlic were comprehensively evaluated under each moisture-maintaining measure using principal component analysis. It was determined that the best soil quality and better bulb quality as well as higher garlic yield and water productivity were obtained when using the 110-day induction period transparent oxo-biodegradable plastic film. It can be used as a more reasonable moisture-maintaining measure and technical reference for the purple garlic industry in the China Hexi Corridor oasis agricultural area, which can ensure the improvement of quality and stabilization of yield and also solve the risk of environmental pollution caused by plastic film mulching at the source.

Succinate Activates Uncoupling Protein 2 to Suppress Neuroinflammation and Confer Protection Following Intracerebral Hemorrhage.

Aims: Succinate, a metabolite in the tricarboxylic acid cycle, is increasingly recognized to play essential roles in inflammation by functioning either as an intracellular or extracellular signaling molecule. However, the role and mechanisms of succinate in inflammation remain elusive. Here, we investigated the mechanism underlying the effects of succinate on neuroinflammation in intracerebral hemorrhage (ICH) models. Results: We unexpectedly found that succinate robustly inhibited neuroinflammation and conferred protection following ICH. Mechanistically, the oxidation of succinate by succinate dehydrogenase (SDH) drove reverse electron transport (RET) at mitochondrial complex I, leading to mitochondrial superoxide production in microglia. Complex I-derived superoxides, in turn, activated uncoupling protein 2 (UCP2). By using mice with specific deletion of UCP2 in microglia/macrophages, we showed that UCP2 was needed for succinate to inhibit neuroinflammation, confer protection, and activate downstream 5'-adenosine monophosphate-activated protein kinase (AMPK) following ICH. Moreover, knockdown of SDH, complex I, or AMPK abolished the therapeutic effects of succinate following ICH. Innovation and Conclusion: We provide evidence that driving complex I RET to activate UCP2 is a novel mechanism of succinate-mediated intracellular signaling and a mechanism underlying the inhibition of neuroinflammation by succinate.

Applying minimal RNA-seq of peripheral blood platelet mRNA to reveal novel biomarkers in male patients with cerebral stroke.

Cerebral stroke is caused by the reduction or disruption of the blood supply to the brain, which results in cell death. Currently, the diagnosis of stroke is troublesome and expensive. In this study, samples of peripheral blood from eight male stroke patients and four male healthy controls were collected. RNA-seq of platelets was performed to detect the differential expression of mRNA in platelets isolated from the samples. Totally, 1091 (429 up-regulated and 662 down-regulated) differentially expressed genes were identified in patients with stroke compared with healthy controls. Analyses based on Gene Ontology and the KEGG pathway revealed that most annotated genes were involved in graft-versus-host disease, cell adhesion molecules signaling pathways, inflammation-related pathways, and so on. RNA expression levels of 15 inflammation-related genes were analyzed using qRT-PCR, especially egr2, which acts as a protector against stroke. In brief, RNA-seq analysis of platelets from all the samples indicated novel candidate genes and pathways that had the potential to be applied to clinical molecular diagnosis of stroke. Besides, this study provided insights into the function and underlying mechanism of stroke.

Near-infrared mediated chemo/photodynamic synergistic therapy with DOX-UCNPs@mSiO2/TiO2-TC nanocomposite.

To integrate photodynamic therapy (PDT) with chemotherapy for enhanced anticancer efficiency, near infrared (NIR) light mediated upconversion nanoparticles@mesoporous silica (UCNPs@mSiO2) nanovehicle was constructed as the nanocarrier. Based on the novel ultraviolet (UV) emission, TiO2 (3.0-3.2eV) was adopted as the photosensitiver (PS) on account of the high activity and excellent stability. Here, a simple host-assembly method was exploited to graft it onto the inner and outer surface of the mSiO2 shell. On the other hand, a UV cleavable o-nitrobenzyl derivative linker (TC linker) was prepared as "gate" to encapsulate anticancer agent doxorubicin (DOX) inside mSiO2, insuring the few prematurity. Under NIR irradiation, the UV emission can excite TiO2 to produce reactive oxygen species (ROS) and also can induce the photodegradation of TC linker and drug release as well. The detailed release kinetics was studied to reveal that it is TC linker to manipulate the NIR-sensitive drug release and the amount of TC linker also can be used to adjust the release performance. The synergistic action of PDT and chemotherapy displays the improved cytotoxicity of DOX-UCNPs@mSiO2/TiO2-TC to HeLa cells under NIR irradiation that makes the potential application in anticancer field due to the superior to any single means.

Synthesis and evaluation of a C8 stationary phase on a silica hydride surface by hydrosilation of 1-octyne.

The silanization/hydrosilation method is used to bond an alkyne (1-octyne) to a silica hydride surface. The new bonded material is characterized by elemental analysis and diffuse reflectance infrared Fourier transform spectroscopy. The hydrophobic behavior of this material was determined by the retention characteristics of aromatic solutes and the shape selectivity as well as phase classification (monomeric or polymeric) was measured by the polycyclic aromatic hydrocarbon mixture standard reference material 869. The presence of residual silanols on the bonded phase was probed by several basic solutes at pH 7. Long-term stability studies were conducted by measuring retention and peak symmetry of basic compounds over several thousand column volumes at pH 10.