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Even after decades of research, the preparation of mesoporous silica still depends on the sol–gel method. The major problem of sol–gel method is its infeasibility in industrial manufacturing. A large-scale preparation method is desired to meet the growing demand of mesoporous silica in multiple applications. A cost-effective and industrially feasible method was proposed to prepare mesoporous silica. The well-developed acid leaching technology was used as a novel pore forming method for treating coal fly ash. And mesoporous silica with specific surface area as high as 585.02 m 2 /g and pore volume of 0.54 cm 3 /g was successfully prepared under a control of reaction parameters. Reaction intensity was introduced as a new parameter to describe reaction conditions and help explain the variation of pore structure and shape prepared under different reaction conditions. This method is feasible in large-scale manufacturing of mesoporous silica and will satisfy the great demand for its wide applications. [ABSTRACT FROM AUTHOR]

A straightforward and economical synthetic route for the preparation of cholesterol was developed from plant origin bisnoralcohol. [Display omitted] • Plant-derived cholesterol was synthesized from bisnoralcohol. • This promising route for production of cholesterol has a high overall yield. • The epicholesteorl and cholestanol were also synthesized. Currently, the market demand of the non-animal-derived cholesterol is increasing. A novel synthetic route of producing cholesterol was developed through multiple reactions from plant-sourced and commercially available bisnoralcohol (BA). The key reaction conditions, including solvents, reaction temperatures, bases and reducing agents of the route were investigated and optimized. In this straightforward synthetic pathway of cholesterol, most of the reaction steps possess high conversions with average yields of 94%, and the overall yield is up to 74% (5 steps) from the BA. The epicholesterol and were also synthesized. This promising route offers economical and efficient strategies for potential large-scale production of plant-derived cholesterol. [ABSTRACT FROM AUTHOR]

Tryptophan (TRP) metabolism could occur both peripherally and centrally, which plays an essential role in brain and gastrointestinal disorders. The participation of TRP metabolism in the bidirectional brain-gut interactions is of value to better understand the mechanism of the pathophysiology of depression. To compare the difference between peripheral and cerebral TRP metabolism in depression, the chronic unpredicted mild stress (CUMS) was used to induce depressive-like syndrome in rats. After the rats were subjected to CUMS for five weeks, TRP and its metabolites were determined by prominence ultrafast liquid chromatography (UFLC) coupled with a QTRAP 5500 mass spectrometer (UFLC-QTRAP-5500/MS), and the expression of TRP metabolic enzymes were examined by Real-time quantitative PCR (qRT-PCR). CUMS induced TRP metabolism abnormalities in the colon, cortex and hippocampus of rats. There were regional metabolism differences, but the common points were the upregulation of indoleamine-2,3-dioxygenase 1 (IDO1) and the increased contents of Kynurenine (KYN), which suggested that KYN pathway (KP) was more favored than the serotonin (5-HT) pathway in the TRP metabolism under CUMS in the three regions studied. More importantly, KYN was preferentially metabolized into neurotoxic 3-hydroxycaninuric acid (3-HK) branch in the cortex and hippocampus while Kynurenic acid (KA) branch in the colon under CUMS. Interestingly, according to the Pearson's correlation coefficients, there may be correlations between the colonic KYN and cerebral 3-HK and KA. It advances our understanding of the role of TRP metabolism in gut-brain communication and provides new research ideas and methods for depression. Image 1 • Tryptophan (TRP) metabolism plays an essential role in brain and gastrointestinal disorders. • Region-specific differences of TRP metabolism. • Correlations between colonic Kynurenine (KYN) and cerebral KYN,3-hydroxycaninuric acid (3-HK) and Kynurenic acid (KA). [ABSTRACT FROM AUTHOR]

Recent studies have shown that adding active oxygen scavengers to edible coatings can maintain the storage quality and commercial value of postharvest fruit. In this research, the effect of a chitosan-based edible coating containing ascorbic acid (CH, 1% + AA, 1%) on Annona squamosa at storage conditions of 15 ± 1 °C was investigated for twelve days. The results showed that CH+AA could delay the decrease of firmness, appearance deterioration, weight loss, and accumulation of MDA content during the storage of Annona squamosa. The CH+AA composite coating also delayed the deterioration of quality by maintaining high titratable acidity, moisture content and antioxidant enzyme activities. In addition, CH+AA inhibited the softening of fruit by regulating the activities of cell wall degrading enzymes and their gene expression levels. In conclusion, the CH+AA composite coating can keep the quality of Annona squamosa stored after harvesting. [Display omitted] • CH+AA coating was better than that of single chitosan coating. • CH+AA coating can significantly improve the physicochemical properties of Annona squamosa. • CH+AA coating was significant influence in gene expression. [ABSTRACT FROM AUTHOR]

• SPC can be a good feed ingredient as swimming crab can tolerate up to 75% replacement. • Replacement of dietary fish meal with SPC will inhibit TOR pathway in hepatopancreas. • 51.49% replacement level with SPC is recommended for better PER. A 56-day feeding trial was conducted to evaluate the potential use of soy protein concentrate (SPC) as a partial replacement of fish meal in swimming crab Portunus trituberculatus. Four isonitrogenous and isolipidic diets (450 g/kg protein and 80 g/kg lipid) were formulated to contain graded levels of SPC, and fish meal was replaced with SPC at 25%, 50% and 75% level (SPC25, SPC50 and SPC75, respectively). The control diet (SPC0) contained fish meal, soybean meal and krill meal as the main protein sources. Lysine and methionine were added into SPC replacement diets to maintain the same concentrations as the control diet. Each diet was randomly assigned to triplicate groups of 45 juvenile swimming crabs (5.00 ± 0.23 g / crab) that were stocked in the rectangle plastic baskets. The results indicated that the weight gain (WG), special growth rate (SGR), feed efficiency (FE) and daily feed intake (DFI) were not significantly influenced by the dietary replacement of fish meal with SPC (P > 0.05). Crabs fed the SPC75 diet had lower protein efficiency ratio (PER) and molting frequencey (MF) than those fed the SPC50 diet(P < 0.05). The proximate compositions in whole body and muscle were not significantly influenced by the replacement of fish meal with SPC (P > 0.05), however, there was significant difference in the hepatopancreas moisture content (P < 0.05), and crabs fed the SPC0 diet had the highest lipid in hepatopancreas among all treatments (P < 0.05). Moreover, the essential amino acid (EAA), non-essential amino acid (NEAA) and total amino acid (TAA) contents of muscle significantly increased with the dietary replacement of fish meal with SPC levels increasing from 0 to 75% (P < 0.05). No significant differences in hemolymph enzyme activities and characteristics were observed among all treatments (P > 0.05). Crabs fed the SPC0 diet had higher amylase and lipase activities in hepatopancreas than those fed other diets. The hepatopancreas trypsin activity was not significantly influenced by the replacement of fish meal with SPC (P > 0.05). The hepatopancreas alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities increased when the dietary SPC levels increased from 0 to 25%, and then decreased significantly with the further increase of SPC replacement levels (P < 0.05). The relative expression of genes in target of rapamycin (TOR) pathway, crabs fed the SPC0 diet had higher relative expressions of tor, akt, s6k1, s6, 4ebp1, eif4e1a, eif4e2 and eif4e3 genes in hepatopancreas than those fed other diets (P < 0.05), moreover, there were no significant differences in gene expressions of TOR pathway among crabs fed the SPC25, SPC50 and SPC75 diets (P > 0.05). Based on the two slope broken-line regression analysis of PER against the dietary fish meal replacement with SPC levels, the optimum dietary replacement of fish meal with SPC was determined to be 51.49% for juvenile swimming crab. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) releasing molecule (CORM)-3, a water-soluble CORM, has protective effects against inflammatory and ischemia/reperfusion injury. We determined the effect of CORM-3 against neuronal pyroptosis in a model of hemorrhagic shock and resuscitation (HSR) in rats via mitochondrial regulation. Rats were treated with CORM-3 (4 mg/kg) in vitro after HSR. We measured cortical CO content 3–24 h after HSR; assessed neuronal pyroptosis, mitochondrial morphology, ROS production, and mitochondrial membrane potential at 12 h after HSR; and evaluated brain magnetic resonance imaging at 24 h after HSR and learning ability 30 days after HSR. We also measured soluble guanylate-cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway activity using a blocker of sGC, NS2028, and 125I-cGMP assay. Among rats that underwent HSR, CORM-3-treated rats had more CO in the cortical tissue than sham- and iCORM-3-treated rats. CORM-3-treated rats had significantly less neuronal pyroptosis in the cortical tissue; higher sGC activity and cGMP content; lower ROS production; better mitochondrial morphology, function, and membrane potential; and enhanced learning/memory ability than HSR-treated rats. However, these neuroprotective effects of CORM-3 were partially inhibited by NS2028. CORM-3 may alleviate neuronal pyroptosis and improve neurological recovery in HSR through mitochondrial regulation mediated by the sGC–cGMP pathway. Thus, CO administration could be a promising therapeutic strategy for hemorrhagic shock. A proposed diagram tying together the observations involved in CORM-3-induced neuroprotection against HSR. HSR increased neuronal pyroptosis, which might be associated with up-regulation of ROS. CORM-3 not only significantly reduced these neuronal pyroptosis, but also improved long-term learning ability and T2-weighted MRI, which might be associated with inhibition of mitochondrial dysfunction through regulating activity in sGC-cGMP signal pathway, whereas NS2028, a blocker of sGC, could partially inhibit these neuroprotective effects. Image 1 • Hemorrhage shock and resuscitation (HSR) induced cortical neuronal pyroptosis, mitochondrial injury, and decrased learning ability. • CORM-3 administration after resuscitation provided neuroprotection for HSR, and improved learning ability. • The neuroprotective mechanism of CROM-3 against HSR injury could be associated with sGC–cGMP pathway. [ABSTRACT FROM AUTHOR]

Introduction Myocardial ischemia-reperfusion (I/R) injury affects millions of people worldwide and has a very high mortality rate. Since microRNA-497 (miR-497) has been found to be related with cardiomyocyte apoptosis, this study aimed to explore the effect of miR-497 by targeting Mfn2 in a mouse model of myocardial ischemia-reperfusion (I/R) injury. Materials BALB/c mice were modeled with I/R and some were injected with miR-497 agomir before I/R to observe whether miR-497 alleviates the injury that occurs as a result of I/R. Bioinformatics website and dual-luciferase reporter gene assay were employed in order to detect the relations between miR-497 and Mfn2 gene. Next, cells were extracted to be transfected with different mimic, inhibitor and siRNAs to further explore how miR-497 acts to I/R. Western blot analysis and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were conducted to measure expressions of miR-497, Mfn2, Fas, Bcl-2, Bax and Caspase-3 in myocardial tissues and cardiomyocytes after transfection. CCK-8 assay and flow cytometry were used to determine proliferation, cell cycle distribution and apoptosis of cardiomyocytes in each group after transfection. Results Mice with I/R had myocardial dysfunction but before the injection with miR-497 agomir, the impairment was alleviated. Mfn2 was verified as the target gene of miR-497. The inhibition of miR-497 in turn inhibits Mfn2 expressione and cardiomyocyte apoptosis. The overexpression of miR-497 and Mfn2 gene silencing can lead to the promotion of proliferation capability of mice cardiomyocytes in vitro. Overexpressed miR-497 and Mfn2 gene silencing can also facilitate cell cycle entry and inhibit the apoptosis cardiomyocytes of mice in vitro. Conclusion The present study provided strong evidence that miR-497 promotes proliferation and inhibits apoptosis of cardiomyocytes by downregulating the expression of Mfn2 in a mouse model of myocardial I/R injury. [ABSTRACT FROM AUTHOR]

HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol de novo biosynthesis and its degradation may bring therapeutic benefits for the treatment of cardiovascular disease (CVD) and nonalcoholic steatohepatitis (NASH). Before, we disclosed compound HMG499 as a potent HMGCR degrader, which could be a promising agent for treating CVD, however its side-effect of promoting cholesterol accumulation in cells should be eliminated before progression. Herein, a series of novel heterocyclic ring-fused analogs of HMG499 were synthesized and investigated for their activities of stimulating HMGCR degradation using a HMGCR (TM1-8)-GFP reporting system. Among them, the most active compound 29 (QH536) showed an EC 50 of 0.22 μΜ in promoting HMGCR degradation, which was about 2 times more potent than HMG499 (EC 50 = 0.43 μM). Interestingly, 29 was different from HMG499, it had no side-effect of inducing cholesterol accumulation in cells. Mechanistic studies disclosed that 29 could significantly decrease statin-induced accumulation of HMGCR protein via ubiquitination and degradation of HMGCR through ubiquitin-proteasome pathway and inhibit the cholesterol biosynthesis in cells. Therefore, these heterocyclic ring-fused analogs could be used as promising leads for the development of new types of agents against CVD. Furthermore, 29 also lowered cholesterol levels and suppressed TGFβ1-induced proliferation of LX-2 hepatic stellate cells in a dose-dependent manner. In particular, 29 not only decreased the NASH associated fibrotic mRNA and protein expression of α-SMA, COL1A1, TIMP1 and TGFβ1 but also suppressed cholesterol levels and inflammatory genes of TNF-α, IL-6 an IL-1β in RAW264.7 macrophage cells, indicating that 29 may bring therapeutic benefit to treat NASH. A series of heterocyclic ring-fused analogs of HMG499 were synthesized and their activities of promoting HMG-CoA reductase degradation and side-effects of inducing cholesterol accumulation in cells were evaluated. [Display omitted] • A series of novel heterocyclic ring-fused analogs of HMG499 were synthesized. • The activities of promoting HMGCR degradation of these analogs were evaluated. • Compound 29 is the most potent HMGCR degrader. • Compound 29 possessed no side-effect of inducing cholesterol accumulation. [ABSTRACT FROM AUTHOR]

A straightforward and economical synthetic route for the preparation of ursodeoxycholic acid was developed from plant-source bisnoralcohol. • A facile route of producing ursodeoxycholic acid from plant-source BA is provided. • This promising route for production of ursodeoxycholic acid has a high yield. • This route of-fers a method for po-ten-tial large-scale pro-duc-tion of UDCA. A novel synthetic route of producing ursodeoxycholic acid (UDCA) was developed through multiple reactions from cheap and commercially available bisnoralcohol (BA). The key reaction conditions, including solvents, bases and reaction temperatures of the route were investigated and optimized. In the straightforward route for preparation of UDCA, most of the reaction steps have high conversions with average yields of 91%, and overall yield up to 59% (6 steps) from the plant-source BA. Especially in the last step of reduction and hydrolysis, there are five functional groups converted with calcd 97% per conversion in one-pot reaction. This promising route offers economical and efficient strategies for potential large-scale production of UDCA. [ABSTRACT FROM AUTHOR]

Cajaninstilbene acid (CSA), a bioactive constituent isolated from pigeon pea leaves, exhibited neuroprotective activities in previous studies. The present study aims to evaluate the antidepressant effects of CSA by using behavioral despair models of tail suspension test (TST) and forced swimming test (FST), and a chronic unpredictable mild stress (CUMS) model. CSA (30 or 60 mg/kg), intragastrically administrated for 7 days, could significantly reduce the immobility time of mice in TST and FST. CSA treatment (15 or 30 mg/kg) significantly reversed the depressive-like behavioral changes of mice induced by 3 or 6 weeks CUMS that caused the decrease of sucrose preference, the increase of latency to feed in the novelty-suppressed feeding test, and the increase of immobility time in TST of mice. Furthermore, the related mechanisms of the effect were explored by accessing the metabolite levels of kynurenine pathway of tryptophan metabolism and the expression of some related proteins in cerebral cortex of CUMS mice. Our results showed that the kynurenine pathway was upregulated after CUMS, while the alteration could be significantly reversed by CSA. CSA also reversed the CUMS-induced decrease in the levels of BDNF, PSD-95, p-Akt/Akt and p-mTOR/mTOR. Therefore, the antidepressant-like effects of CSA might be achieved through regulating tryptophan metabolism, promoting BDNF and PSD-95 expression, and activating Akt/mTOR pathway in the cerebral cortex. Unlabelled Image [ABSTRACT FROM AUTHOR]