Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which choleste...Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which cholesterol is esterified to be transported to target organs. The newly developed process of making bulky esters from unprecedented tertiary alcohols is applied to synthesize cholesterol esters successfully. Although cholesterol is a secondary alcohol, it is a very bulky and interesting compound due to its immense application. Usually, specific enzymes catalyze cholesterol to cholesterol ester. This project aims to develop a cross-coupling chemistry process to synthesize cholesterol esters and see the broader application of those new cholesterol esters in chemical biology. The mixture of cholesterol, sodium tert-butoxide, aroyl chloride, the catalyst PdCl2 (dtbpf) complex, and the solvent 1,4-dioxane, when microwaved at 100˚C for 2 hours, works well for the formation of cross-coupling cholesterol ester products in good to high yields.展开更多
A series ofpenicillide analogues, with modifications at C-3 and C-9 positions, are synthesized as potential cho-lesteryl ester transfer protein （CETP） inhibitors. The preliminary in vitro inhibition assay provided s...A series ofpenicillide analogues, with modifications at C-3 and C-9 positions, are synthesized as potential cho-lesteryl ester transfer protein （CETP） inhibitors. The preliminary in vitro inhibition assay provided some valuable structure-activity relationship information about penicillide.展开更多
This study screened for the inhibitory peptides from the collagen of barracuda fish skin then determined its inhibitory effect on hyperlipidemia.The results showed that the collagen was type I,mainly containingα1,α2...This study screened for the inhibitory peptides from the collagen of barracuda fish skin then determined its inhibitory effect on hyperlipidemia.The results showed that the collagen was type I,mainly containingα1,α2,andβchains.Scanning electron microscopy revealed the fiber structure,sheet structure,multilayer aggregation structure,which was loose and porous.For an optimal enzymatic digestion process the pH was 10,the dosage of alkaline protease was 3000 U/g,and the temperature 50℃,with a degree of hydrolysis of 26.03%.The peptides of less than 1 KDa were selected by protein ultrafiltration and LC-MS identification revealed 220 peptides.The results indicated that GAPGFPGPR can be the best inhibitory peptide based on its bioactivity,water solubility,toxicity,ADMET and molecular docking technology.In vitro experiment showed that the GAPGFPGPR had significant inhibitory effects on the cholesterol ester transfer protein.The zebrafish experiment further verified that the GAPGFPGPR significantly reduced the total cholesterol,triacylglycerol,low-density lipoprotein cholesterol levels and increased the high-density lipoprotein cholesterol levels in the hyperlipidemia model.Therefore,the study has demonstrated the potented for developing health care products or drugs to improve hyperlipidemia.展开更多
Lipids,defined by low solubility in water and high solubility in nonpolar solvents,can be classified into fatty acids,glycerolipids,glycerophospholipids,sphingolipids,and sterols.Lipids not only regulate integrity and...Lipids,defined by low solubility in water and high solubility in nonpolar solvents,can be classified into fatty acids,glycerolipids,glycerophospholipids,sphingolipids,and sterols.Lipids not only regulate integrity and fluidity of biologi-cal membranes,but also serve as energy storage and bioactive molecules for signaling.Causal mutations in SPTLC1(serine palmitoyltransferase long chain subunit 1)gene within the lipogenic pathway have been identified in amyo-trophic lateral sclerosis(ALS),a paralytic and fatal motor neuron disease.Furthermore,lipid dysmetabolism within the central nervous system and circulation is associated with ALS.Here,we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis.Among the different lipids,accumulation of ceramides,arachidonic acid,and lysophosphatidylcholine is commonly emerging as detri-mental to motor neurons.We end with exploring the potential ALS therapeutics by reducing these toxic lipids.展开更多
Background:Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia(BPSD)in Alzheimer’s disease(AD).This study aimed to develop and validate a novel genetic-clinic...Background:Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia(BPSD)in Alzheimer’s disease(AD).This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods:This retrospective study included 165 patients with AD from the Chinese Imaging,Biomarkers,and Lifestyle(CIBL)cohort between June 1,2021,and March 31,2022.Data on demographics,neuropsychological assessments,single-nucleotide polymorphisms of AD risk genes,and regional brain volumes were collected.A multivariate logistic regression model identified BPSD-associated factors,for subsequently constructing a diagnostic nomogram.This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1,2022,and February 1,2023.Area under receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA)were used to assess the discrimination,calibration,and clinical applicability of the nomogram.Results:Factors independently associated with BPSD were:CETP rs1800775(odds ratio[OR]=4.137,95%confidence interval[CI]:1.276-13.415,P=0.018),decreased Mini Nutritional Assessment score(OR=0.187,95%CI:0.086-0.405,P<0.001),increased caregiver burden inventory score(OR=8.993,95%CI:3.830-21.119,P<0.001),and decreased brain stem volume(OR=0.006,95%CI:0.001-0.191,P=0.004).These variables were incorporated into the nomogram.The area under the ROC curve was 0.925(95%CI:0.884-0.967,P<0.001)in the internal validation and 0.791(95%CI:0.686-0.895,P<0.001)in the external validation.The calibration plots showed favorable consistency between the prediction of nomogram and actual observations,and the DCA showed that the model was clinically useful in both validations.Conclusion:A novel nomogram was established and validated based on lipid metabolism-related genes,nutritional status,and brain stem volumes,which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration:Chictr.org.cn,ChiCTR2100049131.展开更多
文摘Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which cholesterol is esterified to be transported to target organs. The newly developed process of making bulky esters from unprecedented tertiary alcohols is applied to synthesize cholesterol esters successfully. Although cholesterol is a secondary alcohol, it is a very bulky and interesting compound due to its immense application. Usually, specific enzymes catalyze cholesterol to cholesterol ester. This project aims to develop a cross-coupling chemistry process to synthesize cholesterol esters and see the broader application of those new cholesterol esters in chemical biology. The mixture of cholesterol, sodium tert-butoxide, aroyl chloride, the catalyst PdCl2 (dtbpf) complex, and the solvent 1,4-dioxane, when microwaved at 100˚C for 2 hours, works well for the formation of cross-coupling cholesterol ester products in good to high yields.
基金We thank the National Natural Science Foundation of China （20872019） for the research financial support and we are grateful to Fudan University and Shanghai Institute of Organic Chemistry for recording EI-MS or ESI-MS, HRMS, ^1H NMR, and ^13C NMR spectra. We are also grateful to Dr. Hanqing Dong （OSI Pharma-ceuticals, USA） for his help in revising the manuscript.
文摘A series ofpenicillide analogues, with modifications at C-3 and C-9 positions, are synthesized as potential cho-lesteryl ester transfer protein （CETP） inhibitors. The preliminary in vitro inhibition assay provided some valuable structure-activity relationship information about penicillide.
基金supported by the Open Fund of Institute of Ocean Research,Bohai University(BDHYYJY2024003).
文摘This study screened for the inhibitory peptides from the collagen of barracuda fish skin then determined its inhibitory effect on hyperlipidemia.The results showed that the collagen was type I,mainly containingα1,α2,andβchains.Scanning electron microscopy revealed the fiber structure,sheet structure,multilayer aggregation structure,which was loose and porous.For an optimal enzymatic digestion process the pH was 10,the dosage of alkaline protease was 3000 U/g,and the temperature 50℃,with a degree of hydrolysis of 26.03%.The peptides of less than 1 KDa were selected by protein ultrafiltration and LC-MS identification revealed 220 peptides.The results indicated that GAPGFPGPR can be the best inhibitory peptide based on its bioactivity,water solubility,toxicity,ADMET and molecular docking technology.In vitro experiment showed that the GAPGFPGPR had significant inhibitory effects on the cholesterol ester transfer protein.The zebrafish experiment further verified that the GAPGFPGPR significantly reduced the total cholesterol,triacylglycerol,low-density lipoprotein cholesterol levels and increased the high-density lipoprotein cholesterol levels in the hyperlipidemia model.Therefore,the study has demonstrated the potented for developing health care products or drugs to improve hyperlipidemia.
基金National Medical Research Council(NMRC/OFIRG/0042/2017)National Research Foundation(NRF2019-NRF-ISF003-3221)Ministry of Education(MOE-T2EP30220-0029),Singapore to S.-C.L.
文摘Lipids,defined by low solubility in water and high solubility in nonpolar solvents,can be classified into fatty acids,glycerolipids,glycerophospholipids,sphingolipids,and sterols.Lipids not only regulate integrity and fluidity of biologi-cal membranes,but also serve as energy storage and bioactive molecules for signaling.Causal mutations in SPTLC1(serine palmitoyltransferase long chain subunit 1)gene within the lipogenic pathway have been identified in amyo-trophic lateral sclerosis(ALS),a paralytic and fatal motor neuron disease.Furthermore,lipid dysmetabolism within the central nervous system and circulation is associated with ALS.Here,we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis.Among the different lipids,accumulation of ceramides,arachidonic acid,and lysophosphatidylcholine is commonly emerging as detri-mental to motor neurons.We end with exploring the potential ALS therapeutics by reducing these toxic lipids.
基金supported by grants from the National Key Research and Development Program of China(Nos.2021YFC2500100 and 2021YFC2500103)the National Natural Science Foundation of China(Nos.82071187 and 81870821)
文摘Background:Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia(BPSD)in Alzheimer’s disease(AD).This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods:This retrospective study included 165 patients with AD from the Chinese Imaging,Biomarkers,and Lifestyle(CIBL)cohort between June 1,2021,and March 31,2022.Data on demographics,neuropsychological assessments,single-nucleotide polymorphisms of AD risk genes,and regional brain volumes were collected.A multivariate logistic regression model identified BPSD-associated factors,for subsequently constructing a diagnostic nomogram.This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1,2022,and February 1,2023.Area under receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA)were used to assess the discrimination,calibration,and clinical applicability of the nomogram.Results:Factors independently associated with BPSD were:CETP rs1800775(odds ratio[OR]=4.137,95%confidence interval[CI]:1.276-13.415,P=0.018),decreased Mini Nutritional Assessment score(OR=0.187,95%CI:0.086-0.405,P<0.001),increased caregiver burden inventory score(OR=8.993,95%CI:3.830-21.119,P<0.001),and decreased brain stem volume(OR=0.006,95%CI:0.001-0.191,P=0.004).These variables were incorporated into the nomogram.The area under the ROC curve was 0.925(95%CI:0.884-0.967,P<0.001)in the internal validation and 0.791(95%CI:0.686-0.895,P<0.001)in the external validation.The calibration plots showed favorable consistency between the prediction of nomogram and actual observations,and the DCA showed that the model was clinically useful in both validations.Conclusion:A novel nomogram was established and validated based on lipid metabolism-related genes,nutritional status,and brain stem volumes,which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration:Chictr.org.cn,ChiCTR2100049131.
