Neurodegenerative disorde rs such as Alzheimer's and Parkinson s diseases are increasingly associated with metabolic dysfunction,including obesity,type 2 diabetes,and metabolic dysfunction-associated steatotic liv...Neurodegenerative disorde rs such as Alzheimer's and Parkinson s diseases are increasingly associated with metabolic dysfunction,including obesity,type 2 diabetes,and metabolic dysfunction-associated steatotic liver disease.Central to this connection is the dysregulation of lipid metabolism,which extends beyond peripheral tissues to the brain,defective autolysosomal function,oxidative stress,inflammation,and insulin resistance.Lipids,which constitute over half of dry weight of the brain,play critical roles in ene rgy provisio n,structural integrity,and synaptic function.Dys regulation of lipid metabolism contributes to neuroinflammation,impaired neuronal function,and disrupted blood-brain barrier integrity.Palmitic acid,a saturated fatty acid abundant in high-fat diets,serves as a key model for studying lipid-induced toxicity(lipotoxicity)in the brain.Palmitic acid disrupts autophagy and lysosomal function,mitochondrial function,trigge ring oxidative stress,contributing to neuroinflammation and neurodegeneration.These effects are particularly pronounced in neurons,which are highly susceptible to lipid-induced toxicity due to their high metabolic demands.Glial cells,including astrocytes,microglia,and oligodendrocytes,also exhibit distinct vulnerabilities and adaptive responses to lipid metabolism dysregulation,further contributing to neuroinflammation and demyelination.Therapeutic strategies,such as supplementation with polyunsaturated fatty acids,AMP-activated protein kinase activation,and lysosome-ta rgeted interventions,show promise in mitigating palmitic acid-induced lipotoxicity and restoring cellular homeostasis.This review comprehensively examines palmitic acid-induced lipotoxicity and its impact on autolysosomal dysfunction across various central nervous system cell types,including neurons,astrocytes,microglia,and oligodendrocytes.Additionally,it highlights therapeutic approaches to restore autolysosomal function under lipotoxic conditions.Advances in multi-omics technologies and a deeper unde rstanding of intercellular crosstalk offer new avenues for develo ping targeted the rapies to resto re autolysosomal function,and attenuate neuroinflammation and neurodegeneration.展开更多
The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porci...The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porcine enteric coronavirus with intestinal microorganisms during infection remains unclear.In this study,we used 16S-rRNA-based Illumina NovaSeq high-throughput sequencing to identify the changes in the intestinal microbiota of piglets mediated by porcine epidemic diarrhea virus(PEDV)infection and the effects of the alterations in intestinal bacteria on PEDV infection and its molecular mechanisms.The intestinal microbiota of PEDV-infected piglets had significantly less diversity than the healthy group and different bacterial community characteristics.Among the altered intestinal bacteria,the relative abundance of Clostridium perfringens was significantly increased in the PEDV-infected group.A strain of C.perfringens type A,named DQ21,was successfully isolated from the intestines of healthy piglets.The metabolites of swine C.perfringens type A strain DQ21 significantly enhanced PEDV replication in porcine intestinal epithelial cell clone J2(IPEC-J2)cells,and PEDV infection and pathogenicity in suckling piglets.Palmitic acid(PA)was identified as one of those metabolites with metabolomic technology,and significantly enhanced PEDV replication in IPEC-J2 cells and PEDV infection and pathogenicity in suckling piglets.PA also increased the neutralizing antibody titer in the immune sera of mice.Furthermore,PA mediated the palmitoylation of the PEDV S protein,which improved virion stability and membrane fusion,thereby enhancing viral infection.Overall,our study demonstrates a novel mechanism of PEDV infection,with implications for PEDV pathogenicity.展开更多
BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but th...BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but the detailed mechanism is still unclear.Most studies ofβ-cell dedifferentiation rely on rodent models and human pathological specimens.The development of in vitro systems can facilitate the exploration ofβ-cell dedifferentiation.AIM To investigate the molecular mechanism ofβ-cell dedifferentiation.Hence,an in vitro model ofβ-cell dedifferentiation induced by palmitic acid and high glucose was established using the INS-1832/13 cell line.METHODS The study was further analyzed using RNA-sequencing,transmission electron microscopy,quantitative real-time polymerase chain reaction and Western blot.RESULTS Results showed that the treatment of palmitic acid and high glucose significantly up-regulatedβ-cell forbidden genes and endocrine precursor cell marker genes,and down-regulated the expression ofβ-cell specific markers.Data showed that dedifferentiated INS-1 cells up-regulated the expression of endoplasmic reticulum(ER)stressrelated genes.Moreover,the results also showed that forkhead box O1(Foxo1)inhibition potentiated genetic changes inβ-cell dedifferentiation induced by palmitic acid and high glucose.CONCLUSION ER stress is sufficient to triggerβ-cell dedifferentiation and is necessary for palmitic acid and high glucose-inducedβ-cell dedifferentiation.Foxo1 inhibition can further enhance these phenomena.展开更多
Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment resistance.Palmitic acid(PA)has shown promising antitumor properties.This study aims to elucidate the molecular mechanisms by which PA infl...Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment resistance.Palmitic acid(PA)has shown promising antitumor properties.This study aims to elucidate the molecular mechanisms by which PA influences DLBCL progression.We quantified the expression levels of microRNAs(miRNAs),Forkhead box protein O1(FOXO1),and DNA methyltransferase 3A(DNMT3A)in both untreated and PA-treated DLBCL tumors and cell lines.Assessments were made of cell viability,apoptosis,and autophagy-related protein expression following PA administration.Interaction analyses among miR-429,DNMT3A,and FOXO1 were conducted using luciferase reporter assays and methylation-specific(MSP)Polymerase chain reaction(PCR).After transfecting the miR-429 inhibitor,negative control(NC)inhibitor,shRNA against DNMT3A(sh-DNMT3A),shRNA negative control(sh-NC),over-expression vector for DNMT3A(oe-DNMT3A),or overexpression negative control(oe-NC),we evaluated the effects of miR-429 and DNMT3A on cell viability,mortality,and autophagy-related protein expression in PA-treated DLBCL cell lines.The efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse models.MiR-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control group.PA treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of DNMT3A.The luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 methylation.Subsequent experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 axis.In vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 axis.Palmitic acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway,suggesting a novel therapeutic target for DLBCL management.展开更多
Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid ...Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid （PA）, a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species （ROS） and malondialde- hyde （MDA） in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 （PI3K inhibitor）, Akt VIII inhibitor, and PD98059 （ERK1/2 inhibitor）. Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.展开更多
Meso-Ni@HZSM-5 bi-functional catalysts were successfully post-encapsulated with about 3-7 nm Ni nanoparticles within HZSM-5 crystals,which exhibited significantly efficient conversion activity(67.4 g[palmitic acid]g[N...Meso-Ni@HZSM-5 bi-functional catalysts were successfully post-encapsulated with about 3-7 nm Ni nanoparticles within HZSM-5 crystals,which exhibited significantly efficient conversion activity(67.4 g[palmitic acid]g[Ni]^(−1)h^(−1))of palmitic acid and 100%selectivity of hydrocarbons with the outstanding stability during recycling application,compared to the impregnated Ni/HZSM-5 catalyst(14.0 g[palmitic acid]g[Ni]^(−1)h^(−1)).展开更多
Background Negative energy balance(NEB)typically occurs in dairy cows after delivery.Cows with a high yield are more likely to experience significant NEB.This type of metabolic imbalance could cause ketosis,which is o...Background Negative energy balance(NEB)typically occurs in dairy cows after delivery.Cows with a high yield are more likely to experience significant NEB.This type of metabolic imbalance could cause ketosis,which is often accompanied by a decline in reproductive performance.However,the molecular mechanisms underlying NEB have yet to be fully elucidated.During excessive NEB,the body fat is extensively broken down,resulting in the abnormal accumulation of non-esterified fatty acids(NEFAs),represented by palmitic acid(PA),within the uterus.Such an abnormal accumulation has the potential to damage bovine endometrial epithelial cells(BEECs),while the molecular mechanisms underlying its involvement in the PA-induced injury of BEECs remains poorly understood.Melatonin(MT)is recognized for its regulatory role in maintaining the homeostasis of mitochondrial reactive oxygen species(mitoROS).However,little is known as to whether MT could ameliorate the damage incurred by BEECs in response to PA and the mo ecu ar mechanism invo ved.Results Analysis showed that 0.2 mmol/L PA stress increased the level of cellular and mitochondrial oxidative stress,as indicated by increased reactive oxygen species(ROS)level.In addition,we observed mitochondrial dysfunction,including abnormal mitochondrial structure and respiratory function,along with a reduction in mitochondrial membrane potential and mitochondrial copy number,and the induction of apoptosis.Notably,we also observed the upregulation of autophagy proteins(PINK,Parkin,LC3B and Ubiquitin),however,the P62 protein was also increased.As we expected,100 Wmol/L of MT pre-treatment attenuated PA-induced mitochondrial ROS and restored mitochondrial respiratory function,Meanwhile,MT pretreatment reversed the upregulation of P62induced by PA and activated the AMPK-mTOR-Beclin-1 pathway,contributing to an increase of autophagy and decline apoptosis.Conclusions Our findings indicate that PA can induce mitochondrial dysfunction and enhance autophagy in BEECs.In addition,MT is proved to not only reduce mitochondrial oxidative stress but also facilitate the clearance of damaged mitochondria by upregulating autophagy pathways,thereby safeguarding the mitochondrial pool and promoting cellular viability.Our study provides a better understanding of the molecular mechanisms underlying the effect of an excess of NEB on the fertility outcomes of high yielding dairy cows.展开更多
Nutrients from dietary foods not only provide energy and building blocks,but also play critical roles in modulating diverse pathophysiological functions.They achieve these,in part,by accelerating cell signaling transd...Nutrients from dietary foods not only provide energy and building blocks,but also play critical roles in modulating diverse pathophysiological functions.They achieve these,in part,by accelerating cell signaling transduction processes via modulating various types of protein post-translational modifications(PTMs).Notably,accumulating evidence has identified palmitic acid(PA),a major component of high-fat diets,as a significant contributor to various human disorders,including diabetes and cancer.Hence,further understanding the roles of PA and its involvement in protein palmitoylation,a key PTM,is crucial for uncovering the mechanisms underlying these diseases and exploring potential clinical applications in cancer therapy.This review comprehensively summarizes recent advances in the understanding of PA homeostasis and palmitoylation in tumorigenesis.Specifically,it highlights the connections between palmitoylation and key processes such as oncogenic signaling pathways,cell death mechanisms,innate immune responses,and the tumor microenvironment.The review also emphasizes potential therapeutic strategies,including targeting PA homeostasis,palmitoylation-associated processes,or specific palmitoylated proteins for cancer treatment.Finally,the challenges in the field,such as the regulation of PA homeostasis and the dynamic detection or targeting of palmitoylation,are discussed,underscoring the need for further research to address these critical issues.展开更多
Dietary fatty acids(FAs)are associated with the therapeutic intervention under various health conditions.Human γδ-T cells are indispensable for immunosurveillance toward malignant cells.However,their impact onγδ-T...Dietary fatty acids(FAs)are associated with the therapeutic intervention under various health conditions.Human γδ-T cells are indispensable for immunosurveillance toward malignant cells.However,their impact onγδ-T cell metabolism and function remains poorly unexplored.Here,we applied targeted metabolomics analysis to serum FAs among cancer patients undergoing γδ-T cell therapy and discovered that palmitic acid(PA)or oleic acid(OA)levels were associated with the efficacy of Vγ9Vδ2-T cell therapy.We further elucidated that PA suppresses the antitumor activity of Vγ9Vδ2-T cells by disrupting metabolic processes and inhibiting the secretion of lytic granules,whereas OA restores the impaired antitumor activity of Vγ9Vδ2-T cells.Mechanistically,we surprisingly found that PA stimulates Vγ9Vδ2-T cells to secrete excessive IFNγ,which in turn induces cell pyroptosis,ultimately resulting in decreased antitumor activity.展开更多
Objective： To investigate the effects of berberine （BBR） and cinnamic acid （CA）, the main active components in Jiaotai Pill （交泰丸, JTP）, on palmitic acid （PA）-induced intracellular tdglyceride （TG） accumu...Objective： To investigate the effects of berberine （BBR） and cinnamic acid （CA）, the main active components in Jiaotai Pill （交泰丸, JTP）, on palmitic acid （PA）-induced intracellular tdglyceride （TG） accumulation in NIT-1 pancreatic 13 cells. Methods： Cells were incubated in culture medium containing PA （0.25 mmol/L） for 24 h. Then treatments with BBR （10 μmol/L）, CA （100 μmol/L） and the combination of BBR and CA （BBR＋CA） were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase （AMPK） protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase （FAS）, acetyl-coA carboxylase （ACC）, phosphorylation acetyl-coA carboxylase （pACC）, carnitine acyl transferase 1 （CPT-1） and sterol regulating element binding protein lc （SREBP-lc） were determined by Western blot or real time polymerase chain reaction. Results： PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-I. Meanwhile, AMPK downstream lipogenic genes including SREBP-lc mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR＋CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic 13 cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study. Conclusion： It can be concluded that in vitro, BBR and BBR＋CA could inhibit PA-induced lipid accumulation by decreasing lipoqenesis and increasin.cl lipid oxidation in NIT-1 pancreatic B cells.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Triacylglycerol(TAG)components in human milk,infant formulas with different fat sources,and plant oils(palm oil,flaxseed oil,sunflower oil,corn oil,soybean oil,coconut oil,low erucic acid rapeseed oil,and high oleic a...Triacylglycerol(TAG)components in human milk,infant formulas with different fat sources,and plant oils(palm oil,flaxseed oil,sunflower oil,corn oil,soybean oil,coconut oil,low erucic acid rapeseed oil,and high oleic acid rapeseed oil)were analyzed and compared using ultraperformance supercritical fluid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPSFC-Q-TOF-MS).Distinct TAG profiles were identified by lipidomics,principal component analysis(PCA),and heatmap visualization.Human milk was characterized by a high abundance of medium-and long-chain triacylglycerols(MLCTs),saturated-unsaturated-unsaturated(SUU)-type TAGs(sn-2 palmitic acid).In contrast,plant oils lacked MLCTs and SUU-type TAGs,containing mainly TAGs esterified long-chain polyunsaturated fatty acid.Breast milk contains about 27%MLCT,about 50%SUU-type triacylglycerols(which contain about 34%UPU-type triacylglycerols),which is significantly different from plant oils,structured fats and infant formulas.These findings provide a clear basis for optimizing the fat blend in infant formula to better mimic the unique TAG profile of human milk,thereby improving energy delivery and nutrient absorption for infants.展开更多
Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we...Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.展开更多
Mussels are common anchoring organisms that adhere to the surfaces of various substrates with their byssus.The adhesion of mussel to substrates is contingent upon the presence of mussel foot proteins,of which Mytilus ...Mussels are common anchoring organisms that adhere to the surfaces of various substrates with their byssus.The adhesion of mussel to substrates is contingent upon the presence of mussel foot proteins,of which Mytilus edulis foot protein-1(Mefp-1)has been identified as the most abundant protein.It has been found that lipids are involved in the mussel adhesion process and can facilitate Mefp-1adhesion.In this research,the adhesion behavior of Mefp-1 on various substrate surfaces under the effect of typical seawater cations with or without the presence of lipid were investigated using a quartz crystal microbalance with dissipation(QCM-D).Results indicate that the presence of cations Ca^(2+),Mg^(2+),Na^(+),and K^(+)leads to varying degrees of reduction in the adhesion performance of Mefp-1 on different substrates.The degree of this reduction,however,was much alleviated in the presence of palmitic acid,which is involved in the mussel adhesion process.Therefore,the involvement of palmitic acid is advantageous for mussel protein adhesion to the substrate surface in the marine environment.This study illustrated the significant contribution of palmitic acid to mussel adhesion,which can help to better understand biofouling mechanisms and develop biomimetic adhesive materials.展开更多
Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the s...Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.展开更多
Hydrogen isotopes in lipid biomarkers can trace past changes in the hydrologic cycle. Recent studies have revealed the potential of hydrogen isotopes in microalgal lipids for quantitatively reconstructing water δ~2H...Hydrogen isotopes in lipid biomarkers can trace past changes in the hydrologic cycle. Recent studies have revealed the potential of hydrogen isotopes in microalgal lipids for quantitatively reconstructing water δ~2H（δD） values and salinity. In this study we collected suspended particles along a salinity gradient from the Changjiang River Estuary（CRE）, and measured δD values in fatty acids in these particles. The results indicated that δD values of water were correlated highly with salinity from the CRE, in agreement with the results from other estuaries. δD values in palmitic acid and stearic acid had a positive correlation with δD values of water from the CRE. Nevertheless, in the CRE, hydrogen isotope fractionation in fatty acids relative to water increased as salinity increased, opposite the trend in hydrogen isotope fractionation with salinity found in microalgal culture and field studies. We attribute the increase in hydrogen isotope fractionation as salinity increased to light availability, which was likely lower in the particle rich mixing zone at the end of the estuary, and potentially as well to multiple sources of fatty acids in the CRE.展开更多
The selective cleavage of C-O and C-C is facing a challenge in the field of catalysis.In the present work,we studied the influence of doped Ni on the structure and electronic properties,as well as the selective C-O/C-...The selective cleavage of C-O and C-C is facing a challenge in the field of catalysis.In the present work,we studied the influence of doped Ni on the structure and electronic properties,as well as the selective C-O/C-C bond cleavages in the hydrodeoxygenation of palmitic acid over Ni-Mo_(2)C catalyst.The catalytic activity on Ni doped Mo_(2)C with TOF of 6.9×10^(3)h^(-1)is much superior to intrinsic Mo_(2)C catalyst,which is also higher than most noble metal catalysts.Structurally,the doped Ni raises the active particle dispersion and the coordination numbers of Mo species(Mo-C and Mo-O),improves the graphitization degree to promote the electron transfer,and increases the amount of Lewis and Br?nsted acid,which are responsible for the excellent hydrodeoxygenation performance.The Ni promotes simultaneously C-O and C-C bonds cleavage to produce pentadecane and hexadecane owing to the increase of electron-rich Mo sites after Ni doping.These findings contribute to the understanding of the nature of Ni-doped Mo_(2)C on the roles as catalytic active sites for C-O and C-C bonds cleavage.展开更多
In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was elimin...In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.展开更多
Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and ery...Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.展开更多
Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Method...Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques. Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability. Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.展开更多
基金the Department of Biology at Syracuse University(to CHL)a start-up grant from the Department of Biomedical and Chemical Engineering at Syacuse University(to JZ)an NIH grant(R01DK141923)sub-contract to Co-Investigators JZ and CHL from the Principal Investigator Mark W.Grinstaff。
文摘Neurodegenerative disorde rs such as Alzheimer's and Parkinson s diseases are increasingly associated with metabolic dysfunction,including obesity,type 2 diabetes,and metabolic dysfunction-associated steatotic liver disease.Central to this connection is the dysregulation of lipid metabolism,which extends beyond peripheral tissues to the brain,defective autolysosomal function,oxidative stress,inflammation,and insulin resistance.Lipids,which constitute over half of dry weight of the brain,play critical roles in ene rgy provisio n,structural integrity,and synaptic function.Dys regulation of lipid metabolism contributes to neuroinflammation,impaired neuronal function,and disrupted blood-brain barrier integrity.Palmitic acid,a saturated fatty acid abundant in high-fat diets,serves as a key model for studying lipid-induced toxicity(lipotoxicity)in the brain.Palmitic acid disrupts autophagy and lysosomal function,mitochondrial function,trigge ring oxidative stress,contributing to neuroinflammation and neurodegeneration.These effects are particularly pronounced in neurons,which are highly susceptible to lipid-induced toxicity due to their high metabolic demands.Glial cells,including astrocytes,microglia,and oligodendrocytes,also exhibit distinct vulnerabilities and adaptive responses to lipid metabolism dysregulation,further contributing to neuroinflammation and demyelination.Therapeutic strategies,such as supplementation with polyunsaturated fatty acids,AMP-activated protein kinase activation,and lysosome-ta rgeted interventions,show promise in mitigating palmitic acid-induced lipotoxicity and restoring cellular homeostasis.This review comprehensively examines palmitic acid-induced lipotoxicity and its impact on autolysosomal dysfunction across various central nervous system cell types,including neurons,astrocytes,microglia,and oligodendrocytes.Additionally,it highlights therapeutic approaches to restore autolysosomal function under lipotoxic conditions.Advances in multi-omics technologies and a deeper unde rstanding of intercellular crosstalk offer new avenues for develo ping targeted the rapies to resto re autolysosomal function,and attenuate neuroinflammation and neurodegeneration.
基金supported by the National Natural Science Foundation of China(U23A20236)the Key Research and Development Program,Guidance Projects of Heilongjiang Province,China(GZ20220029)。
文摘The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses,and potentially affects the infection processes of enteric viruses.However,the interaction of porcine enteric coronavirus with intestinal microorganisms during infection remains unclear.In this study,we used 16S-rRNA-based Illumina NovaSeq high-throughput sequencing to identify the changes in the intestinal microbiota of piglets mediated by porcine epidemic diarrhea virus(PEDV)infection and the effects of the alterations in intestinal bacteria on PEDV infection and its molecular mechanisms.The intestinal microbiota of PEDV-infected piglets had significantly less diversity than the healthy group and different bacterial community characteristics.Among the altered intestinal bacteria,the relative abundance of Clostridium perfringens was significantly increased in the PEDV-infected group.A strain of C.perfringens type A,named DQ21,was successfully isolated from the intestines of healthy piglets.The metabolites of swine C.perfringens type A strain DQ21 significantly enhanced PEDV replication in porcine intestinal epithelial cell clone J2(IPEC-J2)cells,and PEDV infection and pathogenicity in suckling piglets.Palmitic acid(PA)was identified as one of those metabolites with metabolomic technology,and significantly enhanced PEDV replication in IPEC-J2 cells and PEDV infection and pathogenicity in suckling piglets.PA also increased the neutralizing antibody titer in the immune sera of mice.Furthermore,PA mediated the palmitoylation of the PEDV S protein,which improved virion stability and membrane fusion,thereby enhancing viral infection.Overall,our study demonstrates a novel mechanism of PEDV infection,with implications for PEDV pathogenicity.
基金Supported by the Natural Science Foundation of China,No.81471081the Natural Science Foundation of Fujian Province,No.2023D009+1 种基金the Natural Science Foundation of Xiamen City,No.3502Z202373104 and No.3502Z20227162Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University,No.PM201809170005。
文摘BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but the detailed mechanism is still unclear.Most studies ofβ-cell dedifferentiation rely on rodent models and human pathological specimens.The development of in vitro systems can facilitate the exploration ofβ-cell dedifferentiation.AIM To investigate the molecular mechanism ofβ-cell dedifferentiation.Hence,an in vitro model ofβ-cell dedifferentiation induced by palmitic acid and high glucose was established using the INS-1832/13 cell line.METHODS The study was further analyzed using RNA-sequencing,transmission electron microscopy,quantitative real-time polymerase chain reaction and Western blot.RESULTS Results showed that the treatment of palmitic acid and high glucose significantly up-regulatedβ-cell forbidden genes and endocrine precursor cell marker genes,and down-regulated the expression ofβ-cell specific markers.Data showed that dedifferentiated INS-1 cells up-regulated the expression of endoplasmic reticulum(ER)stressrelated genes.Moreover,the results also showed that forkhead box O1(Foxo1)inhibition potentiated genetic changes inβ-cell dedifferentiation induced by palmitic acid and high glucose.CONCLUSION ER stress is sufficient to triggerβ-cell dedifferentiation and is necessary for palmitic acid and high glucose-inducedβ-cell dedifferentiation.Foxo1 inhibition can further enhance these phenomena.
基金supported by Henan Province Science and Technology Research and Development in 2023(Guiding Project Approval):Study on the role and mechanism of Xiakucao extract in regulating autophagy therapy for diffuse large B-cell lymphoma through the PI3K/AKT signaling pathway(No.232102310451)Henan Province Traditional Chinese Medicine Top Talents Project:Study on the effect and mechanism of Xiakucao extract on diffuse large B-cell lymphoma(No.2022ZYBJ18).
文摘Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment resistance.Palmitic acid(PA)has shown promising antitumor properties.This study aims to elucidate the molecular mechanisms by which PA influences DLBCL progression.We quantified the expression levels of microRNAs(miRNAs),Forkhead box protein O1(FOXO1),and DNA methyltransferase 3A(DNMT3A)in both untreated and PA-treated DLBCL tumors and cell lines.Assessments were made of cell viability,apoptosis,and autophagy-related protein expression following PA administration.Interaction analyses among miR-429,DNMT3A,and FOXO1 were conducted using luciferase reporter assays and methylation-specific(MSP)Polymerase chain reaction(PCR).After transfecting the miR-429 inhibitor,negative control(NC)inhibitor,shRNA against DNMT3A(sh-DNMT3A),shRNA negative control(sh-NC),over-expression vector for DNMT3A(oe-DNMT3A),or overexpression negative control(oe-NC),we evaluated the effects of miR-429 and DNMT3A on cell viability,mortality,and autophagy-related protein expression in PA-treated DLBCL cell lines.The efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse models.MiR-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control group.PA treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of DNMT3A.The luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 methylation.Subsequent experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 axis.In vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 axis.Palmitic acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway,suggesting a novel therapeutic target for DLBCL management.
基金supported by the National Natural Science Foundation of China,No.U1304815a grant from Key Project of Science and Technology Research of Henan Province of China,No.132102310097
文摘Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid （PA）, a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species （ROS） and malondialde- hyde （MDA） in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 （PI3K inhibitor）, Akt VIII inhibitor, and PD98059 （ERK1/2 inhibitor）. Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.
基金financial supports from the Natural Science Foundation of China (No.21908225)the National Key Research and Development Program (No.2018YFC1801501)。
文摘Meso-Ni@HZSM-5 bi-functional catalysts were successfully post-encapsulated with about 3-7 nm Ni nanoparticles within HZSM-5 crystals,which exhibited significantly efficient conversion activity(67.4 g[palmitic acid]g[Ni]^(−1)h^(−1))of palmitic acid and 100%selectivity of hydrocarbons with the outstanding stability during recycling application,compared to the impregnated Ni/HZSM-5 catalyst(14.0 g[palmitic acid]g[Ni]^(−1)h^(−1)).
基金supported by the Central Public-interest Scientific Institution Basal Research Fund(2023-YWF-ZX-07)The National Key R&D Program of Ningxia(2021BEF02023)+4 种基金The China Agriculture Research System of MOF and MARA(CARS-36)The National Natural Science Foundation of China(32102549)The Agricultural Science and Technology Innovation Program(ASTIP-IAS06)Key technological innovations in advanced dairy breeding and efficient breeding(2022JBGS0021)Supported by the Earmarked Fund for Hebei Dairy Cattle Innovation Team of Modern Agro-industry Technology Research System(HBCT2023180203)。
文摘Background Negative energy balance(NEB)typically occurs in dairy cows after delivery.Cows with a high yield are more likely to experience significant NEB.This type of metabolic imbalance could cause ketosis,which is often accompanied by a decline in reproductive performance.However,the molecular mechanisms underlying NEB have yet to be fully elucidated.During excessive NEB,the body fat is extensively broken down,resulting in the abnormal accumulation of non-esterified fatty acids(NEFAs),represented by palmitic acid(PA),within the uterus.Such an abnormal accumulation has the potential to damage bovine endometrial epithelial cells(BEECs),while the molecular mechanisms underlying its involvement in the PA-induced injury of BEECs remains poorly understood.Melatonin(MT)is recognized for its regulatory role in maintaining the homeostasis of mitochondrial reactive oxygen species(mitoROS).However,little is known as to whether MT could ameliorate the damage incurred by BEECs in response to PA and the mo ecu ar mechanism invo ved.Results Analysis showed that 0.2 mmol/L PA stress increased the level of cellular and mitochondrial oxidative stress,as indicated by increased reactive oxygen species(ROS)level.In addition,we observed mitochondrial dysfunction,including abnormal mitochondrial structure and respiratory function,along with a reduction in mitochondrial membrane potential and mitochondrial copy number,and the induction of apoptosis.Notably,we also observed the upregulation of autophagy proteins(PINK,Parkin,LC3B and Ubiquitin),however,the P62 protein was also increased.As we expected,100 Wmol/L of MT pre-treatment attenuated PA-induced mitochondrial ROS and restored mitochondrial respiratory function,Meanwhile,MT pretreatment reversed the upregulation of P62induced by PA and activated the AMPK-mTOR-Beclin-1 pathway,contributing to an increase of autophagy and decline apoptosis.Conclusions Our findings indicate that PA can induce mitochondrial dysfunction and enhance autophagy in BEECs.In addition,MT is proved to not only reduce mitochondrial oxidative stress but also facilitate the clearance of damaged mitochondria by upregulating autophagy pathways,thereby safeguarding the mitochondrial pool and promoting cellular viability.Our study provides a better understanding of the molecular mechanisms underlying the effect of an excess of NEB on the fertility outcomes of high yielding dairy cows.
基金supported in part by the National Key Research and Development Program of China(2023YFC3402100 to J.G.)the National Nature Science Foundation of China(82473404 to W.X.)the Natural Science Foundation of Guangdong Province(2022A1515220004 to J.G.,2024A1515010945 to W.X.,and 2023A1515010384 to Q.J.).
文摘Nutrients from dietary foods not only provide energy and building blocks,but also play critical roles in modulating diverse pathophysiological functions.They achieve these,in part,by accelerating cell signaling transduction processes via modulating various types of protein post-translational modifications(PTMs).Notably,accumulating evidence has identified palmitic acid(PA),a major component of high-fat diets,as a significant contributor to various human disorders,including diabetes and cancer.Hence,further understanding the roles of PA and its involvement in protein palmitoylation,a key PTM,is crucial for uncovering the mechanisms underlying these diseases and exploring potential clinical applications in cancer therapy.This review comprehensively summarizes recent advances in the understanding of PA homeostasis and palmitoylation in tumorigenesis.Specifically,it highlights the connections between palmitoylation and key processes such as oncogenic signaling pathways,cell death mechanisms,innate immune responses,and the tumor microenvironment.The review also emphasizes potential therapeutic strategies,including targeting PA homeostasis,palmitoylation-associated processes,or specific palmitoylated proteins for cancer treatment.Finally,the challenges in the field,such as the regulation of PA homeostasis and the dynamic detection or targeting of palmitoylation,are discussed,underscoring the need for further research to address these critical issues.
基金supported in part by the General Research Fund(17122519,17126317,1712222217119123,17106624)+5 种基金the Collaborative Research Fund(C4008-23W)Research Grants Council of Hong Kongthe Health and Medical Research Fund,Food and Health Bureau(18192021)Hong Kong SAR GovernmentSeed Funding for Strategic Interdisciplinary Research Scheme,University of Hong Kong Hong Kong SAR,ChinaShenzhen Institute of Synthetic Biology Scientific Research Program(ZTXM20214004),Shenzhen,China.
文摘Dietary fatty acids(FAs)are associated with the therapeutic intervention under various health conditions.Human γδ-T cells are indispensable for immunosurveillance toward malignant cells.However,their impact onγδ-T cell metabolism and function remains poorly unexplored.Here,we applied targeted metabolomics analysis to serum FAs among cancer patients undergoing γδ-T cell therapy and discovered that palmitic acid(PA)or oleic acid(OA)levels were associated with the efficacy of Vγ9Vδ2-T cell therapy.We further elucidated that PA suppresses the antitumor activity of Vγ9Vδ2-T cells by disrupting metabolic processes and inhibiting the secretion of lytic granules,whereas OA restores the impaired antitumor activity of Vγ9Vδ2-T cells.Mechanistically,we surprisingly found that PA stimulates Vγ9Vδ2-T cells to secrete excessive IFNγ,which in turn induces cell pyroptosis,ultimately resulting in decreased antitumor activity.
基金Supported by the National Natural Science Foundation of China(No.81373871 and 81273683)
文摘Objective： To investigate the effects of berberine （BBR） and cinnamic acid （CA）, the main active components in Jiaotai Pill （交泰丸, JTP）, on palmitic acid （PA）-induced intracellular tdglyceride （TG） accumulation in NIT-1 pancreatic 13 cells. Methods： Cells were incubated in culture medium containing PA （0.25 mmol/L） for 24 h. Then treatments with BBR （10 μmol/L）, CA （100 μmol/L） and the combination of BBR and CA （BBR＋CA） were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase （AMPK） protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase （FAS）, acetyl-coA carboxylase （ACC）, phosphorylation acetyl-coA carboxylase （pACC）, carnitine acyl transferase 1 （CPT-1） and sterol regulating element binding protein lc （SREBP-lc） were determined by Western blot or real time polymerase chain reaction. Results： PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-I. Meanwhile, AMPK downstream lipogenic genes including SREBP-lc mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR＋CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic 13 cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study. Conclusion： It can be concluded that in vitro, BBR and BBR＋CA could inhibit PA-induced lipid accumulation by decreasing lipoqenesis and increasin.cl lipid oxidation in NIT-1 pancreatic B cells.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
基金supported by the National Key Research and Development Program of China(2021YFD2100700).
文摘Triacylglycerol(TAG)components in human milk,infant formulas with different fat sources,and plant oils(palm oil,flaxseed oil,sunflower oil,corn oil,soybean oil,coconut oil,low erucic acid rapeseed oil,and high oleic acid rapeseed oil)were analyzed and compared using ultraperformance supercritical fluid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPSFC-Q-TOF-MS).Distinct TAG profiles were identified by lipidomics,principal component analysis(PCA),and heatmap visualization.Human milk was characterized by a high abundance of medium-and long-chain triacylglycerols(MLCTs),saturated-unsaturated-unsaturated(SUU)-type TAGs(sn-2 palmitic acid).In contrast,plant oils lacked MLCTs and SUU-type TAGs,containing mainly TAGs esterified long-chain polyunsaturated fatty acid.Breast milk contains about 27%MLCT,about 50%SUU-type triacylglycerols(which contain about 34%UPU-type triacylglycerols),which is significantly different from plant oils,structured fats and infant formulas.These findings provide a clear basis for optimizing the fat blend in infant formula to better mimic the unique TAG profile of human milk,thereby improving energy delivery and nutrient absorption for infants.
基金supported by National Natural Science Foundation of China(Nos.81273569,81001465)Natural Science Foundation of Jiangsu Province,China(No.BK2012726)the Ph.D. Programs Foundation of Ministry of Education of China(No.20100091120028)
文摘Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.
基金Supported by the National Natural Science Foundation of China(No.41776177)the Qingdao Marine Science and Technology Pilot National Laboratory Fund(Nos.2016ASKJ14,QNLM2016ORP0403)。
文摘Mussels are common anchoring organisms that adhere to the surfaces of various substrates with their byssus.The adhesion of mussel to substrates is contingent upon the presence of mussel foot proteins,of which Mytilus edulis foot protein-1(Mefp-1)has been identified as the most abundant protein.It has been found that lipids are involved in the mussel adhesion process and can facilitate Mefp-1adhesion.In this research,the adhesion behavior of Mefp-1 on various substrate surfaces under the effect of typical seawater cations with or without the presence of lipid were investigated using a quartz crystal microbalance with dissipation(QCM-D).Results indicate that the presence of cations Ca^(2+),Mg^(2+),Na^(+),and K^(+)leads to varying degrees of reduction in the adhesion performance of Mefp-1 on different substrates.The degree of this reduction,however,was much alleviated in the presence of palmitic acid,which is involved in the mussel adhesion process.Therefore,the involvement of palmitic acid is advantageous for mussel protein adhesion to the substrate surface in the marine environment.This study illustrated the significant contribution of palmitic acid to mussel adhesion,which can help to better understand biofouling mechanisms and develop biomimetic adhesive materials.
基金supported by a National Natural Science Foundation of China grant(31701558)the Young Elite Scientists Sponsorship Program by CAST(2017QNRC001)+1 种基金the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,B90719028)the national first-class discipline program of Food Science and Technology(JUFSTR20180202).
文摘Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41476058 & 41221004)the Program for New Century Excellent Talents in University (Grant No. NCET-13-0535)
文摘Hydrogen isotopes in lipid biomarkers can trace past changes in the hydrologic cycle. Recent studies have revealed the potential of hydrogen isotopes in microalgal lipids for quantitatively reconstructing water δ~2H（δD） values and salinity. In this study we collected suspended particles along a salinity gradient from the Changjiang River Estuary（CRE）, and measured δD values in fatty acids in these particles. The results indicated that δD values of water were correlated highly with salinity from the CRE, in agreement with the results from other estuaries. δD values in palmitic acid and stearic acid had a positive correlation with δD values of water from the CRE. Nevertheless, in the CRE, hydrogen isotope fractionation in fatty acids relative to water increased as salinity increased, opposite the trend in hydrogen isotope fractionation with salinity found in microalgal culture and field studies. We attribute the increase in hydrogen isotope fractionation as salinity increased to light availability, which was likely lower in the particle rich mixing zone at the end of the estuary, and potentially as well to multiple sources of fatty acids in the CRE.
基金financially supported by the National Natural Science Foundation of China(21972099)the Application Foundation Program of Sichuan Province(2021YJ0305)+1 种基金the 111 project(B17030).Shanghai Synchrotron Radiation Facility(SSRF)for XAS experiments and the support by the project from NPL of CAEP(2019BB08)。
文摘The selective cleavage of C-O and C-C is facing a challenge in the field of catalysis.In the present work,we studied the influence of doped Ni on the structure and electronic properties,as well as the selective C-O/C-C bond cleavages in the hydrodeoxygenation of palmitic acid over Ni-Mo_(2)C catalyst.The catalytic activity on Ni doped Mo_(2)C with TOF of 6.9×10^(3)h^(-1)is much superior to intrinsic Mo_(2)C catalyst,which is also higher than most noble metal catalysts.Structurally,the doped Ni raises the active particle dispersion and the coordination numbers of Mo species(Mo-C and Mo-O),improves the graphitization degree to promote the electron transfer,and increases the amount of Lewis and Br?nsted acid,which are responsible for the excellent hydrodeoxygenation performance.The Ni promotes simultaneously C-O and C-C bonds cleavage to produce pentadecane and hexadecane owing to the increase of electron-rich Mo sites after Ni doping.These findings contribute to the understanding of the nature of Ni-doped Mo_(2)C on the roles as catalytic active sites for C-O and C-C bonds cleavage.
文摘In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.
文摘Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.
基金supported by a grant from Department of Animal Biology and Research Center for Bioscience and Biotechnology(RCBB),University of Tabriz(6906).
文摘Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques. Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability. Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.
