Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic...Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.展开更多
Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent ye...Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.展开更多
Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabo...Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under investigation.Methods:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis.OPA3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were examined.OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR.OPA3 subcellular localization was detected using immunofluorescence.Proliferation and apoptosis were assessed via colony formation andflow cytometry.Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC cells.Results:Bioinformatics analysis revealed that OPA3 was downregulated in CRC.Overexpression of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of HUVECs.OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells.Additionally,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab treatment.Conclusion:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells.Therefore,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.展开更多
BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous stud...BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism.AIM To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance.METHODS We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC.The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells.We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells.Finally,we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells.RESULTS Compared to normal mucosa,REG4 mRNA expression was high in CRC(P<0.05)but protein expression was low.An inverse correlation existed between lymph node and distant metastases,tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression(P<0.05),but vice versa for REG4 protein expression.REG4-related genes included:Chemokine activity;taste receptors;protein-DNA and DNA packing complexes;nucleosomes and chromatin;generation of second messenger molecules;programmed cell death signals;epigenetic regulation and DNA methylation;transcription repression and activation by DNA binding;insulin signaling pathway;sugar metabolism and transfer;and neurotransmitter receptors(P<0.05).REG4 exposure or overexpression promoted proliferation,antiapoptosis,migration,and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway.REG4 was involved in chemoresistance not through de novo lipogenesis,but lipid droplet assembly.REG4 inhibited the transcription of acetyl-CoA carboxylase 1(ACC1)and ATP-citrate lyase(ACLY)by disassociating the complex formation of anti-acetyl(AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY.CONCLUSION REG4 may be involved in chemoresistance through lipid droplet assembly.REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.展开更多
Amphiphilic lipid molecules can form various micelles depending on not only their molecular composition but also their self-assembly pathway. In this work, coarse-grained molecular dynamics simulations have been appli...Amphiphilic lipid molecules can form various micelles depending on not only their molecular composition but also their self-assembly pathway. In this work, coarse-grained molecular dynamics simulations have been applied to study the micellization behaviors of mixed dipalmitoylphosphatidylcholine （DPPC）/hexadecylphosphocholine （HPC） droplets. By vary- ing DPPC/HPC composition and the size of lipid droplets, various micelles such as spherical and nonspherical （oblate or prolate） vesicles, disk-like micelles, double or single ring-like and worm-like micelles were observed. It is found that the lipid droplet as an initial state favors forming vesicles and ring-like micelles due to in situ micellization. Our simulation results demonstrate that using special initial conditions combined with various molecular compositions is an effective way to tune lipid micellar structure.展开更多
An implicit solvent coarse-grained （CG） lipid model using three beads to reflect the basically molecular structure of two-tailed lipid is developed. In this model, the nonbonded interaction employs a variant MIE pot...An implicit solvent coarse-grained （CG） lipid model using three beads to reflect the basically molecular structure of two-tailed lipid is developed. In this model, the nonbonded interaction employs a variant MIE potential and the bonded interaction utilizes a Harmonic potential form. The CG force field parameters are achieved by matching the structural and mechan-ical properties of dipalmitoylphosphatidylcholine （DPPC） bilayers. The model successfully reproduces the formation of lipid bilayer from a random initial state and the spontaneous vesiculation of lipid bilayer from a disk-like structure. After that, the model is used to sys-tematically study the vesiculation processes of spherical and cylindrical lipid droplets. The results show that the present CG model can effectively simulate the formation and evolution of mesoscale complex vesicles.展开更多
Background: Milk lipids originate from cytoplasmic lipid droplets(LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1 A1(BTN1 A1) is one of the ...Background: Milk lipids originate from cytoplasmic lipid droplets(LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1 A1(BTN1 A1) is one of the membrane proteins that surrounds LD, but its role in bovine mammary lipid droplet synthesis and secretion is not well known.Methods: The objective was to knockout BTN1 A1 in bovine mammary epithelial cells(BMEC) via the CRISPR/Cas9 system and evaluate LD formation, abundance of lipogenic enzymes, and content of cell membrane phospholipid(PL) species. Average LD diameter was determined via Oil Red O staining, and profiling of cell membrane phospholipid species via liquid chromatography-tandem mass spectrometry(LC-MS/MS).Results: Lentivirus-mediated infection of the Cas9/sg RNA expression vector into BMEC resulted in production of a homozygous clone BTN1 A1^((-/-)). The LD size and content decreased following BTN1 A1 gene knockout. The m RNA abundance of fatty acid synthase(FASN) and peroxisome proliferator-activated receptor-gamma(PPARG) was downregulated in the BTN1 A1^((-/-))clone. Subcellular analyses indicated that BTN1 A1 and LD were co-localized in the cytoplasm. BTN1 A1 gene knockout increased the percentage of phosphatidylethanolamine(PE) and decreased phosphatidylcholine(PC), which resulted in a lower PC/PE ratio.Conclusions: Results suggest that BTN1 A1 plays an important role in regulating LD synthesis via a mechanism involving membrane phospholipid composition.展开更多
Aim: In order to reveal the histochemical alteration that might occur during the processes of the spermatogenic dis-ruption induced by testicular capsulotomy, the location and alteration of lipid droplets in the semin...Aim: In order to reveal the histochemical alteration that might occur during the processes of the spermatogenic dis-ruption induced by testicular capsulotomy, the location and alteration of lipid droplets in the seminiferous tubules wereobserved in the present study. Methods: Osmium tetroxide was used to demonstrate the lipid droplets in the semi-niferous tubules of capsulotomized and sham-operated control testes. Results: In the seminiferous tubules of thesham-operated rat testes, many small lipid droplets were located close to the basement membrane of the seminiferoustubules. But for the capsulotomized testes, the lipid droplets in the seminiferous tubules had increased in size and num-ber, with many lipid droplets migrated towards the lumen of the tubules. Conclusion: The results indicated that aprogressive fatty degeneration occurred in the seminiferous tubules after testicular capsulotomy.展开更多
Background:Oleic acid is an abundant free fatty acid present in livestock that are in a negative energy-balance state,and it may have detrimental effects on female reproduction and fertility.Oleic acid induces lipid a...Background:Oleic acid is an abundant free fatty acid present in livestock that are in a negative energy-balance state,and it may have detrimental effects on female reproduction and fertility.Oleic acid induces lipid accumulation in bovine granulosa cells,which leads to a foam cell-like morphology and reduced steroidogenesis.However,why oleic acid increases lipid accumulation but decreases steroidogenesis remains unclear.This study focused on oleic acid’s effects on lipid type and steroidogenesis.Results:Oleic acid increased the lipid accumulation in a concentration-dependent manner and mainly increased the triglyceride level and decreased the cholesterol ester level.Oleic acid also led to a decline in estradiol and progesterone production in porcine granulosa cells in vitro.In addition,oleic acid up-regulated the expression of CD36 and diacylglycerol acyltransferase 2,but down-regulated the expression of 3-hydroxy-3-methylglutarylcoenzyme A reductase,scavenger receptor class B member 1 and acetyl-Coenzyme A acetyltransferase 2,as well as steroidogenesis-related genes,including cytochrome P450 family 11 subfamily A member 1,cytochrome P450family 19 subfamily A member 1 and 3 as well as steroidogenic acute regulatory protein at the mRNA and protein levels.An oleic acid-rich diet also enhanced the triglyceride levels and reduced the cholesterol levels in ovarian tissues of female mice,which resulted in lower estradiol levels than in control-fed mice.Compared with the control,decreases in estrus days and the numbers of antral follicles and corpora lutea,as well as an increase in the numbers of the atretic follicles,were found in the oleic acid-fed female mice.Conclusions:Oleic acid changed the lipid type stored in lipid droplets of ovarian granulosa cells,and led to a decrease in steroidogenesis.These results improve our understanding of fertility decline in livestock that are in a negative energy-balance state.展开更多
Previously regarded as simple fat storage particles,new evidence suggests thatlipid droplets(LDs)are dynamic and functional organelles involved in keycellular processes such as membrane biosynthesis,lipid metabolism,c...Previously regarded as simple fat storage particles,new evidence suggests thatlipid droplets(LDs)are dynamic and functional organelles involved in keycellular processes such as membrane biosynthesis,lipid metabolism,cellsignalling and inflammation.Indeed,an increased LD content is one of the mostapparent features resulting from lipid metabolism reprogramming necessary tosupport the basic functions of cancer cells.LDs have been associated to differentcellular processes involved in cancer progression and aggressiveness,such astumorigenicity,invasion and metastasis,as well as chemoresistance.Interestingly,all of these processes are controlled by a subpopulation of highly aggressivetumoral cells named cancer stem cells(CSCs),suggesting that LDs may befundamental elements for stemness in cancer.Considering the key role of CSCs onchemoresistance and disease relapse,main factors of therapy failure,the design ofnovel therapeutic approaches targeting these cells may be the only chance forlong-term survival in cancer patients.In this sense,their biology and functionalproperties render LDs excellent candidates for target discovery and design ofcombined therapeutic strategies.In this review,we summarise the currentknowledge identifying LDs and CSCs as main contributors to cancer aggressiveness,metastasis and chemoresistance.展开更多
The Annona genus is a member of Annonaceae,one of the largest families of plants across tropical and subtropical regions.This family has been used in several ethnomedicinal practices to treat a multitude of human dise...The Annona genus is a member of Annonaceae,one of the largest families of plants across tropical and subtropical regions.This family has been used in several ethnomedicinal practices to treat a multitude of human diseases.However,the molecular mechanism underlying its effect on the lipid droplet formation and on the expression of adipogenic markers of this plant remain to be investigated.In this study,we examined whether the extracts from the aerial part of Annona montana affect in vitro differentiation of preadipocytes.For our investigations,both mouse embryo fibroblast 3T3-L1 and normal human primary subcutaneous preadipocytes were incubated with Annona montana extracts(-and its subfractions-)and then analyzed on preadipocyte differentiation,lipid content,lipid droplet size and number,the expression of adipogenic-specific transcriptional factors,as well as cell survival.From our examinations,we found the Annona montana ethyl acetate extract to exhibit a potent inhibitory effect on adipogenesis,without affecting cell survival,in a dose-dependent manner.Such inhibitory effects included a significant decrease in the accumulation of lipid content by both a dramatic reduction of size and number of lipid droplets.This extract strongly attenuated the expression of PPARγand HMGB2.It also inhibited the expression of CEBPα,FAS,and Akt without influencing Erk1/2 activities.Our findings suggest that specifically,the Annona montana ethyl acetate extract has a prominent inhibitory effect in cellular pathways of adipocyte differentiation by modulating specific gene expression,which is known to perform a pivotal role during adipogenesis.展开更多
Metabolic changes play a crucial role in determining the status and function of macrophages,but how lipid reprogramming in macrophages contributes to tumor progression is not yet fully understood.Here,we investigated ...Metabolic changes play a crucial role in determining the status and function of macrophages,but how lipid reprogramming in macrophages contributes to tumor progression is not yet fully understood.Here,we investigated the phenotype,contribution,and regulatory mechanisms of lipid droplet(LD)-laden macrophages(LLMs)in hepatocellular carcinoma(HCC).Enriched LLMs were found in tumor tissues and were associated with disease progression in HCC patients.The LLMs displayed immunosuppressive phenotypes(with extensive expression of TREM2,PD-L1,CD206,and CD163)and attenuated the antitumor activities of CD8^(+)T cells.Mechanistically,tumor-induced reshuffling of cellular lipids and TNFα-mediated uptake of tumoral fatty acids contribute to the generation of triglycerides and LDs in macrophages.LDs prolong LLM survival and promote CCL20 secretion,which further recruits CCR6^(+)Tregs to HCC tissue.Inhibiting LLM formation by targeting DGAT1 and DGAT2,which catalyze the synthesis of triglycerides,significantly reduced Treg recruitment,and delayed tumor growth in a mouse hepatic tumor model.Our results reveal the suppressive phenotypes and mechanisms of LLM enrichment in HCC and suggest the therapeutic potential of targeting LLMs for HCC patients.展开更多
Lipid droplets(LDs),which are the hubs of lipid metabolism,play a critical role in maintaining cellular energy homeostasis.The construction of advanced photo-sensitizers(PSs)capable of manipulating LD-mediated cell fa...Lipid droplets(LDs),which are the hubs of lipid metabolism,play a critical role in maintaining cellular energy homeostasis.The construction of advanced photo-sensitizers(PSs)capable of manipulating LD-mediated cell fate regulation is highly desirable though rarely reported.In this study,a near-infrared emissive PS(DPCMP)with LDs specificity was synthesized and successfully applied to induce ferroptosis and apoptosis.DPCMP exhibited typical aggregation-induced emission charac-teristics owing to its twisted molecular conformation.Excellent biocompatibility and suitable lipophilicity allowed DPCMP to specifically stain the LDs in living cells.Under white light illumination,the DPCMP displayed potent reactive oxygen species(ROS)generation capacity through both type I and II photochemistry.The massive accumulation of lethal ROS generated by DPCMP-mediated photosensiti-zation initiated lipid peroxidation,impaired cellular redox homeostasis,and led to endoplasmic reticulum oxidative stress,ultimately inhibiting cellular proliferation via concurrent ferroptosis and apoptosis in both living cancer cells and multicellular tumor spheroids.展开更多
Abnormal accumulation and metabolism of lipid droplets can lead to a variety of diseases.Polarity,a key parameter of the microenvironment,is closely associated with many diseases and dysfunctions in the body.It is imp...Abnormal accumulation and metabolism of lipid droplets can lead to a variety of diseases.Polarity,a key parameter of the microenvironment,is closely associated with many diseases and dysfunctions in the body.It is important to elucidate the relationship between the physiological activity of lipid droplets(LDs)and the polarity of the microenvironment.In this work,based on push-pull mechanism,a fluorescent probe(E)-3-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one(PPTH)with aggregation-induced emission(AIE)properties for the detection of polarity changes in cells was synthesized.PPTH not only visualize intracellular polarity fluctuation of iron death and inflammation but also distinguish between normal and fatty liver tissue.展开更多
Long-term fluorescence monitoring of subcellular organelles is crucial for cellular physiology and pathology studies.Lipid droplets(LDs)are increasingly recognized for their involvement in various biological processes...Long-term fluorescence monitoring of subcellular organelles is crucial for cellular physiology and pathology studies.Lipid droplets(LDs)are increasingly recognized for their involvement in various biological processes,to influence disease development through diverse behaviors However,existing LD probes face challenges in achieving high targeting and long-term monitoring due to poor photostability and long-term phototoxicity.Carbon quantum dots(CQDs)have gained prominence due to their exceptional fluorescence properties,but their prevalent blue excitation wavelength presents difficulties for long-term imaging.Herein,we synthesized red-emissive carbon quantum dot(R-CQDs)with superior photobleaching resistance and red-emission,thus enabling harmlessly fluorescence monitoring of cells longer than3 h.In addition,R-CQD exhibits suitable amphiphilicity and remarkable solvatochromic effect,allowing rapid targeting to LDs for immediate imaging without cumbersome washing steps.Hence,R-CQD shows high performance for extended observation of dynamic LD behavior in various biological processes,which is confirmed by documenting the course of LDs during starvation as well as lipotoxicity.Compared to commercial probes,R-CQD extends live cell imaging time by at least 9-fold,facilitating the study of LD behavioral characteristics under diverse physiological or pathological conditions.This work provides a reliable fluorescence tool for tracking intercellular microenvironment dynamically thus to understand the divers biological or disease mechanism.展开更多
Lipid droplets(LDs)participating in various cellular activities and are increasingly being emphasized.Fluorescence imaging provides powerful tool for dynamic tracking of LDs,however,most current LDs probes remain inco...Lipid droplets(LDs)participating in various cellular activities and are increasingly being emphasized.Fluorescence imaging provides powerful tool for dynamic tracking of LDs,however,most current LDs probes remain inconsistent performance such as low Photoluminescence Quantum Yield(PLQY),poor photostability and tedious washing procedures.Herein,a novel yellow-emissive carbon dot(OT-cD)has been synthesized conveniently with high PLQY up to 90%.Besides,OT-CD exhibits remarkable amphiphilicity and solvatochromic property with lipid-water partition coefficient higher than 2,which is much higher than most LDs probes.These characters enable OT-CD high brightness,stable and wash-free LDs probing,and feasible for in vivo imaging.Then,detailed observation of LDs morphological and polarity variation dynamically in different cellular states were recorded,including ferroptosis and other diseases processes.Furthermore,fast whole imaging of zebrafish and identifed LD enrichment in injured liver indicate its further feasibility for in vivo application.In contrast to the reported studies to date,this approach provides a versatile conventional synthesis system for high-performance LDs targeting probes,combing the advantages of easy and high-yield production,as well as robust brightness and stability for long-term imaging,facilitating investigations into organelle interactions and LD-associated diseases.展开更多
Two-photon photodynamic therapy(TP-PDT)has garnered significant attention because of its excellent depth of tissue penetration and high spatiotemporal selectivity.However,the limited targeting ability and oxygen depen...Two-photon photodynamic therapy(TP-PDT)has garnered significant attention because of its excellent depth of tissue penetration and high spatiotemporal selectivity.However,the limited targeting ability and oxygen dependency of photosensitizers(PSs)significantly hinder the effectiveness of photodynamic therapy in hypoxic tumor treatment.Herein,we designed and synthesized two lipid droplet(LD)-targeted two-photon PSs(TBPCP and TBCP)by reducing benzene rings to achieve“acceptor planarization”.Notably,acceptor planarization not only enhanced the intramolecular charge transfer but also transferred the photochemical reaction from typeⅡ(TBPCP)to typeⅠ(TBCP).Under the irradiation of 940 nm femtosecond pulsed laser,TBPCP and TBCP showed bright two-photon-excited fluorescence and excellent LD targeting in living cells.Comparing TBPCP(typeⅡPS),the outstanding TP-PDT efficacy of TBCP(typeⅠPS)under hypoxic conditions could be obtained in both cellular experiments and multicellular tumor spheroids(MCTS)model.Additionally,both TBPCP and TBCP could induce the lipid peroxidation in the typeⅠor typeⅡPDT due to the location of LD,depleting GSH and inactivating GPX4 to induce nonprogrammed ferroptosis in cells.展开更多
The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of brig...The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of bright organic luminogens with typical electron-donating(D)and electron-accepting(A)structures(abbreviated as LDs-BDM,LDs-BTM,and LDs-BHM)was synthesized through a simple single-step reaction.They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70%(e.g.,83.7%for LDs-BTM).Their light-emission properties could be tuned by the modulation ofπ-conjugation effect with methoxy groups at different substituent positions.Their resulting fluorescent nanoparticles(NPs)were demonstrated as specific lipid droplets(LDs)targeting probes with high brightness,good biocompatibility,and satisfactory photostability.LDs-BTM NPs with a large two-photon absorption cross section(σ2=249 GM)were further utilized as ultrabright two-photon fluorescence(2PF)nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration(0.5μmol/L).Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated.This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique.These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.展开更多
Lipid droplet(LD)in vegetative tissues has recently been implicated in environmental responses in plants,but its regulation and its function in stress tolerance are not well understood.Here,we identified a Membrane Oc...Lipid droplet(LD)in vegetative tissues has recently been implicated in environmental responses in plants,but its regulation and its function in stress tolerance are not well understood.Here,we identified a Membrane Occupation and Recognition Nexus 1(MORN1)gene as a contributor to natural variations of stress tolerance through genome-wide association study in Arabidopsis thaliana.Characterization of its loss-of-function mutant and natural variants revealed that the MORN1 gene is a positive regulator of plant growth,disease resistance,cold tolerance,and heat tolerance.The MORN1 protein is associated with the Golgi and is also partly associated with LD.Protein truncations that disrupt these associations abolished the biological function of the MORN1 protein.Furthermore,the MORN1 gene is a positive regulator of LD abundance,and its role in LD number regulation and stress tolerance is highly linked.Therefore,this study identifies MORN1 as a positive regulator of LD abundance and a contributor to natural variations of stress tolerance.It implicates a potential involvement of Golgi in LD biogenesis and strongly suggests a contribution of LD to diverse processes of plant growth and stress responses.展开更多
基金funded by Basic Research Program of Shanghai,No.20JC1412200(to JW)the National Key Research and Development Program of China,No.2020YFA0113000(to RCZ)。
文摘Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
基金funded by the National Natural Science Foundation of China(32102646)the Natural Science Foundation of Guangdong Province,China(2020A1515110315)+1 种基金the Start-up Research Project of Maoming Laboratory,China(2021TDQD002)the China Agriculture Research System of MOF and MARA(cars-35)。
文摘Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.
文摘Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under investigation.Methods:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis.OPA3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were examined.OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR.OPA3 subcellular localization was detected using immunofluorescence.Proliferation and apoptosis were assessed via colony formation andflow cytometry.Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC cells.Results:Bioinformatics analysis revealed that OPA3 was downregulated in CRC.Overexpression of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of HUVECs.OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells.Additionally,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab treatment.Conclusion:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells.Therefore,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.
基金Natural Science Foundation of Hebei Province,No.21377772DNo.H2022406034National Natural Scientific Foundation of China,No.81672700.
文摘BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism.AIM To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance.METHODS We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC.The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells.We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells.Finally,we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells.RESULTS Compared to normal mucosa,REG4 mRNA expression was high in CRC(P<0.05)but protein expression was low.An inverse correlation existed between lymph node and distant metastases,tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression(P<0.05),but vice versa for REG4 protein expression.REG4-related genes included:Chemokine activity;taste receptors;protein-DNA and DNA packing complexes;nucleosomes and chromatin;generation of second messenger molecules;programmed cell death signals;epigenetic regulation and DNA methylation;transcription repression and activation by DNA binding;insulin signaling pathway;sugar metabolism and transfer;and neurotransmitter receptors(P<0.05).REG4 exposure or overexpression promoted proliferation,antiapoptosis,migration,and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway.REG4 was involved in chemoresistance not through de novo lipogenesis,but lipid droplet assembly.REG4 inhibited the transcription of acetyl-CoA carboxylase 1(ACC1)and ATP-citrate lyase(ACLY)by disassociating the complex formation of anti-acetyl(AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY.CONCLUSION REG4 may be involved in chemoresistance through lipid droplet assembly.REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.
基金This work was supported by the National Natural Science Foundation of China （No.20974078 and No.91127046）, Computation was carried out in High Performance Computing Center of Tianjin University.
文摘Amphiphilic lipid molecules can form various micelles depending on not only their molecular composition but also their self-assembly pathway. In this work, coarse-grained molecular dynamics simulations have been applied to study the micellization behaviors of mixed dipalmitoylphosphatidylcholine （DPPC）/hexadecylphosphocholine （HPC） droplets. By vary- ing DPPC/HPC composition and the size of lipid droplets, various micelles such as spherical and nonspherical （oblate or prolate） vesicles, disk-like micelles, double or single ring-like and worm-like micelles were observed. It is found that the lipid droplet as an initial state favors forming vesicles and ring-like micelles due to in situ micellization. Our simulation results demonstrate that using special initial conditions combined with various molecular compositions is an effective way to tune lipid micellar structure.
基金We thank Professor Dr. Markus Deserno （Department of Physics, Carnegie Mellon University）, Jemal Guven （Institute of Nuclear Science, Universidad Nacional Autonoma de Mexico）, and Zhan-chun Tu （Department of Physics, Beijing Normal University） for their valuable advice. This work is supported by the National Natural Science Foundation of China （No.20974078, No.21274107, and No.91127046）. The computation and simulation are partly carried out in High Performance Computing Center of Tianjin University.
文摘An implicit solvent coarse-grained （CG） lipid model using three beads to reflect the basically molecular structure of two-tailed lipid is developed. In this model, the nonbonded interaction employs a variant MIE potential and the bonded interaction utilizes a Harmonic potential form. The CG force field parameters are achieved by matching the structural and mechan-ical properties of dipalmitoylphosphatidylcholine （DPPC） bilayers. The model successfully reproduces the formation of lipid bilayer from a random initial state and the spontaneous vesiculation of lipid bilayer from a disk-like structure. After that, the model is used to sys-tematically study the vesiculation processes of spherical and cylindrical lipid droplets. The results show that the present CG model can effectively simulate the formation and evolution of mesoscale complex vesicles.
基金supported by the National Natural Science Foundation of China (U1904116)Special Funds for Modern Agricultural Industry Technology System (CARS-37)+1 种基金National Key Research and Development Program of China (Beijing, China2016YFD0500503)。
文摘Background: Milk lipids originate from cytoplasmic lipid droplets(LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1 A1(BTN1 A1) is one of the membrane proteins that surrounds LD, but its role in bovine mammary lipid droplet synthesis and secretion is not well known.Methods: The objective was to knockout BTN1 A1 in bovine mammary epithelial cells(BMEC) via the CRISPR/Cas9 system and evaluate LD formation, abundance of lipogenic enzymes, and content of cell membrane phospholipid(PL) species. Average LD diameter was determined via Oil Red O staining, and profiling of cell membrane phospholipid species via liquid chromatography-tandem mass spectrometry(LC-MS/MS).Results: Lentivirus-mediated infection of the Cas9/sg RNA expression vector into BMEC resulted in production of a homozygous clone BTN1 A1^((-/-)). The LD size and content decreased following BTN1 A1 gene knockout. The m RNA abundance of fatty acid synthase(FASN) and peroxisome proliferator-activated receptor-gamma(PPARG) was downregulated in the BTN1 A1^((-/-))clone. Subcellular analyses indicated that BTN1 A1 and LD were co-localized in the cytoplasm. BTN1 A1 gene knockout increased the percentage of phosphatidylethanolamine(PE) and decreased phosphatidylcholine(PC), which resulted in a lower PC/PE ratio.Conclusions: Results suggest that BTN1 A1 plays an important role in regulating LD synthesis via a mechanism involving membrane phospholipid composition.
文摘Aim: In order to reveal the histochemical alteration that might occur during the processes of the spermatogenic dis-ruption induced by testicular capsulotomy, the location and alteration of lipid droplets in the seminiferous tubules wereobserved in the present study. Methods: Osmium tetroxide was used to demonstrate the lipid droplets in the semi-niferous tubules of capsulotomized and sham-operated control testes. Results: In the seminiferous tubules of thesham-operated rat testes, many small lipid droplets were located close to the basement membrane of the seminiferoustubules. But for the capsulotomized testes, the lipid droplets in the seminiferous tubules had increased in size and num-ber, with many lipid droplets migrated towards the lumen of the tubules. Conclusion: The results indicated that aprogressive fatty degeneration occurred in the seminiferous tubules after testicular capsulotomy.
基金supported by grants from the National Natural Science Foundation(No.31802047)the National Science and Technology Major Project of China(No.2016ZX08006003)。
文摘Background:Oleic acid is an abundant free fatty acid present in livestock that are in a negative energy-balance state,and it may have detrimental effects on female reproduction and fertility.Oleic acid induces lipid accumulation in bovine granulosa cells,which leads to a foam cell-like morphology and reduced steroidogenesis.However,why oleic acid increases lipid accumulation but decreases steroidogenesis remains unclear.This study focused on oleic acid’s effects on lipid type and steroidogenesis.Results:Oleic acid increased the lipid accumulation in a concentration-dependent manner and mainly increased the triglyceride level and decreased the cholesterol ester level.Oleic acid also led to a decline in estradiol and progesterone production in porcine granulosa cells in vitro.In addition,oleic acid up-regulated the expression of CD36 and diacylglycerol acyltransferase 2,but down-regulated the expression of 3-hydroxy-3-methylglutarylcoenzyme A reductase,scavenger receptor class B member 1 and acetyl-Coenzyme A acetyltransferase 2,as well as steroidogenesis-related genes,including cytochrome P450 family 11 subfamily A member 1,cytochrome P450family 19 subfamily A member 1 and 3 as well as steroidogenic acute regulatory protein at the mRNA and protein levels.An oleic acid-rich diet also enhanced the triglyceride levels and reduced the cholesterol levels in ovarian tissues of female mice,which resulted in lower estradiol levels than in control-fed mice.Compared with the control,decreases in estrus days and the numbers of antral follicles and corpora lutea,as well as an increase in the numbers of the atretic follicles,were found in the oleic acid-fed female mice.Conclusions:Oleic acid changed the lipid type stored in lipid droplets of ovarian granulosa cells,and led to a decrease in steroidogenesis.These results improve our understanding of fertility decline in livestock that are in a negative energy-balance state.
基金Miguel Servet Fellowship,No.CP16/00121FIS(Fondo Investigaciones Sanitarias)grants,No.PI17/00082 and No.PI20/00942,all from Instituto de Salud Carlos Ⅲ and Cofinanced by European Funds(FSE:“El FSE invierte en tu futuro”and FEDER:“Una manera de hacer Europa,”respectively)and the Worldwide Cancer Research Charity together with Fundación Científica Asociación Española contra el Cáncer(FCAECC),No.19-0250.
文摘Previously regarded as simple fat storage particles,new evidence suggests thatlipid droplets(LDs)are dynamic and functional organelles involved in keycellular processes such as membrane biosynthesis,lipid metabolism,cellsignalling and inflammation.Indeed,an increased LD content is one of the mostapparent features resulting from lipid metabolism reprogramming necessary tosupport the basic functions of cancer cells.LDs have been associated to differentcellular processes involved in cancer progression and aggressiveness,such astumorigenicity,invasion and metastasis,as well as chemoresistance.Interestingly,all of these processes are controlled by a subpopulation of highly aggressivetumoral cells named cancer stem cells(CSCs),suggesting that LDs may befundamental elements for stemness in cancer.Considering the key role of CSCs onchemoresistance and disease relapse,main factors of therapy failure,the design ofnovel therapeutic approaches targeting these cells may be the only chance forlong-term survival in cancer patients.In this sense,their biology and functionalproperties render LDs excellent candidates for target discovery and design ofcombined therapeutic strategies.In this review,we summarise the currentknowledge identifying LDs and CSCs as main contributors to cancer aggressiveness,metastasis and chemoresistance.
基金supported by the National Institutes of Health Grant SC1DK084343the U.S.Department of Defense Grant W911NF-13-0167(to MAB).
文摘The Annona genus is a member of Annonaceae,one of the largest families of plants across tropical and subtropical regions.This family has been used in several ethnomedicinal practices to treat a multitude of human diseases.However,the molecular mechanism underlying its effect on the lipid droplet formation and on the expression of adipogenic markers of this plant remain to be investigated.In this study,we examined whether the extracts from the aerial part of Annona montana affect in vitro differentiation of preadipocytes.For our investigations,both mouse embryo fibroblast 3T3-L1 and normal human primary subcutaneous preadipocytes were incubated with Annona montana extracts(-and its subfractions-)and then analyzed on preadipocyte differentiation,lipid content,lipid droplet size and number,the expression of adipogenic-specific transcriptional factors,as well as cell survival.From our examinations,we found the Annona montana ethyl acetate extract to exhibit a potent inhibitory effect on adipogenesis,without affecting cell survival,in a dose-dependent manner.Such inhibitory effects included a significant decrease in the accumulation of lipid content by both a dramatic reduction of size and number of lipid droplets.This extract strongly attenuated the expression of PPARγand HMGB2.It also inhibited the expression of CEBPα,FAS,and Akt without influencing Erk1/2 activities.Our findings suggest that specifically,the Annona montana ethyl acetate extract has a prominent inhibitory effect in cellular pathways of adipocyte differentiation by modulating specific gene expression,which is known to perform a pivotal role during adipogenesis.
基金supported by project grants from the National Key R&D Program of China(2023YFA0915703)the Guangdong Basic and Applied Basic Research Foundation(2022A1515111205)+1 种基金the National Natural Science Foundation of China(32230034,82273296)the Open Fund Project of Guangdong Academy of Medical Sciences(YKY-KF202207).
文摘Metabolic changes play a crucial role in determining the status and function of macrophages,but how lipid reprogramming in macrophages contributes to tumor progression is not yet fully understood.Here,we investigated the phenotype,contribution,and regulatory mechanisms of lipid droplet(LD)-laden macrophages(LLMs)in hepatocellular carcinoma(HCC).Enriched LLMs were found in tumor tissues and were associated with disease progression in HCC patients.The LLMs displayed immunosuppressive phenotypes(with extensive expression of TREM2,PD-L1,CD206,and CD163)and attenuated the antitumor activities of CD8^(+)T cells.Mechanistically,tumor-induced reshuffling of cellular lipids and TNFα-mediated uptake of tumoral fatty acids contribute to the generation of triglycerides and LDs in macrophages.LDs prolong LLM survival and promote CCL20 secretion,which further recruits CCR6^(+)Tregs to HCC tissue.Inhibiting LLM formation by targeting DGAT1 and DGAT2,which catalyze the synthesis of triglycerides,significantly reduced Treg recruitment,and delayed tumor growth in a mouse hepatic tumor model.Our results reveal the suppressive phenotypes and mechanisms of LLM enrichment in HCC and suggest the therapeutic potential of targeting LLMs for HCC patients.
基金National Natural Science Foundation of China,Grant/Award Numbers:22077077,22275119,21975149,21672135Fundamental Research Funds for the Central Universities,Grant/Award Numbers:GK202301010,18QNGG007,2021TS033。
文摘Lipid droplets(LDs),which are the hubs of lipid metabolism,play a critical role in maintaining cellular energy homeostasis.The construction of advanced photo-sensitizers(PSs)capable of manipulating LD-mediated cell fate regulation is highly desirable though rarely reported.In this study,a near-infrared emissive PS(DPCMP)with LDs specificity was synthesized and successfully applied to induce ferroptosis and apoptosis.DPCMP exhibited typical aggregation-induced emission charac-teristics owing to its twisted molecular conformation.Excellent biocompatibility and suitable lipophilicity allowed DPCMP to specifically stain the LDs in living cells.Under white light illumination,the DPCMP displayed potent reactive oxygen species(ROS)generation capacity through both type I and II photochemistry.The massive accumulation of lethal ROS generated by DPCMP-mediated photosensiti-zation initiated lipid peroxidation,impaired cellular redox homeostasis,and led to endoplasmic reticulum oxidative stress,ultimately inhibiting cellular proliferation via concurrent ferroptosis and apoptosis in both living cancer cells and multicellular tumor spheroids.
基金the financial supports from Scientific and Technological Key Project in Henan Province(No.22170015)National Natural Science Foundation of China(No.U1704161)+2 种基金Zhengzhou University(No.32211807)Henan Provincial Science and Technology Research Project(No.JC21253010)Basic Research Foundation of Shenzhen Science and Technology Innovation(No.JCYJ20190806144605441)。
文摘Abnormal accumulation and metabolism of lipid droplets can lead to a variety of diseases.Polarity,a key parameter of the microenvironment,is closely associated with many diseases and dysfunctions in the body.It is important to elucidate the relationship between the physiological activity of lipid droplets(LDs)and the polarity of the microenvironment.In this work,based on push-pull mechanism,a fluorescent probe(E)-3-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one(PPTH)with aggregation-induced emission(AIE)properties for the detection of polarity changes in cells was synthesized.PPTH not only visualize intracellular polarity fluctuation of iron death and inflammation but also distinguish between normal and fatty liver tissue.
基金supported by the National Natural Science Foundation of China(Nos.52003178,52273141 and 51973132)Natural Science Foundation of Sichuan Province(No.2023NSFSC0338)。
文摘Long-term fluorescence monitoring of subcellular organelles is crucial for cellular physiology and pathology studies.Lipid droplets(LDs)are increasingly recognized for their involvement in various biological processes,to influence disease development through diverse behaviors However,existing LD probes face challenges in achieving high targeting and long-term monitoring due to poor photostability and long-term phototoxicity.Carbon quantum dots(CQDs)have gained prominence due to their exceptional fluorescence properties,but their prevalent blue excitation wavelength presents difficulties for long-term imaging.Herein,we synthesized red-emissive carbon quantum dot(R-CQDs)with superior photobleaching resistance and red-emission,thus enabling harmlessly fluorescence monitoring of cells longer than3 h.In addition,R-CQD exhibits suitable amphiphilicity and remarkable solvatochromic effect,allowing rapid targeting to LDs for immediate imaging without cumbersome washing steps.Hence,R-CQD shows high performance for extended observation of dynamic LD behavior in various biological processes,which is confirmed by documenting the course of LDs during starvation as well as lipotoxicity.Compared to commercial probes,R-CQD extends live cell imaging time by at least 9-fold,facilitating the study of LD behavioral characteristics under diverse physiological or pathological conditions.This work provides a reliable fluorescence tool for tracking intercellular microenvironment dynamically thus to understand the divers biological or disease mechanism.
基金the National Natural Science Foundation of China(grant numbers:52003178 and 51973132)Intermnational Science and Technology Innovation Cooperation Foundation of Sichuan Province(grant number:2022YFH0086)Natural Science Foundation of Sichuan Province(grant number:2023NSFSC0338 and 2023NSFSC1067).
文摘Lipid droplets(LDs)participating in various cellular activities and are increasingly being emphasized.Fluorescence imaging provides powerful tool for dynamic tracking of LDs,however,most current LDs probes remain inconsistent performance such as low Photoluminescence Quantum Yield(PLQY),poor photostability and tedious washing procedures.Herein,a novel yellow-emissive carbon dot(OT-cD)has been synthesized conveniently with high PLQY up to 90%.Besides,OT-CD exhibits remarkable amphiphilicity and solvatochromic property with lipid-water partition coefficient higher than 2,which is much higher than most LDs probes.These characters enable OT-CD high brightness,stable and wash-free LDs probing,and feasible for in vivo imaging.Then,detailed observation of LDs morphological and polarity variation dynamically in different cellular states were recorded,including ferroptosis and other diseases processes.Furthermore,fast whole imaging of zebrafish and identifed LD enrichment in injured liver indicate its further feasibility for in vivo application.In contrast to the reported studies to date,this approach provides a versatile conventional synthesis system for high-performance LDs targeting probes,combing the advantages of easy and high-yield production,as well as robust brightness and stability for long-term imaging,facilitating investigations into organelle interactions and LD-associated diseases.
基金supported by the National Key Research and Development Program of China(2022YFA1207600)the National Natural Science Foundation of China(62375272,62005294)。
文摘Two-photon photodynamic therapy(TP-PDT)has garnered significant attention because of its excellent depth of tissue penetration and high spatiotemporal selectivity.However,the limited targeting ability and oxygen dependency of photosensitizers(PSs)significantly hinder the effectiveness of photodynamic therapy in hypoxic tumor treatment.Herein,we designed and synthesized two lipid droplet(LD)-targeted two-photon PSs(TBPCP and TBCP)by reducing benzene rings to achieve“acceptor planarization”.Notably,acceptor planarization not only enhanced the intramolecular charge transfer but also transferred the photochemical reaction from typeⅡ(TBPCP)to typeⅠ(TBCP).Under the irradiation of 940 nm femtosecond pulsed laser,TBPCP and TBCP showed bright two-photon-excited fluorescence and excellent LD targeting in living cells.Comparing TBPCP(typeⅡPS),the outstanding TP-PDT efficacy of TBCP(typeⅠPS)under hypoxic conditions could be obtained in both cellular experiments and multicellular tumor spheroids(MCTS)model.Additionally,both TBPCP and TBCP could induce the lipid peroxidation in the typeⅠor typeⅡPDT due to the location of LD,depleting GSH and inactivating GPX4 to induce nonprogrammed ferroptosis in cells.
基金the National Natural Science Foundation of China(Nos.81902356,82072581,21971265 and 82272842)Programs for Medical Science and Technology Research Project of Henan Province Health Commission(Nos.2018020025,SB201901029)+2 种基金Henan Province Young and Middle-Aged Health Science and Technology Innovation Talent Project(No.YXKC2022032)Shenzhen Key Laboratory of Functional Aggregate Materials(No.ZDSYS20211021111400001)Provincial Science and Technology R&D Program Joint Fund of the Department of Science and Technology of Henan Province(superior discipline cultivation category)Key Project(No.222301420018)。
文摘The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of bright organic luminogens with typical electron-donating(D)and electron-accepting(A)structures(abbreviated as LDs-BDM,LDs-BTM,and LDs-BHM)was synthesized through a simple single-step reaction.They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70%(e.g.,83.7%for LDs-BTM).Their light-emission properties could be tuned by the modulation ofπ-conjugation effect with methoxy groups at different substituent positions.Their resulting fluorescent nanoparticles(NPs)were demonstrated as specific lipid droplets(LDs)targeting probes with high brightness,good biocompatibility,and satisfactory photostability.LDs-BTM NPs with a large two-photon absorption cross section(σ2=249 GM)were further utilized as ultrabright two-photon fluorescence(2PF)nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration(0.5μmol/L).Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated.This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique.These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.
基金supported by National Science Foundation USA(IOS-1946174)to J.H.Cornell-ZJU seed grant+1 种基金Seed Grant of Cornell Institute of Biotechnologythe Major Science and Technology Research Projects of Guangdong Laboratory for Lingnan Modern Agriculture(NT2021001)。
文摘Lipid droplet(LD)in vegetative tissues has recently been implicated in environmental responses in plants,but its regulation and its function in stress tolerance are not well understood.Here,we identified a Membrane Occupation and Recognition Nexus 1(MORN1)gene as a contributor to natural variations of stress tolerance through genome-wide association study in Arabidopsis thaliana.Characterization of its loss-of-function mutant and natural variants revealed that the MORN1 gene is a positive regulator of plant growth,disease resistance,cold tolerance,and heat tolerance.The MORN1 protein is associated with the Golgi and is also partly associated with LD.Protein truncations that disrupt these associations abolished the biological function of the MORN1 protein.Furthermore,the MORN1 gene is a positive regulator of LD abundance,and its role in LD number regulation and stress tolerance is highly linked.Therefore,this study identifies MORN1 as a positive regulator of LD abundance and a contributor to natural variations of stress tolerance.It implicates a potential involvement of Golgi in LD biogenesis and strongly suggests a contribution of LD to diverse processes of plant growth and stress responses.
