Background:Hepatocellular carcinoma(HCC)is an aggressive and lethal malignancy.Metabolic reprogramming dynamically remodels the tumor microenvironment(TME)and drives HCC progression.This study investigated the mechani...Background:Hepatocellular carcinoma(HCC)is an aggressive and lethal malignancy.Metabolic reprogramming dynamically remodels the tumor microenvironment(TME)and drives HCC progression.This study investigated the mechanism through which metabolic reprogramming remodels the TME in HCC.Methods:HCC patient transcriptome data were subjected to bioinformatics analysis to identify differentially expressed genes and immune infiltration status.Immunohistochemical analysis was performed to determine the correlation between succinate dehydrogenase complex subunit A(SDHA)expression and M2 macrophage infiltration.SDHA-knockdown or SDHA-overexpressing HCC cells were used for in vitro experiments,including co-culturing,flow cytometry,and enzyme-linked immunosorbent assay.Western blotting assay,functional assays,and subcutaneous tumor model mice were used to elucidate the molecular mechanisms underlying succinate-mediated HCC cell-macrophage interactions in the TME.Results:Higher infiltration of M2 macrophages correlated with worse prognosis in HCC patients.SDHA was downregulated in HCC tumor tissues and showed a negative correlation with M2 macrophage infiltration.SDHA knockdown promoted M2 macrophage polarization,whereas SDHA overexpression reversed this effect.Mechanistically,SDHA deficiency in HCC cells induced succinate accumulation,which promoted M2 macrophage polarization by activating the G protein-coupled receptor 91(GPR91)/signal transducer and activator of transcription 3(STAT3)pathway.Concurrently,succinate stimulation enhanced mitochondrial oxidative phosphorylation in M2 macrophages,thereby promoting HCC progression.Serum succinate levels were elevated in HCC patients.The receiver operating characteristic curve analysis indicated that serum succinate is a promising diagnostic marker for HCC(area under the curve=0.815).Conclusion:SDHA deficiency leads to succinate accumulation,which promotes M2 macrophage polarization through the GPR91/STAT3 pathway,thereby facilitating HCC progression.Based on these findings,serum succinate could be a promising diagnostic biomarker for HCC.展开更多
Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic d...Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic dysregulation across multiple organs.While current research largely centers on adipogenesis within adipose tissue,a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive.Results Here,we employed a high-fat diet(HFD)model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers.Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits.Through 16S rRNA amplicon sequencing,we identified significant gut microbiota dysbiosis in HFD-fed chickens,manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus.However,jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens.Metabolomic profiling revealed that HFD elevated the level of succinic acid,a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus.This increase in succinic acid(SA)further triggered metabolic inflammation response in both jejunal tissue and serum.In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue,enhancing intestinal lipid uptake and subsequent abdominal fat deposition.Bulk and single-nucleus RNA sequencing(snRNA-seq)revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk.Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition.Conclusion This study delineates a succinic acid-driven"gut-fat axis"governing abdominal fat deposition in broilers,integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis.By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis,we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism.These findings redefine fat deposition as a process extending beyond adipose-centric models,advancing multi-omics-guided strategies for sustainable poultry production.展开更多
The biodegradable polybutylene succinate(PBS)material offers a sustainable solution for a circular economy to address the global issue of marine plastic waste.Its cross-linkage with non-biodegradable xanthan gum(XG)bi...The biodegradable polybutylene succinate(PBS)material offers a sustainable solution for a circular economy to address the global issue of marine plastic waste.Its cross-linkage with non-biodegradable xanthan gum(XG)biopolymer to ameliorate residual granitic soil(RGS)in arid and semiarid regions can significantly mitigate soil erosion.This study investigates the enhancement of RGS by cross-linking the PBS and XG biopolymers.Employing a multitude of geotechnical tests(liquid limit,linear shrinkage,specific gravity,compaction,and UCS tests)at 3 d,28 d,and 90 d of steam-curing at a controlled temperature of 16℃,the outcomes were validated through scanning electron microscopy(SEM),thermogravimetric analysis(TGA),Fourier transform infrared spectroscopy(FTIR),and Brunauer-Emmett-Teller(BET)analyses.In addition,a comprehensive experimental database of 150 tests and nine parameters from the current study was utilized to model the UCS90-d(i.e.unconfined compressive strength after 90 d of curing)of the PBS-XG-treated RGS mixtures by deploying the random forest(RF)and eXtreme Gradient Boost(XGBoost)methods.The results found that the two biopolymers significantly improve the mechanical properties of RGS,with optimal UCS achieved at specific dosages(0.4PBS,1.5XG,and 0.2PBS+1.5XG dosage levels)and curing times.The UCS of PBS-XG-treated RGS showed up to a 57%increase after 90 d of curing.Furthermore,SEM and FTIR analyses revealed the formation of stronger microstructures and chemical bonds,respectively,whereas BET analysis indicated that pore volume and diameter are critical in affecting UCS.The proposed RF model outperformed XGBoost in predictive accuracy and generalization,demonstrating robustness and versatility.Moreover,SHAP values highlighted the significant impact of input parameters on UCS90-d,with curing time and specific material properties being key determinants.The study concludes with the proposal of a novel PyCharm intuitive graphical user interface as a"UCS Prediction App"for engineers and practitioners to forecast the UCS90-d of granitic residual soil.展开更多
Aging involves the accumulation of various forms of molecular and cellular damage over time.Key features of aging,such as mitochondrial dysfunction,dysbiosis,and oxidative stress,are closely linked and largely driven ...Aging involves the accumulation of various forms of molecular and cellular damage over time.Key features of aging,such as mitochondrial dysfunction,dysbiosis,and oxidative stress,are closely linked and largely driven by inflammation.This study examines the role of succinate,a key metabolite produced and utilized by cells of both host and microbes,and its receptor,succinate receptor 1(SUCNR1),in age-related oral dysbiosis and inflammation.We examined young and aged wild-type(WT)and SUCNR1 knockout(KO)mice for this analysis.Our findings revealed significant aging-associated alveolar bone loss and succinate elevation in aged WT mice,along with notable changes in the oral microbiome.Conversely,aged KO mice showed reduced bone loss,lower succinate levels,less inflammation,and better-maintained microbial function.These results suggest that SUCNR1 is crucial in influencing aging-related succinate elevation,oral dysbiosis,and inflammation.Analysis of gene families and pathways in the oral microbiome demonstrated distinct aging-related changes between WT and KO mice,with the functional potential being preserved in the KO-aged group.This study underscores the importance of succinate elevation and signaling through SUCNR1 in regulating inflammation,alveolar bone loss,and shifts in the oral microbiome,offering potential targets for therapeutic interventions in age-related oral health issues.展开更多
In this study,we investigated improving the performance of a layered double hydroxide(LDH)for the adsorption of As(III)and As(V)by controlling the morphology of LDH crystals.The LDH was synthesized via a simple coprec...In this study,we investigated improving the performance of a layered double hydroxide(LDH)for the adsorption of As(III)and As(V)by controlling the morphology of LDH crystals.The LDH was synthesized via a simple coprecipitation method using barely soluble MgO as a precursor and succinic acid(SA)as a morphological control agent.Doping the LDH crystals with carboxylate ions(RCOO−)derived from SA caused the crystals to develop in a radial direction.This changed the pore characteristics and increased the density of active surface sites.Subsequently,SA/MgFe-LDH showed excellent affinity for As(III)and As(V)with maximum sorption densities of 2.42 and 1.60 mmol/g,respectively.By comparison,the pristine MgFe-LDH had sorption capacities of 1.56 and 1.31 mmol/g for As(III)and As(V),respectively.The LDH was effective over a wide pH range for As(III)adsorption(pH 3-8.5)and As(V)adsorption(pH 3-6.5).Using a combination of spectroscopy and sorption modeling calculations,the main sorption mechanism of As(III)and As(V)on SA/MgFe-LDH was identified as inner-sphere complexation via ligand exchangewith hydroxyl group(-OH)and RCOO−.Specifically,bidentate As-Fe complexeswere proposed for both As(III)and As(V)uptake,with the magnitude of formation varying with the initial As concentration.Importantly,the As-laden adsorbent had satisfactory stability in simulated real landfill leachate.These findings demonstrate that SA/MgFe-LDH exhibits considerable potential for remediation of As-contaminated water.展开更多
A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynami...A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.展开更多
The materialization of polybutylene succinate(PBS)belongs to the family of polyesters which are degrad-able and biodegradable,their biodegradability properties have attracted enormous interest for product development ...The materialization of polybutylene succinate(PBS)belongs to the family of polyesters which are degrad-able and biodegradable,their biodegradability properties have attracted enormous interest for product development towards different polymer-based applications.Besides its biodegradability,PBS can be derived from petroleum and biobased monomers.At the same time,the latter is the driving factor for its growing interest in bioplastics for fully green and sustainable biobased-derived polymer products.The processes and techniques presented herein,are based on the production of biobased succinic acid monomer to PBS.However,the counterpart biobased monomer 1,4-butanediol(1,4-BDO)production has not been commercially demonstrated.This review discusses the progress in state-of-the-art developments in the synthesis strategies of PBS,its copolymers,and composites with the view to improve molecular weight,thermal,and mechanical properties.It further analyzes the different strategies to synthesize modified PBS polymer composites from organic and inorganic nanofillers to enhance their chemical,thermal,stability and mechanical structural properties.Importantly,the review highlights the progress in the applications of PBS copolymers and composites with tailored structure-designed properties for specific sectors such as packaging films,biomedical and drug release,fire retardants,and agricultural products.The structure-functional performance characteristics of these developments in the PBS,copolymers,and composites are highlighted to provide baseline insights for future developments in engineering the specific applications,and structural interface PBS composites with enhanced structure-functional performance properties.展开更多
Bone-related diseases,including osteoporosis(OP),osteoarthritis(OA),rheumatoid arthritis(RA),fracture,and periodontitis,significantly impact human health.Succinate,primarily known as a metabolic intermediate in the tr...Bone-related diseases,including osteoporosis(OP),osteoarthritis(OA),rheumatoid arthritis(RA),fracture,and periodontitis,significantly impact human health.Succinate,primarily known as a metabolic intermediate in the tricarboxylic acid(TCA)cycle,has emerged as a regulator of cellular functions beyond its metabolic role.Under stress,succinate accumulates in mitochondria and acts as a signaling molecule,modulating cellular processes.Notably,succinate activates angiogenesis and inflammation by stabilizing hypoxia-inducible factor-1α(HIF-1α).Moreover,it influences various pathophysiological processes by interacting with the succinate receptor 1(SUCNR1),thereby impacting immune response,inflammation,cancer metastasis,and bone homeostasis.The multifaceted roles of succinate as a signaling molecule vary depending on its cellular location and concentration.Recent metabolomic analyses have revealed elevated succinate levels in bone-related diseases,indicating its potential association with these conditions.The objective of this review is to elucidate the impacts of succinate on different bone-related diseases and to discuss potential therapeutic targets and drug molecules based on its mechanisms of action.展开更多
[Objectives]To observe the clinical efficacy of external application of Scorzonera Herpes Ointment combined with Methylprednisolone Sodium Succinate for Injection in the treatment of herpes zoster oticus(HZO).[Methods...[Objectives]To observe the clinical efficacy of external application of Scorzonera Herpes Ointment combined with Methylprednisolone Sodium Succinate for Injection in the treatment of herpes zoster oticus(HZO).[Methods]A total of 100 HZO patients admitted to the 988 th Hospital of the Joint Logistics Support Force and Henan Provincial People's Hospital from June 2021 to June 2023 were selected.They were divided into a treatment group and a control group using a random number table method,with 50 cases in each group.Both groups received Methylprednisolone Sodium Succinate for Injection.Additionally,the treatment group was treated with external application of Scorzonera Herpes Ointment,while the control group received acyclovir ointment.Both groups were treated for 10 d.The comparisons included clinical efficacy,total symptom and sign scores,pain level[Visual Analogue Scale(VAS)],time for erythema reduction,cessation of blister formation,scab formation,and scab shedding,incidence of post-herpetic neuralgia(PHN),air conduction hearing threshold,and air-bone gap.[Results]After 10 d of treatment,the total effective rate was 98.00%(49/50)in the treatment group and 84.00%(42/50)in the control group,with a statistically significant difference between the two groups(P<0.05).After 10 d of treatment,the total symptom and sign scores and VAS scores of both groups decreased compared to those before treatment.The treatment group had significantly lower scores than the control group(P<0.05).The treatment group showed significantly shorter time for erythema reduction,cessation of blister formation,scab formation,and scab shedding compared to the control group(P<0.05).During the 1-month follow-up after treatment,no PHN cases occurred in the treatment group,while the incidence of PHN in the control group was 24.00%(12/50),showing a statistically significant difference(P<0.05).After 10 d of treatment,both groups showed reduced air conduction hearing thresholds,and the treatment group exhibited significantly lower air conduction thresholds and air-bone gaps compared to the control group(P<0.05).No statistically significant difference was observed in the air-bone gap before and after treatment in the control group(P>0.05).[Conclusions]The combination of external application of Scorzonera Herpes Ointment and Methylprednisolone Sodium Succinate for Injection can alleviate pain and other discomforts,reduce PHN incidence,shorten disease duration,and improve hearing in HZO patients.展开更多
Liposomal drugs have significantly improved cancer treatment in recent years.However,the clinical application of conventional liposomes is limited by factors such as the complexity of the preparation process and the m...Liposomal drugs have significantly improved cancer treatment in recent years.However,the clinical application of conventional liposomes is limited by factors such as the complexity of the preparation process and the multitude of auxiliary components.By replacing phospholipids and cholesterol with vitamin E succinate(VES),this study addresses these shortcomings by developing a novel modified nanoprodrug,and the new formulation is used to deliver cisplatin.Concurrently,liposomes encapsulating cisplatin were prepared by conventional formulations for comparative experiments.Moreover,VES can inhibit the expression of mitochondrial uncoupling protein 2(UCP2),further enhancing mitochondrial damage in tumor cells within the tumor microenvironment(TME)and suppressing the tricarboxylic acid cycle,thereby reducing ATP production.Additionally,cisplatin damages DNA structure,affecting the binding of Nrf2 to the antioxidant response element(ARE),thereby inhibiting the signaling expression of heme oxygenase1(HO-1).The combined action of cisplatin and VES disrupts the redox balanceleading to a significant accumulation of reactive oxygen species(ROS).The nanoprodrug effectively alters the redox state of the TME and inhibits antioxidant defenses,thereby amplifying oxidative stress damage and enhancing the efficacy of cisplatin.Notably,compared to free cisplatin,the nanoprodrug demonstrates greater efficacy in both cell line-derived xenograft(CDX)and patient-derived tumor xenograft(PDX)liver cancer models.Overall,this study successfully develops a novel mitochondrial-targeted nanoprodrug by modifying the conventional liposome formulation.This provides a new strategy for amplifying oxidative stress in order to disrupt redox balance,and enhance cisplatin efficacy.展开更多
High mortality of choroidal melanoma(CM)is mainly attributed to the high likelihood of tumorous recurrence.The essential challenge lies in the presence of residual CM cells survived from the antitumor treatment.These ...High mortality of choroidal melanoma(CM)is mainly attributed to the high likelihood of tumorous recurrence.The essential challenge lies in the presence of residual CM cells survived from the antitumor treatment.These residual tumorous cells are most likely to cause tumorous recurrence.This article reports the preparation of a multifunctional nanocomposite which can be used to treat CM efficiently via a chemotherapyassisted-photothermal therapy(CTH-PTT).The nanocomposite comprises of alpha-tocopheryl succinate(α-TOS)and carboxylic chitosan modified graphene(CG).α-TOS has been potentially seen as an efficient CTH antitumor drug while its deficiency such as easy being hydrolyzed by gastrointestinal esterase and poor hydrophilicity inevitable limits the clinic application ofα-TOS.CG is introduced to overcome these shortcomings,offering additional advantages such as the PTT possibility for the antitumor application.The employment of CG-α-TOS on ocular CM cells caused more than 80%inhibition rates after irradiation under an 808 nm laser for 10 min.The outcomes of this work provide a facile and advantageous way to resolve the essential issue of the treatment of ocular tumors such as CM.展开更多
Oceans absorb about one-third of atmospheric carbon dioxide emissions,but converting this dissolved inorganic carbon into useful products has remained a major challenge.A research team led by Dr.GAO Xiang from the She...Oceans absorb about one-third of atmospheric carbon dioxide emissions,but converting this dissolved inorganic carbon into useful products has remained a major challenge.A research team led by Dr.GAO Xiang from the Shenzhen Institutes of Advanced Technology(SIAT)of the Chinese Academy of Sciences and Dr.XIA Chuan from the University of Electronic Science and Technology of China has now developed an artificial oceanic carbon recycling system that captures CO_(2) from seawater and directly converts it into succinic acid-a key building block for biodegradable plastics.展开更多
Rice bakanae disease(RBD)is a devastating plant disease caused by Fusarium fujikuroi.This study aimed to evaluate the potential of cyclobutrifuram,a novel succinate dehydrogenase inhibitor(SDHI),to control RBD,and det...Rice bakanae disease(RBD)is a devastating plant disease caused by Fusarium fujikuroi.This study aimed to evaluate the potential of cyclobutrifuram,a novel succinate dehydrogenase inhibitor(SDHI),to control RBD,and determine the risk and mechanism of resistance to cyclobutrifuram in F.fujikuroi.In vitro experiments showed that cyclobutrifuram significantly inhibited mycelial growth and spore germination,and altered the morphology of mycelia and conidia.Treatment with cyclobutrifuram signifcantly decreased mycotoxin production and increased cell membrane permeability in F.fujikuroi.The baseline sensitivity of 72 F.fujikuroi isolates to cyclobutrifuram was determined using mycelial growth and spore germination inhibition assays,which revealed EC50values of 0.0114-0.1304 and 0.0012-0.016μg mL^(-1),with mean EC50values of(0.0410±0.0470)and(0.0038±0.0015)μg mL^(-1),respectively.Pot experiments demonstrated that the protective effect of cyclobutrifluram against F.fujikuroi was more significant than that of phenamacril and azoxystrobin,indicating that cyclobutrifuram is a promising antifungal agent for the control of RBD.Six cyclobutrifuramresistant mutants of F.fujikuroi were obtained via fungicide adaptation.Moreover,these mutants exhibited weaker ftness than their parental isolate and positive cross-resistance with other SDHI fungicides,including pydifumetofen and penfufen;however,no cross-resistance was detected with other classes of fungicides,including phenamacril,fudioxonil,prochloraz,or azoxystrobin.These results indicated that the resistance risk of F.fujikuroi to cyclobutrifuram might be moderate.Sequencing analysis revealed that mutations,including H248D in Ff Sdh B,A83V in Ff Sdh C2,and S106F and E166K in Ff Sdh D,contributed to resistance,which was confrmed by molecular docking and homologous replacement experiments.The results suggest a high potential for cyclobutrifuram to control RBD and a moderate resistance risk of F.fujikuroi to cyclobutrifuram,which are meaningful fndings for the scientifc application of cyclobutrifuram.展开更多
As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systemati...As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systematically expounds the coordinated mechanism of the dual axes of succinate/H3K9ac andα-ketoglutarate(α-KG)/TET enzymes:Succinate activates regeneration-related genes by regulating histone acetylation(H3K9ac),whileα-KG relieves the epigenetic repression of the Wnt pathway through TET-mediated DNA demethylation.The dynamic balance between the two maintains epigenetic plasticity.Multi-omics integration strategies(such as Gaussian graphical models and deep learning frameworks)and single-cell epigenetic tracking technologies(such as spatial metabolomics)have revealed the regulation of metabolite gradients on cellular heterogeneity and the immune microenvironment.The coordinated application of metabolite precursor supplementation(such as NAD precursors)and dynamic monitoring systems(such as isotope tracing and artifi cial intelligence models)has promoted the shift of metabolic medicine from the“static replacement”paradigm to the“dynamic reshaping”paradigm.However,technical bottlenecks(such as insuffi cient multimodal integration)and clinical translation pitfalls(such as challenges in standardized production)still need to be overcome.In the future,through the development of“metabolism-immunity”co-regulatory strategies and intelligent closed-loop systems,it is expected to achieve precise interventions for kidney regeneration and disease treatment.展开更多
In order to recover propylene carbonate(PC)from waste lithium-ion battery electrolyte,the electrolyte was coupled with dimethyl succinate(DMSu)to prepare degradable polyester PPS.To further enhance the performance of ...In order to recover propylene carbonate(PC)from waste lithium-ion battery electrolyte,the electrolyte was coupled with dimethyl succinate(DMSu)to prepare degradable polyester PPS.To further enhance the performance of PPS,ethylene glycol(EG)was introduced to prepare copolyester PPSG,and the effects of the amount of added EG on the performance of copolyester were explored.The results show that the synthesized polyester was the target product.With the increase in the amount of added EG,the molecular weight of the copolyester gradually rose,but the glass transition temperature(T g)of PPSG gradually decreased,and the degradation rate was significantly faster than that of PPS.Within 24 d,the mass loss rate of PPSG-30%reached 75.8%.展开更多
基金supported by the Central Government-Guided Local Science and Technology Development Fund Project(Science and Technology Innovation Base Project)(Grant No.236Z7749G)Hebei Provincial Precision Medicine Innovation and Development Joint Fund Incubation Project(Grant No.H2025206547)Hebei Provincial Basic Research Special Youth Science Fund Project(Grant No.H2025206274).
文摘Background:Hepatocellular carcinoma(HCC)is an aggressive and lethal malignancy.Metabolic reprogramming dynamically remodels the tumor microenvironment(TME)and drives HCC progression.This study investigated the mechanism through which metabolic reprogramming remodels the TME in HCC.Methods:HCC patient transcriptome data were subjected to bioinformatics analysis to identify differentially expressed genes and immune infiltration status.Immunohistochemical analysis was performed to determine the correlation between succinate dehydrogenase complex subunit A(SDHA)expression and M2 macrophage infiltration.SDHA-knockdown or SDHA-overexpressing HCC cells were used for in vitro experiments,including co-culturing,flow cytometry,and enzyme-linked immunosorbent assay.Western blotting assay,functional assays,and subcutaneous tumor model mice were used to elucidate the molecular mechanisms underlying succinate-mediated HCC cell-macrophage interactions in the TME.Results:Higher infiltration of M2 macrophages correlated with worse prognosis in HCC patients.SDHA was downregulated in HCC tumor tissues and showed a negative correlation with M2 macrophage infiltration.SDHA knockdown promoted M2 macrophage polarization,whereas SDHA overexpression reversed this effect.Mechanistically,SDHA deficiency in HCC cells induced succinate accumulation,which promoted M2 macrophage polarization by activating the G protein-coupled receptor 91(GPR91)/signal transducer and activator of transcription 3(STAT3)pathway.Concurrently,succinate stimulation enhanced mitochondrial oxidative phosphorylation in M2 macrophages,thereby promoting HCC progression.Serum succinate levels were elevated in HCC patients.The receiver operating characteristic curve analysis indicated that serum succinate is a promising diagnostic marker for HCC(area under the curve=0.815).Conclusion:SDHA deficiency leads to succinate accumulation,which promotes M2 macrophage polarization through the GPR91/STAT3 pathway,thereby facilitating HCC progression.Based on these findings,serum succinate could be a promising diagnostic biomarker for HCC.
基金supported by the National Key Research and Development Program of China(2022YFF1000201)National Scientific Foundation of China(32272861)the China Agriculture Research System of MOF and MARA(CARS-41)。
文摘Background Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns.This pathological overaccumulation results from complex metabolic dysregulation across multiple organs.While current research largely centers on adipogenesis within adipose tissue,a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive.Results Here,we employed a high-fat diet(HFD)model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers.Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits.Through 16S rRNA amplicon sequencing,we identified significant gut microbiota dysbiosis in HFD-fed chickens,manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus.However,jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens.Metabolomic profiling revealed that HFD elevated the level of succinic acid,a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus.This increase in succinic acid(SA)further triggered metabolic inflammation response in both jejunal tissue and serum.In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue,enhancing intestinal lipid uptake and subsequent abdominal fat deposition.Bulk and single-nucleus RNA sequencing(snRNA-seq)revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk.Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition.Conclusion This study delineates a succinic acid-driven"gut-fat axis"governing abdominal fat deposition in broilers,integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis.By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis,we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism.These findings redefine fat deposition as a process extending beyond adipose-centric models,advancing multi-omics-guided strategies for sustainable poultry production.
基金supported by the National Natural Science Foundation of China(Grant Nos.52379104 and 52090084).
文摘The biodegradable polybutylene succinate(PBS)material offers a sustainable solution for a circular economy to address the global issue of marine plastic waste.Its cross-linkage with non-biodegradable xanthan gum(XG)biopolymer to ameliorate residual granitic soil(RGS)in arid and semiarid regions can significantly mitigate soil erosion.This study investigates the enhancement of RGS by cross-linking the PBS and XG biopolymers.Employing a multitude of geotechnical tests(liquid limit,linear shrinkage,specific gravity,compaction,and UCS tests)at 3 d,28 d,and 90 d of steam-curing at a controlled temperature of 16℃,the outcomes were validated through scanning electron microscopy(SEM),thermogravimetric analysis(TGA),Fourier transform infrared spectroscopy(FTIR),and Brunauer-Emmett-Teller(BET)analyses.In addition,a comprehensive experimental database of 150 tests and nine parameters from the current study was utilized to model the UCS90-d(i.e.unconfined compressive strength after 90 d of curing)of the PBS-XG-treated RGS mixtures by deploying the random forest(RF)and eXtreme Gradient Boost(XGBoost)methods.The results found that the two biopolymers significantly improve the mechanical properties of RGS,with optimal UCS achieved at specific dosages(0.4PBS,1.5XG,and 0.2PBS+1.5XG dosage levels)and curing times.The UCS of PBS-XG-treated RGS showed up to a 57%increase after 90 d of curing.Furthermore,SEM and FTIR analyses revealed the formation of stronger microstructures and chemical bonds,respectively,whereas BET analysis indicated that pore volume and diameter are critical in affecting UCS.The proposed RF model outperformed XGBoost in predictive accuracy and generalization,demonstrating robustness and versatility.Moreover,SHAP values highlighted the significant impact of input parameters on UCS90-d,with curing time and specific material properties being key determinants.The study concludes with the proposal of a novel PyCharm intuitive graphical user interface as a"UCS Prediction App"for engineers and practitioners to forecast the UCS90-d of granitic residual soil.
基金supported by NIH grants DE027074,DE028212,and AG055787 to Xin Li
文摘Aging involves the accumulation of various forms of molecular and cellular damage over time.Key features of aging,such as mitochondrial dysfunction,dysbiosis,and oxidative stress,are closely linked and largely driven by inflammation.This study examines the role of succinate,a key metabolite produced and utilized by cells of both host and microbes,and its receptor,succinate receptor 1(SUCNR1),in age-related oral dysbiosis and inflammation.We examined young and aged wild-type(WT)and SUCNR1 knockout(KO)mice for this analysis.Our findings revealed significant aging-associated alveolar bone loss and succinate elevation in aged WT mice,along with notable changes in the oral microbiome.Conversely,aged KO mice showed reduced bone loss,lower succinate levels,less inflammation,and better-maintained microbial function.These results suggest that SUCNR1 is crucial in influencing aging-related succinate elevation,oral dysbiosis,and inflammation.Analysis of gene families and pathways in the oral microbiome demonstrated distinct aging-related changes between WT and KO mice,with the functional potential being preserved in the KO-aged group.This study underscores the importance of succinate elevation and signaling through SUCNR1 in regulating inflammation,alveolar bone loss,and shifts in the oral microbiome,offering potential targets for therapeutic interventions in age-related oral health issues.
文摘In this study,we investigated improving the performance of a layered double hydroxide(LDH)for the adsorption of As(III)and As(V)by controlling the morphology of LDH crystals.The LDH was synthesized via a simple coprecipitation method using barely soluble MgO as a precursor and succinic acid(SA)as a morphological control agent.Doping the LDH crystals with carboxylate ions(RCOO−)derived from SA caused the crystals to develop in a radial direction.This changed the pore characteristics and increased the density of active surface sites.Subsequently,SA/MgFe-LDH showed excellent affinity for As(III)and As(V)with maximum sorption densities of 2.42 and 1.60 mmol/g,respectively.By comparison,the pristine MgFe-LDH had sorption capacities of 1.56 and 1.31 mmol/g for As(III)and As(V),respectively.The LDH was effective over a wide pH range for As(III)adsorption(pH 3-8.5)and As(V)adsorption(pH 3-6.5).Using a combination of spectroscopy and sorption modeling calculations,the main sorption mechanism of As(III)and As(V)on SA/MgFe-LDH was identified as inner-sphere complexation via ligand exchangewith hydroxyl group(-OH)and RCOO−.Specifically,bidentate As-Fe complexeswere proposed for both As(III)and As(V)uptake,with the magnitude of formation varying with the initial As concentration.Importantly,the As-laden adsorbent had satisfactory stability in simulated real landfill leachate.These findings demonstrate that SA/MgFe-LDH exhibits considerable potential for remediation of As-contaminated water.
文摘A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.
文摘The materialization of polybutylene succinate(PBS)belongs to the family of polyesters which are degrad-able and biodegradable,their biodegradability properties have attracted enormous interest for product development towards different polymer-based applications.Besides its biodegradability,PBS can be derived from petroleum and biobased monomers.At the same time,the latter is the driving factor for its growing interest in bioplastics for fully green and sustainable biobased-derived polymer products.The processes and techniques presented herein,are based on the production of biobased succinic acid monomer to PBS.However,the counterpart biobased monomer 1,4-butanediol(1,4-BDO)production has not been commercially demonstrated.This review discusses the progress in state-of-the-art developments in the synthesis strategies of PBS,its copolymers,and composites with the view to improve molecular weight,thermal,and mechanical properties.It further analyzes the different strategies to synthesize modified PBS polymer composites from organic and inorganic nanofillers to enhance their chemical,thermal,stability and mechanical structural properties.Importantly,the review highlights the progress in the applications of PBS copolymers and composites with tailored structure-designed properties for specific sectors such as packaging films,biomedical and drug release,fire retardants,and agricultural products.The structure-functional performance characteristics of these developments in the PBS,copolymers,and composites are highlighted to provide baseline insights for future developments in engineering the specific applications,and structural interface PBS composites with enhanced structure-functional performance properties.
基金supported by the National Natural Science Foundation of China(No.82170984)the Zhejiang Provincial Natural Science Foundation of China(No.LQ24H140004)the Open Project of Guangxi Key Laboratory of the Rehabilitation and Reconstruction for Oral and Maxillofacial Research(No.GXKLOMRR2402).
文摘Bone-related diseases,including osteoporosis(OP),osteoarthritis(OA),rheumatoid arthritis(RA),fracture,and periodontitis,significantly impact human health.Succinate,primarily known as a metabolic intermediate in the tricarboxylic acid(TCA)cycle,has emerged as a regulator of cellular functions beyond its metabolic role.Under stress,succinate accumulates in mitochondria and acts as a signaling molecule,modulating cellular processes.Notably,succinate activates angiogenesis and inflammation by stabilizing hypoxia-inducible factor-1α(HIF-1α).Moreover,it influences various pathophysiological processes by interacting with the succinate receptor 1(SUCNR1),thereby impacting immune response,inflammation,cancer metastasis,and bone homeostasis.The multifaceted roles of succinate as a signaling molecule vary depending on its cellular location and concentration.Recent metabolomic analyses have revealed elevated succinate levels in bone-related diseases,indicating its potential association with these conditions.The objective of this review is to elucidate the impacts of succinate on different bone-related diseases and to discuss potential therapeutic targets and drug molecules based on its mechanisms of action.
基金Supported by the Joint Construction Project of Medical Science and Technology Research Plan in Henan Province(LHGJ20190879).
文摘[Objectives]To observe the clinical efficacy of external application of Scorzonera Herpes Ointment combined with Methylprednisolone Sodium Succinate for Injection in the treatment of herpes zoster oticus(HZO).[Methods]A total of 100 HZO patients admitted to the 988 th Hospital of the Joint Logistics Support Force and Henan Provincial People's Hospital from June 2021 to June 2023 were selected.They were divided into a treatment group and a control group using a random number table method,with 50 cases in each group.Both groups received Methylprednisolone Sodium Succinate for Injection.Additionally,the treatment group was treated with external application of Scorzonera Herpes Ointment,while the control group received acyclovir ointment.Both groups were treated for 10 d.The comparisons included clinical efficacy,total symptom and sign scores,pain level[Visual Analogue Scale(VAS)],time for erythema reduction,cessation of blister formation,scab formation,and scab shedding,incidence of post-herpetic neuralgia(PHN),air conduction hearing threshold,and air-bone gap.[Results]After 10 d of treatment,the total effective rate was 98.00%(49/50)in the treatment group and 84.00%(42/50)in the control group,with a statistically significant difference between the two groups(P<0.05).After 10 d of treatment,the total symptom and sign scores and VAS scores of both groups decreased compared to those before treatment.The treatment group had significantly lower scores than the control group(P<0.05).The treatment group showed significantly shorter time for erythema reduction,cessation of blister formation,scab formation,and scab shedding compared to the control group(P<0.05).During the 1-month follow-up after treatment,no PHN cases occurred in the treatment group,while the incidence of PHN in the control group was 24.00%(12/50),showing a statistically significant difference(P<0.05).After 10 d of treatment,both groups showed reduced air conduction hearing thresholds,and the treatment group exhibited significantly lower air conduction thresholds and air-bone gaps compared to the control group(P<0.05).No statistically significant difference was observed in the air-bone gap before and after treatment in the control group(P>0.05).[Conclusions]The combination of external application of Scorzonera Herpes Ointment and Methylprednisolone Sodium Succinate for Injection can alleviate pain and other discomforts,reduce PHN incidence,shorten disease duration,and improve hearing in HZO patients.
基金financed by National Natural Science Foundation of China(Nos.81773642,52073139)Guangdong Provincial Clinical Research Center for Laboratory Medicine(No.2023B110008)the Provincial subsidies for the construction of high-level hospitals(No.K202201)。
文摘Liposomal drugs have significantly improved cancer treatment in recent years.However,the clinical application of conventional liposomes is limited by factors such as the complexity of the preparation process and the multitude of auxiliary components.By replacing phospholipids and cholesterol with vitamin E succinate(VES),this study addresses these shortcomings by developing a novel modified nanoprodrug,and the new formulation is used to deliver cisplatin.Concurrently,liposomes encapsulating cisplatin were prepared by conventional formulations for comparative experiments.Moreover,VES can inhibit the expression of mitochondrial uncoupling protein 2(UCP2),further enhancing mitochondrial damage in tumor cells within the tumor microenvironment(TME)and suppressing the tricarboxylic acid cycle,thereby reducing ATP production.Additionally,cisplatin damages DNA structure,affecting the binding of Nrf2 to the antioxidant response element(ARE),thereby inhibiting the signaling expression of heme oxygenase1(HO-1).The combined action of cisplatin and VES disrupts the redox balanceleading to a significant accumulation of reactive oxygen species(ROS).The nanoprodrug effectively alters the redox state of the TME and inhibits antioxidant defenses,thereby amplifying oxidative stress damage and enhancing the efficacy of cisplatin.Notably,compared to free cisplatin,the nanoprodrug demonstrates greater efficacy in both cell line-derived xenograft(CDX)and patient-derived tumor xenograft(PDX)liver cancer models.Overall,this study successfully develops a novel mitochondrial-targeted nanoprodrug by modifying the conventional liposome formulation.This provides a new strategy for amplifying oxidative stress in order to disrupt redox balance,and enhance cisplatin efficacy.
基金financially supported by the National Natural Science Foundation of China(Nos.82202354,U20A20338)the Summit Advancement Disciplines of Zhejiang Province(Wenzhou Medical University Pharmaceutics)Key R&D Program of Zhejiang Province(No.2021C04019)。
文摘High mortality of choroidal melanoma(CM)is mainly attributed to the high likelihood of tumorous recurrence.The essential challenge lies in the presence of residual CM cells survived from the antitumor treatment.These residual tumorous cells are most likely to cause tumorous recurrence.This article reports the preparation of a multifunctional nanocomposite which can be used to treat CM efficiently via a chemotherapyassisted-photothermal therapy(CTH-PTT).The nanocomposite comprises of alpha-tocopheryl succinate(α-TOS)and carboxylic chitosan modified graphene(CG).α-TOS has been potentially seen as an efficient CTH antitumor drug while its deficiency such as easy being hydrolyzed by gastrointestinal esterase and poor hydrophilicity inevitable limits the clinic application ofα-TOS.CG is introduced to overcome these shortcomings,offering additional advantages such as the PTT possibility for the antitumor application.The employment of CG-α-TOS on ocular CM cells caused more than 80%inhibition rates after irradiation under an 808 nm laser for 10 min.The outcomes of this work provide a facile and advantageous way to resolve the essential issue of the treatment of ocular tumors such as CM.
文摘Oceans absorb about one-third of atmospheric carbon dioxide emissions,but converting this dissolved inorganic carbon into useful products has remained a major challenge.A research team led by Dr.GAO Xiang from the Shenzhen Institutes of Advanced Technology(SIAT)of the Chinese Academy of Sciences and Dr.XIA Chuan from the University of Electronic Science and Technology of China has now developed an artificial oceanic carbon recycling system that captures CO_(2) from seawater and directly converts it into succinic acid-a key building block for biodegradable plastics.
基金the National Natural Science Fundation of China(32302392)the Key Project of the Natural Science Foundation of Anhui Provincial Department of Education,China(2022AH050877 and 2023AH040129)+4 种基金the Programs for the Scientific Research Activities of Academic and Technical Leaders of Anhui Province,China(2020D251)the Development Fund for Talent Personnel of Anhui Agricultural University,China(rc342006 and rc342008)the University Synergy Innovation Program of Anhui Province,China(GXXT-2021-059)the Grants from Anhui Agricultural University,China(2020zd27)the Anhui Province Agricultural Eco-Environmental Protection and Quality Safety Industry Technology System,China。
文摘Rice bakanae disease(RBD)is a devastating plant disease caused by Fusarium fujikuroi.This study aimed to evaluate the potential of cyclobutrifuram,a novel succinate dehydrogenase inhibitor(SDHI),to control RBD,and determine the risk and mechanism of resistance to cyclobutrifuram in F.fujikuroi.In vitro experiments showed that cyclobutrifuram significantly inhibited mycelial growth and spore germination,and altered the morphology of mycelia and conidia.Treatment with cyclobutrifuram signifcantly decreased mycotoxin production and increased cell membrane permeability in F.fujikuroi.The baseline sensitivity of 72 F.fujikuroi isolates to cyclobutrifuram was determined using mycelial growth and spore germination inhibition assays,which revealed EC50values of 0.0114-0.1304 and 0.0012-0.016μg mL^(-1),with mean EC50values of(0.0410±0.0470)and(0.0038±0.0015)μg mL^(-1),respectively.Pot experiments demonstrated that the protective effect of cyclobutrifluram against F.fujikuroi was more significant than that of phenamacril and azoxystrobin,indicating that cyclobutrifuram is a promising antifungal agent for the control of RBD.Six cyclobutrifuramresistant mutants of F.fujikuroi were obtained via fungicide adaptation.Moreover,these mutants exhibited weaker ftness than their parental isolate and positive cross-resistance with other SDHI fungicides,including pydifumetofen and penfufen;however,no cross-resistance was detected with other classes of fungicides,including phenamacril,fudioxonil,prochloraz,or azoxystrobin.These results indicated that the resistance risk of F.fujikuroi to cyclobutrifuram might be moderate.Sequencing analysis revealed that mutations,including H248D in Ff Sdh B,A83V in Ff Sdh C2,and S106F and E166K in Ff Sdh D,contributed to resistance,which was confrmed by molecular docking and homologous replacement experiments.The results suggest a high potential for cyclobutrifuram to control RBD and a moderate resistance risk of F.fujikuroi to cyclobutrifuram,which are meaningful fndings for the scientifc application of cyclobutrifuram.
基金funded by Medical Science Research Project of Hebei(No.20220364).
文摘As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systematically expounds the coordinated mechanism of the dual axes of succinate/H3K9ac andα-ketoglutarate(α-KG)/TET enzymes:Succinate activates regeneration-related genes by regulating histone acetylation(H3K9ac),whileα-KG relieves the epigenetic repression of the Wnt pathway through TET-mediated DNA demethylation.The dynamic balance between the two maintains epigenetic plasticity.Multi-omics integration strategies(such as Gaussian graphical models and deep learning frameworks)and single-cell epigenetic tracking technologies(such as spatial metabolomics)have revealed the regulation of metabolite gradients on cellular heterogeneity and the immune microenvironment.The coordinated application of metabolite precursor supplementation(such as NAD precursors)and dynamic monitoring systems(such as isotope tracing and artifi cial intelligence models)has promoted the shift of metabolic medicine from the“static replacement”paradigm to the“dynamic reshaping”paradigm.However,technical bottlenecks(such as insuffi cient multimodal integration)and clinical translation pitfalls(such as challenges in standardized production)still need to be overcome.In the future,through the development of“metabolism-immunity”co-regulatory strategies and intelligent closed-loop systems,it is expected to achieve precise interventions for kidney regeneration and disease treatment.
文摘In order to recover propylene carbonate(PC)from waste lithium-ion battery electrolyte,the electrolyte was coupled with dimethyl succinate(DMSu)to prepare degradable polyester PPS.To further enhance the performance of PPS,ethylene glycol(EG)was introduced to prepare copolyester PPSG,and the effects of the amount of added EG on the performance of copolyester were explored.The results show that the synthesized polyester was the target product.With the increase in the amount of added EG,the molecular weight of the copolyester gradually rose,but the glass transition temperature(T g)of PPSG gradually decreased,and the degradation rate was significantly faster than that of PPS.Within 24 d,the mass loss rate of PPSG-30%reached 75.8%.
