Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic a...Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.展开更多
Lactic acid bacteria(LAB)exopolysaccharides(EPS)reveal high safety and multiple activities,and are typical postbiotics produced by LAB during fermentation.In this paper,6583 articles on LAB-EPS from Web of Science and...Lactic acid bacteria(LAB)exopolysaccharides(EPS)reveal high safety and multiple activities,and are typical postbiotics produced by LAB during fermentation.In this paper,6583 articles on LAB-EPS from Web of Science and Elsevier databases were retrieved,and 236 articles related to this review were screened.The EPS from 90 LAB strains were summarized in terms of their extraction methods,yield,molecular weight,monosaccharide composition,glycosidic bond configuration and the structural and activity relationships(SARs).However,there exist great challenges as for the low yield and high cost in EPS production.Therefore,this review further elaborated the mechanism of EPS secretion,the anabolic pathway of EPS,the structure and mechanism of key enzymes involving in EPS synthesis process,the prospect of gene regulation for EPS secretion,and proposed the engineering strategies for increasing EPS yield or tailored EPS design in recent years.In addition,CRISPR/Cas9 gene editing technology was also discussed in the production control of EPS in LAB.Finally,the engineering strategy of increasing EPS yield in recent years was proposed.This work might provide important theoretical support for the production and application of LAB-based EPS.展开更多
Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Ge...Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Genetic variants that regulate gene expression,known as expression quantitative trait loci(eQTL),are primarily shaped by human migration history and evolutionary forces,likewise,regulation of gene expression in principle could have been influenced by these events.Therefore,a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped.Recent studies,however,suggest that eQTL is enriched in genes that are selectively constrained.Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations.In addition,such studies are primarily dominated by the major populations of European ancestry,leaving many marginalized populations underrepresented.These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity,which potentially hinders precision medicine.This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective,subsequently discuss their influence on phenomics,as well as challenges and opportunities in the applications to precision medicine.展开更多
BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unkno...BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.展开更多
Trehalose production via a one-step enzymatic route using trehalose synthase(TreS)holds significant promise for industrial-scale applications due to its simplicity and utilization of low-cost substrates.However,the de...Trehalose production via a one-step enzymatic route using trehalose synthase(TreS)holds significant promise for industrial-scale applications due to its simplicity and utilization of low-cost substrates.However,the development of a robust whole-cell biocatalyst expressing TreS remains crucial for enabling practical and economically viable production.In this study,a high-sugar tolerant strain of S.cerevisiae was screened and employed as a host cell for the cell surface display of TreS from Acidiplasma aeolicum.The resultant strain,S.cerevisiae I3A,exhibited remarkable surface displayed TreS activity of 3358 U/g CDW and achieved approximately 64%trehalose yield(10.8 g/L/h productivity)from maltose.Interestingly,no glucose by-product was observed during trehalose production.The S.cerevisiae I3A cells exhibited reusability for up to 12 cycles leading to potential cost reduction of trehalose products.Therefore,our study demonstrated the development of a high-sugar tolerant S.cerevisiae strain expressing TreS on its surface as a whole-cell biocatalyst for efficient and economical trehalose production with potential applications in the food and pharmaceutical industries.展开更多
An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex ...An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex vascular network,thus restricting the supply of oxygen and essential nutrients.Coupled with their inherent size constraints and metabolite accumulation,it is challenging for organoids to replicate the natural intricacies of organs,thereby limiting their applicability.To overcome the challenges associated with this technology,we developed a culture platform to cultivate tumors or organ-derived organoids up to the centimeter scale.Initially,a customized organoid-on-a-chip including a microvascular network at the micron scale was designed using 3D printing.Further,by integrating an infusion device,the chip ensures an adequate supply of nutrients and fluid immersion while mimicking blood flow dynamics.Our method overcomes the issue of the limited size of organoids due to insufficient nutrient access,making it possible to produce large-scale tumor and normal tissue models in vitro,while providing insights into drug efficacy and toxicology evaluation as well as standardized organoid production.展开更多
Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the ...Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin.The hallmarks of the disease include ineffective erythropoiesis,chronic hemolytic anemia,and iron overload.Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications.The management of patients with severeβ-thalassemia represents a global health problem,particularly in low-income countries.Until recently,management strategies were limited to regular transfusions and iron chelation therapy,with allogeneic hematopoietic stem cell transplantation available only for a subset of patients.Better understanding of the underlying pathophysiological mechanisms ofβ-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options,including pharmacologic enhancers of effective erythropoiesis and gene therapy.展开更多
The present study investigated the potential therapeutic potential of Ficus carica polysaccharides(FCPS)in type 2 diabetic mellitus(T2DM)mice,focusing on elucidating the underlying molecular mechanisms.Network pharmac...The present study investigated the potential therapeutic potential of Ficus carica polysaccharides(FCPS)in type 2 diabetic mellitus(T2DM)mice,focusing on elucidating the underlying molecular mechanisms.Network pharmacology analysis identified 37 shared targets between FCPS and T2DM,including perixisome proliferator activated receptor alpha(PPARα),highlighting the significance of PPAR signaling pathways in FCPS-mediated T2DM treatment.The results demonstrated that FCPS treatment significantly reduced markers of glucose and lipid metabolism(fasting blood glucose(FBG),nonestesterified fatty acid(NEFA),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)),inflammatory cytokines(tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1beta(IL-1β),monocyte chemoattractant protein-1(MCP-1)),and liver damage(glutamic pyruvic transaminase(GPT)and glutamic oxaloacetic transaminase(GOT))in T2DM mice.Additionally,FCPS ameliorated hepatic lipid droplet accumulation,fatty degeneration,and hepatocyte structural abnormalities.Western blot analysis confirmed FCPS-induced upregulation of key proteins in the IRS-1/AKT/PPARαsignaling pathway,(insulin receptor substrate 1(IRS-1),phosphatidyqinositol-3 kinase(PI3K),phospho-protein kinase B(p-AKT),glucose transporter 2(GLUT2),phospho-glycogen synthase kinase 3 beta(p-GSK-3β),phospho-adenosine 5′-monophosphate-activated protein kinase alpha(p-AMPKα),peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α),PPARα,peroxisome proliferator-activated receptor gamma(PPARγ))and downregulation of GSK-3β,sterol regulatory element binding protein 1c(SREBP-1c),fatty acid synthase(FAS),and 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR).16S r RNA sequencing results revealed FCPS's ability to modulate gut microbiota dysbiosis in T2DM mice by promoting beneficial bacteria(e.g.,Lactobacillus_reuteri,Candidatus_Saccharimonas)and suppressing opportunistic pathogens(e.g.,Proteobacteria,Gammaproteobacteria,Escherichia-Shigella).These findings collectively suggest that FCPS has a marked effectiveness in improving glucose and lipid metabolism,decreasing inflammatory responses,as well as modulating the gut microbiota in T2DM mice via the gut-hepatic axis,demonstrating its potential as a functional food for diabetes prevention and management.展开更多
Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in hu...Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in humans and other species have demonstrated its pivotal role in regulating the sodium ion balance and mediating sodium and water reabsorption in the kidney's proximal tubules.However,the impact of EGFR gene in how the Yarkand hare(Lepus yarkandensis)adapts to extreme environmental habitat remains unclear,The Yarkand hare is a desert-dwelling animal with multiple adaptations to cope with drought.Given the important physiological function of EGFR gene,we strived to understand its role in arid environment and explore the molecular mechanism of drought tolerance in the Yarkand hare.We first performed segmental cloning of the CDS of the Yarkand hare EGFR gene.Then,We constructed the phylogenetic tree of the Yarkand hare's EGFR gene and compared it with that of other species.The results showed that the Yarkand hare was most closely related to the Tolai hare(Lepus tolai).Through quantitative reverse transcription polymerase chain reaction(RT-qPCR),we discovered that EGFR expression in the kidneys of the Yarkand hare was higher than in the allopatric Tolai hare from non-arid areas.Therefore,we hypothesized that EGFR gene overexpression in the kidney of the Yarkand hare may play a crucial role in drought adaptability.Subsequently,we inserted CDS of EGFR gene into a pcDNA3.1-EGFP expression vector to construct recombinant plasmid,which was transfected into HeLa cells and overexpressed.RT-qPCR demonstrated a notable and statistically significant increase in EGFR mRNA expression and western blot proved stable expression of this protein in HeLa cells.Through cell experiments,EGFR gene overexpression markedly enhanced the survival of Hela cells subjected to NaCl,H_(2)O_(2),and heat stresses,increased superoxide dismutase activity,and decreased malondialdehyde content.In conclusion,these findings preliminarily suggest that EGFR might help the Yarkand hare adapt to extreme environmental conditions.EGFR manipulation in vivo could be a promising strategy to enhance the resilience of animals to extreme conditions.展开更多
Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address t...Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address this issue,advances have been made in therapies targeting molecular pathways related to the murine double minute 2 protooncogene(MDM2)-tumor proteinp53(TP53)interaction.This review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells,as evidenced by clinical studies,reviews,and trials.TP53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of TP53.MDM2 and TP53 activity is tightly regulated.However,cancerous breast cells overexpress MDM2 through five hypothesized mechanisms.Consequently,TP53 levels decrease with increased tumor cell proliferation.Three strategies have been identified for controlling MDM2 upregulation in cells with wild-type or mutated TP53.MDM2 inhibitors(MDM2i)are administered in combination with existing chemotherapies to reduce their effects on healthy cells.Few clinical and preclinical studies have been conducted using MDM2i,which necessitates high-quality clinical trials to support their therapeutic potential in breast cancer therapy.展开更多
Background:Bonducellin is one of the bioactive compounds present in Caesalpinia bonduc Roxb(L).It is a homoisoflavonoid recognized for its anti-cancer,anti-androgenic,and anti-estrogenic properties and could potential...Background:Bonducellin is one of the bioactive compounds present in Caesalpinia bonduc Roxb(L).It is a homoisoflavonoid recognized for its anti-cancer,anti-androgenic,and anti-estrogenic properties and could potentially treat polycystic ovary syndrome(PCOS).However,the underlying molecular mechanism remains unexplored.This study aims to elucidate the potential molecular mechanisms of bonducellin in treating PCOS and its associated symptoms through an integrated approach combining network pharmacology,molecular docking,molecular dynamics simulation,and in vivo validation.Methods:Bonducellin-associated and PCOS-related genes were intersected using VENN analysis to determine common gene targets.KEGG pathway analysis was conducted to investigate the biological pathways involving the co-targeted genes.The protein-protein interactions of the target genes were performed to identify the key proteins interacting with bonducellin.Molecular docking and 100 ns molecular simulations were carried out to evaluate the binding affinity and conformational stability of bonducellin with the target proteins.Additionally,the acute toxicity of bonducellin was assessed on zebrafish embryos and in vivo gene expression studies were performed to examine its regulatory effect on the top co-targeted gene.Results:The intersection of bonducellin-associated and PCOS-related genes identified 76 co-targeted genes.KEGG pathway analysis revealed their involvement in 15 critical pathways,including steroid hormone biosynthesis.Protein-protein interaction and pathway enrichment analysis highlighted key targets,including MMP9,AR,KDR,PRKACA,KIT,CYP19A1,HSD11B1,ESR1,STAT3,ESR2,PRKCA,ROCK1,BRAF,HSD17B2,PIK3R1,and RAF1,all of which exhibited strong binding to bonducellin.Molecular simulations confirmed the stability of bonducellin to the top proteins,MMP9 and AR,with high binding scores.Acute toxicity studies in zebrafish embryos determined the LC50 value of bonducellin as 0.8μg/mL at 48 hpf.Gene expression analysis revealed that bonducellin differentially regulates the MMP9 gene that is involved in modulating PCOS-related pathways.Conclusion:This study suggests potential gene pathways and protein interactions through which bonducellin could exert therapeutic effects on PCOS and its associated disorders.This provides valuable insights for future research into understanding and developing bonducellin-based treatments for PCOS.展开更多
Bio-magnesium(Mg)alloys exhibit excellent biocompatibility and biodegradability,making them highly promising for implant applications.However,their limited strength-ductility balance remains a critical challenge restr...Bio-magnesium(Mg)alloys exhibit excellent biocompatibility and biodegradability,making them highly promising for implant applications.However,their limited strength-ductility balance remains a critical challenge restricting widespread use.In this study,ultra-fine-grained and homogeneous Mg alloys were fabricated using double-sided friction stir processing(DS-FSP)with liquid CO_(2) rapid cooling,leading to a significant enhancement in the strength-ductility synergy of the stirred zone.The results demonstrate that DS-FSP samples exhibit simultaneous improvements in ultimate tensile strength(UTS)and elongation,reaching 334.1±15 MPa and 28.2±7.3%,respectively.Compared to the non-uniform fine-grained microstructure obtained through single-sided friction stir processing,DS-FSP generates a uniform ultra-fine-grained structure,fundamentally altering the fracture behavior and mechanisms of Mg alloys.The DS-FSP samples exhibit irregular fracture patterns due to variations in basal slip system activation among different grains.In contrast,single-sided friction stir processing samples,characterized by a fine-grained yet heterogeneous microstructure,display flat shear fractures dominated by high-density dislocation initiation induced by twin formation,with fracture propagation dictated by the non-uniform texture.By achieving an ultra-fine grain size and homogeneous texture,DS-FSP effectively modifies the fracture mechanisms,thereby enhancing the strength-ductility balance of bio-magnesium alloys.展开更多
During obesity treatment,clinicians have been burdened by the ever-increasing number of patients and the side effects of drug treatment.Finding new plant-derived active ingredients as an intervention for obesity has b...During obesity treatment,clinicians have been burdened by the ever-increasing number of patients and the side effects of drug treatment.Finding new plant-derived active ingredients as an intervention for obesity has become a research focus.In this study,Plackett-Burman and Central Composite Design experiments,plant-wide target metabolomics technology,simulated human colon fermentation test,and cell experiment in vitro were successively used to investigate the effects of fermented and unfermented polyphenols(FP and UP,respectively)of blue honeysuckle on obesity.After the optimization of the response surface method,polyphenol content((1878.08±14.53)mg/100 g)increased by 2.63 times after Lactobacillus rhamnosus 6224 and Saccharomyces cerevisiae W5 mixed fermentation.There were 23 significantly different metabolites were observed in FP and UP.Of them,7 different metabolites were significantly and positively correlated with short-chain fatty acids(SCFAs),whereas negatively correlated with lipopolysaccharides(LPS).The contents of these 7 metabolites were significantly increased in FP.Furthermore,the effects of FP and UP on the SCFA biosynthesis pathway were different.Cell experiments revealed that polyphenols can significantly promote the secretion of gastrointestinal endogenous hormones and insulin and inhibit interleukin-6 levels.Linear regression analysis revealed SCFAs had a positive regulatory effect on glycolipid metabolism,whereas LPS had a negative effect.Overall,these crucial findings provide an economical and simple method for obtaining blue honeysuckle polyphenols and laying a theoretical foundation for its application in the therapeutic intervention against obesity.展开更多
Salt stress is a critical factor affecting the growth and yield of rice.Egypt,the largest rice producer in North Africa and the Middle East,is facing contrasting challenges related to salinity in its agroecosystems.In...Salt stress is a critical factor affecting the growth and yield of rice.Egypt,the largest rice producer in North Africa and the Middle East,is facing contrasting challenges related to salinity in its agroecosystems.In this study,we compared the salt-induced responses among three rice varieties:Giza 176(Egyptian variety),Kaituodao(Chinese variety),and Pokkali(Sri Lanka variety,used as control)under normal and saline stress(100 mmol/L NaCl)conditions at two seedling stages through RNA-seq expression analysis.Giza 176 displayed a salt tolerance score of 7 on the SES(Standard Evaluation Score).Its transcriptome showed dynamic changes,with the number of upregulated genes increasing from 180 to 735,and downregulated genes increasing from 918 to 2930 from the one-week to two-week stress stages,with activated pathways in ion transport,reactive oxygen species(ROS)scavenging,and protein biosynthesis.展开更多
Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans...Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin switching.Here,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at onset.Gene-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb F.Finally,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control regions.This study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.展开更多
Floral color and scent are crucial for plant-environment interactions,especially in reproduction by attracting pollinators for fertilization.They also have wide applications in cosmetic,pharmaceutical,and nutraceutica...Floral color and scent are crucial for plant-environment interactions,especially in reproduction by attracting pollinators for fertilization.They also have wide applications in cosmetic,pharmaceutical,and nutraceutical industries.Plant pigments are typically classified as chlorophylls,flavonoids,carotenoids,and betalains,while volatile organic compounds(VOCs)are grouped as terpenes,phenylpropanoids/benzenoids,and fatty acid derivatives.Significant progresses have been made in understanding the biosynthesis and regulation of these floral pigments and VOCs.Despite differences in their biosynthetic pathways,floral pigments and VOCs are biochemically connected and exhibit synergistic interactions during flower development and in response to biotic and abiotic stresses,suggesting the existence of pleiotropic regulators or complex mechanisms co-regulating their biosynthesis.In this review,we summarize and outline the metabolite pathways mainly integrating flavonoids,carotenoids,terpenes,and phenylpropanoids/benzenoids.We also provide a series of scenarios illustrating the coordinated regulation of floral color and scent.Finally,we suggest areas for future research.We hope this review will spark interest in this research direction and stimulate further studies.展开更多
Anticancer drug resistance remains a major challenge in cancer treatment hindering the efficacy of chemotherapy and targeted therapies.Conventional two-dimensional(2D)cell cultures cannot replicate the complexity of t...Anticancer drug resistance remains a major challenge in cancer treatment hindering the efficacy of chemotherapy and targeted therapies.Conventional two-dimensional(2D)cell cultures cannot replicate the complexity of the in vivo tumor microenvironment(TME),limiting their utility for drug resistance research.Therefore,three-dimensional(3D)tumor models have proven to be a promising alternative for investigating chemoresistance mechanisms.In this review,various cancer 3D models,including spheroids,organoids,scaffold-based models,and bioprinted models,are comprehensively evaluated with a focus on their application in drug resistance studies.We discuss the materials,properties,and advantages of each model,highlighting their ability to better mimic the TME and represent complex mechanisms of drug resistance such as epithelial-mesenchymal transition(EMT),drug efflux,and tumor-stroma interactions.Furthermore,we investigate the limitations of these models,including scalability,reproducibility and technical challenges,as well as their potential therapeutic impact on personalized medicine.Through a thorough comparison of model performance,we provide insights into the strengths and weaknesses of each approach and offer guidance for model selection based on specific research needs.展开更多
BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabo...BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabolomic approach to explore the mechanisms involved in severe CAP.METHODS:We integrated proteomics and metabolomics data to identify potential biomarkers for early diagnosis of severe CAP.Plasma samples were collected from 46 CAP patients(including27 with severe CAP and 19 with non-severe CAP)and 19 healthy controls upon admission.A comprehensive analysis of the combined proteomics and metabolomics data was then performed to elucidate the key pathological features associated with CAP severity.RESULTS:The proteomic and metabolic signature was markedly dif ferent between CAPs and healthy controls.Pathway analysis of changes revealed complement and coagulation cascades,ribosome,tumor necrosis factor(TNF)signaling pathway and lipid metabolic process as contributors to CAP.Furthermore,alterations in lipid metabolism,including sphingolipids and phosphatidylcholines(PCs),and dysregulation of cadherin binding were observed,potentially contributing to the development of severe CAP.Specifi cally,within the severe CAP group,sphingosine-1-phosphate(S1P)and apolipoproteins(APOC1 and APOA2)levels were downregulated,while S100P level was signifi cantly upregulated.CONCLUSION:The combined proteomic and metabolomic analysis may elucidate the complexity of CAP severity and inform the development of improved diagnostic tools.展开更多
基金supported by the National Natural Science Foundation of China(32171347)the Foundation of Leading Talents from Shanghai Health Commission(2022XD038)+1 种基金Training Program for Research Physicians in Innovation,the Funda-mental Research Funds for the Central Universities(YG2023QNA23)Transforma-tion from shanghai hospital development center(SHDC2022CRD002).
文摘Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
基金supported by the Natural Science Foundation of Heilongjiang Province(LH2021C075)Basic Research Business Expenses and Research Projects of Provincial Higher Education Institutions in Heilongjiang Province(2022-KYYWF-1077).
文摘Lactic acid bacteria(LAB)exopolysaccharides(EPS)reveal high safety and multiple activities,and are typical postbiotics produced by LAB during fermentation.In this paper,6583 articles on LAB-EPS from Web of Science and Elsevier databases were retrieved,and 236 articles related to this review were screened.The EPS from 90 LAB strains were summarized in terms of their extraction methods,yield,molecular weight,monosaccharide composition,glycosidic bond configuration and the structural and activity relationships(SARs).However,there exist great challenges as for the low yield and high cost in EPS production.Therefore,this review further elaborated the mechanism of EPS secretion,the anabolic pathway of EPS,the structure and mechanism of key enzymes involving in EPS synthesis process,the prospect of gene regulation for EPS secretion,and proposed the engineering strategies for increasing EPS yield or tailored EPS design in recent years.In addition,CRISPR/Cas9 gene editing technology was also discussed in the production control of EPS in LAB.Finally,the engineering strategy of increasing EPS yield in recent years was proposed.This work might provide important theoretical support for the production and application of LAB-based EPS.
基金supported by the Ministry of Higher Education(MOHE)Malaysia through Fundamental Research Grant Scheme(FRGS)with project code:FRGS/1/2021/STG01/UCSI/01/.SX was funded by the National Natural Science Foundation of China(NSFC)grants 32030020 and 32288101funded by the NSFC grant 32270665.
文摘Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Genetic variants that regulate gene expression,known as expression quantitative trait loci(eQTL),are primarily shaped by human migration history and evolutionary forces,likewise,regulation of gene expression in principle could have been influenced by these events.Therefore,a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped.Recent studies,however,suggest that eQTL is enriched in genes that are selectively constrained.Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations.In addition,such studies are primarily dominated by the major populations of European ancestry,leaving many marginalized populations underrepresented.These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity,which potentially hinders precision medicine.This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective,subsequently discuss their influence on phenomics,as well as challenges and opportunities in the applications to precision medicine.
基金Supported by the Faculty of Medicine,Ramathibodi Hospital,Mahidol University。
文摘BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.
基金financially supported by the National Science,Research and Innovation Fund,Thailand Science Research and Innovation(TSRI)[Grant No.:FFB670076/0337]the National Science and Technology Development Agency(NSTDA)[grant number P-20-51068]the NSRF via the Program Management Unit for Human Resources&Institutional Development,Research and Innovation[grant number B13F670055].
文摘Trehalose production via a one-step enzymatic route using trehalose synthase(TreS)holds significant promise for industrial-scale applications due to its simplicity and utilization of low-cost substrates.However,the development of a robust whole-cell biocatalyst expressing TreS remains crucial for enabling practical and economically viable production.In this study,a high-sugar tolerant strain of S.cerevisiae was screened and employed as a host cell for the cell surface display of TreS from Acidiplasma aeolicum.The resultant strain,S.cerevisiae I3A,exhibited remarkable surface displayed TreS activity of 3358 U/g CDW and achieved approximately 64%trehalose yield(10.8 g/L/h productivity)from maltose.Interestingly,no glucose by-product was observed during trehalose production.The S.cerevisiae I3A cells exhibited reusability for up to 12 cycles leading to potential cost reduction of trehalose products.Therefore,our study demonstrated the development of a high-sugar tolerant S.cerevisiae strain expressing TreS on its surface as a whole-cell biocatalyst for efficient and economical trehalose production with potential applications in the food and pharmaceutical industries.
基金supported by the National Key Research and Development Program of China(No.2024YFA1300128)the National Natural Science Foundation of China(No.82372663)+2 种基金the Key Research and Development Program of Yunnan Province(No.202302AA310024)the Key Research and Development Program of Jiangxi Province(No.20232BBG70024)the Natural Science Foundation of Shandong Province(No.ZR2023LSW008).
文摘An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex vascular network,thus restricting the supply of oxygen and essential nutrients.Coupled with their inherent size constraints and metabolite accumulation,it is challenging for organoids to replicate the natural intricacies of organs,thereby limiting their applicability.To overcome the challenges associated with this technology,we developed a culture platform to cultivate tumors or organ-derived organoids up to the centimeter scale.Initially,a customized organoid-on-a-chip including a microvascular network at the micron scale was designed using 3D printing.Further,by integrating an infusion device,the chip ensures an adequate supply of nutrients and fluid immersion while mimicking blood flow dynamics.Our method overcomes the issue of the limited size of organoids due to insufficient nutrient access,making it possible to produce large-scale tumor and normal tissue models in vitro,while providing insights into drug efficacy and toxicology evaluation as well as standardized organoid production.
文摘Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin.The hallmarks of the disease include ineffective erythropoiesis,chronic hemolytic anemia,and iron overload.Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications.The management of patients with severeβ-thalassemia represents a global health problem,particularly in low-income countries.Until recently,management strategies were limited to regular transfusions and iron chelation therapy,with allogeneic hematopoietic stem cell transplantation available only for a subset of patients.Better understanding of the underlying pathophysiological mechanisms ofβ-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options,including pharmacologic enhancers of effective erythropoiesis and gene therapy.
基金supported by the Open Project Fund of Key Laboratory of Xinjiang Uygur Autonomous Region(2021D04019)the Natural Science Foundation of Xinjiang Uygur Autonomous Region(2024D01C57)+1 种基金the National Natural Science Foundation of China(32460188)the Key Research and Development Program in Xinjiang Uygur Autonomous Region to Weilan Wang(2024B02025 and 2024B02025-2)。
文摘The present study investigated the potential therapeutic potential of Ficus carica polysaccharides(FCPS)in type 2 diabetic mellitus(T2DM)mice,focusing on elucidating the underlying molecular mechanisms.Network pharmacology analysis identified 37 shared targets between FCPS and T2DM,including perixisome proliferator activated receptor alpha(PPARα),highlighting the significance of PPAR signaling pathways in FCPS-mediated T2DM treatment.The results demonstrated that FCPS treatment significantly reduced markers of glucose and lipid metabolism(fasting blood glucose(FBG),nonestesterified fatty acid(NEFA),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)),inflammatory cytokines(tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1beta(IL-1β),monocyte chemoattractant protein-1(MCP-1)),and liver damage(glutamic pyruvic transaminase(GPT)and glutamic oxaloacetic transaminase(GOT))in T2DM mice.Additionally,FCPS ameliorated hepatic lipid droplet accumulation,fatty degeneration,and hepatocyte structural abnormalities.Western blot analysis confirmed FCPS-induced upregulation of key proteins in the IRS-1/AKT/PPARαsignaling pathway,(insulin receptor substrate 1(IRS-1),phosphatidyqinositol-3 kinase(PI3K),phospho-protein kinase B(p-AKT),glucose transporter 2(GLUT2),phospho-glycogen synthase kinase 3 beta(p-GSK-3β),phospho-adenosine 5′-monophosphate-activated protein kinase alpha(p-AMPKα),peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α),PPARα,peroxisome proliferator-activated receptor gamma(PPARγ))and downregulation of GSK-3β,sterol regulatory element binding protein 1c(SREBP-1c),fatty acid synthase(FAS),and 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR).16S r RNA sequencing results revealed FCPS's ability to modulate gut microbiota dysbiosis in T2DM mice by promoting beneficial bacteria(e.g.,Lactobacillus_reuteri,Candidatus_Saccharimonas)and suppressing opportunistic pathogens(e.g.,Proteobacteria,Gammaproteobacteria,Escherichia-Shigella).These findings collectively suggest that FCPS has a marked effectiveness in improving glucose and lipid metabolism,decreasing inflammatory responses,as well as modulating the gut microbiota in T2DM mice via the gut-hepatic axis,demonstrating its potential as a functional food for diabetes prevention and management.
基金supported by the Central Guidance for Local Projects of Xinjiang(ZYYD2024ZY04)the National Natural Science Foundation of China(32260116).
文摘Epidermal growth factor receptor(EGFR)is one of the most important tyrosine kinase receptor families,which plays a pivotal role in cell signaling transduction and physiological processes.Studies on the EGFR gene in humans and other species have demonstrated its pivotal role in regulating the sodium ion balance and mediating sodium and water reabsorption in the kidney's proximal tubules.However,the impact of EGFR gene in how the Yarkand hare(Lepus yarkandensis)adapts to extreme environmental habitat remains unclear,The Yarkand hare is a desert-dwelling animal with multiple adaptations to cope with drought.Given the important physiological function of EGFR gene,we strived to understand its role in arid environment and explore the molecular mechanism of drought tolerance in the Yarkand hare.We first performed segmental cloning of the CDS of the Yarkand hare EGFR gene.Then,We constructed the phylogenetic tree of the Yarkand hare's EGFR gene and compared it with that of other species.The results showed that the Yarkand hare was most closely related to the Tolai hare(Lepus tolai).Through quantitative reverse transcription polymerase chain reaction(RT-qPCR),we discovered that EGFR expression in the kidneys of the Yarkand hare was higher than in the allopatric Tolai hare from non-arid areas.Therefore,we hypothesized that EGFR gene overexpression in the kidney of the Yarkand hare may play a crucial role in drought adaptability.Subsequently,we inserted CDS of EGFR gene into a pcDNA3.1-EGFP expression vector to construct recombinant plasmid,which was transfected into HeLa cells and overexpressed.RT-qPCR demonstrated a notable and statistically significant increase in EGFR mRNA expression and western blot proved stable expression of this protein in HeLa cells.Through cell experiments,EGFR gene overexpression markedly enhanced the survival of Hela cells subjected to NaCl,H_(2)O_(2),and heat stresses,increased superoxide dismutase activity,and decreased malondialdehyde content.In conclusion,these findings preliminarily suggest that EGFR might help the Yarkand hare adapt to extreme environmental conditions.EGFR manipulation in vivo could be a promising strategy to enhance the resilience of animals to extreme conditions.
文摘Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address this issue,advances have been made in therapies targeting molecular pathways related to the murine double minute 2 protooncogene(MDM2)-tumor proteinp53(TP53)interaction.This review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells,as evidenced by clinical studies,reviews,and trials.TP53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of TP53.MDM2 and TP53 activity is tightly regulated.However,cancerous breast cells overexpress MDM2 through five hypothesized mechanisms.Consequently,TP53 levels decrease with increased tumor cell proliferation.Three strategies have been identified for controlling MDM2 upregulation in cells with wild-type or mutated TP53.MDM2 inhibitors(MDM2i)are administered in combination with existing chemotherapies to reduce their effects on healthy cells.Few clinical and preclinical studies have been conducted using MDM2i,which necessitates high-quality clinical trials to support their therapeutic potential in breast cancer therapy.
文摘Background:Bonducellin is one of the bioactive compounds present in Caesalpinia bonduc Roxb(L).It is a homoisoflavonoid recognized for its anti-cancer,anti-androgenic,and anti-estrogenic properties and could potentially treat polycystic ovary syndrome(PCOS).However,the underlying molecular mechanism remains unexplored.This study aims to elucidate the potential molecular mechanisms of bonducellin in treating PCOS and its associated symptoms through an integrated approach combining network pharmacology,molecular docking,molecular dynamics simulation,and in vivo validation.Methods:Bonducellin-associated and PCOS-related genes were intersected using VENN analysis to determine common gene targets.KEGG pathway analysis was conducted to investigate the biological pathways involving the co-targeted genes.The protein-protein interactions of the target genes were performed to identify the key proteins interacting with bonducellin.Molecular docking and 100 ns molecular simulations were carried out to evaluate the binding affinity and conformational stability of bonducellin with the target proteins.Additionally,the acute toxicity of bonducellin was assessed on zebrafish embryos and in vivo gene expression studies were performed to examine its regulatory effect on the top co-targeted gene.Results:The intersection of bonducellin-associated and PCOS-related genes identified 76 co-targeted genes.KEGG pathway analysis revealed their involvement in 15 critical pathways,including steroid hormone biosynthesis.Protein-protein interaction and pathway enrichment analysis highlighted key targets,including MMP9,AR,KDR,PRKACA,KIT,CYP19A1,HSD11B1,ESR1,STAT3,ESR2,PRKCA,ROCK1,BRAF,HSD17B2,PIK3R1,and RAF1,all of which exhibited strong binding to bonducellin.Molecular simulations confirmed the stability of bonducellin to the top proteins,MMP9 and AR,with high binding scores.Acute toxicity studies in zebrafish embryos determined the LC50 value of bonducellin as 0.8μg/mL at 48 hpf.Gene expression analysis revealed that bonducellin differentially regulates the MMP9 gene that is involved in modulating PCOS-related pathways.Conclusion:This study suggests potential gene pathways and protein interactions through which bonducellin could exert therapeutic effects on PCOS and its associated disorders.This provides valuable insights for future research into understanding and developing bonducellin-based treatments for PCOS.
基金financial support from the National Key Research and Development Program of China(2021YFC2400703)Zhengzhou City Major Special Project for Collaborative InnovationChina Scholarship Council。
文摘Bio-magnesium(Mg)alloys exhibit excellent biocompatibility and biodegradability,making them highly promising for implant applications.However,their limited strength-ductility balance remains a critical challenge restricting widespread use.In this study,ultra-fine-grained and homogeneous Mg alloys were fabricated using double-sided friction stir processing(DS-FSP)with liquid CO_(2) rapid cooling,leading to a significant enhancement in the strength-ductility synergy of the stirred zone.The results demonstrate that DS-FSP samples exhibit simultaneous improvements in ultimate tensile strength(UTS)and elongation,reaching 334.1±15 MPa and 28.2±7.3%,respectively.Compared to the non-uniform fine-grained microstructure obtained through single-sided friction stir processing,DS-FSP generates a uniform ultra-fine-grained structure,fundamentally altering the fracture behavior and mechanisms of Mg alloys.The DS-FSP samples exhibit irregular fracture patterns due to variations in basal slip system activation among different grains.In contrast,single-sided friction stir processing samples,characterized by a fine-grained yet heterogeneous microstructure,display flat shear fractures dominated by high-density dislocation initiation induced by twin formation,with fracture propagation dictated by the non-uniform texture.By achieving an ultra-fine grain size and homogeneous texture,DS-FSP effectively modifies the fracture mechanisms,thereby enhancing the strength-ductility balance of bio-magnesium alloys.
基金supported by the Key Program of Heilongjiang Provincial Natural Science Foundation of China(ZD2020C008)the National Natural Science Foundation of China(32071519)+2 种基金the Heilongjiang University Graduate Innovation Research Project(YJSCX2022-031HLJU)the Qiqihar Science and Technology Plan Joint Guidance Project(LSFGG-2022037)Scientific Research Project of Ecological Environment Protection of Heilongjiang Provincial Department of Ecological Environment(HST2022TR004)。
文摘During obesity treatment,clinicians have been burdened by the ever-increasing number of patients and the side effects of drug treatment.Finding new plant-derived active ingredients as an intervention for obesity has become a research focus.In this study,Plackett-Burman and Central Composite Design experiments,plant-wide target metabolomics technology,simulated human colon fermentation test,and cell experiment in vitro were successively used to investigate the effects of fermented and unfermented polyphenols(FP and UP,respectively)of blue honeysuckle on obesity.After the optimization of the response surface method,polyphenol content((1878.08±14.53)mg/100 g)increased by 2.63 times after Lactobacillus rhamnosus 6224 and Saccharomyces cerevisiae W5 mixed fermentation.There were 23 significantly different metabolites were observed in FP and UP.Of them,7 different metabolites were significantly and positively correlated with short-chain fatty acids(SCFAs),whereas negatively correlated with lipopolysaccharides(LPS).The contents of these 7 metabolites were significantly increased in FP.Furthermore,the effects of FP and UP on the SCFA biosynthesis pathway were different.Cell experiments revealed that polyphenols can significantly promote the secretion of gastrointestinal endogenous hormones and insulin and inhibit interleukin-6 levels.Linear regression analysis revealed SCFAs had a positive regulatory effect on glycolipid metabolism,whereas LPS had a negative effect.Overall,these crucial findings provide an economical and simple method for obtaining blue honeysuckle polyphenols and laying a theoretical foundation for its application in the therapeutic intervention against obesity.
基金funded by the National Key R&D Program of China(Grant No.2022YFE0139400)the Egyptian-Chinese Research Fund,and Science,Technology&Innovation Funding Authority Egypt(Grant No.46512)the National Natural Science Foundation of China(Grant No.261143470).
文摘Salt stress is a critical factor affecting the growth and yield of rice.Egypt,the largest rice producer in North Africa and the Middle East,is facing contrasting challenges related to salinity in its agroecosystems.In this study,we compared the salt-induced responses among three rice varieties:Giza 176(Egyptian variety),Kaituodao(Chinese variety),and Pokkali(Sri Lanka variety,used as control)under normal and saline stress(100 mmol/L NaCl)conditions at two seedling stages through RNA-seq expression analysis.Giza 176 displayed a salt tolerance score of 7 on the SES(Standard Evaluation Score).Its transcriptome showed dynamic changes,with the number of upregulated genes increasing from 180 to 735,and downregulated genes increasing from 918 to 2930 from the one-week to two-week stress stages,with activated pathways in ion transport,reactive oxygen species(ROS)scavenging,and protein biosynthesis.
基金supported by the National Natural Science Foundation of China(U20A20353 to X.Xu and 81900185 to Y.Ye).
文摘Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this region.Identification of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin switching.Here,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at onset.Gene-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb F.Finally,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control regions.This study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.
基金supported by the National Natural Science Foundation of China(Grant Nos.32272751,32272750,31972445)the Department of Science and Technology of Jilin Province(Grant Nos.20220508112RC,20210101005JC)+1 种基金the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(Grant No.2023C02028)the China Scholarship Council(Grant No.202006625007)。
文摘Floral color and scent are crucial for plant-environment interactions,especially in reproduction by attracting pollinators for fertilization.They also have wide applications in cosmetic,pharmaceutical,and nutraceutical industries.Plant pigments are typically classified as chlorophylls,flavonoids,carotenoids,and betalains,while volatile organic compounds(VOCs)are grouped as terpenes,phenylpropanoids/benzenoids,and fatty acid derivatives.Significant progresses have been made in understanding the biosynthesis and regulation of these floral pigments and VOCs.Despite differences in their biosynthetic pathways,floral pigments and VOCs are biochemically connected and exhibit synergistic interactions during flower development and in response to biotic and abiotic stresses,suggesting the existence of pleiotropic regulators or complex mechanisms co-regulating their biosynthesis.In this review,we summarize and outline the metabolite pathways mainly integrating flavonoids,carotenoids,terpenes,and phenylpropanoids/benzenoids.We also provide a series of scenarios illustrating the coordinated regulation of floral color and scent.Finally,we suggest areas for future research.We hope this review will spark interest in this research direction and stimulate further studies.
基金funded by the Ministry of Science,Technological Development and Innovation of the Republic of Serbia(grant numbers 451-03-136/2025-03/200007 and 451-03-136/2025-03/200042).
文摘Anticancer drug resistance remains a major challenge in cancer treatment hindering the efficacy of chemotherapy and targeted therapies.Conventional two-dimensional(2D)cell cultures cannot replicate the complexity of the in vivo tumor microenvironment(TME),limiting their utility for drug resistance research.Therefore,three-dimensional(3D)tumor models have proven to be a promising alternative for investigating chemoresistance mechanisms.In this review,various cancer 3D models,including spheroids,organoids,scaffold-based models,and bioprinted models,are comprehensively evaluated with a focus on their application in drug resistance studies.We discuss the materials,properties,and advantages of each model,highlighting their ability to better mimic the TME and represent complex mechanisms of drug resistance such as epithelial-mesenchymal transition(EMT),drug efflux,and tumor-stroma interactions.Furthermore,we investigate the limitations of these models,including scalability,reproducibility and technical challenges,as well as their potential therapeutic impact on personalized medicine.Through a thorough comparison of model performance,we provide insights into the strengths and weaknesses of each approach and offer guidance for model selection based on specific research needs.
基金supported by the National Key Research and Development Program of China(2021YFC2501800,2023YFC0872500 and 2024YFC3044600)the National Natural Science Foundation of China(82072214,82272198,82202373)+1 种基金the Science and Technology of Shanghai Committee(21MC1930400,22Y11900100 and 23Y31900100)the Shanghai Municipal Health Commission(2023ZDFC0101)。
文摘BACKGROUND:Community-acquired pneumonia(CAP)represents a significant public health concern due to its widespread prevalence and substantial healthcare costs.This study was to utilize an integrated proteomic and metabolomic approach to explore the mechanisms involved in severe CAP.METHODS:We integrated proteomics and metabolomics data to identify potential biomarkers for early diagnosis of severe CAP.Plasma samples were collected from 46 CAP patients(including27 with severe CAP and 19 with non-severe CAP)and 19 healthy controls upon admission.A comprehensive analysis of the combined proteomics and metabolomics data was then performed to elucidate the key pathological features associated with CAP severity.RESULTS:The proteomic and metabolic signature was markedly dif ferent between CAPs and healthy controls.Pathway analysis of changes revealed complement and coagulation cascades,ribosome,tumor necrosis factor(TNF)signaling pathway and lipid metabolic process as contributors to CAP.Furthermore,alterations in lipid metabolism,including sphingolipids and phosphatidylcholines(PCs),and dysregulation of cadherin binding were observed,potentially contributing to the development of severe CAP.Specifi cally,within the severe CAP group,sphingosine-1-phosphate(S1P)and apolipoproteins(APOC1 and APOA2)levels were downregulated,while S100P level was signifi cantly upregulated.CONCLUSION:The combined proteomic and metabolomic analysis may elucidate the complexity of CAP severity and inform the development of improved diagnostic tools.
