Asplactones A-E(1-5),five unique diphenyl ether hybrids,along with two rare spiro-diphenyl ethers,aspviolaceols A(6)and B(7),were isolated and characterized from Aspergillus sp.F1-8A,an endophytic fungus associated wi...Asplactones A-E(1-5),five unique diphenyl ether hybrids,along with two rare spiro-diphenyl ethers,aspviolaceols A(6)and B(7),were isolated and characterized from Aspergillus sp.F1-8A,an endophytic fungus associated with the parotoid glands of Bufo gargarizans Cantor.Compounds 1-5 represent the first examples of diphenyl ether hybrids fused with unusual moieties,including conjugatedγ-butyrolactone and cyclopentenone.Compounds 6 and 7 are the first known natural spiro-diphenyl ethers,with 6 featuring an uncommon 6/6/6/6-membered carbon skeleton,and 7 possessing a distinct 6/6/6/6/6/6-membered diphenyl ether spiro-heterodimer carbon framework.Structural elucidation was performed using a combination of spectroscopic techniques,X-ray crystallography,and quantum-chemical calculations,and plausible biosynthetic pathways were proposed.Biologically,compounds 1,2,4,6,and 7 exhibited antioxidant activity comparable to or surpassing that of vitamin C in 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate)(ABTS),and ferric reducing power assays.They also significantly improved cell viability in H2O2-induced oxidative injury assays using A549 cells.展开更多
The plant life cycle and the promise of crop yield start with successful seed germination,which requires an optimal balance between the phytohormones abscisic acid(ABA)and gibberellin(GA).Here,we report that the APETA...The plant life cycle and the promise of crop yield start with successful seed germination,which requires an optimal balance between the phytohormones abscisic acid(ABA)and gibberellin(GA).Here,we report that the APETALA 2-type transcription factor SALT AND ABA RESPONSE ERF 1(OsSAE1)antagonistically modulates ABA and GA signaling to control seed germination in rice(Oryza sativa L.).We show that knocking out OsSAE1 delays seed germination,concomitant with the accumulation of SLENDER RICE1(OsSLR1),a GA signaling repressor DELLA protein;importantly,GA application rescued the seed germination defect of ossae1 mutants.OsSAE1 directly activates transcription of the GA biosynthesis gene OsKS1 and represses that of the GA metabolism gene OsGA2ox3,resulting in higher GA levels.Moreover,OsSLR1physically interacts with ABA-INSENSITIVE 5(OsABI5),a key ABA signaling component,enhancing the transcriptional activation capacity of OsABI5 toward its target genes to regulate seed germination.The temporal expression pattern of OsSAE1 supports its role in orchestrating GA and ABA signaling to modulate seed germination and seed dormancy.Different OsSAE1 haplotypes differentially affected OsSAE1 transcript levels and seed germination rates,illustrating the potential of the elite OsSAE1 haplotype for genetic improvement of seed germination.Overall,our study reveals that OsSAE1 controls rice seed germination by regulating the balance between ABA and GA,providing a pivotal selection target for breeding rice cultivars suitable for direct seeding.展开更多
Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male m...Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.展开更多
Rice seedling blight,caused by various fungi,including Fusarium oxysporum,poses a severe threat to rice production.As awareness grows regarding the environmental and safety hazards associated with the application of f...Rice seedling blight,caused by various fungi,including Fusarium oxysporum,poses a severe threat to rice production.As awareness grows regarding the environmental and safety hazards associated with the application of fungicides for managing rice seedling blight,there has been a shift in focus towards biological control agents.In this study,we isolated biocontrol bacteria from paddy fields that significantly inhibited the growth of F.oxysporum in vitro and identified the strains as Bacillus amyloliquefaciens T40 and Bacillus pumilus T208.Additionally,our findings indicated that the combined application of these Bacillus strains in soil was more effective in reducing the incidence of rice seedling blight than their individual use.Analysis of 16S and internal transcribed spacer rRNA gene sequencing data revealed that the mixture of the T40 and T208 strains exhibited the lowest average clustering coefficients,which were negatively correlated with the biomass of F.oxysporum-inoculated rice seedlings.Furthermore,this mixture led to higher stochastic assembly(average|βNTI|<2)and reduced selection pressures on rice rhizosphere bacteria compared with individual strain applications.The mixture of the T40 and T208 strains also significantly increased the expression of defense-related genes.In conclusion,the mixture of the T40 and T208 strains effectively modulates microbial community structures,enhances microbial network stability,and boosts the resistance against rice seedling blight.Our study supports the development and utilization of biological resources for crop protection.展开更多
Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional bree...Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional breeding methods raise concerns about reduced genetic diversity,epibreeding propels crop improvement through epigenetic variations that regulate gene expression,ultimately impacting crop yield.Epigenetic regulation in crops encompasses various modes,including histone modification,DNA modification,RNA modification,non-coding RNA,and chromatin remodeling.This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process.We propose a valuable strategy for improving maize yield through epibreeding,combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics(SynEpi).Finally,we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.展开更多
Volatile aromatic aldehydes,including benzaldehyde(BzH),4-fluorobenzaldehyde(4-F-BzH),4-isobutylbenzaldehyde(4-iBu-BzH),3-trifluoromethylbenzaldehyde(3-CF_(3)-BzH),p-methoxybenzaldehyde(4-MeO-BzH),and o-trifluoromethy...Volatile aromatic aldehydes,including benzaldehyde(BzH),4-fluorobenzaldehyde(4-F-BzH),4-isobutylbenzaldehyde(4-iBu-BzH),3-trifluoromethylbenzaldehyde(3-CF_(3)-BzH),p-methoxybenzaldehyde(4-MeO-BzH),and o-trifluoromethylbenzaldehyde(2-CF_(3)-BzH),are crucial raw materials for the synthesis of various pesticides and pharmaceuticals[1].展开更多
Peel color is an important appearance quality of melons that significantly affects consumer preferences.In this study,a near-isogenic line NIL-G(dark green peel)was generated from B8(grey-green peel)and B15(white peel...Peel color is an important appearance quality of melons that significantly affects consumer preferences.In this study,a near-isogenic line NIL-G(dark green peel)was generated from B8(grey-green peel)and B15(white peel).The F_2 population constructed by crossing NIL-G and B15 was used to study the inheritance pattern of peel color,and bulked-segregant analysis sequencing(BSA-seq)was employed to identify the interval in which the target gene was located.Genetic analysis showed that a dominant gene controls the dark green peel trait at maturity.BSAseq and molecular markers were used to localize the candidate gene in a 263.7 kb interval of chromosome 4,which contained the CmAPRR2 gene with known functions.Moreover,allelic sequence analysis revealed four SNP variations of the CmAPRR2 gene in B15,of which SNP.G614331A was located at the junction of the 6th exon and 6th intron.The G-to-A mutation caused alternative splicing of the transcript of CmAPRR2 in B15,generating two transcripts(CmAPRR2-A and CmAPRR2-B)with premature termination codons.Furthermore,the Kompetitive Allele Specific PCR(KASP)marker,APRR2-G/A,was developed based on this SNP and shown to co-segregate with the peel color phenotype in the F_(2) population.Compared to white-peel B15,the expression level of CmAPRR2 in dark green peel NIL-G was higher at each growth stage.Therefore,CmAPRR2 may be the key gene controlling the fruit color of melons.This study identified a novel allelic variant of CmAPRR2 that leads to white peel formation in mature melons.We also provides a theoretical basis for further research on the gene regulatory mechanism of melon peel colors,which promotes using molecular marker-assisted selection to modify melon peel colors in the future.展开更多
The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurodegenerative diseases.Pharmacolo...The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurodegenerative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effectively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC_(50))of 0.478 mM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.展开更多
Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be f...Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis.To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments.We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages(BMMs)at various concentrations.TRAc P experiments were conducted to examine BQTL's impact on osteoclast differentiation.RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation.Finally,in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings.This study revealed that BQTL suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity.The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity,primarily through attenuation of the MAPK,NF-κB,and Calcineurin signaling pathways.BQTL's inhibitory capacity was further examined in vivo using an ovariectomized(OVX)rat model,demonstrating a strong protective effect against bone loss.BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.展开更多
Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal ...Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.展开更多
The global rise in CO_(2)concentration is having a profound impact on the structure and function of aquatic ecosystems.However,little information is available on the responses of odorproducing cyanobacteria to the inc...The global rise in CO_(2)concentration is having a profound impact on the structure and function of aquatic ecosystems.However,little information is available on the responses of odorproducing cyanobacteria to the increase in CO_(2)concentration.In this study,the effects of different CO_(2)concentrations on 2-methylisoborneol(MIB)-producing Pseudanabaena and non-2-MIB-producing Pseudanabaena under monoculture and co-culture conditions were investigated.Results show that the specific growth rate of Pseudanabaena gradually increased with the rise in CO_(2)concentration,and for the 2-MIB-producing strain,this increase was significantly higher than the non-2-MIB-producing strain.Under co-culture conditions,the proportion of non-2-MIB-producing Pseudanabaena was significantly higher than that of 2-MIB-producing Pseudanabaena,suggesting a superior competitive ability of non-2-MIB-producing Pseudanabaena over 2-MIB-producing Pseudanabaena.Under monoculture conditions,the total 2-MIB production at the 300-μg/g CO_(2)concentration was significantly higher than that at 600-and 1200-μg/g CO_(2)concentrations.The 2-MIB concentration produced by Pseudanabaena decreased with the increasing in CO_(2)concentration.Therefore,we believe that with the future increase in CO_(2)concentration,2-MIB concentration would be decreased and so would the risk of 2-MIB outbreaks.展开更多
Phosphorus(P)is the main limiting factor in eutrophication.Sediment P can be released decades after its accumulation.Lake restoration requires the reduction of internal sediment P loading.Although we tried to provide ...Phosphorus(P)is the main limiting factor in eutrophication.Sediment P can be released decades after its accumulation.Lake restoration requires the reduction of internal sediment P loading.Although we tried to provide a comprehensive summary of the state-of-the-art sediment P control technologies,our analyses in this review are focused on the mechanisms,control effects,and application conditions of different in-situ technologies including physical control,chemical control,ecological remediation,and combined control technology.The design principles,feasibility,operation parameters,and pros&cons of these technologies are analyzed and compared.More efforts are needed to improve in-situ sediment P control technologies so as to enhance the interaction between materials and plant communities and promote the adsorption and fixation of active P in sediments.The control materials for internal sediment P loading need to be further studied in terms of their functional properties,pre-evaluation of the P control effect,and engineering applications.展开更多
The oilseed crop Camelina sativa exhibits salinity tolerance,but the effects on early growth stages across a range of different salts and in combination with salicylic acid(SA)have not been thoroughly evaluated.In thi...The oilseed crop Camelina sativa exhibits salinity tolerance,but the effects on early growth stages across a range of different salts and in combination with salicylic acid(SA)have not been thoroughly evaluated.In this study,seeds were germinated in varying concentrations of six salts(NaCl,CaCl_(2),ZnCl_(2),KCl,MgSO_(4),and Na2SO_(4))with or without 0.5 mM SA.Using the halotime model,we estimated salt thresholds for germination and parameters of seedling growth.Germination and seedling growth parameters of camelina significantly decreased with increasing salt concentration across all salt types.Salts containing Zn and SO_(4) were most detrimental to germination and seedling growth.Except for KCl,0.5 mM SA generally reduced the salinity tolerance threshold(Saltb(50))of camelina.Specifically,Saltb(50)was 21.5%higher for KCl and 16.1%,25.0%,54.9%,21.0%,and 5.6%lower for CaCl_(2),NaCl,MgSO_(4),Na2SO_(4),and ZnCl_(2),respectively,when 0.5 mM SA was compared to 0 mM SA.Furthermore,camelina seedling growth was consistently more sensitive than germination across all salt types.SA did not significantly enhance germination or seedling growth and was harmful when combined with certain salts or at the germination stage.It can be concluded that both the type of salt and the concentration of SA are as critical as the salt concentration in saline irrigation water.展开更多
Background:Over the past 50 years,the incidence of obesity has gradually increased,necessitating investigation into the multifactorial contributors to this disease,including the gut microbiota.Bacteria within the huma...Background:Over the past 50 years,the incidence of obesity has gradually increased,necessitating investigation into the multifactorial contributors to this disease,including the gut microbiota.Bacteria within the human gut microbiome communicate using a density-dependent process known as quorum sensing(QS),in which autoinducer(AI)molecules(e.g.,N-acyl-homoserine lactones[AHLs])are produced to enable bacterial interactions and regulate gene expression.Methods:We aimed to disrupt QS using quorum quenching(QQ)lactonases GcL and SsoPox,which cleave AHL signaling molecules in a taxa-specific manner based on differing enzyme affinities for different substrates.We hypothesized that QQ hinders signals from obesity-associated pathobionts,thereby slowing or preventing obesity.Results:In a murine model of dietinduced obesity,we observed GcL and SsoPox treatments have separate sex-dependent and dose-dependent effects on intestinal community composition and diversity.Notably,male mice given 2 mg/mL SsoPox exhibited significant changes in the relative abundances of gram-negative taxa,including Porphyromonadaceae,Akkermansiaceae,Muribaculaceae,and Bacteroidales(Kruskal-Wallis p<0.001).Additionally,we used covariance matrix network analysis to model bacterial taxa co-occurrence due to QQ enzyme administration.There were more associations among taxa in control mice,particularly among gram-negative bacteria,whereas mice receiving SsoPox had the fewest associations.Conclusions:Overall,our study establishes proof of concept that QQ is a targetable strategy for microbial control in vivo.Further characterization and dosage optimization of QQ enzymes are necessary to harness their therapeutic capability for the treatment of chronic microbial-associated diseases.展开更多
Leaf color mutants (LCMs) provide crucial insights into the regulatory mechanisms underlying chloroplast development,photo synthesis,and stre ss adaptation.In this study,we identified a temperature-sensitive albino mu...Leaf color mutants (LCMs) provide crucial insights into the regulatory mechanisms underlying chloroplast development,photo synthesis,and stre ss adaptation.In this study,we identified a temperature-sensitive albino mutant,tsa4,characterized by an albino phenotype at the seedling stage and abnormal chloroplast development at temperatures below 25℃.展开更多
Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.Thi...Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.展开更多
Given the increasing concern regarding antibacterial resistance,the antimicrobial properties of naphthoquinones have recently attracted significant attention.While 1,4-naphthoquinone and its derivatives have been exte...Given the increasing concern regarding antibacterial resistance,the antimicrobial properties of naphthoquinones have recently attracted significant attention.While 1,4-naphthoquinone and its derivatives have been extensively studied,the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored.This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone.Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus(MRSA),with one compound(PNP-02)demonstrating activity comparable to vancomycin in minimum inhibitory concentration,minimum bactericidal concentration(MBC),and time-kill assays.Microscopic and biochemical analyses revealed that PNP-02adversely affects the cell wall and cell membrane of MRSA.Mechanistic investigations,including proteomic sequencing analyses,Western blotting,and RT-q PCR assays,indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways,thereby increasing membrane permeability and inducing bacterial death.In an in vivo mouse model of skin wound healing,PNP-02 exhibited antibacterial efficacy similar to vancomycin.The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation.These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.展开更多
The interaction between nanoparticles (NPs) and pollutants affects their bioavailability and toxicity.However,the processes by which NPs and pollutants change in vivo have rarely been explored.Here,using laser ablatio...The interaction between nanoparticles (NPs) and pollutants affects their bioavailability and toxicity.However,the processes by which NPs and pollutants change in vivo have rarely been explored.Here,using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS),we found that both nanoplastics and ZnO NPs caused more Cd to accumulate in zebrafish larvae,but with distinct pathways.Nanoplastics could adsorb Cd^(2+) and transfer it into the larvae through the“Trojan horse”effect.The coexposure of nanoplastics and Cd^(2+) caused Cd to accumulate in the abdomen where the nanoplastics were located without dissociation,showing a lower toxic effect than Cd^(2+) exposure alone.ZnO NPs weakly adsorbed Cd^(2+),but they increased the Zn and Cd contents in larvae by enhancing the expression of metal transporters.The coexposure of ZnO and Cd^(2+) evenly distributed Cd in the larvae,revealing a more severe toxic effect than Cd^(2+) exposure alone.Our results demonstrated the changing bioavailability and toxicity of Cd induced by different NPs.This also shows the vital role LA-ICP-MS plays in revealing the relationship between toxicity and bioavailability.In addition,the long-term effect of bioavailability on heavy metal toxicity and nanosafety deserves further investigation.展开更多
Pre-harvest sprouting(PHS)or vivipary is a major problem affecting cereal quality and grain quantity and is primarily linked to the dysregulation of abscisic acid(ABA)biosynthesis in plants.Therefore,elucidating the m...Pre-harvest sprouting(PHS)or vivipary is a major problem affecting cereal quality and grain quantity and is primarily linked to the dysregulation of abscisic acid(ABA)biosynthesis in plants.Therefore,elucidating the molecular mechanisms governing seed dormancy is crucial for developing strategies to improve crop productivity.In this study,we identified a novel viviparous maize mutant,viviparous-like 5(vp-like5),which exhibits precocious germination in developing seeds.Through map-based cloning,we discovered that ZmCNX6,which encodes a small subunit of molybdopterin synthase essential for molybdenum cofactor(MoCo)biosynthesis,is the causal gene responsible for the vp-like5 phenotype.Biochemical assays have demonstrated significantly reduced activities of MoCo-dependent enzymes,including aldehyde oxidase(AO),xanthine dehydrogenase(XDH),and nitrate reductase(NR),in vplike5.AO is essential for the ABA biosynthesis,and the observed ABA deficiency in vp-like5 likely drives the viviparous phenotype.Expression analysis showed that ZmCNX6 was stably expressed during seed development,indicating its significant role in seed development.Furthermore,overexpression of ZmCNX6 not only enhanced the activities of MoCo-dependent enzymes but also improved drought tolerance in maize.Collectively,our study revealed ZmCNX6 as a multifunctional hub coordinating MoCo metabolism,ABA-dependent dormancy regulation,and abiotic stress responses,offering a potential target for simultaneously mitigating vivipary and improving drought resistance in maize.展开更多
Following the publication of Liu et al.(2024),an error was identified in Figure 4B,in which the image representing the lung from the E529G group was inadvertently duplicated with the image of the lung from the WT grou...Following the publication of Liu et al.(2024),an error was identified in Figure 4B,in which the image representing the lung from the E529G group was inadvertently duplicated with the image of the lung from the WT group during figure preparation.展开更多
基金supported by the National Natural Science Foundation of China(No.82073721)Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.23KJA310003).
文摘Asplactones A-E(1-5),five unique diphenyl ether hybrids,along with two rare spiro-diphenyl ethers,aspviolaceols A(6)and B(7),were isolated and characterized from Aspergillus sp.F1-8A,an endophytic fungus associated with the parotoid glands of Bufo gargarizans Cantor.Compounds 1-5 represent the first examples of diphenyl ether hybrids fused with unusual moieties,including conjugatedγ-butyrolactone and cyclopentenone.Compounds 6 and 7 are the first known natural spiro-diphenyl ethers,with 6 featuring an uncommon 6/6/6/6-membered carbon skeleton,and 7 possessing a distinct 6/6/6/6/6/6-membered diphenyl ether spiro-heterodimer carbon framework.Structural elucidation was performed using a combination of spectroscopic techniques,X-ray crystallography,and quantum-chemical calculations,and plausible biosynthetic pathways were proposed.Biologically,compounds 1,2,4,6,and 7 exhibited antioxidant activity comparable to or surpassing that of vitamin C in 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate)(ABTS),and ferric reducing power assays.They also significantly improved cell viability in H2O2-induced oxidative injury assays using A549 cells.
基金funded by the National Natural Science Foundation of China(32472037,32030079)the National Key Research and Development Program of China(2022YFD1201700)+2 种基金the Youth innovation of Chinese Academy of Agricultural Sciences(Y2024QC14)the Central Public-Interest Scientific Institution Basal Research Fund(1610392023004)Agricultural Science and Technology Innovation Program(CAAS-ZDRW202407)。
文摘The plant life cycle and the promise of crop yield start with successful seed germination,which requires an optimal balance between the phytohormones abscisic acid(ABA)and gibberellin(GA).Here,we report that the APETALA 2-type transcription factor SALT AND ABA RESPONSE ERF 1(OsSAE1)antagonistically modulates ABA and GA signaling to control seed germination in rice(Oryza sativa L.).We show that knocking out OsSAE1 delays seed germination,concomitant with the accumulation of SLENDER RICE1(OsSLR1),a GA signaling repressor DELLA protein;importantly,GA application rescued the seed germination defect of ossae1 mutants.OsSAE1 directly activates transcription of the GA biosynthesis gene OsKS1 and represses that of the GA metabolism gene OsGA2ox3,resulting in higher GA levels.Moreover,OsSLR1physically interacts with ABA-INSENSITIVE 5(OsABI5),a key ABA signaling component,enhancing the transcriptional activation capacity of OsABI5 toward its target genes to regulate seed germination.The temporal expression pattern of OsSAE1 supports its role in orchestrating GA and ABA signaling to modulate seed germination and seed dormancy.Different OsSAE1 haplotypes differentially affected OsSAE1 transcript levels and seed germination rates,illustrating the potential of the elite OsSAE1 haplotype for genetic improvement of seed germination.Overall,our study reveals that OsSAE1 controls rice seed germination by regulating the balance between ABA and GA,providing a pivotal selection target for breeding rice cultivars suitable for direct seeding.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFF0702200Science and Technology Projects in Guangzhou,Grant/Award Number:202206010084,202206010197 and 202206060002+1 种基金Guangdong S&T programme,Grant/Award Number:2009A081000002 and 2023B0303040004Technology Planning Project of Linzhi,Grant/Award Number:2023-YZ-01。
文摘Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.
基金supported by the Zhejiang Provincial Natural Science Foundation,China(Grant No.LQ24C010007)Zhejiang Science and Technology Major Program on Rice New Variety Breeding,China(Grant No.2021C02063)+4 种基金the Agricultural Sciences and Technologies Innovation Program,China(Grant No.CAAS-CSCB-202301)the Key Projects of Zhejiang Provincial Natural Science Foundation,China(Grant No.LZ23C130002)the Youth Innovation Program of Chinese Academy of Agricultural Sciences(Grant No.Y2023QC22)the Joint Open Competitive Project of the Yazhou Bay Seed Laboratory and China National Seed Company Limited(Grant Nos.B23YQ1514 and B23CQ15EP)the External Cooperation Projects of Biotechnology Research Institute,Fujian Academy of Agricultural Sciences,China(Grant No.DWHZ2024-07).
文摘Rice seedling blight,caused by various fungi,including Fusarium oxysporum,poses a severe threat to rice production.As awareness grows regarding the environmental and safety hazards associated with the application of fungicides for managing rice seedling blight,there has been a shift in focus towards biological control agents.In this study,we isolated biocontrol bacteria from paddy fields that significantly inhibited the growth of F.oxysporum in vitro and identified the strains as Bacillus amyloliquefaciens T40 and Bacillus pumilus T208.Additionally,our findings indicated that the combined application of these Bacillus strains in soil was more effective in reducing the incidence of rice seedling blight than their individual use.Analysis of 16S and internal transcribed spacer rRNA gene sequencing data revealed that the mixture of the T40 and T208 strains exhibited the lowest average clustering coefficients,which were negatively correlated with the biomass of F.oxysporum-inoculated rice seedlings.Furthermore,this mixture led to higher stochastic assembly(average|βNTI|<2)and reduced selection pressures on rice rhizosphere bacteria compared with individual strain applications.The mixture of the T40 and T208 strains also significantly increased the expression of defense-related genes.In conclusion,the mixture of the T40 and T208 strains effectively modulates microbial community structures,enhances microbial network stability,and boosts the resistance against rice seedling blight.Our study supports the development and utilization of biological resources for crop protection.
基金supported by funding from the National Key R&D Program of China(2023ZD0407304)the Sci-Tech Innovation 2030 Agenda(2022ZD0115703)Fundamental Research Funds for Central Non-Profit of Chinese Academy of Agricultural Sciences(Y2023PT20).
文摘Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional breeding methods raise concerns about reduced genetic diversity,epibreeding propels crop improvement through epigenetic variations that regulate gene expression,ultimately impacting crop yield.Epigenetic regulation in crops encompasses various modes,including histone modification,DNA modification,RNA modification,non-coding RNA,and chromatin remodeling.This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process.We propose a valuable strategy for improving maize yield through epibreeding,combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics(SynEpi).Finally,we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.
基金supported by National Natural Science Foundation of China(22361031,22308260).
文摘Volatile aromatic aldehydes,including benzaldehyde(BzH),4-fluorobenzaldehyde(4-F-BzH),4-isobutylbenzaldehyde(4-iBu-BzH),3-trifluoromethylbenzaldehyde(3-CF_(3)-BzH),p-methoxybenzaldehyde(4-MeO-BzH),and o-trifluoromethylbenzaldehyde(2-CF_(3)-BzH),are crucial raw materials for the synthesis of various pesticides and pharmaceuticals[1].
基金supported by the Innovation and Development Program of Beijing Vegetable Research Center,China(KYCX202301)the Construction of Cucurbits Collaboration and Innovation Center,China(XTCX202301)+3 种基金the Youth Research Fund of Beijing Academy of Agriculture and Forestry Sciences,China(QNJJ202426)the National Natural Science Foundation of China(U21A20229 and 32102397)the Scientific Research Foundation of the Higher Education Institutions for Distinguished Young Scholars in Anhui Province,China(2022AH020037)and the Key Research and Development Projects of Anhui Province,China(2023z04020019)。
文摘Peel color is an important appearance quality of melons that significantly affects consumer preferences.In this study,a near-isogenic line NIL-G(dark green peel)was generated from B8(grey-green peel)and B15(white peel).The F_2 population constructed by crossing NIL-G and B15 was used to study the inheritance pattern of peel color,and bulked-segregant analysis sequencing(BSA-seq)was employed to identify the interval in which the target gene was located.Genetic analysis showed that a dominant gene controls the dark green peel trait at maturity.BSAseq and molecular markers were used to localize the candidate gene in a 263.7 kb interval of chromosome 4,which contained the CmAPRR2 gene with known functions.Moreover,allelic sequence analysis revealed four SNP variations of the CmAPRR2 gene in B15,of which SNP.G614331A was located at the junction of the 6th exon and 6th intron.The G-to-A mutation caused alternative splicing of the transcript of CmAPRR2 in B15,generating two transcripts(CmAPRR2-A and CmAPRR2-B)with premature termination codons.Furthermore,the Kompetitive Allele Specific PCR(KASP)marker,APRR2-G/A,was developed based on this SNP and shown to co-segregate with the peel color phenotype in the F_(2) population.Compared to white-peel B15,the expression level of CmAPRR2 in dark green peel NIL-G was higher at each growth stage.Therefore,CmAPRR2 may be the key gene controlling the fruit color of melons.This study identified a novel allelic variant of CmAPRR2 that leads to white peel formation in mature melons.We also provides a theoretical basis for further research on the gene regulatory mechanism of melon peel colors,which promotes using molecular marker-assisted selection to modify melon peel colors in the future.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82101417,81920108017,and 82130036)the STI2030-Major Projects(Project No.:2022ZD0211800)+2 种基金Jiangsu Province Key Medical Discipline(Grant No.:ZDXK202216)the Key Research and Development Program of Jiangsu Province of China(Program No.:BE2020620)Nanjing Medical Science and technology development Foundation,China(Grant No.:YKK20061).
文摘The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurodegenerative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effectively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC_(50))of 0.478 mM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.
基金supported by the Natural Science Foundation of Guangdong Province,China(No.2021A1515012168)the Administration of Traditional Chinese Medicine of Guangdong Province,China(Nos.20221146 and 20241091)+5 种基金the Basic and Applied Basic Research Fund Project in Guangdong Province,China(No.2020A1515110948)the Basic and Applied Basic Research in Jointly Funded Projects of City Schools(Institutes)Projects,China(Nos.202201020500 and 202201020295)the Project of Guangzhou Science and Technology Department,China(No.202102021040)the Guangzhou Science and Technology Plan Project,China(No.2023B03J0379)the Chinese Society of Traditional Chinese Medicine Youth Talent Lifting Project(No.2022-QNRC2-B11)the Hospital Young and Middle-aged Key Talent Cultivation Project of The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine(2023-10)。
文摘Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength,leading to increased fragility.Buqi-Tongluo(BQTL)decoction,a traditional Chinese medicine(TCM)prescription,has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis.To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments.We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages(BMMs)at various concentrations.TRAc P experiments were conducted to examine BQTL's impact on osteoclast differentiation.RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation.Finally,in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings.This study revealed that BQTL suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity.The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity,primarily through attenuation of the MAPK,NF-κB,and Calcineurin signaling pathways.BQTL's inhibitory capacity was further examined in vivo using an ovariectomized(OVX)rat model,demonstrating a strong protective effect against bone loss.BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
基金supported by the National Natural Science Foundation of China,Nos.81920108017(to YX),82130036(to YX),82371326(to XC),82171310(to XC)the STI2030-Major Projects,No.2022ZD0211800(to YX)Jiangsu Province Key Medical Discipline,No.ZDXK202216(to YX)。
文摘Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.
基金Supported by the National Key R&D Program of China(No.2021YFC3200900)the National Natural Science Foundation of China(No.31971477)。
文摘The global rise in CO_(2)concentration is having a profound impact on the structure and function of aquatic ecosystems.However,little information is available on the responses of odorproducing cyanobacteria to the increase in CO_(2)concentration.In this study,the effects of different CO_(2)concentrations on 2-methylisoborneol(MIB)-producing Pseudanabaena and non-2-MIB-producing Pseudanabaena under monoculture and co-culture conditions were investigated.Results show that the specific growth rate of Pseudanabaena gradually increased with the rise in CO_(2)concentration,and for the 2-MIB-producing strain,this increase was significantly higher than the non-2-MIB-producing strain.Under co-culture conditions,the proportion of non-2-MIB-producing Pseudanabaena was significantly higher than that of 2-MIB-producing Pseudanabaena,suggesting a superior competitive ability of non-2-MIB-producing Pseudanabaena over 2-MIB-producing Pseudanabaena.Under monoculture conditions,the total 2-MIB production at the 300-μg/g CO_(2)concentration was significantly higher than that at 600-and 1200-μg/g CO_(2)concentrations.The 2-MIB concentration produced by Pseudanabaena decreased with the increasing in CO_(2)concentration.Therefore,we believe that with the future increase in CO_(2)concentration,2-MIB concentration would be decreased and so would the risk of 2-MIB outbreaks.
基金financially supported by the National Natural Science Foundation of China(Nos.32201384,31830013,U20A2010)。
文摘Phosphorus(P)is the main limiting factor in eutrophication.Sediment P can be released decades after its accumulation.Lake restoration requires the reduction of internal sediment P loading.Although we tried to provide a comprehensive summary of the state-of-the-art sediment P control technologies,our analyses in this review are focused on the mechanisms,control effects,and application conditions of different in-situ technologies including physical control,chemical control,ecological remediation,and combined control technology.The design principles,feasibility,operation parameters,and pros&cons of these technologies are analyzed and compared.More efforts are needed to improve in-situ sediment P control technologies so as to enhance the interaction between materials and plant communities and promote the adsorption and fixation of active P in sediments.The control materials for internal sediment P loading need to be further studied in terms of their functional properties,pre-evaluation of the P control effect,and engineering applications.
基金the Genetics and Agricultural Biotechnology Institute of Tabarestan (GABIT) Sari Agricultural Sciences and Natural Resources University (SANRU) for the use of the services and financial supports of this research
文摘The oilseed crop Camelina sativa exhibits salinity tolerance,but the effects on early growth stages across a range of different salts and in combination with salicylic acid(SA)have not been thoroughly evaluated.In this study,seeds were germinated in varying concentrations of six salts(NaCl,CaCl_(2),ZnCl_(2),KCl,MgSO_(4),and Na2SO_(4))with or without 0.5 mM SA.Using the halotime model,we estimated salt thresholds for germination and parameters of seedling growth.Germination and seedling growth parameters of camelina significantly decreased with increasing salt concentration across all salt types.Salts containing Zn and SO_(4) were most detrimental to germination and seedling growth.Except for KCl,0.5 mM SA generally reduced the salinity tolerance threshold(Saltb(50))of camelina.Specifically,Saltb(50)was 21.5%higher for KCl and 16.1%,25.0%,54.9%,21.0%,and 5.6%lower for CaCl_(2),NaCl,MgSO_(4),Na2SO_(4),and ZnCl_(2),respectively,when 0.5 mM SA was compared to 0 mM SA.Furthermore,camelina seedling growth was consistently more sensitive than germination across all salt types.SA did not significantly enhance germination or seedling growth and was harmful when combined with certain salts or at the germination stage.It can be concluded that both the type of salt and the concentration of SA are as critical as the salt concentration in saline irrigation water.
基金Biotechnology Institute and the MnDrive initiative(to MHE)。
文摘Background:Over the past 50 years,the incidence of obesity has gradually increased,necessitating investigation into the multifactorial contributors to this disease,including the gut microbiota.Bacteria within the human gut microbiome communicate using a density-dependent process known as quorum sensing(QS),in which autoinducer(AI)molecules(e.g.,N-acyl-homoserine lactones[AHLs])are produced to enable bacterial interactions and regulate gene expression.Methods:We aimed to disrupt QS using quorum quenching(QQ)lactonases GcL and SsoPox,which cleave AHL signaling molecules in a taxa-specific manner based on differing enzyme affinities for different substrates.We hypothesized that QQ hinders signals from obesity-associated pathobionts,thereby slowing or preventing obesity.Results:In a murine model of dietinduced obesity,we observed GcL and SsoPox treatments have separate sex-dependent and dose-dependent effects on intestinal community composition and diversity.Notably,male mice given 2 mg/mL SsoPox exhibited significant changes in the relative abundances of gram-negative taxa,including Porphyromonadaceae,Akkermansiaceae,Muribaculaceae,and Bacteroidales(Kruskal-Wallis p<0.001).Additionally,we used covariance matrix network analysis to model bacterial taxa co-occurrence due to QQ enzyme administration.There were more associations among taxa in control mice,particularly among gram-negative bacteria,whereas mice receiving SsoPox had the fewest associations.Conclusions:Overall,our study establishes proof of concept that QQ is a targetable strategy for microbial control in vivo.Further characterization and dosage optimization of QQ enzymes are necessary to harness their therapeutic capability for the treatment of chronic microbial-associated diseases.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.32341026 and 32171998)the Hunan Provincial Science and Technology Innovation Program,China(Grant No.2023NK1010)the Changsha Natural Science Foundation,China(Grant No.20209001).
文摘Leaf color mutants (LCMs) provide crucial insights into the regulatory mechanisms underlying chloroplast development,photo synthesis,and stre ss adaptation.In this study,we identified a temperature-sensitive albino mutant,tsa4,characterized by an albino phenotype at the seedling stage and abnormal chloroplast development at temperatures below 25℃.
基金supported by the Russian Science Foundation,project no.23-14-00285。
文摘Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.
基金financially supported by the National Natural Science Foundation of China(Nos.U1903201,21702100,21907051)the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT_14R27)+1 种基金the Natural Science Foundation of Jiangsu Bureau of Science and Technology(No.BK20191254)the Fundamental Research Funds for Central Universities(No.020814380151)。
文摘Given the increasing concern regarding antibacterial resistance,the antimicrobial properties of naphthoquinones have recently attracted significant attention.While 1,4-naphthoquinone and its derivatives have been extensively studied,the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored.This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone.Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus(MRSA),with one compound(PNP-02)demonstrating activity comparable to vancomycin in minimum inhibitory concentration,minimum bactericidal concentration(MBC),and time-kill assays.Microscopic and biochemical analyses revealed that PNP-02adversely affects the cell wall and cell membrane of MRSA.Mechanistic investigations,including proteomic sequencing analyses,Western blotting,and RT-q PCR assays,indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways,thereby increasing membrane permeability and inducing bacterial death.In an in vivo mouse model of skin wound healing,PNP-02 exhibited antibacterial efficacy similar to vancomycin.The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation.These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
基金financially supported by the National Natural Science Foundation of China(NSFC,Nos.22174103 and 21575107)。
文摘The interaction between nanoparticles (NPs) and pollutants affects their bioavailability and toxicity.However,the processes by which NPs and pollutants change in vivo have rarely been explored.Here,using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS),we found that both nanoplastics and ZnO NPs caused more Cd to accumulate in zebrafish larvae,but with distinct pathways.Nanoplastics could adsorb Cd^(2+) and transfer it into the larvae through the“Trojan horse”effect.The coexposure of nanoplastics and Cd^(2+) caused Cd to accumulate in the abdomen where the nanoplastics were located without dissociation,showing a lower toxic effect than Cd^(2+) exposure alone.ZnO NPs weakly adsorbed Cd^(2+),but they increased the Zn and Cd contents in larvae by enhancing the expression of metal transporters.The coexposure of ZnO and Cd^(2+) evenly distributed Cd in the larvae,revealing a more severe toxic effect than Cd^(2+) exposure alone.Our results demonstrated the changing bioavailability and toxicity of Cd induced by different NPs.This also shows the vital role LA-ICP-MS plays in revealing the relationship between toxicity and bioavailability.In addition,the long-term effect of bioavailability on heavy metal toxicity and nanosafety deserves further investigation.
基金supported by the Open Project of Key Laboratory,Xinjiang Uygur Autonomous Region(2023D04070)the Agricultural Science and Technology Innovation Program of CAAS(CAAS-CSCB-202403)。
文摘Pre-harvest sprouting(PHS)or vivipary is a major problem affecting cereal quality and grain quantity and is primarily linked to the dysregulation of abscisic acid(ABA)biosynthesis in plants.Therefore,elucidating the molecular mechanisms governing seed dormancy is crucial for developing strategies to improve crop productivity.In this study,we identified a novel viviparous maize mutant,viviparous-like 5(vp-like5),which exhibits precocious germination in developing seeds.Through map-based cloning,we discovered that ZmCNX6,which encodes a small subunit of molybdopterin synthase essential for molybdenum cofactor(MoCo)biosynthesis,is the causal gene responsible for the vp-like5 phenotype.Biochemical assays have demonstrated significantly reduced activities of MoCo-dependent enzymes,including aldehyde oxidase(AO),xanthine dehydrogenase(XDH),and nitrate reductase(NR),in vplike5.AO is essential for the ABA biosynthesis,and the observed ABA deficiency in vp-like5 likely drives the viviparous phenotype.Expression analysis showed that ZmCNX6 was stably expressed during seed development,indicating its significant role in seed development.Furthermore,overexpression of ZmCNX6 not only enhanced the activities of MoCo-dependent enzymes but also improved drought tolerance in maize.Collectively,our study revealed ZmCNX6 as a multifunctional hub coordinating MoCo metabolism,ABA-dependent dormancy regulation,and abiotic stress responses,offering a potential target for simultaneously mitigating vivipary and improving drought resistance in maize.
文摘Following the publication of Liu et al.(2024),an error was identified in Figure 4B,in which the image representing the lung from the E529G group was inadvertently duplicated with the image of the lung from the WT group during figure preparation.
