The monofloral honey derived from Bauhinia championii(Benth.)Benth.(MH-Bc)possesses significant nutritional and bioactive value,making it highly suitable for commercial exploitation.However,the poorly defined characte...The monofloral honey derived from Bauhinia championii(Benth.)Benth.(MH-Bc)possesses significant nutritional and bioactive value,making it highly suitable for commercial exploitation.However,the poorly defined characteristics and unknown composition have hindered MH-Bc product development.In this study,we employed a combination of untargeted and targeted mass spectrometry analyses to characterize MH-Bc honey.As a result,4,7,8-trimethoxydibenzo[b,d]furan-3-ol(TDBF)was identified as a robust chemical marker for distinguishing MH-Bc from other types of honey.This specific marker was detected in both MH-Bc and the Bc plant but was absent in other honey varieties.Furthermore,a targeted mass spectrometry quantitative method was developed and validated to accurately determine the content of TDBF in honey samples.Overall,the presence of TDBF serves as a discerning indicator for future commercial MH-Bc products.展开更多
Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,poly...Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,polyphenols,and flavonoids that contribute to its antimicrobial,antioxidant,and immuno-modulatory properties.Additionally,honey is effective in managing some conditions,such as antibiotic-resistant infections,inflammation,and oxidative stress-related diseases.This review explores the extensive health benefits of honey,emphasizing the homology between food and medicine,as proposed by TCM philosophy.Further,this review explores the traditional applications of honey in respiratory health,wound healing,and gastrointestinal support,along with modern scientific validation of these uses.Moreover,the role of honey as a dietary supplement,functional food,and preservative in culinary practices is examined.Overall,this review highlights the synergy between ancient wisdom and contemporary science,advocating for the continued exploration of the role of honey in health,nutrition,and medicine.展开更多
Terpenoids,as crucial plant secondary metabolites in honey,possess various bioactivities.This study aimed at investigating terpenoids of longan,litchi,and schefflera honey.Our results reveal that these three species o...Terpenoids,as crucial plant secondary metabolites in honey,possess various bioactivities.This study aimed at investigating terpenoids of longan,litchi,and schefflera honey.Our results reveal that these three species of honey are characterized by abundant terpenoids,with eight terpenoids and one phenylpropanoid identified.Callunene,3,4,5-trimethoxyphenylpropanal,schefflerin(4-2'-(3',4'-dihydroxy-5'-methylfuran)-3,5,5-trimethyl-2-cyclohexenone)or abscisic acids may be as the characteristic components of longan,litchi,or schefflera honey.Abscisic acids were the most abundant components,average contents reached up to 53.67,96.89 and 21.11 mg/kg,respectively,and the content ranges in three types of honey were 13.75-85.40,19.93-177.31,14.69-28.38 mg/kg,respectively.To our knowledge,the presence of schefflerin,(6R,9S)-vomifoliol,and 3,4,5-trimethoxyphenylpropanal in honey is a novel finding.We distinguish Thailand from Chinese mainland and Taiwan longan honeys,based on the ratio of abscisic acid and callunene content.Overall,our proposal to combine terpenoids with standard fingerprints seems to provide a novel and reliable solution for evaluating the authenticity of commercial honey.展开更多
The effect of superheated steam(SHS)treatment on the quality characteristics of rape bee pollen were studied,and the efficiency of inactivation and inhibition of lipid oxidation were analyzed to investigate the differ...The effect of superheated steam(SHS)treatment on the quality characteristics of rape bee pollen were studied,and the efficiency of inactivation and inhibition of lipid oxidation were analyzed to investigate the differences between SHS and cobalt-60 isotope(^(60)Co)radiation treatment.The number of total plate count(TPC)and mold colonies(MC)remained within the limits of the standards after SHS treatment at 140℃for 2 min.Neither TPC nor MC were detected after^(60)Co irradiation.Peroxidase(POD)and polyphenol oxidase(PPO)activities significantly decreased with increasing temperature and duration of SHS,while^(60)Co radiation completely inactivated PPO.Compared to^(60)Co radiation,SHS treatment inhibited the deterioration of rape bee pollen by avoiding hydroperoxide production and lipid oxidation due to lack of oxygen.These results suggested SHS under 140℃for 2 min was the most suitable to inactivate the microorganisms and enzymes in rape bee pollen with minimal lipid oxidation.展开更多
The domesticated silkworm(Bombyx mori)has evolved a highly efficient nitrogen utilization system to support silk production.The silk glands play a pleiotropic role in sequestering nitrogen resources for silk synthesis...The domesticated silkworm(Bombyx mori)has evolved a highly efficient nitrogen utilization system to support silk production.The silk glands play a pleiotropic role in sequestering nitrogen resources for silk synthesis,mitigating aminoacidemia by assimilating free amino acids,and reallocating nitrogen during metamorphosis through programmed cell death.However,the specific functions of nitrogen metabolism-related genes in this process remain unclear.Using CRISPR/Cas9-based gene editing,mutations were generated in glutamine synthetase(GS),glutamate synthetase(GOGAT),asparagine synthetase(AS),glutamate dehydrogenase(GDH)and glutamate oxaloacetate transaminase 1(GOT1).Disruption of GS,GOGAT,and AS consistently reduced silkworm cocoon and pupal weight and significantly down-regulated silk protein gene transcription,whereas GOT1 mutation had no such effect.GOGAT mutants exhibited abnormally enlarged silk glands,whereas GS and AS mutants showed delayed programmed cell death in the silk glands.In contrast,GOT1 mutants displayed normal silk gland morphology but were consistently smaller.Disruption of GS,GOGAT,and AS led to more extensive transcriptional changes,including altered expression of transcription factors in the silk glands,compared with GOT1 mutants.Both GS and GOGAT mutants exhibited up-regulation of AS and GDH,while only GOGAT mutants displayed elevated AS enzymatic activity,suggesting that GOGAT may compete with AS for glutamine in the silk glands to support silk protein synthesis.AS mutants showed significantly elevated GOT activity and up-regulation of several metabolic pathways,indicating that AS may functionally interact with GOT in regulating both silk gland development and programmed cell death during metamorphosis.展开更多
Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the si...Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023.With a focus on recent research findings,the review explores the rich biodiversity of marine organisms,including sponges,corals,algae,and microorganisms,which have yielded numerous compounds exhibiting promising anticancer properties.Emphasizing the multifaceted mechanisms of action,the review discusses the molecular targets and pathways targeted by these compounds,such as cell cycle regulation,apoptosis induction,angiogenesis inhibition,and modulation of signaling pathways.Additionally,the review highlights the innovative strategies employed in the isolation,structural elucidation,and chemical modification of marine natural products to enhance their potency,selectivity,and pharmacological properties.Furthermore,it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs,including issues related to supply,sustainability,synthesis,and clinical translation.Finally,the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy.展开更多
Mulberry is a fundamental component of the global sericulture industry,and its positive impact on our health and the environment cannot be overstated.However,the mulberry reference genomes reported previously remained...Mulberry is a fundamental component of the global sericulture industry,and its positive impact on our health and the environment cannot be overstated.However,the mulberry reference genomes reported previously remained unassembled or unplaced sequences.Here,we report the assembly and analysis of the telomere-to-telomere gap-free reference genome of the mulberry species,Morus notabilis,which has emerged as an important reference in mulberry gene function research and genetic improvement.The mulberry gap-free reference genome produced here provides an unprecedented opportunity for us to study the structure and function of centromeres.Our results revealed that all mulberry centromeric regions share conserved centromeric satellite repeats with different copies.Strikingly,we found that M.notabilis is a species with polycentric chromosomes and the only reported polycentric chromosome species up to now.We propose a compelling model that explains the formation mechanism of new centromeres and addresses the unsolved scientific question of the chromosome fusion-fission cycle in mulberry species.Our study sheds light on the functional genomics,chromosome evolution,and genetic improvement of mulberry species.展开更多
The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed ...The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.展开更多
The mirid bug Apolygus lucorum(Hemiptera:Miridae)is a polyphagous pest that affects a wide range of host plants.Its control remains challenging mainly due to its rapid reproduction,necessitating an understanding of se...The mirid bug Apolygus lucorum(Hemiptera:Miridae)is a polyphagous pest that affects a wide range of host plants.Its control remains challenging mainly due to its rapid reproduction,necessitating an understanding of sex pheromone communication.The recognition of sex pheromones is vital for courtship and mating behaviors,and is mediated by various chemosensory-associated proteins.Among these,sensory neuron membrane protein(SNMP),a CD36-related protein,is suggested to play crucial roles in detecting sex pheromones.In this study,we employed transcriptomic and genomic data from A.lucorum and phylogenetic approaches,and identified four putative SNMP genes(AlucSNMP1a,AlucSNMP1b,AlucSNMP2a,and AlucSNMP2b)with full open reading frames.Expression analysis revealed the ubiquitous presence of AlucSNMP transcripts in multiple tissues,with only AlucSNMP1a exhibiting male-biased expression in the antennae,suggesting its potential role in male chemosensation.Functional analysis using the Xenopus oocyte expression system,coupled with two-electrode voltage clamp recording,demonstrated that the co-expression of AlucSNMP1a with specific pheromone receptors(PRs)and the Odorant receptor co-receptor(Orco)significantly enhanced electrophysiological responses to sex pheromones compared to the co-expression of PRs and Orco alone.Moreover,the results indicated that the presence of AlucSNMP1a not only affected the responsiveness to sex pheromones but also influenced the kinetics(activation and inactivation)of the induced signals.In contrast,the co-expression of AlucSNMP1b with AlucPR/Orco complexes had no impact on the inward currents induced by two pheromone compounds.An examination of the selective pressures on SNMP1 genes across 20 species indicated strong purifying selection,implying potential functional conservation in various insects.These findings highlight the crucial role of AlucSNMP1a in the response to sex pheromones.展开更多
There is an increasing need to reduce the use of pesticides to reduce their potential threat to food/environmental safety.At the same time,an increase in reactive oxygen species(ROS)induced by abiotic stresses in plan...There is an increasing need to reduce the use of pesticides to reduce their potential threat to food/environmental safety.At the same time,an increase in reactive oxygen species(ROS)induced by abiotic stresses in plants can lead to an increase in ROS in the plant and affect yield.In this paper,ROS-SPC was synthesised by two reactions and used as an efficient pesticide nanocarrier/adjuvant and scavenger of reactive oxygen species(ROS)in plants.By hydrophobic interaction,ROS-SPC spontaneously conjugated tofluazinam with a pesticide loading capacity(PLC)of 15.1%.Afterfluazinam was conjugated to ROS-SPC,the particle size offluazinam was reduced from 64.70 nm reduced to 19.82 nm,and the contact angle of pesticide droplets on plant leaves was significantly reduced from 59.44°to 26.76°.ROS-SPC as a carrier was tested to inhibit phytopathogenic fungi by 200%more than conventional delivery methods.In addition,we also learned that ROS-SPC with endocytosis capability can indeed remove reactive oxygen species from plants.Tests using HUVEC cells showed that ROS-SPC has low cytotoxicity within a reasonable range of applications,and ROS-SPC was tested to have low toxicity to pollinating bees.展开更多
Propolis is a resinous complex mixture made from plant resins collected by worker bees and mixed with their own secretions.It is rich in polyphenols and flavonoids and thus has a wide range of biological activities an...Propolis is a resinous complex mixture made from plant resins collected by worker bees and mixed with their own secretions.It is rich in polyphenols and flavonoids and thus has a wide range of biological activities and is considered a functional source for promoting human health.However,propolis and its bioactive compounds have poor water solubility,rapid and intense metabolism,and low oral bioavailability,which limits their wide application.In this paper,the main bioactive substances in propolis were summarized,and the biological characteristics and therapeutic potential of propolis and its bioactive substances were discussed.In addition,this paper discussed the factors affecting the bioavailability of propolis and its functional ingredients,focusing on the research progress in improving the bioavailability and bioactivity of propolis and its functional ingredients using nanoencapsulation technology.Finally,the current situation of the global propolis market and the applications of propolis products in the pharmaceutical,food,cosmetic and other industrial fields were discussed,providing useful references for promoting the development of the propolis industry.展开更多
Ionogels have demonstrated substantial applications in smart wearable systems,soft robotics,and biomedical engineering due to the exceptional ionic conductivity and optical transparency.However,achieving ionogels with...Ionogels have demonstrated substantial applications in smart wearable systems,soft robotics,and biomedical engineering due to the exceptional ionic conductivity and optical transparency.However,achieving ionogels with desirable mechanical properties,environmental stability,and multi-mode sensing remains challenging.Here,we propose a simple strategy for the fabrication of multifunctional silk fabric-based ionogels(BSFIGs).The resulting fabric ionogels exhibits superior mechanical properties,with high tensile strength(11.3 MPa)and work of fracture(2.53 MJ/m^(3)).And its work of fracture still has 1.42 MJ/m^(3)as the notch increased to 50%,indicating its crack growth insensitivity.These ionogels can be used as sensors for strain,temperature,and tactile multimode sensing,demonstrating a gauge factor of 1.19 and a temperature coefficient of resistance of3.17/℃^(-1).Furthermore,these ionogels can be used for the detection of different roughness and as touch screens.The ionogels also exhibit exceptional optical transmittance and environmental stability even at80℃.Our scalable fabrication process broadens the application potential of these multifunctional ionogels in diverse fields,from smart systems to extreme environments.展开更多
Phyllanthus emblica L.contains abundant flavonoids with multiple biological effects,drawing interest from the functional food industry.This research employed a deep eutectic solvent(DES)ultrasonic-assisted extraction ...Phyllanthus emblica L.contains abundant flavonoids with multiple biological effects,drawing interest from the functional food industry.This research employed a deep eutectic solvent(DES)ultrasonic-assisted extraction method to extract flavonoids from Phyllanthus emblica L.To optimize the extraction process and assess total flavonoid yield,response surface methodology and artificial neural networks(ANNs)were employed to model the extraction process and predict the total flavonoids,yielding the optimal extraction conditions:47℃,20%water content,30 min of ultrasound time,and a liquid-solid ratio of 40.Under the optimal extraction condition,the extraction yield of total flavonoids reached 22.896 mg/100g.In addition,the extraction mechanism of different solvents was studied using molecular dynamics simulation.It was found that the use of choline chlorideethylene glycol as the extraction solvent showed greater solvent accessibility surface area,more hydrogen bonds between choline chloride-ethylene glycol and the extract,and lower intermolecular interaction,resulting in higher extraction efficiency.Further research on the antioxidant and thermal stability of Phyllanthus emblica L.flavonoid extracts evaluated the application potential of total flavonoids.The DES ultrasonic-assisted extraction method effectively enhanced the flavonoid extraction yield from Phyllanthus emblica L.and reduced thermal decomposition,making it more suitable for application in the functional food industry.展开更多
Steviol glycosides(SGs)from Stevia rebaudiana Bertoni is a widely used sweetener with the advantage of high sweet and low in calories.Stevioside(ST)and Rebaudioside A(Reb A)with a bitter aftertaste are the main sweete...Steviol glycosides(SGs)from Stevia rebaudiana Bertoni is a widely used sweetener with the advantage of high sweet and low in calories.Stevioside(ST)and Rebaudioside A(Reb A)with a bitter aftertaste are the main sweetening components in SGs.Reb M is a highly potency sweetener with almost no bitter aftertaste but is found in low content in S.rebaudiana Bertoni.In this study,the pre-and post-catalytic differences of stevioside gly-cosyltransferase SrUGT76G1 were investigated through long-time molecular dynamics simulations.SrUGT76G1 was mutated to enhance its efficiency in catalyzing the synthesis of Reb D to Reb M by identifying the enzyme mutation site through an integrated three-in-one approach that combines hinge region analysis,coevolutionary conservation,and energy calculations.The kcat and k_(cat)/K_(m) values of the M88V mutant with Reb D as substrate were 2.18-fold and 4.85-fold higher than those of wild-type SrUGT76G1,respectively.In addition,the M88V mutant coupled with sucrose synthase StSUS1 increased the yield of Reb M synthesis from Reb D to 92.40%.The present study provides an effective method for rapid search for mutation sites in the enzyme and for increasing the yield of Reb M.展开更多
The global goat milk market has expanded rapidly,driven by its reputed hypoallergenic properties and associ-ated health benefits.Here we present the first single-cell RNA sequencing(scRNA-seq)atlas of somatic cells in...The global goat milk market has expanded rapidly,driven by its reputed hypoallergenic properties and associ-ated health benefits.Here we present the first single-cell RNA sequencing(scRNA-seq)atlas of somatic cells in mid-lactation Saanen goat milk,revealing cellular heterogeneity and immune-regulatory mechanisms.Analysis of 7276 high-quality cells from five biological replicates revealed seven populations:myofibroblasts,dendritic cells(DCs),epithelial cells(EPCs),monocytes,bone marrow-derived progenitor cells,neutrophils,and T cells.The proportion of EPCs varied markedly between individuals(23.18%-94.09%,p=0.0295)and was positively correlated with somatic cell count(R=0.6087,based on five biological replicates),suggesting a moderate as-sociation.Pseudotime analysis revealed two differentiation trajectories:high-epithelial samples(HPG;>80%EPCs)were dominated by immune-cell-dominated,whereas low-epithelial samples(LPG;<60%EPCs)primarily exhibited epithelial differentiation.Cell-cell communication analyses showed distinct signaling:SELL/CXCL-mediated immune pathways were activated in HPG,while TGF-β/SPP1 signaling-linked to cell migration and immune suppression-was upregulated in LPG.A total of 214 differentially expressed genes(DEGs)were identified.Pro-inflammatory factors,such as SAA and PAEP,were enriched in HPG,whereas anti-inflammatory markers,including SERPIN B3 and C3,were elevated in LPG.Notably,casein genes(CSN1S2,CSN2,CSN3)were markedly upregulated in immune cells of HPG(T cells,monocytes and DCs).In conclusion,this work unveils a key cellular biomarker for milk quality,which is expected to guide the dairy industry towards producing safer and hypoallergenic goat milk products.展开更多
Grapevine is one of the most economically important crops worldwide.However,the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres,li...Grapevine is one of the most economically important crops worldwide.However,the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres,limiting the accessibility of the repetitive sequences,the centromeric and telomeric regions,and the study of inheritance of important agronomic traits in these regions.Here,we assembled a telomere-to-telomere(T2T)gap-free reference genome for the cultivar PN40024 using PacBio HiFi long reads.The T2T reference genome(PN_T2T)is 69 Mb longer with 9018 more genes identified than the 12X.v0 version.We annotated 67%repetitive sequences,19 centromeres and 36 telomeres,and incorporated gene annotations of previous versions into the PN_T2T assembly.We detected a total of 377 gene clusters,which showed associations with complex traits,such as aroma and disease resistance.Even though PN40024 derives from nine generations of selfing,we still found nine genomic hotspots of heterozygous sites associated with biological processes,such as the oxidation–reduction process and protein phosphorylation.The fully annotated complete reference genome therefore constitutes an important resource for grapevine genetic studies and breeding programs.展开更多
Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,m...Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(Ros)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.展开更多
The CRISPR-Cas13 system,an RNA-guided editing tool,has emerged as a highly efficient and stable RNA editing technique.Although the CRISPR-Cas13 system has been developed in several insect species,its application in le...The CRISPR-Cas13 system,an RNA-guided editing tool,has emerged as a highly efficient and stable RNA editing technique.Although the CRISPR-Cas13 system has been developed in several insect species,its application in lepidopterans has not yet been reported.In the present study,we evaluated the RNA cleavage activity of the CRISPR-Cas13 system in the silkworm(Bombyx mori),a model lepidopteran insect,both ex vivo and in vivo.We established two stable silkworm BmE cell lines expressing PspCas13b and CasRx,respectively.Further analysis demonstrated that both PspCas13b and CasRx effectively down-regulated the transcription of exogenouslyintroduced target and endogenous genes in these cell lines.In addition,we generated two transgenic silkworm strains,one expressing CasRx and the other expressing RNA-guided CRISPR RNA targeting Sex combs reduced(Scr).Further crossing experiments showed that CasRx induced a down-regulation of Scr transcription in silkworms,which impaired systemic growth of larvae.Overall,this study demonstrated that the CRISPR-Cas13RNA editing system works efficiently in the silkworm,providing a potential alternative approach for RNA manipulation in lepidopteran insects.展开更多
To the Editor:Melanoma is the most aggressive and lethal cutaneous malignancy,with its incidence increasing annually.Surgical resection is effective for early-stage melanoma;however,therapeutic strategies for metastat...To the Editor:Melanoma is the most aggressive and lethal cutaneous malignancy,with its incidence increasing annually.Surgical resection is effective for early-stage melanoma;however,therapeutic strategies for metastatic melanoma are limited by poor prognosis and adverse effects.[1]Our research team previously screened six compounds(Sanggenon C,Kuwanon A[KA],Kuwanon E,Moracin O,Moracin P,and 3′-geranyl-3-prenyl-2′,4′,5,7-tetrahydroxyflavone)with strong anti-melanoma effects from 28 compounds in Morus alba L.We focused on KA,whose structure is shown in Supplementary Figure 1A,http://links.lww.com/CM9/C458 with anti-inflammatory,antioxidant,and anticancer properties.[2,3]Its anti-tumor mechanisms in melanoma remain unclear.展开更多
The silk gland of the silkworm Bombyx mori serves as a valuable model for investigating the morphological structure and physiological functions of organs.Previous studies have demonstrated the notable regulatory role ...The silk gland of the silkworm Bombyx mori serves as a valuable model for investigating the morphological structure and physiological functions of organs.Previous studies have demonstrated the notable regulatory role of let-7 microRNA in the silk gland,but its specific molecular mechanism remains to be elucidated across different segments of this organ.In this study,we further investigated the functional mechanism of let-7 in the middle silk gland(MSG).The MSG of a let-7 knockout strain was analyzed using a combined proteomic and metabolomic technique,revealing the enrichment of differential proteins and metabolites in the DNA synthesis and energy metabolism pathways.BmCentrin was identified as a novel target gene of let-7 in the MSG,and its downregulation inhibited the proliferation of BmN4-SID1 cells,which is exactly opposite to the role of let-7 in these cells.CRISPR/Cas9 genome editing and transgenic technologies were employed to manipulate BmCentrin in the MSG.Knockout of BmCentrin led to severe MSG atrophy,whereas the overexpression of BmCentrin resulted in beaded MSG.Further measurements of these knockout or overexpression strains revealed significant changes in the expression levels of sericin protein genes,the weight of the cocoon and the mechanical properties of the silk.Investigating the biological role of BmCentrin in the silk gland offers valuable insights for elucidating the molecular mechanisms by which let-7 controls silk gland development and silk protein synthesis in the silkworm.展开更多
基金supported by the Natural Science Foundation of Beijing Municipality(6252026)the Youth Innovation Program of CAAS(Y2024QC11)the Agricultural Science and Technology Innovation Program under Grant(CAAS-ASTIP-2024-IAR).
文摘The monofloral honey derived from Bauhinia championii(Benth.)Benth.(MH-Bc)possesses significant nutritional and bioactive value,making it highly suitable for commercial exploitation.However,the poorly defined characteristics and unknown composition have hindered MH-Bc product development.In this study,we employed a combination of untargeted and targeted mass spectrometry analyses to characterize MH-Bc honey.As a result,4,7,8-trimethoxydibenzo[b,d]furan-3-ol(TDBF)was identified as a robust chemical marker for distinguishing MH-Bc from other types of honey.This specific marker was detected in both MH-Bc and the Bc plant but was absent in other honey varieties.Furthermore,a targeted mass spectrometry quantitative method was developed and validated to accurately determine the content of TDBF in honey samples.Overall,the presence of TDBF serves as a discerning indicator for future commercial MH-Bc products.
基金supported by the National Natural Science Foundation of China(32322079)Beijing Nova Program(20220484101)Talented Young Scientist Program,Ministry of Science and Technology of the People's Republic of China,and China Postdoctoral Science Foundation(2024M753576).
文摘Honey,a natural substance,has long been valued for its dual role in both food and medicine in diverse cultural traditions,particularly in traditional Chinese medicine(TCM).It is rich in sugars,amino acids,enzymes,polyphenols,and flavonoids that contribute to its antimicrobial,antioxidant,and immuno-modulatory properties.Additionally,honey is effective in managing some conditions,such as antibiotic-resistant infections,inflammation,and oxidative stress-related diseases.This review explores the extensive health benefits of honey,emphasizing the homology between food and medicine,as proposed by TCM philosophy.Further,this review explores the traditional applications of honey in respiratory health,wound healing,and gastrointestinal support,along with modern scientific validation of these uses.Moreover,the role of honey as a dietary supplement,functional food,and preservative in culinary practices is examined.Overall,this review highlights the synergy between ancient wisdom and contemporary science,advocating for the continued exploration of the role of honey in health,nutrition,and medicine.
基金supported by the Modern Agro-industry Technology Research System(CARS-45-KXJ19)the Agricultural Science and Technology Innovation Program from the Ministry of Agriculture of the People’s Republic of China(CAAS-ASTIP-2019-IAR)。
文摘Terpenoids,as crucial plant secondary metabolites in honey,possess various bioactivities.This study aimed at investigating terpenoids of longan,litchi,and schefflera honey.Our results reveal that these three species of honey are characterized by abundant terpenoids,with eight terpenoids and one phenylpropanoid identified.Callunene,3,4,5-trimethoxyphenylpropanal,schefflerin(4-2'-(3',4'-dihydroxy-5'-methylfuran)-3,5,5-trimethyl-2-cyclohexenone)or abscisic acids may be as the characteristic components of longan,litchi,or schefflera honey.Abscisic acids were the most abundant components,average contents reached up to 53.67,96.89 and 21.11 mg/kg,respectively,and the content ranges in three types of honey were 13.75-85.40,19.93-177.31,14.69-28.38 mg/kg,respectively.To our knowledge,the presence of schefflerin,(6R,9S)-vomifoliol,and 3,4,5-trimethoxyphenylpropanal in honey is a novel finding.We distinguish Thailand from Chinese mainland and Taiwan longan honeys,based on the ratio of abscisic acid and callunene content.Overall,our proposal to combine terpenoids with standard fingerprints seems to provide a novel and reliable solution for evaluating the authenticity of commercial honey.
基金supported by National Natural Science Foundations of China(32472396,31871861 and 31501548)The Apicultural Industry Technology System(NCYTI-43-KXJ17)The Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2015-IAR)。
文摘The effect of superheated steam(SHS)treatment on the quality characteristics of rape bee pollen were studied,and the efficiency of inactivation and inhibition of lipid oxidation were analyzed to investigate the differences between SHS and cobalt-60 isotope(^(60)Co)radiation treatment.The number of total plate count(TPC)and mold colonies(MC)remained within the limits of the standards after SHS treatment at 140℃for 2 min.Neither TPC nor MC were detected after^(60)Co irradiation.Peroxidase(POD)and polyphenol oxidase(PPO)activities significantly decreased with increasing temperature and duration of SHS,while^(60)Co radiation completely inactivated PPO.Compared to^(60)Co radiation,SHS treatment inhibited the deterioration of rape bee pollen by avoiding hydroperoxide production and lipid oxidation due to lack of oxygen.These results suggested SHS under 140℃for 2 min was the most suitable to inactivate the microorganisms and enzymes in rape bee pollen with minimal lipid oxidation.
基金supported by the National Natural Science Foundation of China(32270458,32070411,2023A1515010657)State Key Laboratory of Resource Insects(SKLSGB-ORP202209)。
文摘The domesticated silkworm(Bombyx mori)has evolved a highly efficient nitrogen utilization system to support silk production.The silk glands play a pleiotropic role in sequestering nitrogen resources for silk synthesis,mitigating aminoacidemia by assimilating free amino acids,and reallocating nitrogen during metamorphosis through programmed cell death.However,the specific functions of nitrogen metabolism-related genes in this process remain unclear.Using CRISPR/Cas9-based gene editing,mutations were generated in glutamine synthetase(GS),glutamate synthetase(GOGAT),asparagine synthetase(AS),glutamate dehydrogenase(GDH)and glutamate oxaloacetate transaminase 1(GOT1).Disruption of GS,GOGAT,and AS consistently reduced silkworm cocoon and pupal weight and significantly down-regulated silk protein gene transcription,whereas GOT1 mutation had no such effect.GOGAT mutants exhibited abnormally enlarged silk glands,whereas GS and AS mutants showed delayed programmed cell death in the silk glands.In contrast,GOT1 mutants displayed normal silk gland morphology but were consistently smaller.Disruption of GS,GOGAT,and AS led to more extensive transcriptional changes,including altered expression of transcription factors in the silk glands,compared with GOT1 mutants.Both GS and GOGAT mutants exhibited up-regulation of AS and GDH,while only GOGAT mutants displayed elevated AS enzymatic activity,suggesting that GOGAT may compete with AS for glutamine in the silk glands to support silk protein synthesis.AS mutants showed significantly elevated GOT activity and up-regulation of several metabolic pathways,indicating that AS may functionally interact with GOT in regulating both silk gland development and programmed cell death during metamorphosis.
文摘Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023.With a focus on recent research findings,the review explores the rich biodiversity of marine organisms,including sponges,corals,algae,and microorganisms,which have yielded numerous compounds exhibiting promising anticancer properties.Emphasizing the multifaceted mechanisms of action,the review discusses the molecular targets and pathways targeted by these compounds,such as cell cycle regulation,apoptosis induction,angiogenesis inhibition,and modulation of signaling pathways.Additionally,the review highlights the innovative strategies employed in the isolation,structural elucidation,and chemical modification of marine natural products to enhance their potency,selectivity,and pharmacological properties.Furthermore,it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs,including issues related to supply,sustainability,synthesis,and clinical translation.Finally,the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy.
基金This project was supported by the National Natural Science Foundation of China(32101544)the Chongqing Research Program of Basic Research and Frontier Technology(cstc2021yszxjcyj0004).
文摘Mulberry is a fundamental component of the global sericulture industry,and its positive impact on our health and the environment cannot be overstated.However,the mulberry reference genomes reported previously remained unassembled or unplaced sequences.Here,we report the assembly and analysis of the telomere-to-telomere gap-free reference genome of the mulberry species,Morus notabilis,which has emerged as an important reference in mulberry gene function research and genetic improvement.The mulberry gap-free reference genome produced here provides an unprecedented opportunity for us to study the structure and function of centromeres.Our results revealed that all mulberry centromeric regions share conserved centromeric satellite repeats with different copies.Strikingly,we found that M.notabilis is a species with polycentric chromosomes and the only reported polycentric chromosome species up to now.We propose a compelling model that explains the formation mechanism of new centromeres and addresses the unsolved scientific question of the chromosome fusion-fission cycle in mulberry species.Our study sheds light on the functional genomics,chromosome evolution,and genetic improvement of mulberry species.
基金supported by National Natural Science Foundation of China(Nos.31871861 and 31501548)The Apicultural Industry Technology System(NCYTI-43-KXJ17)The Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2015-IAR)。
文摘The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.
基金supported by the National Natural Science Foundation of China(32150410366,31972338,and32372639)the earmarked fund for China Agriculture Research System(CARS-02-26)+1 种基金the National Key Research and Development Program of China(2021YFD1400700)the Special Grant of China Postdoctoral Science Foundation(2022T150712)。
文摘The mirid bug Apolygus lucorum(Hemiptera:Miridae)is a polyphagous pest that affects a wide range of host plants.Its control remains challenging mainly due to its rapid reproduction,necessitating an understanding of sex pheromone communication.The recognition of sex pheromones is vital for courtship and mating behaviors,and is mediated by various chemosensory-associated proteins.Among these,sensory neuron membrane protein(SNMP),a CD36-related protein,is suggested to play crucial roles in detecting sex pheromones.In this study,we employed transcriptomic and genomic data from A.lucorum and phylogenetic approaches,and identified four putative SNMP genes(AlucSNMP1a,AlucSNMP1b,AlucSNMP2a,and AlucSNMP2b)with full open reading frames.Expression analysis revealed the ubiquitous presence of AlucSNMP transcripts in multiple tissues,with only AlucSNMP1a exhibiting male-biased expression in the antennae,suggesting its potential role in male chemosensation.Functional analysis using the Xenopus oocyte expression system,coupled with two-electrode voltage clamp recording,demonstrated that the co-expression of AlucSNMP1a with specific pheromone receptors(PRs)and the Odorant receptor co-receptor(Orco)significantly enhanced electrophysiological responses to sex pheromones compared to the co-expression of PRs and Orco alone.Moreover,the results indicated that the presence of AlucSNMP1a not only affected the responsiveness to sex pheromones but also influenced the kinetics(activation and inactivation)of the induced signals.In contrast,the co-expression of AlucSNMP1b with AlucPR/Orco complexes had no impact on the inward currents induced by two pheromone compounds.An examination of the selective pressures on SNMP1 genes across 20 species indicated strong purifying selection,implying potential functional conservation in various insects.These findings highlight the crucial role of AlucSNMP1a in the response to sex pheromones.
基金support by the Natural Science Foundation of Beijing(No.2232004)National Key Research and Development Program of China(No.2023YFD1700600)。
文摘There is an increasing need to reduce the use of pesticides to reduce their potential threat to food/environmental safety.At the same time,an increase in reactive oxygen species(ROS)induced by abiotic stresses in plants can lead to an increase in ROS in the plant and affect yield.In this paper,ROS-SPC was synthesised by two reactions and used as an efficient pesticide nanocarrier/adjuvant and scavenger of reactive oxygen species(ROS)in plants.By hydrophobic interaction,ROS-SPC spontaneously conjugated tofluazinam with a pesticide loading capacity(PLC)of 15.1%.Afterfluazinam was conjugated to ROS-SPC,the particle size offluazinam was reduced from 64.70 nm reduced to 19.82 nm,and the contact angle of pesticide droplets on plant leaves was significantly reduced from 59.44°to 26.76°.ROS-SPC as a carrier was tested to inhibit phytopathogenic fungi by 200%more than conventional delivery methods.In addition,we also learned that ROS-SPC with endocytosis capability can indeed remove reactive oxygen species from plants.Tests using HUVEC cells showed that ROS-SPC has low cytotoxicity within a reasonable range of applications,and ROS-SPC was tested to have low toxicity to pollinating bees.
基金supported by the National Natural Science Foundation of China(31972087)the earmarked fund for China Agriculture Research System-Bee(CARS-44-KXJ17)the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2021-IAR)。
文摘Propolis is a resinous complex mixture made from plant resins collected by worker bees and mixed with their own secretions.It is rich in polyphenols and flavonoids and thus has a wide range of biological activities and is considered a functional source for promoting human health.However,propolis and its bioactive compounds have poor water solubility,rapid and intense metabolism,and low oral bioavailability,which limits their wide application.In this paper,the main bioactive substances in propolis were summarized,and the biological characteristics and therapeutic potential of propolis and its bioactive substances were discussed.In addition,this paper discussed the factors affecting the bioavailability of propolis and its functional ingredients,focusing on the research progress in improving the bioavailability and bioactivity of propolis and its functional ingredients using nanoencapsulation technology.Finally,the current situation of the global propolis market and the applications of propolis products in the pharmaceutical,food,cosmetic and other industrial fields were discussed,providing useful references for promoting the development of the propolis industry.
基金supported by the National Natural Science Foundation of China(No.12302192)the Fundamental Research Funds for the Central Universities(No.SWU-KQ22025)+4 种基金the Science and Technology Research Program of Chongqing Municipal Education Commission(No.KJQN202300222)Natural Science Foundation of Chongqing(No.cstc2021jcyj-msxmX0241)the Fund for Innovative Research Groups of Natural Science Foundation of Hebei Province(No.A2024202045)Key Technologies and Demonstration Application Research Project for Large-scale Lithium-ion Hybrid Energy Storage Equipment(No.HC23118)Major Basic Research Project of Hebei Province Natural Science Foundation(No.A2023202049).
文摘Ionogels have demonstrated substantial applications in smart wearable systems,soft robotics,and biomedical engineering due to the exceptional ionic conductivity and optical transparency.However,achieving ionogels with desirable mechanical properties,environmental stability,and multi-mode sensing remains challenging.Here,we propose a simple strategy for the fabrication of multifunctional silk fabric-based ionogels(BSFIGs).The resulting fabric ionogels exhibits superior mechanical properties,with high tensile strength(11.3 MPa)and work of fracture(2.53 MJ/m^(3)).And its work of fracture still has 1.42 MJ/m^(3)as the notch increased to 50%,indicating its crack growth insensitivity.These ionogels can be used as sensors for strain,temperature,and tactile multimode sensing,demonstrating a gauge factor of 1.19 and a temperature coefficient of resistance of3.17/℃^(-1).Furthermore,these ionogels can be used for the detection of different roughness and as touch screens.The ionogels also exhibit exceptional optical transmittance and environmental stability even at80℃.Our scalable fabrication process broadens the application potential of these multifunctional ionogels in diverse fields,from smart systems to extreme environments.
基金supported by the National Natural Science Foundation of China(32202022)the Science and Technology Planning Project of Guangzhou City of China(2023A04J1467)+1 种基金Hong Kong Scholars Program(XJ2023050)the Innovation and Entrepreneurship Training Program for University Students(S202310564096).
文摘Phyllanthus emblica L.contains abundant flavonoids with multiple biological effects,drawing interest from the functional food industry.This research employed a deep eutectic solvent(DES)ultrasonic-assisted extraction method to extract flavonoids from Phyllanthus emblica L.To optimize the extraction process and assess total flavonoid yield,response surface methodology and artificial neural networks(ANNs)were employed to model the extraction process and predict the total flavonoids,yielding the optimal extraction conditions:47℃,20%water content,30 min of ultrasound time,and a liquid-solid ratio of 40.Under the optimal extraction condition,the extraction yield of total flavonoids reached 22.896 mg/100g.In addition,the extraction mechanism of different solvents was studied using molecular dynamics simulation.It was found that the use of choline chlorideethylene glycol as the extraction solvent showed greater solvent accessibility surface area,more hydrogen bonds between choline chloride-ethylene glycol and the extract,and lower intermolecular interaction,resulting in higher extraction efficiency.Further research on the antioxidant and thermal stability of Phyllanthus emblica L.flavonoid extracts evaluated the application potential of total flavonoids.The DES ultrasonic-assisted extraction method effectively enhanced the flavonoid extraction yield from Phyllanthus emblica L.and reduced thermal decomposition,making it more suitable for application in the functional food industry.
基金supported by the fund of Beijing Natural Science Foundation(No.6242001)the fund of the Cultivation Project of the Double First-Class Disciplines of Food Science and Engineering,Beijing Technology and Business University(No.BTBUYXTD202207)+1 种基金Discipline Construction——Food Science and Engineering(No.SPKX-202204)the Research Foundation for Youth Scholars of Beijing Technology and Business University(No.QNJJ2022-06)‘Xinjiang’Two Zones'Science and Technology Development Plan Project(No.2022LQ02003).
文摘Steviol glycosides(SGs)from Stevia rebaudiana Bertoni is a widely used sweetener with the advantage of high sweet and low in calories.Stevioside(ST)and Rebaudioside A(Reb A)with a bitter aftertaste are the main sweetening components in SGs.Reb M is a highly potency sweetener with almost no bitter aftertaste but is found in low content in S.rebaudiana Bertoni.In this study,the pre-and post-catalytic differences of stevioside gly-cosyltransferase SrUGT76G1 were investigated through long-time molecular dynamics simulations.SrUGT76G1 was mutated to enhance its efficiency in catalyzing the synthesis of Reb D to Reb M by identifying the enzyme mutation site through an integrated three-in-one approach that combines hinge region analysis,coevolutionary conservation,and energy calculations.The kcat and k_(cat)/K_(m) values of the M88V mutant with Reb D as substrate were 2.18-fold and 4.85-fold higher than those of wild-type SrUGT76G1,respectively.In addition,the M88V mutant coupled with sucrose synthase StSUS1 increased the yield of Reb M synthesis from Reb D to 92.40%.The present study provides an effective method for rapid search for mutation sites in the enzyme and for increasing the yield of Reb M.
基金supported by the National Natural Science Foundation of China(32272834)Fundamental Research Funds for the Central Universities(SWU-XDJH202301).
文摘The global goat milk market has expanded rapidly,driven by its reputed hypoallergenic properties and associ-ated health benefits.Here we present the first single-cell RNA sequencing(scRNA-seq)atlas of somatic cells in mid-lactation Saanen goat milk,revealing cellular heterogeneity and immune-regulatory mechanisms.Analysis of 7276 high-quality cells from five biological replicates revealed seven populations:myofibroblasts,dendritic cells(DCs),epithelial cells(EPCs),monocytes,bone marrow-derived progenitor cells,neutrophils,and T cells.The proportion of EPCs varied markedly between individuals(23.18%-94.09%,p=0.0295)and was positively correlated with somatic cell count(R=0.6087,based on five biological replicates),suggesting a moderate as-sociation.Pseudotime analysis revealed two differentiation trajectories:high-epithelial samples(HPG;>80%EPCs)were dominated by immune-cell-dominated,whereas low-epithelial samples(LPG;<60%EPCs)primarily exhibited epithelial differentiation.Cell-cell communication analyses showed distinct signaling:SELL/CXCL-mediated immune pathways were activated in HPG,while TGF-β/SPP1 signaling-linked to cell migration and immune suppression-was upregulated in LPG.A total of 214 differentially expressed genes(DEGs)were identified.Pro-inflammatory factors,such as SAA and PAEP,were enriched in HPG,whereas anti-inflammatory markers,including SERPIN B3 and C3,were elevated in LPG.Notably,casein genes(CSN1S2,CSN2,CSN3)were markedly upregulated in immune cells of HPG(T cells,monocytes and DCs).In conclusion,this work unveils a key cellular biomarker for milk quality,which is expected to guide the dairy industry towards producing safer and hypoallergenic goat milk products.
基金This work was supported by the National Natural Science Fund for Excellent Young Scientists Fund Program(Overseas)to Y.Z.,the National Key Research and Development Program of China(grant 2019YFA0906200)the Agricultural Science and Technology Innovation Program(CAAS-ZDRW202101)+1 种基金the Shenzhen Science and Technology Program(grant KQTD2016113010482651)the BMBF-funded de.
文摘Grapevine is one of the most economically important crops worldwide.However,the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres,limiting the accessibility of the repetitive sequences,the centromeric and telomeric regions,and the study of inheritance of important agronomic traits in these regions.Here,we assembled a telomere-to-telomere(T2T)gap-free reference genome for the cultivar PN40024 using PacBio HiFi long reads.The T2T reference genome(PN_T2T)is 69 Mb longer with 9018 more genes identified than the 12X.v0 version.We annotated 67%repetitive sequences,19 centromeres and 36 telomeres,and incorporated gene annotations of previous versions into the PN_T2T assembly.We detected a total of 377 gene clusters,which showed associations with complex traits,such as aroma and disease resistance.Even though PN40024 derives from nine generations of selfing,we still found nine genomic hotspots of heterozygous sites associated with biological processes,such as the oxidation–reduction process and protein phosphorylation.The fully annotated complete reference genome therefore constitutes an important resource for grapevine genetic studies and breeding programs.
基金This work was supported by funding from Natural Science Foundation of China(Grant Nos.:82372519 and 81902664)the PostdoctoralFellowshipProgramof CPSF(GrantNo.:GZB20240544)+3 种基金the China Postdoctoral Science Foundation(Grant No.:2024M752432)the Natural Science Foundation of Hebei Province(Grant Nos.:H2022206368 and H2022206446)Medical Science Research Program of the Hebei Provincial Health Commission(Grant No.:20241603)Pilot Program of Southwest University(Program No.:SWU-XDZD22006)。
文摘Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(Ros)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.
基金supported by the National Natural Science Foundation of China(32070496,32370555)Fundamental Research Funds for the Central Universities(SWU120033)Technology Innovation and Application Development Program of Chongqing(CSTB2024TIADKPX0023)。
文摘The CRISPR-Cas13 system,an RNA-guided editing tool,has emerged as a highly efficient and stable RNA editing technique.Although the CRISPR-Cas13 system has been developed in several insect species,its application in lepidopterans has not yet been reported.In the present study,we evaluated the RNA cleavage activity of the CRISPR-Cas13 system in the silkworm(Bombyx mori),a model lepidopteran insect,both ex vivo and in vivo.We established two stable silkworm BmE cell lines expressing PspCas13b and CasRx,respectively.Further analysis demonstrated that both PspCas13b and CasRx effectively down-regulated the transcription of exogenouslyintroduced target and endogenous genes in these cell lines.In addition,we generated two transgenic silkworm strains,one expressing CasRx and the other expressing RNA-guided CRISPR RNA targeting Sex combs reduced(Scr).Further crossing experiments showed that CasRx induced a down-regulation of Scr transcription in silkworms,which impaired systemic growth of larvae.Overall,this study demonstrated that the CRISPR-Cas13RNA editing system works efficiently in the silkworm,providing a potential alternative approach for RNA manipulation in lepidopteran insects.
基金This study was supported by a grant from the Natural Science Foundation of Hebei Province(No.H2022206328).
文摘To the Editor:Melanoma is the most aggressive and lethal cutaneous malignancy,with its incidence increasing annually.Surgical resection is effective for early-stage melanoma;however,therapeutic strategies for metastatic melanoma are limited by poor prognosis and adverse effects.[1]Our research team previously screened six compounds(Sanggenon C,Kuwanon A[KA],Kuwanon E,Moracin O,Moracin P,and 3′-geranyl-3-prenyl-2′,4′,5,7-tetrahydroxyflavone)with strong anti-melanoma effects from 28 compounds in Morus alba L.We focused on KA,whose structure is shown in Supplementary Figure 1A,http://links.lww.com/CM9/C458 with anti-inflammatory,antioxidant,and anticancer properties.[2,3]Its anti-tumor mechanisms in melanoma remain unclear.
基金supported by the National Natural Science Foundation of China(32172797)Chongqing Science and Technology Plan Project(2022NSCQMSX5897)+1 种基金Chongqing Graduate Student Research Innovation Project(CYB21132,CYS22254 and CYS23241)the Fundamental Research Funds for the Central Universities(SWU-XJPY202309).
文摘The silk gland of the silkworm Bombyx mori serves as a valuable model for investigating the morphological structure and physiological functions of organs.Previous studies have demonstrated the notable regulatory role of let-7 microRNA in the silk gland,but its specific molecular mechanism remains to be elucidated across different segments of this organ.In this study,we further investigated the functional mechanism of let-7 in the middle silk gland(MSG).The MSG of a let-7 knockout strain was analyzed using a combined proteomic and metabolomic technique,revealing the enrichment of differential proteins and metabolites in the DNA synthesis and energy metabolism pathways.BmCentrin was identified as a novel target gene of let-7 in the MSG,and its downregulation inhibited the proliferation of BmN4-SID1 cells,which is exactly opposite to the role of let-7 in these cells.CRISPR/Cas9 genome editing and transgenic technologies were employed to manipulate BmCentrin in the MSG.Knockout of BmCentrin led to severe MSG atrophy,whereas the overexpression of BmCentrin resulted in beaded MSG.Further measurements of these knockout or overexpression strains revealed significant changes in the expression levels of sericin protein genes,the weight of the cocoon and the mechanical properties of the silk.Investigating the biological role of BmCentrin in the silk gland offers valuable insights for elucidating the molecular mechanisms by which let-7 controls silk gland development and silk protein synthesis in the silkworm.
