Ultraviolet(UV)-induced photoaging skin has become an urgent issue.The functional foods and cosmetics aiming to improve skin photoaging are developing rapidly,and the demand is gradually increasing year by year.Collag...Ultraviolet(UV)-induced photoaging skin has become an urgent issue.The functional foods and cosmetics aiming to improve skin photoaging are developing rapidly,and the demand is gradually increasing year by year.Collagen peptides have been proven to display diverse physiological activities,such as excellent moisture retention activity,hygroscopicity,tyrosinase inhibitory activity and antioxidant activity,which indicates that they have great potential in amelioration of UV-induced photoaging.The main objective of this article is to recap the main mechanisms to improve photoaging skin by collagen peptides and their physiological activities in photo-protection.Furthermore,the extraction and structural characteristics of collagen peptides are overviewed.More importantly,some clinical trials on the beneficial effect on skin of collagen peptides are also discussed.In addition,prospects and challenges of collagen peptides are emphatically elucidated in this review.This article implies that collagen peptides have great potential as an effective ingredient in food and cosmetics industry with a wide application prospect.展开更多
In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four...In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus(OLP) and normal oral mucosa(NOM) from 14 healthy donors by real-time polymerase chain reaction(PCR) and immunohistochemistry.Synchronous mRNA coexpression of ErbBl,ErbB2,ErbB3and ErbB4 was detected in LP lesions.Out of the receptors,only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues.These were strongly expressed by epithelial keratinocytes in LP lesions,as shown by immunohistochemistry.Regarding the ligands,the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues.Therefore,enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.展开更多
Ginger(Zingiber officinale),the type species of Zingiberaceae,is one of the most widespread medicinal plants and spices.Here,we report a high-quality,chromosome-scale reference genome of ginger‘Zhugen’,a traditional...Ginger(Zingiber officinale),the type species of Zingiberaceae,is one of the most widespread medicinal plants and spices.Here,we report a high-quality,chromosome-scale reference genome of ginger‘Zhugen’,a traditionally cultivated ginger in Southwest China used as a fresh vegetable,assembled from PacBio long reads,Illumina short reads,and high-throughput chromosome conformation capture(Hi-C)reads.The ginger genome was phased into two haplotypes,haplotype 1(1.53 Gb with a contig N50 of 4.68 M)and haplotype 0(1.51 Gb with a contig N50 of 5.28 M).Homologous ginger chromosomes maintained excellent gene pair collinearity.In 17,226 pairs of allelic genes,11.9%exhibited differential expression between alleles.Based on the results of ginger genome sequencing,transcriptome analysis,and metabolomic analysis,we proposed a backbone biosynthetic pathway of gingerol analogs,which consists of 12 enzymatic gene families,PAL,C4H,4CL,CST,C3’H,C3OMT,CCOMT,CSE,PKS,AOR,DHN,and DHT.These analyses also identified the likely transcription factor networks that regulate the synthesis of gingerol analogs.Overall,this study serves as an excellent resource for further research on ginger biology and breeding,lays a foundation for a better understanding of ginger evolution,and presents an intact biosynthetic pathway for species-specific gingerol biosynthesis.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
DEAR EDITOR,Based upon morphological and molecular evidence,the authors revised the genus Rohanixalus Biju,Garg,Gokulakrishnan,Chandrakasan,Thammachoti,Ren,Gopika,Bisht,Hamidy and Shouche,2020(Anura:Rhacophoridae)in C...DEAR EDITOR,Based upon morphological and molecular evidence,the authors revised the genus Rohanixalus Biju,Garg,Gokulakrishnan,Chandrakasan,Thammachoti,Ren,Gopika,Bisht,Hamidy and Shouche,2020(Anura:Rhacophoridae)in China through describing one new species,adding one species to the fauna(R.shyamrupus)and supplementing data on one species(Rohanixalus hansenae;Supplementary Materials).展开更多
AlphaFold3(AF3),as the latest generation of artificial intelligence model jointly developed by Google DeepMind and Isomorphic Labs,has been widely heralded in the scientific research community since its launch.With un...AlphaFold3(AF3),as the latest generation of artificial intelligence model jointly developed by Google DeepMind and Isomorphic Labs,has been widely heralded in the scientific research community since its launch.With unprecedented accuracy,the AF3 model may successfully predict the structure and interactions of virtually all biomolecules,including proteins,ligands,nucleic acids,ions,etc.By accurately simulating the structural information and interactions of biomacromolecules,it has shown great potential in many aspects of structural prediction,mechanism research,drug design,protein engineering,vaccine development,and precision therapy.In order to further understand the characteristics of AF3 and accelerate its promotion,this article sets out to address the development process,working principle,and application in drugs and biomedicine,especially focusing on the intricate differences and some potential pitfalls compared to other deep learning models.We explain how a structure-prediction tool can impact many research fields,and in particular revolutionize the strategies for designing of effective next generation vaccines and chemical and biological drugs.展开更多
Respiration is a vital process essential for organism survival,with most terrestrial insects relying on a sophisticated tubular tracheal network.In the current study,a gene with repetitive sequence was identified with...Respiration is a vital process essential for organism survival,with most terrestrial insects relying on a sophisticated tubular tracheal network.In the current study,a gene with repetitive sequence was identified within the silkworm genome.Designated as BmMuc91C,it contains a dozen repeated motifs“PSSSYGAPX”and“GGYSSGGX”in its sequence.BmMuc91C exhibits specific expression in the tracheal system of silkworm larvae,with significantly higher expression levels during the molting stage.Overexpression of BmMuc91C in individual silkworms resulted in a marked increase in tracheal diameter,particularly during the molting stage.Immunofluorescence staining using a BmMuc91C antibody revealed a noticeable thickening of the apical extracellular matrix in the trachea.Tensile testing confirmed a considerable enhancement in tracheal elasticity.Additionally,a BmMuc91C mutation strain of silkworms was generated using the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease 9 system.Although no significant differences were observed in the growth,development,and molting of BmMuc91C mutant silkworms,mechanical tests demonstrated a decrease in tracheal elasticity.Transcriptomic techniques revealed that a significant number of cuticular and chitin-binding proteins were among the differentially expressed genes between mutant and wild-type silkworms.Furthermore,the recombined BmMuc91C protein was successfully expressed using the Escherichia coli system.Cross-linking experiments with horseradish peroxidase demonstrated the formation of macromolecular complexes of BmMuc91C,which exhibited spontaneous luminescent properties under ultraviolet light.This research sheds light on the role of elastic proteins in insect tracheae and provides valuable insights for the development of elastic biomaterials.展开更多
Chronic non-healing wounds,such as diabetic foot,pressure sores and bedsores have seriously affected the life quality of patients worldwide.GFs provide a potential solution to promote chronic wound healing by promotin...Chronic non-healing wounds,such as diabetic foot,pressure sores and bedsores have seriously affected the life quality of patients worldwide.GFs provide a potential solution to promote chronic wound healing by promoting cell proliferation and differentiation.However,limited resource,high cost,and instability in vivo greatly hin-dered their clinical applications.In present study,two silk gland bioreactor silkworm stains were generated to successfully synthesize functional silk fibers incorporating high expressions of EGF and PDGF-BB.The two GFs functionalized silk raw materials were used to fabricate a dual GFs sericin hydrogel(E/P-SH)delivering system with tunable material performances for better cell adhesion and biocompatibility,sustainable release of the dual GFs to synergistically promote cell proliferation and migration,which realized the significant healing of chronic full-thickness skin wound in diabetic mice within 12 days with more organized collagen arrangement and better epithelialization degree by reducing inflammatory response and promoting vascularization.These findings demonstrated that the biosynthesized dual GFs-SH delivering system provides an opportunity to broaden the wide utility of GFs in clinical treatment of diabetic wound healing.展开更多
Ciliary neurotrophic factor(CNTF)acts as a potent neuroprotective agent in neuronal survival and regeneration,and can also induce the differentiation of several stem cells into neurons,which highlights the broad appli...Ciliary neurotrophic factor(CNTF)acts as a potent neuroprotective agent in neuronal survival and regeneration,and can also induce the differentiation of several stem cells into neurons,which highlights the broad application of CNTF in biomedicine.However,large-scale production of bioactive recombinant human CNTF protein remains to be explored.Herein,this study aims to express a bioactive human CNTF protein on a large scale by genetically engineering a silk gland bioreactor of silkworm.Our results showed that CNTF protein was successfully expressed in the middle silk gland(MSG)of silkworm,which can be secreted into the silks with the amount of 3.2 mg/g cocoons.The fabrication of human CNTF-functionalized silk material was able to promote proliferation and migration of neural cells when compared to the natural silk protein.Importantly,this functional silk material could also facilitate neurite outgrowth of mouse retinal ganglion cell(RGC-5)cells.All these data demonstrated a high bioactivity of the recombinant human CNTF protein expressed in the MSG of silkworm.The further fabrication of different silk materials with CNTF bioactivity will give biomedical applications in tissue engineering and neuroregeneration.展开更多
An increasing body of evidence shows that the lipid droplet,a neutral lipid storage organelle,plays a role in lipid metabolism and energy homeostasis through its interaction with mitochondria.However,the cellular func...An increasing body of evidence shows that the lipid droplet,a neutral lipid storage organelle,plays a role in lipid metabolism and energy homeostasis through its interaction with mitochondria.However,the cellular functions and molecular mechanisms of the interaction remain ambiguous.Here we present data from transmission electron microscopy,fluorescence imaging,and reconstitution assays,demonstrating that lipid droplets physically contact mitochondria in vivo and in vitro.Using a bimolecular fluorescence complementation assay in Saccharomyces cerevisiae,we generated an interactomic map of protein-protein contacts of lipid droplets with mitochondria and peroxisomes.The lipid droplet proteins Erg6 and Pet10 were found to be involved in 75%of the interactions detected.Interestingly,interactions between 3 pairs of lipid metabolic enzymes were detected.Collectively,these data demonstrate that lipid droplets make physical contacts with mitochondria and peroxisomes,and reveal specific molecular interactions that suggest active participation of lipid droplets in lipid metabolism in yeast.展开更多
Prime editing(PE)is a versatile CRISPR-Cas based precise genome-editing platform widely used to introduce a range of possible base conversions in various organisms.However,no PE systems have been shown to induce herit...Prime editing(PE)is a versatile CRISPR-Cas based precise genome-editing platform widely used to introduce a range of possible base conversions in various organisms.However,no PE systems have been shown to induce heritable mutations in tobacco,nor in any other dicot.In this study,we generated an efficient PE system in tobacco that not only introduced heritable mutations,but also enabled anthocyanin-based reporter selection of transgene-free T_(1) plants.This system was used to confer Zabienol biosynthesis in the allotetraploid tobacco cultivar HHDJY by restoring a G>T conversion in the NtCPS2 gene.High levels of Z-abienol were detected in the leaves of homozygous T_(1) plants at two weeks after topping.This study describes an advance in PE systems and expands genome-editing toolbox in tobacco,even in dicots,for use in basic research and molecular breeding.And restoring biosynthesis of Z-abienol in tobacco might provide an efficient way to obtain Z-abienol in plants.展开更多
Mycophenolic acid(MPA,1)and its derivatives are first-line immunosuppressants used in organ transplantation and for treating autoimmune diseases.Despite chemical synthetic achievements,the biosynthetic formation of a ...Mycophenolic acid(MPA,1)and its derivatives are first-line immunosuppressants used in organ transplantation and for treating autoimmune diseases.Despite chemical synthetic achievements,the biosynthetic formation of a seven-carbon carboxylic acid pharmacophore side chain of 1,especially the processes involving the cleavage of the prenyl side chain between DHMP(4)and DMMPA(5),remains unknown.In this work,we identified a membrane-bound prenyltransferase,PgMpaA,that transfers FPP to 4 to yield FDHMP(6).Compound 6 undergoes the first cleavage step via a new globin-like enzyme PgMpaB to form a cryptic intermediate 12.Heterologous expression of PgMpa genes in Aspergillus nidulans demonstrates that the second cleavage step(from 12 to 5)of 1 is a PgMpa clusterindependent process in vivo.Our results,especially the discovery of the broad tolerance of substrates recognized by PgMpaB,set up a strategy for the formation of"pseudo-isopentenyl"natural products using fungal globin-like enzymes.展开更多
MicroRNAs play critical roles in multiple developmental processes in insects.Our previous study showed that CRISPR/Cas9-mediated knock down of the microRNA let-7 in silkworms increased the size of larvae and silk glan...MicroRNAs play critical roles in multiple developmental processes in insects.Our previous study showed that CRISPR/Cas9-mediated knock down of the microRNA let-7 in silkworms increased the size of larvae and silk glands,thereby improving the silk production capacity.In this study,we elucidate the molecular mechanism underlying of let-7 regulates growth.Identification of differentially expressed genes in response to let-7 knock down revealed enrichment of pathways associated with cell proliferation and DNA replication.let-7 dysregulation affected the cell cycle and proliferation of the Bombyx mori cell line BmN.Dual-luciferase and target site mutation assays showed that BmCDK1 is a direct target gene of let-7,with only 1 binding site on its 3′-untranslated region.RNA interference of BmCDK1 inhibited cell proliferation,but this effect was counteracted by co-transfection with let-7 antagomir.Moreover,let-7 knock down induced BmCDK1 expression and promoted cell proliferation in multiple tissues,and further induced endomitosis in the silk gland in vivo.Knock down of BmCDK1 resulted in abnormal formation of a new epidermis,and larval development was arrested at the 2nd or 3rd molt stage.Taken together,our results demonstrated that BmCDK1 is a novel target of let-7 in cell fate determination,possessing potential for improving silk yield in silkworm.展开更多
Clip-domain serine proteases (CLIPs) play important roles in insect innate immunity and development. Our previous studies indicated that CLIP13, an epidermis-specific gene, was involved in cuticle remodeling during mo...Clip-domain serine proteases (CLIPs) play important roles in insect innate immunity and development. Our previous studies indicated that CLIP13, an epidermis-specific gene, was involved in cuticle remodeling during molting and metamorphosis in the silkworm, Bombyx mori. However, the transcriptional regulatory mechanism and regulatory pathways of CLIP13 remained unclear. In the present study, we investigated CLIP13 expression and the regulation pathway controlled by 20-hydroxyecdysone (20E) in the silkworm. At the transcriptional level, expression of CLIP13 exhibited pronounced spatial and temporal specificity in different regions of the epidermis;homeodomain transcription factors POU-M2, antennapedia (Antp), and abdominal-B (Abd-B) showed similar expression change trends as CLIP13 in the head capsule, thorax, and abdomen, respectively. Furthermore, results of cell transfection assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation demonstrated that POU-M2, Antp, and Abd-B were involved in the transcriptional regulation of CLIP13 by directly binding to their cis-response elements in CLIP13 promoter. RNA interference-mediated silencing of POU-M2, Antp, and Abd-B led to a decrease of CLIP13 expression in the head capsule, the epidermis of the 1st to 3rd thoracic segments and the 7th to 10th abdominal segments, respectively. Consistent with CLIP13, 20E treatment significantly upregulated expression of POU-M2, Antp, and Abd-B in the silkworm epidermis. Taken together, these data suggest that 20E positively regulates transcription of CLIP13 via homeodomain proteins POU-M2, Antp, and Abd-B in different regions of the silkworm epidermis during metamorphosis, thus affecting the molting process. Our findings provide new insight into the functions of homeodomain transcription factors in insect molting.展开更多
Clustered regularly interspaced short palindromic repeats(CRISPR)-associated systems(Cas)are efficient tools for targeting specific genes for laboratory research,agricultural engineering,biotechnology,and human diseas...Clustered regularly interspaced short palindromic repeats(CRISPR)-associated systems(Cas)are efficient tools for targeting specific genes for laboratory research,agricultural engineering,biotechnology,and human disease treatment.Cas9,by far the most extensively used gene-editing nuclease,has shown great promise for the treatment of hereditary diseases,viral infection,cancers,and so on.Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications.Despite the rapid progress in basic research and clinical tests,some underlying problems present continuous,significant challenges,such as editing efficiency,relative difficulty in delivery,off-target effects,immunogenicity,etc.This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development.CRISPR-Cas systems,as a powerful gene-editing approach,will offer great hopes in clinical treatments for many individuals with currently incurable diseases.展开更多
Transcription factor Broad Complex(BR-C)is an ecdysone primary response gene in insects and participates in the regulation of insect growth and development.In this study,we performed a genome-wide identification of BR...Transcription factor Broad Complex(BR-C)is an ecdysone primary response gene in insects and participates in the regulation of insect growth and development.In this study,we performed a genome-wide identification of BR-C target genes in silkworm(Bombyx mori)using chromatin immunoprecipitation followed by high-throughput sequencing(ChIP-seq).As a result,a total of 1006 BR-C ChIP peaks were identified,and 15%of peaks were located in the promoter regions of 133 protein-coding genes.Functional annotation revealed that these ChIP peak-associated genes,as potential BR-C targets,were enriched in pathways related to biosynthetic process,metabolic process,and development.Transcriptome analysis and quantitative real-time polymerase chain reaction(PCR)examination revealed that developmental changes in expression patterns of a portion of potential BR-C targets,including HR96 and GC-otl,were similar to those of BR-C.ChIP-PCR examination confirmed that BR-C could directly bind to the promoters of potential targets.Further,dual luciferase assays demonstrated that HR96 promoter activity was significantly upregulated following BR-C overexpression,and this upregu-lation was abolished when the binding motif in the promoter was truncated.This study will be helpful for deciphering the regulatory roles of BR-C during insect growth and development.展开更多
BACKGROUND： Cell surface hydrophobicity （CSH） is one of the key physicochemical features of biodemulsifier-producing bacteria that influence their demulsification capability maintenance in petroleum contaminated en...BACKGROUND： Cell surface hydrophobicity （CSH） is one of the key physicochemical features of biodemulsifier-producing bacteria that influence their demulsification capability maintenance in petroleum contaminated environments. METHODS： In present study, biodemulsifier-producing bacteria were isolated from petroleum contaminated environments using different isolation media and the correlation between their CSH and demulsifying ability was investigated. The demutsifying ability of isolates was measured through demulsification tests on water in kerosene emulsions. The microbial adhesion to the hydrocarbon （MATH） assay was used to denote their CSH. RESULTS： The evaluation of CSH showed that majority of biodemulsifier producing bacteria have high CSH which indicating a positive correlation between CSH and demulsifying capability. CONCLUSIONS： According to these results it can be concluded that CSH can be used as an indicator for assessment of biodemulsifier-producing bacteria and screening of new isolates for their biodemulsifier production.展开更多
Endometrial injury can cause intrauterine adhesions(IUA)and induce the formation of endometrial fibrosis,leading to infertility and miscarriage.At present,there is no effective treatment method for severe IUA and uter...Endometrial injury can cause intrauterine adhesions(IUA)and induce the formation of endometrial fibrosis,leading to infertility and miscarriage.At present,there is no effective treatment method for severe IUA and uterine basal injury with adhesion area larger than one-third of the uterus.In this study,we prepared FGF1 silk sericin hydrogel material(FGF1-SS hydrogel)to treat endometrial injury and prevent endometrial fibrosis.Compared with the silk sericin hydrogel material(WT-SS hydrogel),FGF1-SS hydrogel significantly promotes the cell migration and infiltration ability of endometrial stromal cells(ESCs).More importantly,FGF1-SS hydrogel can release FGF1 stably for a long time and inhibit the ESCs injury model forms fibrosis through the TGF-β/Smad pathway.In the IUA rat model,FGF1-SS hydrogel treatment effectively restored the number of uterine glands and uterine wall thickness in rats,with a fertility rate of 65.1%66.4%.The results show that FGF1-SS hydrogel is expected to be a candidate to prevent IUA.展开更多
Inducible gene-expression systems play important roles in gene functional assays in the post-genome era.Streptomyces phage-derived phiC31 integrase,which mediates an irreversible site-specific cassette exchange betwee...Inducible gene-expression systems play important roles in gene functional assays in the post-genome era.Streptomyces phage-derived phiC31 integrase,which mediates an irreversible site-specific cassette exchange between the phage attachment site(attP)and the bacterial attachment site(attB),provides a promising option for the construction of a controllable gene-expression system.Here,we report a phiC3I integrase-mediated promoter flip system(FLIP)for the inducible expression of target genes in silk-worm(Bombyx mori).First,we constructed a FLIP reporter system,in which a BmAct4 promoter with enhanced translational efficiency was flanked by the attB and attP sites in a head-to-head orientation and further linked in a reverse orientation to a DsRed reporter gene.The coexpression of a C-terminal modified phiC3 I-NLS integrase carrying a simian virus 40(SV40)nuclear localization signal(NLS)effectively flipped the BmAct4 promoter through an attBlattP exchange,thereby activating the downstream expression of DsRed in a silkworm embryo-derived cell line,BmE.Subsequently,the FLIP system,together with a system continuously expressing the phiC3 I-NLS integrase,was used to construct binary transgenic silkworm lines.Hybridization between FLIP and phiC31-NLS transgenic silkworm lines resulted in the successful flipping of the BmAct4 promoter,with an approximately 39%heritable transformation efficiency in silkworm offispring,leading to the constitutive and high-level expression of DsRed in silkworms,which accounted for approximately 0.81%of the silkworm pupal weight.Our successful development of the FLIP system offers an effective alternative for manipulating gene expression in silkworms and other lepidopteran species.展开更多
Bitter receptors function primarily in sensing taste,but may also have other functions,such as detecting pathogenic organisms due to their agile response to foreign objects.The mouse taste receptor type-2 member 138(T...Bitter receptors function primarily in sensing taste,but may also have other functions,such as detecting pathogenic organisms due to their agile response to foreign objects.The mouse taste receptor type-2 member 138(TAS2R138)is a member of the G-protein-coupled bitter receptor family,which is not only found in the tongue and nasal cavity,but also widely distributed in other organs,such as the respiratory tract,gut,and lungs.Despite its diverse functions,the role of TAS2R138 in host defense against bacterial infection is largely unknown.Here,we show that TAS2R138 facilitates the degradation of lipid droplets(LDs)in neutrophils during Pseudomonas aeruginosa infection through competitive binding with PPARG(peroxisome proliferator-activated receptor gamma)antagonist:A/-(3-oxododecanoyl)-L-homoserine lactone(AHL-12),which coincidently is a virulence-bound signal produced by this bacterium(P.aeruginosa).The released PPARG then migrates from nuclei to the cytoplasm to accelerate the degradation of LDs by binding PLIN2(perilipin-2).Subsequently,the TAS2R138-AHL-12 complex targets LDs to augment their degradation,and thereby facilitating the clearance of AHL-12 in neutrophils to maintain homeostasis in the local environment.These findings reveal a crucial role for TAS2R138 in neutrophil-mediated host immunity against P.aeruginosa infection.展开更多
基金financially supported by National Key R&D Program of China(No.2016YFD0400200)National Natural Science Foundation of China(No.31972102,31671881,and 31901683)+4 种基金Chongqing Research Program of Basic Research and Frontier Technology(No.cstc2018jcyj A0939)Chongqing Technology Innovation and Application Demonstration Project(No.cstc2018jscx-msyb X0204)Fundamental Research Funds for the Central Universities(No.XDJK2019B028)Innovation Program for Chongqing’s Overseas Returnees(cx2019072)Fundamental Research Funds for the Central Universities,China(SWU 019009)。
文摘Ultraviolet(UV)-induced photoaging skin has become an urgent issue.The functional foods and cosmetics aiming to improve skin photoaging are developing rapidly,and the demand is gradually increasing year by year.Collagen peptides have been proven to display diverse physiological activities,such as excellent moisture retention activity,hygroscopicity,tyrosinase inhibitory activity and antioxidant activity,which indicates that they have great potential in amelioration of UV-induced photoaging.The main objective of this article is to recap the main mechanisms to improve photoaging skin by collagen peptides and their physiological activities in photo-protection.Furthermore,the extraction and structural characteristics of collagen peptides are overviewed.More importantly,some clinical trials on the beneficial effect on skin of collagen peptides are also discussed.In addition,prospects and challenges of collagen peptides are emphatically elucidated in this review.This article implies that collagen peptides have great potential as an effective ingredient in food and cosmetics industry with a wide application prospect.
基金supported by a Grant-in-Aid for Young Scientists B 23792391 from the Ministry of Education,Culture,Sports, Science and Technology,Japan
文摘In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus(OLP) and normal oral mucosa(NOM) from 14 healthy donors by real-time polymerase chain reaction(PCR) and immunohistochemistry.Synchronous mRNA coexpression of ErbBl,ErbB2,ErbB3and ErbB4 was detected in LP lesions.Out of the receptors,only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues.These were strongly expressed by epithelial keratinocytes in LP lesions,as shown by immunohistochemistry.Regarding the ligands,the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues.Therefore,enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.
基金This work was supported by funding from the Ginger Genome Project of Chongqing University of Arts and Sciences(2018)the Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0300,cstc2019jcyj-msxmX0697,CQYC201903201,cstc2019jscx-dxwtBX0028)+4 种基金the Foundation for High-level Talents of Chongqing University of Arts and Science(2017RTZ21,P2018TZ05)the Scientific and Technological Research Program of Chongqing Municipal Education Commission(KJZD-K202001304,KJQN201801339,KJQN201801330,KJQN201801335)the Foundation of Hubei Rural Science and Technology(2020BBA037)the State Key Research and Development Program of Hubei(2020BBA037)the Foundation of Laiwu Experimental Station of the National Characteristic Vegetable Industry System.
文摘Ginger(Zingiber officinale),the type species of Zingiberaceae,is one of the most widespread medicinal plants and spices.Here,we report a high-quality,chromosome-scale reference genome of ginger‘Zhugen’,a traditionally cultivated ginger in Southwest China used as a fresh vegetable,assembled from PacBio long reads,Illumina short reads,and high-throughput chromosome conformation capture(Hi-C)reads.The ginger genome was phased into two haplotypes,haplotype 1(1.53 Gb with a contig N50 of 4.68 M)and haplotype 0(1.51 Gb with a contig N50 of 5.28 M).Homologous ginger chromosomes maintained excellent gene pair collinearity.In 17,226 pairs of allelic genes,11.9%exhibited differential expression between alleles.Based on the results of ginger genome sequencing,transcriptome analysis,and metabolomic analysis,we proposed a backbone biosynthetic pathway of gingerol analogs,which consists of 12 enzymatic gene families,PAL,C4H,4CL,CST,C3’H,C3OMT,CCOMT,CSE,PKS,AOR,DHN,and DHT.These analyses also identified the likely transcription factor networks that regulate the synthesis of gingerol analogs.Overall,this study serves as an excellent resource for further research on ginger biology and breeding,lays a foundation for a better understanding of ginger evolution,and presents an intact biosynthetic pathway for species-specific gingerol biosynthesis.
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supported by the Fundamental Research Fund for Central Universities (SWU-KR22014)National Natural Science Foundation of China (NSFC32170478,32370478)+8 种基金Yunnan Fundamental Research Project (202001AW070016,202005AC160046)“Special Fund for Youth Team of Southwest University” (SWU-XJPY202302)to Y.Z.Y.National Key R&D Program of China (2022YFC2602500)the Second Tibetan Plateau Scientific Expedition and Research Program (STEP) (2019QZKK0501)Survey of Wildlife Resources in Key Areas of Xizang (ZL202203601)China’s Biodiversity Observation Network (Sino-BON)Animal Branch of Germplasm Bank of Wild Species,Chinese Academy of Sciences (Large Research Infrastructure Fund)to J.C.Unit of Excellence 2024 on Integrative diversity assessment of aquatic animals from Thailand (Fundamental FundFF67)to C.S。
文摘DEAR EDITOR,Based upon morphological and molecular evidence,the authors revised the genus Rohanixalus Biju,Garg,Gokulakrishnan,Chandrakasan,Thammachoti,Ren,Gopika,Bisht,Hamidy and Shouche,2020(Anura:Rhacophoridae)in China through describing one new species,adding one species to the fauna(R.shyamrupus)and supplementing data on one species(Rohanixalus hansenae;Supplementary Materials).
基金supported by funds of the Key Research and Development Grant of MOST(grant No.2023YFA095000)the Affiliated Xiangshan Hospital of Wenzhou Medical University,the National Science Foundation of China(grant No.82470005)Wenzhou Institute University of Chinese Academy of Sciences.
文摘AlphaFold3(AF3),as the latest generation of artificial intelligence model jointly developed by Google DeepMind and Isomorphic Labs,has been widely heralded in the scientific research community since its launch.With unprecedented accuracy,the AF3 model may successfully predict the structure and interactions of virtually all biomolecules,including proteins,ligands,nucleic acids,ions,etc.By accurately simulating the structural information and interactions of biomacromolecules,it has shown great potential in many aspects of structural prediction,mechanism research,drug design,protein engineering,vaccine development,and precision therapy.In order to further understand the characteristics of AF3 and accelerate its promotion,this article sets out to address the development process,working principle,and application in drugs and biomedicine,especially focusing on the intricate differences and some potential pitfalls compared to other deep learning models.We explain how a structure-prediction tool can impact many research fields,and in particular revolutionize the strategies for designing of effective next generation vaccines and chemical and biological drugs.
基金supportedbytheNational Key Research and Development ProgramofChina(2022YFD1201600)the Program of NationaNl atural Science of China(No.32030103)Technology Innovation andApplication Development Program of Chongqing(CSTB2024TIAD-KPX0023,CSTB2024TIAD-KPX0026)。
文摘Respiration is a vital process essential for organism survival,with most terrestrial insects relying on a sophisticated tubular tracheal network.In the current study,a gene with repetitive sequence was identified within the silkworm genome.Designated as BmMuc91C,it contains a dozen repeated motifs“PSSSYGAPX”and“GGYSSGGX”in its sequence.BmMuc91C exhibits specific expression in the tracheal system of silkworm larvae,with significantly higher expression levels during the molting stage.Overexpression of BmMuc91C in individual silkworms resulted in a marked increase in tracheal diameter,particularly during the molting stage.Immunofluorescence staining using a BmMuc91C antibody revealed a noticeable thickening of the apical extracellular matrix in the trachea.Tensile testing confirmed a considerable enhancement in tracheal elasticity.Additionally,a BmMuc91C mutation strain of silkworms was generated using the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease 9 system.Although no significant differences were observed in the growth,development,and molting of BmMuc91C mutant silkworms,mechanical tests demonstrated a decrease in tracheal elasticity.Transcriptomic techniques revealed that a significant number of cuticular and chitin-binding proteins were among the differentially expressed genes between mutant and wild-type silkworms.Furthermore,the recombined BmMuc91C protein was successfully expressed using the Escherichia coli system.Cross-linking experiments with horseradish peroxidase demonstrated the formation of macromolecular complexes of BmMuc91C,which exhibited spontaneous luminescent properties under ultraviolet light.This research sheds light on the role of elastic proteins in insect tracheae and provides valuable insights for the development of elastic biomaterials.
基金supported by the National Key Research and Devel-opment Program of China(2022YFD1201600)Chongqing Science and Technology Commission(CSTB2024NSCQ-QCXMX0017)National Natural Science Foundation of China(32030103).
文摘Chronic non-healing wounds,such as diabetic foot,pressure sores and bedsores have seriously affected the life quality of patients worldwide.GFs provide a potential solution to promote chronic wound healing by promoting cell proliferation and differentiation.However,limited resource,high cost,and instability in vivo greatly hin-dered their clinical applications.In present study,two silk gland bioreactor silkworm stains were generated to successfully synthesize functional silk fibers incorporating high expressions of EGF and PDGF-BB.The two GFs functionalized silk raw materials were used to fabricate a dual GFs sericin hydrogel(E/P-SH)delivering system with tunable material performances for better cell adhesion and biocompatibility,sustainable release of the dual GFs to synergistically promote cell proliferation and migration,which realized the significant healing of chronic full-thickness skin wound in diabetic mice within 12 days with more organized collagen arrangement and better epithelialization degree by reducing inflammatory response and promoting vascularization.These findings demonstrated that the biosynthesized dual GFs-SH delivering system provides an opportunity to broaden the wide utility of GFs in clinical treatment of diabetic wound healing.
基金supported by National Key Research and Development Program of China(No.2022YFD1201600)National Natural Science Foundation of China(Nos.32030103 and 32172798)+1 种基金Natural Science Foundation of Chongqing(Nos.cstc2020jcyjcxttX0001andCSTB2023NSCQ-MSX0814)Innovation and Entrepreneurship Training Program of Southwest University(No.S202210635112)。
文摘Ciliary neurotrophic factor(CNTF)acts as a potent neuroprotective agent in neuronal survival and regeneration,and can also induce the differentiation of several stem cells into neurons,which highlights the broad application of CNTF in biomedicine.However,large-scale production of bioactive recombinant human CNTF protein remains to be explored.Herein,this study aims to express a bioactive human CNTF protein on a large scale by genetically engineering a silk gland bioreactor of silkworm.Our results showed that CNTF protein was successfully expressed in the middle silk gland(MSG)of silkworm,which can be secreted into the silks with the amount of 3.2 mg/g cocoons.The fabrication of human CNTF-functionalized silk material was able to promote proliferation and migration of neural cells when compared to the natural silk protein.Importantly,this functional silk material could also facilitate neurite outgrowth of mouse retinal ganglion cell(RGC-5)cells.All these data demonstrated a high bioactivity of the recombinant human CNTF protein expressed in the MSG of silkworm.The further fabrication of different silk materials with CNTF bioactivity will give biomedical applications in tissue engineering and neuroregeneration.
基金supported by grants from the National Basic Research Program of China(Grant Nos.2009CB919000 and 2010CB833703)the National Natural Science Foundation of China(Grant Nos.30871229 and 30971431)the 21C Frontier Functional Proteomics Project(FPR08A1-060)funded by the Ministry of Education,Science and Technology,Republic of Korea.
文摘An increasing body of evidence shows that the lipid droplet,a neutral lipid storage organelle,plays a role in lipid metabolism and energy homeostasis through its interaction with mitochondria.However,the cellular functions and molecular mechanisms of the interaction remain ambiguous.Here we present data from transmission electron microscopy,fluorescence imaging,and reconstitution assays,demonstrating that lipid droplets physically contact mitochondria in vivo and in vitro.Using a bimolecular fluorescence complementation assay in Saccharomyces cerevisiae,we generated an interactomic map of protein-protein contacts of lipid droplets with mitochondria and peroxisomes.The lipid droplet proteins Erg6 and Pet10 were found to be involved in 75%of the interactions detected.Interestingly,interactions between 3 pairs of lipid metabolic enzymes were detected.Collectively,these data demonstrate that lipid droplets make physical contacts with mitochondria and peroxisomes,and reveal specific molecular interactions that suggest active participation of lipid droplets in lipid metabolism in yeast.
基金supported by Beijing Scholars Program (BSP041)Financial Special Fund of Beijing Academy of Agriculture and Forestry Sciences (CZZJ202206)+1 种基金the key projects of YNZY (2022JY02)CNTC (110202101034,JY-11)。
文摘Prime editing(PE)is a versatile CRISPR-Cas based precise genome-editing platform widely used to introduce a range of possible base conversions in various organisms.However,no PE systems have been shown to induce heritable mutations in tobacco,nor in any other dicot.In this study,we generated an efficient PE system in tobacco that not only introduced heritable mutations,but also enabled anthocyanin-based reporter selection of transgene-free T_(1) plants.This system was used to confer Zabienol biosynthesis in the allotetraploid tobacco cultivar HHDJY by restoring a G>T conversion in the NtCPS2 gene.High levels of Z-abienol were detected in the leaves of homozygous T_(1) plants at two weeks after topping.This study describes an advance in PE systems and expands genome-editing toolbox in tobacco,even in dicots,for use in basic research and molecular breeding.And restoring biosynthesis of Z-abienol in tobacco might provide an efficient way to obtain Z-abienol in plants.
基金supported by the National Natural Science Foundation of China(31870022)the Fundamental Research Funds for the Central Universities(XDJK2018B035 and 201941001,China)+3 种基金the Scientific Research Starting Foundation of Southwest University(SWU117034,China)the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao,China)(No.2018SDKJ0401-2)Taishan Scholar Youth Expert Program in Shandong Province(tsqn201812021,China)supported by the Venture&Innovation Support Program for Chongqing Overseas Returnees and the Thousand Young Talents Program of China.
文摘Mycophenolic acid(MPA,1)and its derivatives are first-line immunosuppressants used in organ transplantation and for treating autoimmune diseases.Despite chemical synthetic achievements,the biosynthetic formation of a seven-carbon carboxylic acid pharmacophore side chain of 1,especially the processes involving the cleavage of the prenyl side chain between DHMP(4)and DMMPA(5),remains unknown.In this work,we identified a membrane-bound prenyltransferase,PgMpaA,that transfers FPP to 4 to yield FDHMP(6).Compound 6 undergoes the first cleavage step via a new globin-like enzyme PgMpaB to form a cryptic intermediate 12.Heterologous expression of PgMpa genes in Aspergillus nidulans demonstrates that the second cleavage step(from 12 to 5)of 1 is a PgMpa clusterindependent process in vivo.Our results,especially the discovery of the broad tolerance of substrates recognized by PgMpaB,set up a strategy for the formation of"pseudo-isopentenyl"natural products using fungal globin-like enzymes.
基金supported by grants from the National Natural Science Foundation of China(No.32102614)the National Key Research and Development Program of China(No.2022YFD1201600)+1 种基金the Natural Science Foundation of Chongqing,China(No.cstc2021jcyj-bsh0151)the Chongqing Special Support fund for Post Doctor(No.2010010006115189).
文摘MicroRNAs play critical roles in multiple developmental processes in insects.Our previous study showed that CRISPR/Cas9-mediated knock down of the microRNA let-7 in silkworms increased the size of larvae and silk glands,thereby improving the silk production capacity.In this study,we elucidate the molecular mechanism underlying of let-7 regulates growth.Identification of differentially expressed genes in response to let-7 knock down revealed enrichment of pathways associated with cell proliferation and DNA replication.let-7 dysregulation affected the cell cycle and proliferation of the Bombyx mori cell line BmN.Dual-luciferase and target site mutation assays showed that BmCDK1 is a direct target gene of let-7,with only 1 binding site on its 3′-untranslated region.RNA interference of BmCDK1 inhibited cell proliferation,but this effect was counteracted by co-transfection with let-7 antagomir.Moreover,let-7 knock down induced BmCDK1 expression and promoted cell proliferation in multiple tissues,and further induced endomitosis in the silk gland in vivo.Knock down of BmCDK1 resulted in abnormal formation of a new epidermis,and larval development was arrested at the 2nd or 3rd molt stage.Taken together,our results demonstrated that BmCDK1 is a novel target of let-7 in cell fate determination,possessing potential for improving silk yield in silkworm.
基金This work was supported by grants from the National Natural Science Foundation of China(31772532,31702187)the China Postdoctoral Science Foundation(2019M663880XB)Natural Science Foundation of Chongqing,China(cstc2019jcyj-bshX0033).
文摘Clip-domain serine proteases (CLIPs) play important roles in insect innate immunity and development. Our previous studies indicated that CLIP13, an epidermis-specific gene, was involved in cuticle remodeling during molting and metamorphosis in the silkworm, Bombyx mori. However, the transcriptional regulatory mechanism and regulatory pathways of CLIP13 remained unclear. In the present study, we investigated CLIP13 expression and the regulation pathway controlled by 20-hydroxyecdysone (20E) in the silkworm. At the transcriptional level, expression of CLIP13 exhibited pronounced spatial and temporal specificity in different regions of the epidermis;homeodomain transcription factors POU-M2, antennapedia (Antp), and abdominal-B (Abd-B) showed similar expression change trends as CLIP13 in the head capsule, thorax, and abdomen, respectively. Furthermore, results of cell transfection assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation demonstrated that POU-M2, Antp, and Abd-B were involved in the transcriptional regulation of CLIP13 by directly binding to their cis-response elements in CLIP13 promoter. RNA interference-mediated silencing of POU-M2, Antp, and Abd-B led to a decrease of CLIP13 expression in the head capsule, the epidermis of the 1st to 3rd thoracic segments and the 7th to 10th abdominal segments, respectively. Consistent with CLIP13, 20E treatment significantly upregulated expression of POU-M2, Antp, and Abd-B in the silkworm epidermis. Taken together, these data suggest that 20E positively regulates transcription of CLIP13 via homeodomain proteins POU-M2, Antp, and Abd-B in different regions of the silkworm epidermis during metamorphosis, thus affecting the molting process. Our findings provide new insight into the functions of homeodomain transcription factors in insect molting.
基金This work was supported by the National Institutes of Health(NIH)(Grant No.AI138203-3)the American Association of Immunologists through a Careers in Immunology Fellowship.This work was also supported by the National Natural Science Foundation of China(Grants No.82020108021 and 32000033).
文摘Clustered regularly interspaced short palindromic repeats(CRISPR)-associated systems(Cas)are efficient tools for targeting specific genes for laboratory research,agricultural engineering,biotechnology,and human disease treatment.Cas9,by far the most extensively used gene-editing nuclease,has shown great promise for the treatment of hereditary diseases,viral infection,cancers,and so on.Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications.Despite the rapid progress in basic research and clinical tests,some underlying problems present continuous,significant challenges,such as editing efficiency,relative difficulty in delivery,off-target effects,immunogenicity,etc.This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development.CRISPR-Cas systems,as a powerful gene-editing approach,will offer great hopes in clinical treatments for many individuals with currently incurable diseases.
基金funded by grants from the National Natural Science Foundation of China(31572464,31772679,and 32070496)the Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0446)the Fundamental Research Funds for the Central Universities(XDJK2020C008).
文摘Transcription factor Broad Complex(BR-C)is an ecdysone primary response gene in insects and participates in the regulation of insect growth and development.In this study,we performed a genome-wide identification of BR-C target genes in silkworm(Bombyx mori)using chromatin immunoprecipitation followed by high-throughput sequencing(ChIP-seq).As a result,a total of 1006 BR-C ChIP peaks were identified,and 15%of peaks were located in the promoter regions of 133 protein-coding genes.Functional annotation revealed that these ChIP peak-associated genes,as potential BR-C targets,were enriched in pathways related to biosynthetic process,metabolic process,and development.Transcriptome analysis and quantitative real-time polymerase chain reaction(PCR)examination revealed that developmental changes in expression patterns of a portion of potential BR-C targets,including HR96 and GC-otl,were similar to those of BR-C.ChIP-PCR examination confirmed that BR-C could directly bind to the promoters of potential targets.Further,dual luciferase assays demonstrated that HR96 promoter activity was significantly upregulated following BR-C overexpression,and this upregu-lation was abolished when the binding motif in the promoter was truncated.This study will be helpful for deciphering the regulatory roles of BR-C during insect growth and development.
文摘BACKGROUND： Cell surface hydrophobicity （CSH） is one of the key physicochemical features of biodemulsifier-producing bacteria that influence their demulsification capability maintenance in petroleum contaminated environments. METHODS： In present study, biodemulsifier-producing bacteria were isolated from petroleum contaminated environments using different isolation media and the correlation between their CSH and demulsifying ability was investigated. The demutsifying ability of isolates was measured through demulsification tests on water in kerosene emulsions. The microbial adhesion to the hydrocarbon （MATH） assay was used to denote their CSH. RESULTS： The evaluation of CSH showed that majority of biodemulsifier producing bacteria have high CSH which indicating a positive correlation between CSH and demulsifying capability. CONCLUSIONS： According to these results it can be concluded that CSH can be used as an indicator for assessment of biodemulsifier-producing bacteria and screening of new isolates for their biodemulsifier production.
基金funded by grants from the National Key Research and Development Program of China(2016YFC1000803)the National Natural Science Foundation of China(No.32030103).
文摘Endometrial injury can cause intrauterine adhesions(IUA)and induce the formation of endometrial fibrosis,leading to infertility and miscarriage.At present,there is no effective treatment method for severe IUA and uterine basal injury with adhesion area larger than one-third of the uterus.In this study,we prepared FGF1 silk sericin hydrogel material(FGF1-SS hydrogel)to treat endometrial injury and prevent endometrial fibrosis.Compared with the silk sericin hydrogel material(WT-SS hydrogel),FGF1-SS hydrogel significantly promotes the cell migration and infiltration ability of endometrial stromal cells(ESCs).More importantly,FGF1-SS hydrogel can release FGF1 stably for a long time and inhibit the ESCs injury model forms fibrosis through the TGF-β/Smad pathway.In the IUA rat model,FGF1-SS hydrogel treatment effectively restored the number of uterine glands and uterine wall thickness in rats,with a fertility rate of 65.1%66.4%.The results show that FGF1-SS hydrogel is expected to be a candidate to prevent IUA.
基金the National Natural Science Foundation of China(31530071)Chongqing Science and Technology C ommission(CSTC2018JCYJAX0298)+1 种基金Fundamental Research Funds for the Central Universities(XDJK2018C064)State Key Laboratory of Silkworm Genome Biology(SKLSGB1819-1).
文摘Inducible gene-expression systems play important roles in gene functional assays in the post-genome era.Streptomyces phage-derived phiC31 integrase,which mediates an irreversible site-specific cassette exchange between the phage attachment site(attP)and the bacterial attachment site(attB),provides a promising option for the construction of a controllable gene-expression system.Here,we report a phiC3I integrase-mediated promoter flip system(FLIP)for the inducible expression of target genes in silk-worm(Bombyx mori).First,we constructed a FLIP reporter system,in which a BmAct4 promoter with enhanced translational efficiency was flanked by the attB and attP sites in a head-to-head orientation and further linked in a reverse orientation to a DsRed reporter gene.The coexpression of a C-terminal modified phiC3 I-NLS integrase carrying a simian virus 40(SV40)nuclear localization signal(NLS)effectively flipped the BmAct4 promoter through an attBlattP exchange,thereby activating the downstream expression of DsRed in a silkworm embryo-derived cell line,BmE.Subsequently,the FLIP system,together with a system continuously expressing the phiC3 I-NLS integrase,was used to construct binary transgenic silkworm lines.Hybridization between FLIP and phiC31-NLS transgenic silkworm lines resulted in the successful flipping of the BmAct4 promoter,with an approximately 39%heritable transformation efficiency in silkworm offispring,leading to the constitutive and high-level expression of DsRed in silkworms,which accounted for approximately 0.81%of the silkworm pupal weight.Our successful development of the FLIP system offers an effective alternative for manipulating gene expression in silkworms and other lepidopteran species.
基金The authors thank the National Institutes of Health for Grants R01 AM 138203,R01 All09317-01 Al,and AI097532-01A1 for M.W.,as well as P20 GM113123 and P20 GM103442 for Imaging,Histology,and Flow Cytometry Core Facility.
文摘Bitter receptors function primarily in sensing taste,but may also have other functions,such as detecting pathogenic organisms due to their agile response to foreign objects.The mouse taste receptor type-2 member 138(TAS2R138)is a member of the G-protein-coupled bitter receptor family,which is not only found in the tongue and nasal cavity,but also widely distributed in other organs,such as the respiratory tract,gut,and lungs.Despite its diverse functions,the role of TAS2R138 in host defense against bacterial infection is largely unknown.Here,we show that TAS2R138 facilitates the degradation of lipid droplets(LDs)in neutrophils during Pseudomonas aeruginosa infection through competitive binding with PPARG(peroxisome proliferator-activated receptor gamma)antagonist:A/-(3-oxododecanoyl)-L-homoserine lactone(AHL-12),which coincidently is a virulence-bound signal produced by this bacterium(P.aeruginosa).The released PPARG then migrates from nuclei to the cytoplasm to accelerate the degradation of LDs by binding PLIN2(perilipin-2).Subsequently,the TAS2R138-AHL-12 complex targets LDs to augment their degradation,and thereby facilitating the clearance of AHL-12 in neutrophils to maintain homeostasis in the local environment.These findings reveal a crucial role for TAS2R138 in neutrophil-mediated host immunity against P.aeruginosa infection.
