F-box proteins are components of the SCF （SkpA-Cullin 1-F-box） E3 ligase complexes, acting as the specificity-determinants in targeting substrate proteins for ubiquitination and degradation. In humans, at least 22 o...F-box proteins are components of the SCF （SkpA-Cullin 1-F-box） E3 ligase complexes, acting as the specificity-determinants in targeting substrate proteins for ubiquitination and degradation. In humans, at least 22 out of 75 F-box proteins have experimentally documented substrates, whereas in Drosophila 12 F-box proteins have been characterized with known substrates. To systematically investigate the genetic and molecular functions of F-box proteins in Drosophila, we performed a survey of the literature and databases. We identified 45 Drosophila genes that encode proteins containing at least one F-box domain. We collected publically available RNAi lines against these genes and used them in a tissue-specific RNAi-based phenotypic screen. Here, we present our systematic phenotypic dataset from the eye, the wing and the notum. This dataset is the first of its kind and represents a useful resource for future studies of the molecular and genetic functions of F-box genes in Drosophila. Our results show that, as expected, F-box genes in Drosophila have regulatory roles in a diverse array of processes including cell proliferation, cell growth, signal transduction, and cellular and animal survival.展开更多
The F-box protein-encoding gene family plays an essential role in plant stress resistance.In present study,126 non-redundant F-box genes were identified in barley(Hordeum vulgare L.,Hv).The corresponding proteins cont...The F-box protein-encoding gene family plays an essential role in plant stress resistance.In present study,126 non-redundant F-box genes were identified in barley(Hordeum vulgare L.,Hv).The corresponding proteins contained 165–887 amino acid residues and all were amphiphilic,except 5 proteins.Phylogenetic analysis of F-box protein sequences in barley and stress-related F-box protein sequences in wheat and Arabidopsis thaliana(At)was used to classify barley F-box genes are divided into 9 subfamilies(A–I).A structure-based sequence alignment demonstrated that F-box proteins were highly conserved with a total of 10 conserved motifs.In total,124 F-box genes were unevenly distributed on 7 chromosomes;another 2 genes have not been anchored yet.The gene structure analysis revealed high variability in the number of exons and introns in F-box genes.Comprehensive analysis of expression profiles and phylogenetic tree analysis,a total of 12 F-box genes that may be related to stress tolerance in barley were screened.Of the 12 detected F-box genes,8 and 10 were upregulated after drought and salt stress treatments,respectively,using quantitative real-time polymerase chain reaction(qRT-PCR).This study is the first systematic analysis conducted on the F-box gene family in barley,which is of great importance for clarifying this family’s bioinformatic characteristics and elucidating its function in barley stress resistance.These results will serve as a theoretical reference for subsequent research on molecular regulation mechanisms,genetic breeding,and improvement.展开更多
In order to reveal the phenomenon of R. rugose pollination incompatibility, the full-length cDNA sequence of S Locus F-box Gene was cloned for the first time from the pollen of Rosa rugose “Zilong wochi” with RT-PCR...In order to reveal the phenomenon of R. rugose pollination incompatibility, the full-length cDNA sequence of S Locus F-box Gene was cloned for the first time from the pollen of Rosa rugose “Zilong wochi” with RT-PCR and RACE methods and named as RrSLF. The full-length cDNA is 1236 bp with an open reading frame of 1122 bp, encoding 343 amino acids. The derived protein has a molecular weight of 43.7 kD, a calculated pI of 6.24, an F-box conserved domain at position 343 - 741, and belongs to F-box family. The derived protein is a Hydrophobicity protein secreted into the cytoplasm. There is no transmembrane domain and no signal peptide cleavage site, twenty-one Ser phosphorylation sites, seven Thr phosphorylation sites, seven Tyr phosphorylation sites, two N-glycosylation sites, and no O-glycosylation sites. There are 22.25% α-helixes, 31.37% random coil, 32.17% extended peptide chain, and 14.21% β-corner structure. This protein and the SFB/SLF protein from Rosaceae Prunus fruit, including Prunus speciose, share a sequence homology of 59% - 61%;all of the proteins contain an F-box conserved domain, two hypervariable regions HVa, HVb, and two variable regions V1, V2. Furthermore, their phylogenetic relationships are consistent with their traditional classifications. These results were meaningful to reveal the molecular mechanism of Rosa rugose pollination incompatibility and improve the theory and techniques of breeding ornamental Rosa rugose.展开更多
Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa su...Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa such as cephalopods,systematic evaluation of reference genes is limited,leading to potential bias.The cuttlefish Sepiella japonica is ecologically and economically important in China,yet previous molecular studies have often relied on single unvalidated reference genes,which may compromise data reliability.This study aimed to systematically evaluate the stability of five commonly used reference genes(18S,ef-1α,ef-1γ,gapdh,andβ-actin)across multiple tissues and sexes of S.japonica,and to identify the most suitable reference genes and optimal number for qPCR normalization.Fifteen to sixteen tissue types were collected from ten healthy adults(five males and five females).Total RNA was extracted,reverse-transcribed,and analyzed by qPCR.Gene stability was assessed using four algorithms(geNorm,NormFinder,BestKeeper,andΔCt)integrated with RefFinder,and the optimal gene number was determined using geNorm pairwise variation(V_(n/n+1)<0.15).Four transcriptome-derived genes(creld2,cd109,acy1,and miox)were used for validation.The C_(t)values of the five genes ranged from 15.47 to 20.83.β-actin and gapdh showed pronounced variability in expression stability among tissues and sexes,indicating their limited suitability for normalization.18S exhibited the highest expression(mean C_(t):15.47-16.29)and lowest variability but displayed sex-biased expression,whereas ef-1αand ef-1γremained consistently stable across most tissues in both sexes,with ef-1αbeing the most robust and showing no sex-related bias.Although specific rankings varied among tissues and sexes,the comprehensive results indicated that ef-1αand ef-1γpossessed the highest overall stability,followed by 18S,whileβ-actin and gapdh were the least stable.The final comprehensive rankings were ef-1γ>ef-1α>18S>gapdh>β-actin(male)and ef-1α>ef-1γ>18S>gapdh>β-actin(female).geNorm analysis(V2/3<0.15)indicated that two genes,mainly ef-1αand ef-1γ,were generally sufficient for reliable normalization in most tissues.Validation confirmed that normalization using the stable ef-1αand ef-1γaccurately reflected the expression differences among tissues,whereasβ-actin and gapdh can bias or confound statistical analyses.ef-1αand ef-1γare identified as the most reliable reference gene combination for qPCR analysis in S.japonica,while 18S can serve as an auxiliary gene for within-sex comparisons.The use ofβ-actin or gapdh alone is not recommended.This study establishes a systematic framework for selecting reliable reference genes in S.japonica,thereby facilitating robust qPCR normalization and providing a foundation for future gene expression research in S.japonica and other cephalopods.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Com...AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their un...Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their unique dimensions and structures.Unfortunately,emerging evidence suggests that NMs may facilitate the transmission of ARGs.It is crucial to elucidate how NMs affect the evolution and dissemination of ARGs.The current review comprehensively examines the role of NMs in the widespread transmission of ARGs in aquatic environments and the underlying mechanisms involved in the process.It aims to clarify the effects and mechanisms of NMs on the horizontal gene transfer processes that are associated with ARGs,including the enhancement of cell membrane permeability,the formation of nanopores on membranes,promotion of mutagenesis,and the generation of reactive oxygen species(ROSs).Furthermore,the trade-off between the removal of ARGs and horizontal transfer has been elucidated.The review aspires to guide future research directions,advance knowledge on the implications of NMs in the field of ARGs' transmission,and provide a theoretical foundation for the development of safer and more effective applications of NMs.展开更多
AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induc...AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.展开更多
The Fujian oyster(Crassostrea angulata)is an economically significant shellfish species distributed mainly along the Fujian coast,Southeast China.However,its genetic diversity and structure remain unclear.The main dis...The Fujian oyster(Crassostrea angulata)is an economically significant shellfish species distributed mainly along the Fujian coast,Southeast China.However,its genetic diversity and structure remain unclear.The main distribution area of the C.angulata is located in Fujian,South China.In total,420 C.angulata were collected from 14 natural habitats(populations)along the Fujian coast,and their genetic diversity and structure were analyzed in the mitochondrial COⅠand nuclear gene ITS2 sequences.Results reveal that all the 14 populations of C.angulata exhibited high levels of genetic diversity,with a total of 57(haplotype diversity:0.811±0.016)and 124(haplotype diversity:0.912±0.007)haplotypes revealed by COⅠand ITS2,respectively.Notably,significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ)population(F_(ST)by COI:0.035-0.142,P<0.05;F_(ST)by ITS2:0.078-0.123,P<0.05)with other populations were observed for the first time,which is also supported by the results of molecular variance analysis(F_(CT)by COⅠ:0.105,P<0.05;F_(CT)by ITS2:0.086,P<0.05)and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree.Furthermore,the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations.In addition,the population dynamics analysis suggests that the C.angulata may have undergone expansion during the third ice age of the Pleistocene.These results provide a reference for the preservation and further genetic improvement of C.angulata.展开更多
[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Qu...[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Quantitative real-time PCR(qRT-PCR)was utilized to analyze the expression patterns of LOX genes at different stages of Botrytis cinerea infection.[Results]The P.patens LOX gene family comprises eight putative proteins,including two 12-LOX-type members and six 13-LOX-type members.Among the eight LOX proteins,PpLOX7 exhibited the lowest molecular weight and shortest amino acid sequence.PpLOX7 was identified as a basic protein with an isoelectric point(pI)of 8.54,while all other members were acidic.Subcellular localization analysis indicated that PpLOX7 was localized to the chloroplast,whereas the remaining members were distributed in the cytoplasm.Secondary structure prediction showed that all eight proteins were predominantly composed of random coils andα-helixes.Chromosomal mapping revealed that the LOX genes were distributed across 7 of the 27 chromosomes in P.patens,with PpLOX1 and PpLOX2 tandemly arranged on chromosome 15.The qRT-PCR analysis demonstrated distinct expression patterns among the eight PpLOX genes following B.cinerea infection.PpLOX1-3 and PpLOX7 were upregulated to varying degrees,suggesting their potential involvement in the early defense response of P.patens against B.cinerea.Notably,PpLOX2 exhibited highly significant differential expression,making it a key candidate for further investigation.[Conclusions]This study provides foundational insights into the functional roles of the LOX gene family in P.patens during biotic stress responses.展开更多
The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural pro...Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural products,thereby endangering human health.Extensive studies on Aspergillus fungi have been conducted on growth and development,aflatoxin biosynthesis,and their interactions with environment.Here,we summarized a series of functional genes of the main Aspergillus fungi relative to toxins occurrence in foods,which revealed the signal transduction mechanisms of their involvement in growth and development,toxin production,and response to light,anticipating providing theoretical guidance on developing control and prevention technologies for mycotoxin contamination in agricultural products to ensure food safety.展开更多
The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2...The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2)is known to regulate aboveground traits,including tiller angle,grain size,and panicle development,its function in root morphogenesis remains uncharacterized.展开更多
Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we develop...Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.展开更多
The accuracy of genomic annotation is crucial for subsequent functional investigations;however,computational protocols used in high-throughput annotation of open reading frames(ORFs)can introduce inconsistencies.These...The accuracy of genomic annotation is crucial for subsequent functional investigations;however,computational protocols used in high-throughput annotation of open reading frames(ORFs)can introduce inconsistencies.These inconsistencies,which lead to non-uniform extension or truncation of sequence ends,pose challenges for downstream analyses.Existing strategies to rectify these inconsistencies are time-consuming and labor-intensive,lacking specific approaches.To address this gap,we developed to GC,a tool that integrates genomic annotation with RNA-seq datasets to rectify annotation inconsistencies.Using to GC,we achieved an accuracy of nearly 100%accuracy in correcting inconsistencies in published Phytophthora sojae ORFs.We applied this innovative pipeline to the GPCR-bigrams gene family,which was predicted to have 42 members in the P.sojae genome but lacked experimental validation.By employing to GC,we identified 32 GPCR-bigram ORFs with inconsistencies between previous annotations and to GC-corrected sequences.Notably,among these were 5 genes(GPCR-TKL9,GPCR-TKL15,GPCR-PDE3,GPCR-AC3,and GPCR-AC4)showed substantial inconsistencies.Experimental gene annotation confirmed the effectiveness of to GC,as sequences obtained through cloning matched those annotated by to GC.Importantly,we discovered two novel GPCRs(GPCR-AC3 and GPCR-AC4),which were previously mispredicted as a single gene.CRISPR/Cas9-mediated knockout experiments revealed the involvement of GPCR-AC4 but not GPCR-AC3 in oospore production,further confirming their status as two separate genes.In addition to P.sojae,the reliability of the to GC pipeline in Phytophthora capsici and Pythium ultimum further emphasizes the robustness of this pipeline.Our findings highlight the utility of to GC for reliable gene model correction,facilitating investigations into biological functions and offering potential applications in diverse species analyses.展开更多
Due to the unique microstructure and diverse opsin genes of the trinocular compound eye,stomatopoda possess an extraordinary ability to perceive multiple properties of light.They not only can detect natural light(NL)a...Due to the unique microstructure and diverse opsin genes of the trinocular compound eye,stomatopoda possess an extraordinary ability to perceive multiple properties of light.They not only can detect natural light(NL)and linearly polarized light(LPL),but also are the only animals capable of recognizing circularly polarized light(CPL).Here,we integrated single-cell RNA sequencing,previously published Illumina data,and in-situ hybridization(ISH)to quantify and localize functional opsin genes in Oratosquilla oratoria,a common stomatopoda species in the China Sea.A total of high-quality 31777 cells were captured for the first time in the O.oratoria compound eye,which were classified into 25 cell subpopulations,and hypothesized that cluster 22 is a critical cell subpopulation responsible for light(whether NL,LPL,or CPL)response in O.oratoria.Furthermore,we propose that the long-wavelengthsensitive opsin gene(lws)gene family,retinol dehydrogenase(rdh),voltage-gated ion channel(vgic),arrestin(arr),and myosin(myo)collectively mediate the light response in O.oratoria.Considering that very few vision-related opsin genes show differential expression in right-handed CPL(RCPL)-vs.-dark(DL),which provides additional evidence that stomatopoda cannot recognize RCPL.Meanwhile,we believe that UV-stimulated scaffold protein A(uvssa)and red pigment concentrating hormone(rpch)play special contributions in the left-handed CPL(LCPL)environment response.ISH revealing that 16 lws,6 middle-wavelength-sensitive(mws),and 2 ultraviolet(uv)opsin genes were expressed in the photoreceptors of the O.oratoria compound eye.Although the inability to determine the functional types of cell subpopulations limits the resolution of opsin genes,these findings systematically elucidate the specific expression patterns of opsin genes in O.oratoria and represent a significant step toward refining the visual ecological theory of O.oratoria and other stomatopod species.展开更多
Osmanthus fragrans is most famous for its strong aroma,and different varieties have different degrees of fragrance and color.Fragrance and color are important factors affecting the ornamental quality of O.fragrans.Ter...Osmanthus fragrans is most famous for its strong aroma,and different varieties have different degrees of fragrance and color.Fragrance and color are important factors affecting the ornamental quality of O.fragrans.Terpenoids are important secondary metabolites in plants,with β-carotene(C40)being the major pigment substance and linalool(C10)being the key aromatic component in O.fragrans.The geranylgeranyl pyrophosphate synthase genes(GGPPSs)play important roles in secondary metabolism in plants.However,the functions of the GGPPS family in floral color and fragrance formation has rarely been reported in O.fragrans.In this study,24 Of GGPPS genes were identified and classified into two subfamilies.The Of GGPPSs showed tissue-specific expression and Of GGPPS13 had highest expression in flowers.The Of GGPPS13 protein was localized to chloroplasts.The transcriptome data of Of GGPPS13 was verified by q RT-PCR and the expression level in‘Wanyingui'with strong aroma was higher than that in‘Zhuangyuanhong'with deep color at different flower development stages.Transient overexpression of Of GGPPS13 in O.fragrans petals showed that Of GGPPS13 increased the β-carotene content,the main color substance of O.fragrans,but decreased the linalool content,the main volatile organic compound(VOC)in the floral aroma of O.fragrans.Of GGPPS13 was indicated as the critical gene related to terpenoid synthesis in the floral aroma and color formation in O.fragrans.Our findings provide gene resources on the GGPPS gene family for further revealing the molecular regulation mechanism of the floral color and aroma formation in O.fragrans.展开更多
Improved yield potential is the goal of barley domestication and cultivation.During this process,two-and six-rowed barley types emerged and have been utilised in breeding and production.The six-rowed type could produc...Improved yield potential is the goal of barley domestication and cultivation.During this process,two-and six-rowed barley types emerged and have been utilised in breeding and production.The six-rowed type could produce three times as many grains as its ancestral two-rowed forms,thus dominating barley cultivation for thousands of years.The deficiens form of the two-rowed type,characterised by extremely suppressed lateral spikelets,has gained dominance over the past few decades in barley-growing regions worldwide.We hypothesised that the absence of lateral spikelets in deficiens barley affects spike architecture and spike-related traits,contributing to its superior yield potential of deficiens barley cultivation.Currently,a deficiens barley variety,RGT Planet,is the most popular barley variety in the world.In this study,we used two F_(2) populations derived from crossing RGT Planet with two canonical two-rowed barley and identified the functional allele Vrs1.t1 associated with deficiens morphology.We observed that the Vrs1.t1 allele may contribute to high yield potential by optimising spike architecture through increased spikelet length,grain number,and grain size.Phylogenetic analysis suggests that the deficiens mutation was likely present from the early stages of barley cultivation in the Fertile Crescent and spread to Ethiopia and beyond with agricultural expansion.We conclude that the ancient deficiens allele Vrs1.t1 has been a critical driver for the recent success of modern barley improvement by optimising spike architecture.展开更多
基金financially supported by the National Basic Research Program of China(973 Program)(No.2009CB918702)the National Natural Science Foundation of China(Nos.31071087 and 31100889)
文摘F-box proteins are components of the SCF （SkpA-Cullin 1-F-box） E3 ligase complexes, acting as the specificity-determinants in targeting substrate proteins for ubiquitination and degradation. In humans, at least 22 out of 75 F-box proteins have experimentally documented substrates, whereas in Drosophila 12 F-box proteins have been characterized with known substrates. To systematically investigate the genetic and molecular functions of F-box proteins in Drosophila, we performed a survey of the literature and databases. We identified 45 Drosophila genes that encode proteins containing at least one F-box domain. We collected publically available RNAi lines against these genes and used them in a tissue-specific RNAi-based phenotypic screen. Here, we present our systematic phenotypic dataset from the eye, the wing and the notum. This dataset is the first of its kind and represents a useful resource for future studies of the molecular and genetic functions of F-box genes in Drosophila. Our results show that, as expected, F-box genes in Drosophila have regulatory roles in a diverse array of processes including cell proliferation, cell growth, signal transduction, and cellular and animal survival.
基金This work was supported by the National Undergraduate Training Programs for Innovation and Entrepreneurship(No.201910346054)for L.Z.
文摘The F-box protein-encoding gene family plays an essential role in plant stress resistance.In present study,126 non-redundant F-box genes were identified in barley(Hordeum vulgare L.,Hv).The corresponding proteins contained 165–887 amino acid residues and all were amphiphilic,except 5 proteins.Phylogenetic analysis of F-box protein sequences in barley and stress-related F-box protein sequences in wheat and Arabidopsis thaliana(At)was used to classify barley F-box genes are divided into 9 subfamilies(A–I).A structure-based sequence alignment demonstrated that F-box proteins were highly conserved with a total of 10 conserved motifs.In total,124 F-box genes were unevenly distributed on 7 chromosomes;another 2 genes have not been anchored yet.The gene structure analysis revealed high variability in the number of exons and introns in F-box genes.Comprehensive analysis of expression profiles and phylogenetic tree analysis,a total of 12 F-box genes that may be related to stress tolerance in barley were screened.Of the 12 detected F-box genes,8 and 10 were upregulated after drought and salt stress treatments,respectively,using quantitative real-time polymerase chain reaction(qRT-PCR).This study is the first systematic analysis conducted on the F-box gene family in barley,which is of great importance for clarifying this family’s bioinformatic characteristics and elucidating its function in barley stress resistance.These results will serve as a theoretical reference for subsequent research on molecular regulation mechanisms,genetic breeding,and improvement.
文摘In order to reveal the phenomenon of R. rugose pollination incompatibility, the full-length cDNA sequence of S Locus F-box Gene was cloned for the first time from the pollen of Rosa rugose “Zilong wochi” with RT-PCR and RACE methods and named as RrSLF. The full-length cDNA is 1236 bp with an open reading frame of 1122 bp, encoding 343 amino acids. The derived protein has a molecular weight of 43.7 kD, a calculated pI of 6.24, an F-box conserved domain at position 343 - 741, and belongs to F-box family. The derived protein is a Hydrophobicity protein secreted into the cytoplasm. There is no transmembrane domain and no signal peptide cleavage site, twenty-one Ser phosphorylation sites, seven Thr phosphorylation sites, seven Tyr phosphorylation sites, two N-glycosylation sites, and no O-glycosylation sites. There are 22.25% α-helixes, 31.37% random coil, 32.17% extended peptide chain, and 14.21% β-corner structure. This protein and the SFB/SLF protein from Rosaceae Prunus fruit, including Prunus speciose, share a sequence homology of 59% - 61%;all of the proteins contain an F-box conserved domain, two hypervariable regions HVa, HVb, and two variable regions V1, V2. Furthermore, their phylogenetic relationships are consistent with their traditional classifications. These results were meaningful to reveal the molecular mechanism of Rosa rugose pollination incompatibility and improve the theory and techniques of breeding ornamental Rosa rugose.
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
文摘Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa such as cephalopods,systematic evaluation of reference genes is limited,leading to potential bias.The cuttlefish Sepiella japonica is ecologically and economically important in China,yet previous molecular studies have often relied on single unvalidated reference genes,which may compromise data reliability.This study aimed to systematically evaluate the stability of five commonly used reference genes(18S,ef-1α,ef-1γ,gapdh,andβ-actin)across multiple tissues and sexes of S.japonica,and to identify the most suitable reference genes and optimal number for qPCR normalization.Fifteen to sixteen tissue types were collected from ten healthy adults(five males and five females).Total RNA was extracted,reverse-transcribed,and analyzed by qPCR.Gene stability was assessed using four algorithms(geNorm,NormFinder,BestKeeper,andΔCt)integrated with RefFinder,and the optimal gene number was determined using geNorm pairwise variation(V_(n/n+1)<0.15).Four transcriptome-derived genes(creld2,cd109,acy1,and miox)were used for validation.The C_(t)values of the five genes ranged from 15.47 to 20.83.β-actin and gapdh showed pronounced variability in expression stability among tissues and sexes,indicating their limited suitability for normalization.18S exhibited the highest expression(mean C_(t):15.47-16.29)and lowest variability but displayed sex-biased expression,whereas ef-1αand ef-1γremained consistently stable across most tissues in both sexes,with ef-1αbeing the most robust and showing no sex-related bias.Although specific rankings varied among tissues and sexes,the comprehensive results indicated that ef-1αand ef-1γpossessed the highest overall stability,followed by 18S,whileβ-actin and gapdh were the least stable.The final comprehensive rankings were ef-1γ>ef-1α>18S>gapdh>β-actin(male)and ef-1α>ef-1γ>18S>gapdh>β-actin(female).geNorm analysis(V2/3<0.15)indicated that two genes,mainly ef-1αand ef-1γ,were generally sufficient for reliable normalization in most tissues.Validation confirmed that normalization using the stable ef-1αand ef-1γaccurately reflected the expression differences among tissues,whereasβ-actin and gapdh can bias or confound statistical analyses.ef-1αand ef-1γare identified as the most reliable reference gene combination for qPCR analysis in S.japonica,while 18S can serve as an auxiliary gene for within-sex comparisons.The use ofβ-actin or gapdh alone is not recommended.This study establishes a systematic framework for selecting reliable reference genes in S.japonica,thereby facilitating robust qPCR normalization and providing a foundation for future gene expression research in S.japonica and other cephalopods.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金Supported by the National Natural Science Foundation of China(No.81873686)Natural Science Foundation of Hunan Province(No.2023JJ30715)+4 种基金Scientific Research Project of Hunan Provincial Health Commission(No.A202303018385)Health Research Project of Hunan Provincial Health Commission(No.W20243024)Distinguished Professor of the Lotus Scholars Award Program of Hunan ProvinceSublimation Scholars Project of Central South UniversityWisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(No.YX202109).
文摘AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金supported by the State Key Laboratory of Urban Water Resource and Environment (Harbin Institute of Technology) (No.2022TS13)the key projects of National Natural Science Foundation of China (No.2019YFC0408503)the Key Research Program of Wuhan (No.2022022202015015)。
文摘Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their unique dimensions and structures.Unfortunately,emerging evidence suggests that NMs may facilitate the transmission of ARGs.It is crucial to elucidate how NMs affect the evolution and dissemination of ARGs.The current review comprehensively examines the role of NMs in the widespread transmission of ARGs in aquatic environments and the underlying mechanisms involved in the process.It aims to clarify the effects and mechanisms of NMs on the horizontal gene transfer processes that are associated with ARGs,including the enhancement of cell membrane permeability,the formation of nanopores on membranes,promotion of mutagenesis,and the generation of reactive oxygen species(ROSs).Furthermore,the trade-off between the removal of ARGs and horizontal transfer has been elucidated.The review aspires to guide future research directions,advance knowledge on the implications of NMs in the field of ARGs' transmission,and provide a theoretical foundation for the development of safer and more effective applications of NMs.
基金Supported by the National Natural Science Fundation of China(No.82101107No.81471575).
文摘AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.
基金Supported by the National Natural Science Foundation of China(No.32172979)the Natural Science Foundation of Fujian Province(No.2021J05159)the 2023 Special Program for Promoting High-Quality Development of Marine and Fishery Industry in Fujian Province(No.PJHYF-L-2023-2)。
文摘The Fujian oyster(Crassostrea angulata)is an economically significant shellfish species distributed mainly along the Fujian coast,Southeast China.However,its genetic diversity and structure remain unclear.The main distribution area of the C.angulata is located in Fujian,South China.In total,420 C.angulata were collected from 14 natural habitats(populations)along the Fujian coast,and their genetic diversity and structure were analyzed in the mitochondrial COⅠand nuclear gene ITS2 sequences.Results reveal that all the 14 populations of C.angulata exhibited high levels of genetic diversity,with a total of 57(haplotype diversity:0.811±0.016)and 124(haplotype diversity:0.912±0.007)haplotypes revealed by COⅠand ITS2,respectively.Notably,significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ)population(F_(ST)by COI:0.035-0.142,P<0.05;F_(ST)by ITS2:0.078-0.123,P<0.05)with other populations were observed for the first time,which is also supported by the results of molecular variance analysis(F_(CT)by COⅠ:0.105,P<0.05;F_(CT)by ITS2:0.086,P<0.05)and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree.Furthermore,the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations.In addition,the population dynamics analysis suggests that the C.angulata may have undergone expansion during the third ice age of the Pleistocene.These results provide a reference for the preservation and further genetic improvement of C.angulata.
基金Supported by the Science and Technology Program of Guizhou Provence(Qiankehejichu-ZK[2023]Yiban 271).
文摘[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Quantitative real-time PCR(qRT-PCR)was utilized to analyze the expression patterns of LOX genes at different stages of Botrytis cinerea infection.[Results]The P.patens LOX gene family comprises eight putative proteins,including two 12-LOX-type members and six 13-LOX-type members.Among the eight LOX proteins,PpLOX7 exhibited the lowest molecular weight and shortest amino acid sequence.PpLOX7 was identified as a basic protein with an isoelectric point(pI)of 8.54,while all other members were acidic.Subcellular localization analysis indicated that PpLOX7 was localized to the chloroplast,whereas the remaining members were distributed in the cytoplasm.Secondary structure prediction showed that all eight proteins were predominantly composed of random coils andα-helixes.Chromosomal mapping revealed that the LOX genes were distributed across 7 of the 27 chromosomes in P.patens,with PpLOX1 and PpLOX2 tandemly arranged on chromosome 15.The qRT-PCR analysis demonstrated distinct expression patterns among the eight PpLOX genes following B.cinerea infection.PpLOX1-3 and PpLOX7 were upregulated to varying degrees,suggesting their potential involvement in the early defense response of P.patens against B.cinerea.Notably,PpLOX2 exhibited highly significant differential expression,making it a key candidate for further investigation.[Conclusions]This study provides foundational insights into the functional roles of the LOX gene family in P.patens during biotic stress responses.
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
基金supported by the key project of National Natural Sciences Foundation of China(U22A20551,32030085)the Major Project of Hubei Hongshan Laboratory,China(2021hszd015)+2 种基金the Hubei Province Major Science and Technology Special Project,China(2023BBA002)the National Natural Sciences Foundation of China(U22A20551)the National Natural Science Foundation of China Excellent Youth Fund(32422072)。
文摘Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural products,thereby endangering human health.Extensive studies on Aspergillus fungi have been conducted on growth and development,aflatoxin biosynthesis,and their interactions with environment.Here,we summarized a series of functional genes of the main Aspergillus fungi relative to toxins occurrence in foods,which revealed the signal transduction mechanisms of their involvement in growth and development,toxin production,and response to light,anticipating providing theoretical guidance on developing control and prevention technologies for mycotoxin contamination in agricultural products to ensure food safety.
基金funded by the Major Science and Technology Projects of Zhejiang Province,China(Grant No.2021C02063-5)the Key Research and Development Projects of Hainan Province,China(Grant No.ZDYF2023XDNY086)+2 种基金the State Key Laboratory for Quality and Safety Hazard Factors and Risk Prevention and Control of Agricultural Products Jointly Constructed by the Ministry and the Province,China(Grant No.2010DS700124)the Zhejiang Province Vanguard Leading Goose Project,China(Grant Nos.2023C02055 and 2022C02034)the Jiaxing Nanhu District Science and Technology Plan Project,China(Grant No.2023017).
文摘The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2)is known to regulate aboveground traits,including tiller angle,grain size,and panicle development,its function in root morphogenesis remains uncharacterized.
基金supported partially by the Australian Government through the Australian Research Council Centres of Excellence funding scheme(project CE200100029)。
文摘Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.
基金supported by the grants to Min Qiu and Ming Wang from the National Natural Science Foundation of China(32100160 and 32100044)the grants to Ming Wang from the Jiangsu“Innovative and Entrepreneurial Talent”Program,China(JSSCRC2021510)the grants to Yuanchao Wang from the Chinese Modern Agricultural Industry Technology System(CARS-004-PS14)。
文摘The accuracy of genomic annotation is crucial for subsequent functional investigations;however,computational protocols used in high-throughput annotation of open reading frames(ORFs)can introduce inconsistencies.These inconsistencies,which lead to non-uniform extension or truncation of sequence ends,pose challenges for downstream analyses.Existing strategies to rectify these inconsistencies are time-consuming and labor-intensive,lacking specific approaches.To address this gap,we developed to GC,a tool that integrates genomic annotation with RNA-seq datasets to rectify annotation inconsistencies.Using to GC,we achieved an accuracy of nearly 100%accuracy in correcting inconsistencies in published Phytophthora sojae ORFs.We applied this innovative pipeline to the GPCR-bigrams gene family,which was predicted to have 42 members in the P.sojae genome but lacked experimental validation.By employing to GC,we identified 32 GPCR-bigram ORFs with inconsistencies between previous annotations and to GC-corrected sequences.Notably,among these were 5 genes(GPCR-TKL9,GPCR-TKL15,GPCR-PDE3,GPCR-AC3,and GPCR-AC4)showed substantial inconsistencies.Experimental gene annotation confirmed the effectiveness of to GC,as sequences obtained through cloning matched those annotated by to GC.Importantly,we discovered two novel GPCRs(GPCR-AC3 and GPCR-AC4),which were previously mispredicted as a single gene.CRISPR/Cas9-mediated knockout experiments revealed the involvement of GPCR-AC4 but not GPCR-AC3 in oospore production,further confirming their status as two separate genes.In addition to P.sojae,the reliability of the to GC pipeline in Phytophthora capsici and Pythium ultimum further emphasizes the robustness of this pipeline.Our findings highlight the utility of to GC for reliable gene model correction,facilitating investigations into biological functions and offering potential applications in diverse species analyses.
基金Supported by the Natural Science Foundation of Shandong Province(No.ZR2021QD110)the National Natural Science Foundation of China(No.42106128)。
文摘Due to the unique microstructure and diverse opsin genes of the trinocular compound eye,stomatopoda possess an extraordinary ability to perceive multiple properties of light.They not only can detect natural light(NL)and linearly polarized light(LPL),but also are the only animals capable of recognizing circularly polarized light(CPL).Here,we integrated single-cell RNA sequencing,previously published Illumina data,and in-situ hybridization(ISH)to quantify and localize functional opsin genes in Oratosquilla oratoria,a common stomatopoda species in the China Sea.A total of high-quality 31777 cells were captured for the first time in the O.oratoria compound eye,which were classified into 25 cell subpopulations,and hypothesized that cluster 22 is a critical cell subpopulation responsible for light(whether NL,LPL,or CPL)response in O.oratoria.Furthermore,we propose that the long-wavelengthsensitive opsin gene(lws)gene family,retinol dehydrogenase(rdh),voltage-gated ion channel(vgic),arrestin(arr),and myosin(myo)collectively mediate the light response in O.oratoria.Considering that very few vision-related opsin genes show differential expression in right-handed CPL(RCPL)-vs.-dark(DL),which provides additional evidence that stomatopoda cannot recognize RCPL.Meanwhile,we believe that UV-stimulated scaffold protein A(uvssa)and red pigment concentrating hormone(rpch)play special contributions in the left-handed CPL(LCPL)environment response.ISH revealing that 16 lws,6 middle-wavelength-sensitive(mws),and 2 ultraviolet(uv)opsin genes were expressed in the photoreceptors of the O.oratoria compound eye.Although the inability to determine the functional types of cell subpopulations limits the resolution of opsin genes,these findings systematically elucidate the specific expression patterns of opsin genes in O.oratoria and represent a significant step toward refining the visual ecological theory of O.oratoria and other stomatopod species.
基金funded by the National Natural Science Foundation of China(32071828 and 32471943)the Central Finance Forestry Science and Technology Promotion Demonstration Project,China(Su2024TG04)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Chinapartly supported by the open funds of the National Key Laboratory for Germplasm Innovation&Utilization of Horticultural Crops,China。
文摘Osmanthus fragrans is most famous for its strong aroma,and different varieties have different degrees of fragrance and color.Fragrance and color are important factors affecting the ornamental quality of O.fragrans.Terpenoids are important secondary metabolites in plants,with β-carotene(C40)being the major pigment substance and linalool(C10)being the key aromatic component in O.fragrans.The geranylgeranyl pyrophosphate synthase genes(GGPPSs)play important roles in secondary metabolism in plants.However,the functions of the GGPPS family in floral color and fragrance formation has rarely been reported in O.fragrans.In this study,24 Of GGPPS genes were identified and classified into two subfamilies.The Of GGPPSs showed tissue-specific expression and Of GGPPS13 had highest expression in flowers.The Of GGPPS13 protein was localized to chloroplasts.The transcriptome data of Of GGPPS13 was verified by q RT-PCR and the expression level in‘Wanyingui'with strong aroma was higher than that in‘Zhuangyuanhong'with deep color at different flower development stages.Transient overexpression of Of GGPPS13 in O.fragrans petals showed that Of GGPPS13 increased the β-carotene content,the main color substance of O.fragrans,but decreased the linalool content,the main volatile organic compound(VOC)in the floral aroma of O.fragrans.Of GGPPS13 was indicated as the critical gene related to terpenoid synthesis in the floral aroma and color formation in O.fragrans.Our findings provide gene resources on the GGPPS gene family for further revealing the molecular regulation mechanism of the floral color and aroma formation in O.fragrans.
基金Funding for this research was provided by the Australia Grain Research and Development Corporation(9176507)the Western Crop Genetics Alliance.Jingye Cheng thanks The University of Tasmania,Australia for the scholarship(495802)。
文摘Improved yield potential is the goal of barley domestication and cultivation.During this process,two-and six-rowed barley types emerged and have been utilised in breeding and production.The six-rowed type could produce three times as many grains as its ancestral two-rowed forms,thus dominating barley cultivation for thousands of years.The deficiens form of the two-rowed type,characterised by extremely suppressed lateral spikelets,has gained dominance over the past few decades in barley-growing regions worldwide.We hypothesised that the absence of lateral spikelets in deficiens barley affects spike architecture and spike-related traits,contributing to its superior yield potential of deficiens barley cultivation.Currently,a deficiens barley variety,RGT Planet,is the most popular barley variety in the world.In this study,we used two F_(2) populations derived from crossing RGT Planet with two canonical two-rowed barley and identified the functional allele Vrs1.t1 associated with deficiens morphology.We observed that the Vrs1.t1 allele may contribute to high yield potential by optimising spike architecture through increased spikelet length,grain number,and grain size.Phylogenetic analysis suggests that the deficiens mutation was likely present from the early stages of barley cultivation in the Fertile Crescent and spread to Ethiopia and beyond with agricultural expansion.We conclude that the ancient deficiens allele Vrs1.t1 has been a critical driver for the recent success of modern barley improvement by optimising spike architecture.
