The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are imm...The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are immunological,and others associated as idiopathic,are undiagnosed by all possible means.Some of the rare diseases are congenital in nature,passing from the parent to the child.Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent.There is a search for newer treatments for such diseases,which is called genomic medicine.Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual.This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use.In the developing era of precision medicine,genomics,epigenomics,environmental exposure,and other data would be used to more accurately guide individual diagnosis and treatment.Genomic medicine is already making an impact in the fields of oncology,pharmacology,rare,infectious and many undiagnosed diseases.It is beginning to fuel new approaches in certain medical specialties.Oncology is at the leading edge of incorporating genomics,as diagnostics for genetic and genomic markers are increasingly included in cancer screening,and to guide tailored treatment strategies.Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways,including genetic testing(hereditary pancreatitis and hereditary gastrointestinal cancer syndromes).Genetic testing can also help subtype diseases,such as classifying pancreatitis as idiopathic or hereditary.Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries.Gene therapy strategies include gene addition,gene editing,messenger RNA therapy,and gene silencing.Understanding genetic determinants,advances in genetics,have led to a better understanding of the genetic factors that contribute to human disease.Family-member risk stratification and genetic diagnosis can help identify family members who are at risk,which can lead to preventive treatments,lifestyle recommendations,and routine follow ups.Selecting target genes helps identify the gene targets associated with each gastrointestinal disease.Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease,gastroesophageal reflux disease,non-alcoholic fatty liver disease,and irritable bowel syndrome.With advancing tools and technology,research in the search of newer and individualized treatment,genes and genetic medicines are expected to play a significant role in human health and gastroenterology.展开更多
Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,wi...Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.展开更多
Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance protei...Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance proteins are a diverse group of molecules that play crucial roles in axon and dendrite growth during nervous system development.Increasing evidence highlights their regulatory functions in spinal cord injury.This review provides a brief overview of the modulation patterns of key neuronal guidance proteins in neuronal axon growth during nervous system formation and subsequently focuses on their roles in neuronal regeneration and functional recovery following spinal cord injury.Neuronal guidance proteins include,but are not limited to,semaphorins and their receptors,plexins;netrins and their receptors,deleted in colorectal cancer and UNC5;Eph receptors and their ligands,ephrins;Slit and its receptor,Robo;repulsive guidance molecules and their receptor,neogenin;Wnt proteins and their receptor,Frizzled;and protocadherins.Localized Netrin-1 at the injury site inhibits motor axon regeneration after adult spinal cord injury while promoting oligodendrocyte growth.Slit2 enhances synapse formation in the injured spinal cord of rats.EphA7 regulates acute apoptosis in the early pathophysiological stages of spinal cord injury,while ephrinA1 plays a role in the nervous system’s injury response,with its reduced expression leading to impaired motor function in rats.EphA3 is upregulated following spinal cord injury,promoting an inhibitory environment for axonal regeneration.After spinal cord injury,bidirectional activation of ephrinB2 and EphB2 in astrocytes and fibroblasts results in the formation of a dense astrocyte-meningeal fibroblast scar.EphB1/ephrinB1 signaling mediates pain processing in spinal cord injury by regulating calpain-1 and caspase-3 in neurons.EphB3 expression increases in white matter after spinal cord injury,further inhibiting axon regeneration.Sema3A,expressed by neurons and fibroblasts in the scar surrounding the injury,inhibits motor neuron and sensory nerve growth after spinal cord injury.Sema4D suppresses neuronal axon myelination and axon regeneration,while its inhibition significantly enhances axon regeneration and motor recovery.Sema7A is involved in glial scar formation and may influence serotonin channel remodeling,thereby affecting motor coordination.Given these findings,the local or systemic application of neuronal guidance proteins represents a promising avenue for spinal cord injury treatment.展开更多
Stichopus chloronotus is a tropical sea cucumber with facultative asexual reproduction in the Indo-Western Pacific,yet its wild populations are decreasing due to extensive harvesting.Understanding the species’genetic...Stichopus chloronotus is a tropical sea cucumber with facultative asexual reproduction in the Indo-Western Pacific,yet its wild populations are decreasing due to extensive harvesting.Understanding the species’genetic characteristics is essential for effective management and conservation.To develop novel microsatellite markers and assess the genetic diversity,clonality,and genetic structure of eight populations of S.chloronotus in the South China Sea,193 individuals from eight populations across Wuzhizhou and Fenjiezhou(Boundary)islands were analyzed using nine newly developed microsatellite markers and five previously established markers.RNA-Seq was employed to obtained 62662 unigenes and identified 16926 microsatellite loci.Fourteen polymorphic microsatellite loci were developed,of which 11 were highly polymorphic(polymorphic information content>0.5).The number of alleles(N_(a))ranged from 3 to 6 per locus,and the average Shannon diversity index(I)was 1.107.All the populations exhibited asexual reproduction,with regional variations in reproductive modes.Asexual reproduction was predominant in the northwestern Wuzhizhou Island population(SY 7)and the Fenjiezhou Island population(LS 8),where four and five predominant clones represented more than 89%of the individuals,which led to reduced genetic diversity.Overall,genetic diversity was moderately low,with significant genetic differentiation among populations(F_(ST)=0.33;P<0.001),suggesting limited gene flow(the number of migrants(N_(m))<1).These findings highlight the role of reproductive strategies in shaping fine-scale genetic differentiation in S.chloronotus.The limited recruitment success of sexually produced larvae and habitat heterogeneity likely constrain clone dispersal,contributing to distinct genetic restructuring.This study provided key insights into the interplay between reproductive strategies and genetic patterns in sea cucumbers,offering a scientific basis for targeted conservation efforts.展开更多
The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-inf...The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.展开更多
HPPD(4-hydroxyphenylpyruvate dioxygenase)inhibitor are widely used in agriculture due to their high efficacy and environmental friendliness.However,many important crops,such as rice,wheat,and soybean,are naturally sen...HPPD(4-hydroxyphenylpyruvate dioxygenase)inhibitor are widely used in agriculture due to their high efficacy and environmental friendliness.However,many important crops,such as rice,wheat,and soybean,are naturally sensitive to these herbicides.In this study,we employed a directed evolution strategy to enhance the metabolic capacity of OsHSL2,OsHSL4,OsHSL6,and SbHSL1 proteins toward HPPD inhibitors,providing a new technological approach as well as theoretical foundation for molecular breeding of herbicide-resistant crops.By combining AlphaFold 3 protein models with crystal structures,we systematically redesigned key residues to resemble the active residues found in HIS1.Catalytic activity assays demonstrated that specific mutations significantly improved the metabolic activity of HSLs proteins toward various HPPD inhibitors.Notably,the OsHSL2-M4 mutant exhibited enhanced metabolic activity for BBC-OH and methyl-benquitrione,while the OsHSL4-M5 mutant completely metabolized BBC-OH and topramezone.Additionally,the SbHSL1-M4 mutant showed significant improvement in the metabolism of BBC-OH and several other herbicides,providing strong evidence to support the use of structure-guided HSL mutations to enhance crop resistance to HPPD inhibitors.展开更多
Genetically encoded biosensors are powerful tools for monitoring plant proteins,which could offer high spatial and temporal resolution and help reveal the molecular mechanisms underlying plant growth and stress respon...Genetically encoded biosensors are powerful tools for monitoring plant proteins,which could offer high spatial and temporal resolution and help reveal the molecular mechanisms underlying plant growth and stress responses.However,a comprehensive review focused on the spatiotemporal monitoring of plant proteins using these biosensors is still lacking.This review highlights key advancements in the field,evaluates the strengths and limitations of current biosensors,and discusses their applications for tracking plant protein dynamics.We aim to provide a thorough understanding of genetically encoded biosensors for plant proteins,promote the development of these technologies,and foster deeper insights into molecular mechanisms in plant cells.Future research should prioritize overcoming challenges such as interference from plant autofluorescence and enhancing the sensitivity of biosensors,particularly in complex cellular compartments like chloroplasts and cell walls,to further improve spatial and temporal resolution.展开更多
In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted t...In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted the critical role of epigenetic modifications in diabetic wound healing,with particular emphasis on DNA and RNA methylation pathways.This editorial discusses the findings of Xiao et al,who identified the Wilms tumor 1-associated protein(WTAP)-DNA methyltransferase 1(DNMT1)axis as a pivotal regulator of endothelial dys-function in DFUs.WTAP,a regulatory subunit of N6-methyladenosine(m6A)methyltransferase,is upregulated under high-glucose conditions and drives the excessive expression of DNMT1 via m6A modification.This contributes to im-paired angiogenesis,reduced cell viability,and delayed wound closure.WTAP knockdown restored endothelial function and significantly improved wound healing in a diabetic mouse model.Furthermore,DNMT1 overexpression ab-rogated the benefits of WTAP suppression,confirming its downstream effector role.Thus,targeting the WTAP-DNMT1 axis provides a new avenue for DFU management.Moreover,epigenetic interventions that modulate both the m6A and RNA methylation pathways could restore endothelial function and enhance tissue repair in patients with diabetes.展开更多
One hundred and fifteen varieties （including cultivars and lines） with different ecotypes in japonica rice （Oryza sativa L.） were analyzed for endosperm storage proteins by sodium dodecyl sulfate polyacrylamide ge...One hundred and fifteen varieties （including cultivars and lines） with different ecotypes in japonica rice （Oryza sativa L.） were analyzed for endosperm storage proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis （SDS-PAGE） to estimate their genetic diversity for the purpose of genetic improving and variety identification. Nineteen types of profile were identified according to 1） presence/absence of 65 kDa bands, 2） staining intensity of 70, 60, 57, 37-39, 22-23, 13 and 10 kDa bands, 3） migration velocity of 35 kDa （α-4） and 4） band number at 57 kDa location. An unweighted-pair group average method with arithmetic mean （UPGMA） dendregram based on the cluster analysis of genetic similarity of the protein bands showed a small genetic variation among the tested materials, with the similarity coefficients varying between 0.75 and 1.00. Three distinct groups were identified from the cluster analysis of the rice varieties studied at the similarity coefficient level of 0.894. The first group included eight varieties with high amylose content, the second group contained fifteen varieties with high protein content, and the third group had the remaining ninety-two varieties, which accounted for 80% of the total materials. Clear relationship between ecotypes distinguished by maturity and groups revealed by cluster analysis was not found in this study. Only the group of high amylose linked with medium-maturity medium japonica ecotype. The bands of 70 kDa and 65 kDa can be used as protein markers to identify F1 seed purity of japonica hybrid rice Liuyanyou 422.展开更多
The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively partici...The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.展开更多
Rice storage proteins(RSPs)are plant proteins with high nutritional quality.As the second largest type of storage substance in rice,it is the main source of protein intake for people who consume rice as a staple food....Rice storage proteins(RSPs)are plant proteins with high nutritional quality.As the second largest type of storage substance in rice,it is the main source of protein intake for people who consume rice as a staple food.The content and type of RSPs affect the appearance,processing quality and eating quality of rice.These effects involve the distribution of RSPs in rice grains as well as the interactions of RSPs with other components such as starch in rice grains.In the past two decades,some progress has been made in the genetic improvement of RSPs.However,the determination mechanism of protein content and composition in rice is still unclear,and the mechanism of the effect of RSPs on rice quality has not been elucidated.In this review,the composition,biosynthesis and distribution of RSPs,and quantitative trait loci mapping and cloning of RSP genes are summarized,the research progress of the influence of RSPs and their components on rice quality are reviewed,and the research directions in the future are proposed.展开更多
The genetic variation of seed proteins was assayed by SDSPAGE for 24 cultivars belonging to 5 species in Vigna and 7 species in its 7 relative genera cultivated in China. There were 48 polymorphic subunit bands discri...The genetic variation of seed proteins was assayed by SDSPAGE for 24 cultivars belonging to 5 species in Vigna and 7 species in its 7 relative genera cultivated in China. There were 48 polymorphic subunit bands discriminated from electrophoretic profiles. Two dendrograms were constructed by UPGMA cluster analyses using PHYLIP3.6 respectively. Variation among genera or species was larger than that among lower taxonomic categories level. Little variation among cuhivars of yardlong bean （Vigna sesquipedalis ） and small variation of lablab （ Lablab purpureus）, pea （Pisum sativum）, or sword bean （Canavalia gladiata）, but large variation of soybean or rice bean in their origin of China were all revealed. The seed proteins profiles of traditionally regarded as typical species in Vigna such as yardlong bean, rice bean and small bean were more similar than mungbean （Vigna radiata） and black gram （Vigna mungo） were. Mungbean and black gram had distinct seed proteins pattern, they should be of two species.展开更多
AIM： To develop a Brown Norway （BN） rat model to determine the potential allergenicity of novel proteins in genetically modified food. METHODS： The allergenicity of different proteins were compared, including oval...AIM： To develop a Brown Norway （BN） rat model to determine the potential allergenicity of novel proteins in genetically modified food. METHODS： The allergenicity of different proteins were compared, including ovalbumin （OVA）, a potent respiratory and food allergen, bovine serum albumin （BSA）, a protein that is considered to have a lesser allergenic potential, and potato acid phosphatase （PAP）, a non-allergenic protein when administered to BN rats via different routes of exposure （intraperitoneally or by gavage）. IgG and IgE antibody responses were determined by ELISA and PEA, respectively. An immunoassay kit was used to determine the plasma histamine level. In addition, possible systemic effect of allergens was investigated by monitoring blood pressure. RESULTS： OVA provoked very vigorous protein-specific IgG and IgE responses, low grade protein-specific IgG and IgE responses were elicited by BSA, while by neither route did PAP elicit anything. In either routes of exposure, plasma histamine level in BN rats sensitized with OVA was higher than that of BSA or PAP. In addition, an oral challenge with BSA and PAP did not induce any effect on blood pressure, while a temporary drop in systolic blood pressure in few animals of each routes of exposure was found by an oral challenge with OVA. CONCLUSION： BN rat model might be a useful and predictive animal model to study the potential allergenicity of novel food proteins.展开更多
The following is the theoretical and experimental analysis of the role of the third nucleotide in codons during protein biosynthesis. Its role is largely enhanced compared to the existing understanding. Third nucleoti...The following is the theoretical and experimental analysis of the role of the third nucleotide in codons during protein biosynthesis. Its role is largely enhanced compared to the existing understanding. Third nucleotide functionally and symmetrically divides codon families in 32 synonyms and 32 SYnonymous-HOMonymous hybrid codons—SYHOMs. Wherein, the syhoms function is to initiate nonlocal ribosome analysis of mRNA, representing real context in DNA language. Such analysis is a natural necessity for selection of one amino acid from two different amino acids, and between amino acids or a stop position, in situations when a ribosome interacts with syhom codons which have dual coding. This was theoretically substantiated earlier?[1] [2] [3]. Experimental work [4] confirmed this theory: It was demonstrated that two different amino acids, selenocysteine and cysteine, are coded by a single UGA-syhom-codon for Euplotes crassus infusoria. This result does not call into question the dogma of unambiguity of amino acids and stop position coding by the cells genome, but it requires amendments to the existing model of genetic coding. These amendments are based on an enhanced understanding of the special linguistic/semantic role of the third nucleotide in codons and on the acceptance of the idea of real, rather than metaphorical, textuality of protein genes (mRNA). Such comprehension of the speech-similarity of genes (mRNA) and the role that third nucleotide in codons plays in this, leads to a simple statement about the quasi-consciousness (biocomputing) of the protein-synthesizing-system and its ability to recognize the context (meaning) of mRNA to make the correct choice of amino acids and stops in a syhom situation, based on the meanings of gene texts (mRNA).展开更多
Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal ves...Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal vesicle oocytes.In the current study,we found that nuclear speckles(NSs),a subnuclear structure mainly composed of serine-arginine(SR)proteins,changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregated pattern in SN oocytes.We also found that the SR protein-specific kinase 1(SRPK1),an enzyme that phosphorylates SR proteins,co-localized with NSs at the SN stage,and that NSN oocytes failed to transition to SN oocytes after the inhibition of SRPK1 activity.Furthermore,the typical structure of the chromatin ring around the nucleolus in SN oocytes collapsed after treatment with an SRPK1 inhibitor.Mechanistically,phosphorylated SR proteins were found to be related to chromatin as shown by a salt extraction experiment,and in situ DNaseⅠassay showed that the accessibility of chromatin was enhanced in SN oocytes when SRPK1 was inhibited,accompanied by a decreased repressive modification on histone and the abnormal recurrence of a transcriptional signal.In conclusion,our results indicated that SRPK1-regulated phosphorylation of SR proteins was involved in the NSN-SN transition and played an important role in maintaining the condensed nucleus of SN oocytes via interacting with chromatin.展开更多
Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb rep...Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb repressive complexes 1 and 2 （PRC1 and PRC2）, are required for maintaining the sternness of embryonic stem cells and many types of adult stem cells. The spectra of target genes for PRCs are dynamically changing with cell differentiation, which is essential for proper decisions on cell fate during developmental processes, Chromobox （CBX） family proteins are canonical components in PRC1, responsible for targeting PRC1 to the chromatin. Recent studies highlight the function specifications among CBX family members in undifferentiated and differentiated stem cells, which reveal the interplay between compositional diversity and functional specificity of PRCI. In this review, we summarize the current knowledge about targeting and functional mechanisms of PRCs, emphasizing the recent breakthroughs related to CBX proteins under a number of physiological and pathological conditions.展开更多
Bone morphogenetic proteins(BMPs)are a family of potent,multifunctional growth factors belonging to transforming growth factor-(TGF-).They are highly conservative in structures.Over 20 members of BMPs with varying fun...Bone morphogenetic proteins(BMPs)are a family of potent,multifunctional growth factors belonging to transforming growth factor-(TGF-).They are highly conservative in structures.Over 20 members of BMPs with varying functions such as embryogenesis,skeletal formation,hematopoiesis and neurogenesis have been identified in human body.BMPs are unique growth factors that can induce the formation of bone tissue individually.BMPs can induce the differentiation of bone marrow mesenchymal stem cells into osteoblastic lineage and promote the proliferation of osteoblasts and chondrocytes.BMPs stimulate the target cells by specific membrane-bound receptors and signal transduced through mothers against decapentaplegic(Smads)and mitogen activated protein kinase(MAPK)pathways.It has been demonstrated that BMP-2,BMP-4,BMP-6,BMP-7,and BMP-9 play an important role in bone formation.This article focuses on the molecular characterization of BMPs family members,mechanism of osteogenesis promotion,related signal pathways of osteogenic function,relationships between structure and osteogenetic activity,and the interactions among family members at bone formation.展开更多
Bone morphogenetic proteins(BMPs)are the largest subfamily of the transforming growth factor-βsuperfamily,and they play important roles in the development of numerous organs,including the inner ear.The inner ear is a...Bone morphogenetic proteins(BMPs)are the largest subfamily of the transforming growth factor-βsuperfamily,and they play important roles in the development of numerous organs,including the inner ear.The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance.Here,we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.展开更多
Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face in...Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.展开更多
The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval ...The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval at the B1 locus on chromosome 5A,which included the candidate gene encoding a zinc finger protein(TraesCS5A01G542800)as an awn length inhibitor(ALI).The Ali-A1 allele for the awnless trait showed abundant sequence differences in the promoter regions compared to the ali-A1 allele for the long-awn trait.The results of the swap experiment on the promoters from the two ALI-A1 alleles showed that the two promoters caused a difference in the protein level,indicating the gene was regulated at the transcript level.However,the ali-A1 allele contained an SNP that caused a premature stop codon in its coding region,resulting in a truncated protein compared to the functional Ali-A1 protein.The Ali-A1 protein contained two ethylene-responsive element binding factor-associated amphiphilic repression(EAR)motifs,one at the N terminus(EAR-N)and the other at the C terminus(EAR-C),and they were involved in interactions with the wheat co-repressor protein TOPLESS(TPL1).The ali-A1 protein retained the EAR-N motif but lost the EAR-C motif,resulting in the attenuated ability to interact with TPL1.The tpl1 mutant produced a longer awn compared to the wild type.Ali-A1 repressed the transcription of two downstream genes,TaLRP-A1 and TaARF-B1,involved in endogenous auxin concentrations and auxin responses in wheat.We concluded that the awn length is regulated not only by the ALI-A1 gene at transcript levels but also by Ali-A1 and TPL1 at the protein level in wheat.展开更多
文摘The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are immunological,and others associated as idiopathic,are undiagnosed by all possible means.Some of the rare diseases are congenital in nature,passing from the parent to the child.Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent.There is a search for newer treatments for such diseases,which is called genomic medicine.Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual.This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use.In the developing era of precision medicine,genomics,epigenomics,environmental exposure,and other data would be used to more accurately guide individual diagnosis and treatment.Genomic medicine is already making an impact in the fields of oncology,pharmacology,rare,infectious and many undiagnosed diseases.It is beginning to fuel new approaches in certain medical specialties.Oncology is at the leading edge of incorporating genomics,as diagnostics for genetic and genomic markers are increasingly included in cancer screening,and to guide tailored treatment strategies.Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways,including genetic testing(hereditary pancreatitis and hereditary gastrointestinal cancer syndromes).Genetic testing can also help subtype diseases,such as classifying pancreatitis as idiopathic or hereditary.Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries.Gene therapy strategies include gene addition,gene editing,messenger RNA therapy,and gene silencing.Understanding genetic determinants,advances in genetics,have led to a better understanding of the genetic factors that contribute to human disease.Family-member risk stratification and genetic diagnosis can help identify family members who are at risk,which can lead to preventive treatments,lifestyle recommendations,and routine follow ups.Selecting target genes helps identify the gene targets associated with each gastrointestinal disease.Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease,gastroesophageal reflux disease,non-alcoholic fatty liver disease,and irritable bowel syndrome.With advancing tools and technology,research in the search of newer and individualized treatment,genes and genetic medicines are expected to play a significant role in human health and gastroenterology.
基金financially supported by the Hainan Province Science and Technology Special Fund(Grant no:ZDYF2024XDNY187).
文摘Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.
基金supported by Shenzhen University General Hospital Scientific Research Project,No.SUGH2019QD002Shenzhen Science and Technology Development Foundation,No.20220810173216001(both to ZS).
文摘Spinal cord injury is a severe neurological condition with limited neuronal regeneration and functional recovery.Currently,no effective treatments exist to improve spinal cord injury prognosis.Neuronal guidance proteins are a diverse group of molecules that play crucial roles in axon and dendrite growth during nervous system development.Increasing evidence highlights their regulatory functions in spinal cord injury.This review provides a brief overview of the modulation patterns of key neuronal guidance proteins in neuronal axon growth during nervous system formation and subsequently focuses on their roles in neuronal regeneration and functional recovery following spinal cord injury.Neuronal guidance proteins include,but are not limited to,semaphorins and their receptors,plexins;netrins and their receptors,deleted in colorectal cancer and UNC5;Eph receptors and their ligands,ephrins;Slit and its receptor,Robo;repulsive guidance molecules and their receptor,neogenin;Wnt proteins and their receptor,Frizzled;and protocadherins.Localized Netrin-1 at the injury site inhibits motor axon regeneration after adult spinal cord injury while promoting oligodendrocyte growth.Slit2 enhances synapse formation in the injured spinal cord of rats.EphA7 regulates acute apoptosis in the early pathophysiological stages of spinal cord injury,while ephrinA1 plays a role in the nervous system’s injury response,with its reduced expression leading to impaired motor function in rats.EphA3 is upregulated following spinal cord injury,promoting an inhibitory environment for axonal regeneration.After spinal cord injury,bidirectional activation of ephrinB2 and EphB2 in astrocytes and fibroblasts results in the formation of a dense astrocyte-meningeal fibroblast scar.EphB1/ephrinB1 signaling mediates pain processing in spinal cord injury by regulating calpain-1 and caspase-3 in neurons.EphB3 expression increases in white matter after spinal cord injury,further inhibiting axon regeneration.Sema3A,expressed by neurons and fibroblasts in the scar surrounding the injury,inhibits motor neuron and sensory nerve growth after spinal cord injury.Sema4D suppresses neuronal axon myelination and axon regeneration,while its inhibition significantly enhances axon regeneration and motor recovery.Sema7A is involved in glial scar formation and may influence serotonin channel remodeling,thereby affecting motor coordination.Given these findings,the local or systemic application of neuronal guidance proteins represents a promising avenue for spinal cord injury treatment.
基金Supported by the National Key Research and Development Program of China(Nos.2022YFD2401305,2022YFD2401303)the National Natural Science Foundation of China(Nos.42166005,42076097)。
文摘Stichopus chloronotus is a tropical sea cucumber with facultative asexual reproduction in the Indo-Western Pacific,yet its wild populations are decreasing due to extensive harvesting.Understanding the species’genetic characteristics is essential for effective management and conservation.To develop novel microsatellite markers and assess the genetic diversity,clonality,and genetic structure of eight populations of S.chloronotus in the South China Sea,193 individuals from eight populations across Wuzhizhou and Fenjiezhou(Boundary)islands were analyzed using nine newly developed microsatellite markers and five previously established markers.RNA-Seq was employed to obtained 62662 unigenes and identified 16926 microsatellite loci.Fourteen polymorphic microsatellite loci were developed,of which 11 were highly polymorphic(polymorphic information content>0.5).The number of alleles(N_(a))ranged from 3 to 6 per locus,and the average Shannon diversity index(I)was 1.107.All the populations exhibited asexual reproduction,with regional variations in reproductive modes.Asexual reproduction was predominant in the northwestern Wuzhizhou Island population(SY 7)and the Fenjiezhou Island population(LS 8),where four and five predominant clones represented more than 89%of the individuals,which led to reduced genetic diversity.Overall,genetic diversity was moderately low,with significant genetic differentiation among populations(F_(ST)=0.33;P<0.001),suggesting limited gene flow(the number of migrants(N_(m))<1).These findings highlight the role of reproductive strategies in shaping fine-scale genetic differentiation in S.chloronotus.The limited recruitment success of sexually produced larvae and habitat heterogeneity likely constrain clone dispersal,contributing to distinct genetic restructuring.This study provided key insights into the interplay between reproductive strategies and genetic patterns in sea cucumbers,offering a scientific basis for targeted conservation efforts.
基金supported by the National Natural Science Foundation of China (No.22007008)the LiaoNing Revitalization Talents Program (No.XLYC1907021)the Fundamental Research Funds for the Central Universities (Nos.DUT23YG120,DUT19RC(3)009)。
文摘The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.
基金supported by the National Key Research and Development Program of China(No.2024YFE0214300)Hubei Provincial Science and Technology Plan Project(2022BEC051)selfdetermined research funds of CCNU from the colleges'basic research and operation of MOE(No.CCNU24JCPT023).
文摘HPPD(4-hydroxyphenylpyruvate dioxygenase)inhibitor are widely used in agriculture due to their high efficacy and environmental friendliness.However,many important crops,such as rice,wheat,and soybean,are naturally sensitive to these herbicides.In this study,we employed a directed evolution strategy to enhance the metabolic capacity of OsHSL2,OsHSL4,OsHSL6,and SbHSL1 proteins toward HPPD inhibitors,providing a new technological approach as well as theoretical foundation for molecular breeding of herbicide-resistant crops.By combining AlphaFold 3 protein models with crystal structures,we systematically redesigned key residues to resemble the active residues found in HIS1.Catalytic activity assays demonstrated that specific mutations significantly improved the metabolic activity of HSLs proteins toward various HPPD inhibitors.Notably,the OsHSL2-M4 mutant exhibited enhanced metabolic activity for BBC-OH and methyl-benquitrione,while the OsHSL4-M5 mutant completely metabolized BBC-OH and topramezone.Additionally,the SbHSL1-M4 mutant showed significant improvement in the metabolism of BBC-OH and several other herbicides,providing strong evidence to support the use of structure-guided HSL mutations to enhance crop resistance to HPPD inhibitors.
基金the National Key Research and Development Program of China(2021YFD1700102)the National Science Fund for Distinguished Young Scholars(22422702)+1 种基金Knowledge Innovation Program of Wuhan-Basic Research(No.2022013301015174)Prof.Alexander Jones at Cambridge University for his guidance and contribution.
文摘Genetically encoded biosensors are powerful tools for monitoring plant proteins,which could offer high spatial and temporal resolution and help reveal the molecular mechanisms underlying plant growth and stress responses.However,a comprehensive review focused on the spatiotemporal monitoring of plant proteins using these biosensors is still lacking.This review highlights key advancements in the field,evaluates the strengths and limitations of current biosensors,and discusses their applications for tracking plant protein dynamics.We aim to provide a thorough understanding of genetically encoded biosensors for plant proteins,promote the development of these technologies,and foster deeper insights into molecular mechanisms in plant cells.Future research should prioritize overcoming challenges such as interference from plant autofluorescence and enhancing the sensitivity of biosensors,particularly in complex cellular compartments like chloroplasts and cell walls,to further improve spatial and temporal resolution.
基金Supported by the Kuwait Foundation for the Advancement of Sciences and Dasman Diabetes Institute,No.RACB-2021-007.
文摘In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted the critical role of epigenetic modifications in diabetic wound healing,with particular emphasis on DNA and RNA methylation pathways.This editorial discusses the findings of Xiao et al,who identified the Wilms tumor 1-associated protein(WTAP)-DNA methyltransferase 1(DNMT1)axis as a pivotal regulator of endothelial dys-function in DFUs.WTAP,a regulatory subunit of N6-methyladenosine(m6A)methyltransferase,is upregulated under high-glucose conditions and drives the excessive expression of DNMT1 via m6A modification.This contributes to im-paired angiogenesis,reduced cell viability,and delayed wound closure.WTAP knockdown restored endothelial function and significantly improved wound healing in a diabetic mouse model.Furthermore,DNMT1 overexpression ab-rogated the benefits of WTAP suppression,confirming its downstream effector role.Thus,targeting the WTAP-DNMT1 axis provides a new avenue for DFU management.Moreover,epigenetic interventions that modulate both the m6A and RNA methylation pathways could restore endothelial function and enhance tissue repair in patients with diabetes.
文摘One hundred and fifteen varieties （including cultivars and lines） with different ecotypes in japonica rice （Oryza sativa L.） were analyzed for endosperm storage proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis （SDS-PAGE） to estimate their genetic diversity for the purpose of genetic improving and variety identification. Nineteen types of profile were identified according to 1） presence/absence of 65 kDa bands, 2） staining intensity of 70, 60, 57, 37-39, 22-23, 13 and 10 kDa bands, 3） migration velocity of 35 kDa （α-4） and 4） band number at 57 kDa location. An unweighted-pair group average method with arithmetic mean （UPGMA） dendregram based on the cluster analysis of genetic similarity of the protein bands showed a small genetic variation among the tested materials, with the similarity coefficients varying between 0.75 and 1.00. Three distinct groups were identified from the cluster analysis of the rice varieties studied at the similarity coefficient level of 0.894. The first group included eight varieties with high amylose content, the second group contained fifteen varieties with high protein content, and the third group had the remaining ninety-two varieties, which accounted for 80% of the total materials. Clear relationship between ecotypes distinguished by maturity and groups revealed by cluster analysis was not found in this study. Only the group of high amylose linked with medium-maturity medium japonica ecotype. The bands of 70 kDa and 65 kDa can be used as protein markers to identify F1 seed purity of japonica hybrid rice Liuyanyou 422.
文摘The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.
基金supported by the Scientific Research Foundation of Hunan Provincial Education Department,China(Grant Nos.19A532,19B594 and 19B597)National Key Research and Development Program of China(Grant No.2022YFD2101303)+1 种基金Hunan Key Research and Development Plan Project,China(Grant No.2022NK2032)the Program for Science&Technology Innovation Platform of Hunan Province in China(Grant Nos.2019TP1028 and 2019TP1029).
文摘Rice storage proteins(RSPs)are plant proteins with high nutritional quality.As the second largest type of storage substance in rice,it is the main source of protein intake for people who consume rice as a staple food.The content and type of RSPs affect the appearance,processing quality and eating quality of rice.These effects involve the distribution of RSPs in rice grains as well as the interactions of RSPs with other components such as starch in rice grains.In the past two decades,some progress has been made in the genetic improvement of RSPs.However,the determination mechanism of protein content and composition in rice is still unclear,and the mechanism of the effect of RSPs on rice quality has not been elucidated.In this review,the composition,biosynthesis and distribution of RSPs,and quantitative trait loci mapping and cloning of RSP genes are summarized,the research progress of the influence of RSPs and their components on rice quality are reviewed,and the research directions in the future are proposed.
基金Supported by Scientific Research Programof Wuhan Municipali-ty, Hubei Province ,China (20015007090) .
文摘The genetic variation of seed proteins was assayed by SDSPAGE for 24 cultivars belonging to 5 species in Vigna and 7 species in its 7 relative genera cultivated in China. There were 48 polymorphic subunit bands discriminated from electrophoretic profiles. Two dendrograms were constructed by UPGMA cluster analyses using PHYLIP3.6 respectively. Variation among genera or species was larger than that among lower taxonomic categories level. Little variation among cuhivars of yardlong bean （Vigna sesquipedalis ） and small variation of lablab （ Lablab purpureus）, pea （Pisum sativum）, or sword bean （Canavalia gladiata）, but large variation of soybean or rice bean in their origin of China were all revealed. The seed proteins profiles of traditionally regarded as typical species in Vigna such as yardlong bean, rice bean and small bean were more similar than mungbean （Vigna radiata） and black gram （Vigna mungo） were. Mungbean and black gram had distinct seed proteins pattern, they should be of two species.
基金Supported by the State 863 Projects, No. 2001AA212291 and 2002AA212041 and the State 973 Project, No. 001CB109007
文摘AIM： To develop a Brown Norway （BN） rat model to determine the potential allergenicity of novel proteins in genetically modified food. METHODS： The allergenicity of different proteins were compared, including ovalbumin （OVA）, a potent respiratory and food allergen, bovine serum albumin （BSA）, a protein that is considered to have a lesser allergenic potential, and potato acid phosphatase （PAP）, a non-allergenic protein when administered to BN rats via different routes of exposure （intraperitoneally or by gavage）. IgG and IgE antibody responses were determined by ELISA and PEA, respectively. An immunoassay kit was used to determine the plasma histamine level. In addition, possible systemic effect of allergens was investigated by monitoring blood pressure. RESULTS： OVA provoked very vigorous protein-specific IgG and IgE responses, low grade protein-specific IgG and IgE responses were elicited by BSA, while by neither route did PAP elicit anything. In either routes of exposure, plasma histamine level in BN rats sensitized with OVA was higher than that of BSA or PAP. In addition, an oral challenge with BSA and PAP did not induce any effect on blood pressure, while a temporary drop in systolic blood pressure in few animals of each routes of exposure was found by an oral challenge with OVA. CONCLUSION： BN rat model might be a useful and predictive animal model to study the potential allergenicity of novel food proteins.
文摘The following is the theoretical and experimental analysis of the role of the third nucleotide in codons during protein biosynthesis. Its role is largely enhanced compared to the existing understanding. Third nucleotide functionally and symmetrically divides codon families in 32 synonyms and 32 SYnonymous-HOMonymous hybrid codons—SYHOMs. Wherein, the syhoms function is to initiate nonlocal ribosome analysis of mRNA, representing real context in DNA language. Such analysis is a natural necessity for selection of one amino acid from two different amino acids, and between amino acids or a stop position, in situations when a ribosome interacts with syhom codons which have dual coding. This was theoretically substantiated earlier?[1] [2] [3]. Experimental work [4] confirmed this theory: It was demonstrated that two different amino acids, selenocysteine and cysteine, are coded by a single UGA-syhom-codon for Euplotes crassus infusoria. This result does not call into question the dogma of unambiguity of amino acids and stop position coding by the cells genome, but it requires amendments to the existing model of genetic coding. These amendments are based on an enhanced understanding of the special linguistic/semantic role of the third nucleotide in codons and on the acceptance of the idea of real, rather than metaphorical, textuality of protein genes (mRNA). Such comprehension of the speech-similarity of genes (mRNA) and the role that third nucleotide in codons plays in this, leads to a simple statement about the quasi-consciousness (biocomputing) of the protein-synthesizing-system and its ability to recognize the context (meaning) of mRNA to make the correct choice of amino acids and stops in a syhom situation, based on the meanings of gene texts (mRNA).
基金National Natural Science Foundation of China(Grant Nos.32070838 and 82301874)Open Fund of State Key Laboratory of Reproductive Medicine,Nanjing Medical University(Grant No.SKLRM K202102)。
文摘Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal vesicle oocytes.In the current study,we found that nuclear speckles(NSs),a subnuclear structure mainly composed of serine-arginine(SR)proteins,changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregated pattern in SN oocytes.We also found that the SR protein-specific kinase 1(SRPK1),an enzyme that phosphorylates SR proteins,co-localized with NSs at the SN stage,and that NSN oocytes failed to transition to SN oocytes after the inhibition of SRPK1 activity.Furthermore,the typical structure of the chromatin ring around the nucleolus in SN oocytes collapsed after treatment with an SRPK1 inhibitor.Mechanistically,phosphorylated SR proteins were found to be related to chromatin as shown by a salt extraction experiment,and in situ DNaseⅠassay showed that the accessibility of chromatin was enhanced in SN oocytes when SRPK1 was inhibited,accompanied by a decreased repressive modification on histone and the abnormal recurrence of a transcriptional signal.In conclusion,our results indicated that SRPK1-regulated phosphorylation of SR proteins was involved in the NSN-SN transition and played an important role in maintaining the condensed nucleus of SN oocytes via interacting with chromatin.
基金Project supported by the Fundamental Research Funds for the Central Universities from Lanzhou University (No.lzujbky-2014-87),China
文摘Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb repressive complexes 1 and 2 （PRC1 and PRC2）, are required for maintaining the sternness of embryonic stem cells and many types of adult stem cells. The spectra of target genes for PRCs are dynamically changing with cell differentiation, which is essential for proper decisions on cell fate during developmental processes, Chromobox （CBX） family proteins are canonical components in PRC1, responsible for targeting PRC1 to the chromatin. Recent studies highlight the function specifications among CBX family members in undifferentiated and differentiated stem cells, which reveal the interplay between compositional diversity and functional specificity of PRCI. In this review, we summarize the current knowledge about targeting and functional mechanisms of PRCs, emphasizing the recent breakthroughs related to CBX proteins under a number of physiological and pathological conditions.
基金This work was supported by National Natural Science Foundation Funding(3110131631371805)Program for New Century Excellent Talents in University of Ministry of Education of China(NCET-11-0796)and Heilongjiang Province Postdoctoral Science Foundation.
文摘Bone morphogenetic proteins(BMPs)are a family of potent,multifunctional growth factors belonging to transforming growth factor-(TGF-).They are highly conservative in structures.Over 20 members of BMPs with varying functions such as embryogenesis,skeletal formation,hematopoiesis and neurogenesis have been identified in human body.BMPs are unique growth factors that can induce the formation of bone tissue individually.BMPs can induce the differentiation of bone marrow mesenchymal stem cells into osteoblastic lineage and promote the proliferation of osteoblasts and chondrocytes.BMPs stimulate the target cells by specific membrane-bound receptors and signal transduced through mothers against decapentaplegic(Smads)and mitogen activated protein kinase(MAPK)pathways.It has been demonstrated that BMP-2,BMP-4,BMP-6,BMP-7,and BMP-9 play an important role in bone formation.This article focuses on the molecular characterization of BMPs family members,mechanism of osteogenesis promotion,related signal pathways of osteogenic function,relationships between structure and osteogenetic activity,and the interactions among family members at bone formation.
基金Project Project supported by the National Key Technologies R&D Program of China(Nos.2017YFA0103900 and 2016YFC0905200)the National Natural Science Foundation of China(Nos.81620108005,8177040802,and 81622013)the Shanghaigng Talents Plan(No.18PJ1401700),China
文摘Bone morphogenetic proteins(BMPs)are the largest subfamily of the transforming growth factor-βsuperfamily,and they play important roles in the development of numerous organs,including the inner ear.The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance.Here,we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.
基金financially supported by the Green Development and Demonstration Programme(GUDP)(case number 34009-19-1585)。
文摘Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.
基金supported by the Grand Science and Technology Special Project in Shanxi Province(202201140601025-2)the National Natural Science Foundation of China(32201749)supported by the Agriculture and Food Research Initiative Competitive Grant 2022-68013-36439(WheatCAP)from the USDA National Institute of Food and Agriculture.
文摘The awn can contribute to photosynthesis and carbohydrates,enhancing grain yield in wheat.We mapped QAwn.sxau-5A,a major QTL for awn development in wheat(Triticum aestivum).This QTL was delimited to a 994-kb interval at the B1 locus on chromosome 5A,which included the candidate gene encoding a zinc finger protein(TraesCS5A01G542800)as an awn length inhibitor(ALI).The Ali-A1 allele for the awnless trait showed abundant sequence differences in the promoter regions compared to the ali-A1 allele for the long-awn trait.The results of the swap experiment on the promoters from the two ALI-A1 alleles showed that the two promoters caused a difference in the protein level,indicating the gene was regulated at the transcript level.However,the ali-A1 allele contained an SNP that caused a premature stop codon in its coding region,resulting in a truncated protein compared to the functional Ali-A1 protein.The Ali-A1 protein contained two ethylene-responsive element binding factor-associated amphiphilic repression(EAR)motifs,one at the N terminus(EAR-N)and the other at the C terminus(EAR-C),and they were involved in interactions with the wheat co-repressor protein TOPLESS(TPL1).The ali-A1 protein retained the EAR-N motif but lost the EAR-C motif,resulting in the attenuated ability to interact with TPL1.The tpl1 mutant produced a longer awn compared to the wild type.Ali-A1 repressed the transcription of two downstream genes,TaLRP-A1 and TaARF-B1,involved in endogenous auxin concentrations and auxin responses in wheat.We concluded that the awn length is regulated not only by the ALI-A1 gene at transcript levels but also by Ali-A1 and TPL1 at the protein level in wheat.
