Tumor necrosis factor-α(TNF-α)is a key player in the pathogenesis of rheumatoid arthritis(RA)and considered a promising target for therapeutic drug development.Activation of the nuclear factor-kappa B(NF-κB)pathway...Tumor necrosis factor-α(TNF-α)is a key player in the pathogenesis of rheumatoid arthritis(RA)and considered a promising target for therapeutic drug development.Activation of the nuclear factor-kappa B(NF-κB)pathway upon TNF-αbinding to its receptor is crucial for progression of RA.Stephanine(SA),an isoquinoline aporphine-type alkaloid recently identified in Stephania plants,exhibits anti-inflammatory properties,but its underlying mechanisms of action are unknown at present.In this study,we explored whether SA could ameliorate RA through inhibition of the NF-κB signaling pathway in association with TNF-αactivity.Our experiments revealed a binding affinity(K_(D))of SA for TNF-αof 2.934×10^(-6)mol/L.Additionally,SA at a concentration of 10μmol/L effectively hindered the binding of TNF-αto its receptors tumor necrosis factor receptor 1(TNFR1)and TNFR2.In vitro,SA prevented TNF-α-induced death of L929 cells and blocked NF-κB activation triggered by TNF-αin 293-TNF-αresponsive,as well as human fibroblast-like synoviocytes(HFLS)and human RA fibroblast-like synoviocytes(MH7A)cell lines.Furthermore,in a collagen-induced arthritis(CIA)mouse model,SA alleviated the symptoms of RA through suppression of NF-κB signaling.Our collective findings support the therapeutic efficacy of SA,a natural compound targeting TNF-α,in the management of RA.展开更多
Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed animals.The non-structural protein 3D plays an important role in FMDV replication and pathogenesis.However,the interaction partners of 3D,an...Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed animals.The non-structural protein 3D plays an important role in FMDV replication and pathogenesis.However,the interaction partners of 3D,and the effects of those interactions on FMDV replication,remain incompletely elucidated.In the present study,using the yeast two-hybrid system,we identified a porcine cell protein,DEAD-box RNA helicase 1(DDX1),which interacted with FMDV 3D.The DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay(IFA)in porcine kidney 15(PK-15)cells.DDX1 was reported to either inhibit or facilitate viral replication and regulate host innate immune responses.However,the roles of DDX1 during FMDV infection remain unclear.Our results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent manner.In addition,DDX1 stimulated IFN-p activation in FMDV-infected cells.Together,our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.展开更多
Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function ...Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.展开更多
Objective.In order to demonstrate the binding of HBV X protein (HBX) with the general transcription factor TFIIB. Methods.In vitro glutathion S transferase (GST) resin Pull Down assay an...Objective.In order to demonstrate the binding of HBV X protein (HBX) with the general transcription factor TFIIB. Methods.In vitro glutathion S transferase (GST) resin Pull Down assay and Far Western Blotting assay, in vivo Co immunoprecipition assay were used. Results.The X199(51 99) domain of HBX is reponsible for HBX binding to TFIIB. While the d10 domain (125 295) of TFIIB is required for TFIIB binding to HBX. When the two basic amino acids(K) at position 178 and 189 of TFIIB were substituted by neutral amino acids(L), the binding of TFIIBK178L and K189L to HBX was siginificantly reduced. When the the basic amino acids were substituted by the acidic amino acids(E),the binding of TFIIB K178E and K189E to HBX were almost lost. In vitro results of HBX binding to TFIIB were further confirmed by in vivo co immunoprecipitation assay. Our results also indicated that the Woodchuck hepatitis virus X protein (WHX) interacts with TFIIB. Conclusion.These results suggested that the communication between HBX and general transcription factor TFIIB is one of the mechanisms which account for its transcriptional transactivation.展开更多
The COP9 signalosome （CSN） is a multiprotein complex which participates in diverse cellular and developmental processes. CSN1, one of the subunits of CSN, is essential for assembly of the multiprotein complex via P...The COP9 signalosome （CSN） is a multiprotein complex which participates in diverse cellular and developmental processes. CSN1, one of the subunits of CSN, is essential for assembly of the multiprotein complex via PCI （proteasome, COP9 signalosome and initiation factor 3） domain in the C-terminal half of CSN 1. However, the role of the N-terminal domain （NTD） of CSN 1, which is critical for the function of CSN, is not completely understood. Using a yeast two-hybrid （Y2H） screen, we found that the NTD of CSN1 interacts with TSK-associating protein 1 （TSA1）, a reported CaZ＋-binding protein. The interaction between CSN1 and TSA1 was confirmed by co-immunoprecipitation in Arabidopsis. tsal mutants exhibited a short hypocotyl phenotype in darkness but were similar to wild-type Arabidopsis under white light, which suggested that TSA1 might regulate Arabidopsis hypocotyl development in the dark. Furthermore, the expression of TSA1 was significantly lower in a csnl null mutant （fus6）, while CSN1 expression did not change in a tsal mutant with weak TSAI expression. Together, these findings suggest a functional relationship between TSAI and CSN1 in seedling development.展开更多
Objective：It has been shown that LRP16 is an estrogen-induced gene through its receptor α（ERα）. Although there is evidence demonstrating that inhibition of LRP16 gene expression in MCF-7 human breast cancer cells...Objective：It has been shown that LRP16 is an estrogen-induced gene through its receptor α（ERα）. Although there is evidence demonstrating that inhibition of LRP16 gene expression in MCF-7 human breast cancer cells partially attenuates its estrogen-responsiveness, the underlying molecular mechanism is still unclear. Here, the effect of LRP16 expression on the ERα signaling transduction was investigated. Methods： Cotransfection assays were used to measure the effect of LRP16 on ERα-mediated transcriptional activity. GST-pulldown and immunoprecipitation （ColP） assays were employed to investigate the physical interaction of LRP16 and ERα. The mammalian two-hybrid method was used to map the functional interaction region. Results： the results of cotransfection assays demonstrated that the transcriptional activities of ERα were enhanced in α LRP16 dose-dependent manner in MCF-7 in the presence of estrogen, however, it was abolished in the absence of E2 in MCF-7 cells. The physical interaction of LRP16 and ERα proteins was confirmed by GST-pulldown in vitro and ColP in vivo assays, which was enhanced by E2 but not dependent on its presence. Furthermore, the results of the mammalian two-hybrid assays indicated that the binding region of ERα to LRP16 located at the A/B AF-1 functional domain and E2 stimulated the binding of LRP16 to the full-length ERα molecule but not to the A/B region alone. Conclusion： These results support a role for estrogenically regulated LRP16 as an ERα coactivator, providing a positive feedback regulatory loop for ERα signal transduction. Based on this function of LRP16, we propose that ERα-positive breast cancer patients with high expression of LRP16 might benefit from targeting LRP16 therapy.展开更多
Cytoskeletal microtubule rearrangement and movement are crucial in the repair of spinal cord injury.Spastin plays an important role in the regulation of microtubule severing.Both spastin and collapsin response mediato...Cytoskeletal microtubule rearrangement and movement are crucial in the repair of spinal cord injury.Spastin plays an important role in the regulation of microtubule severing.Both spastin and collapsin response mediator proteins can regulate neurite growth and branching;however,whether spastin interacts with collapsin response mediator protein 3(CRMP3)during this process remains unclear,as is the mechanism by which CRMP3 participates in the repair of spinal cord injury.In this study,we used a proteomics approach to identify key proteins associated with spinal cord injury repair.We then employed liquid chromatography-mass spectrometry to identify proteins that were able to interact with glutathione S-transferase-spastin.Then,co-immunoprecipitation and staining approaches were used to evaluate potential interactions between spastin and CRMP3.Finally,we co-transfected primary hippocampal neurons with CRMP3 and spastin to evaluate their role in neurite outgrowth.Mass spectrometry identified the role of CRMP3 in the spinal cord injury repair process.Liquid chromatography-mass spectrometry pulldown assays identified three CRMP3 peptides that were able to interact with spastin.CRMP3 and spastin were co-expressed in the spinal cord and were able to interact with one another in vitro and in vivo.Lastly,CRMP3 overexpression was able to enhance the ability of spastin to promote neurite growth and branching.Therefore,our results confirm that spastin and CRMP3 play roles in spinal cord injury repair by regulating neurite growth and branching.These proteins may therefore be novel targets for spinal cord injury repair.The Institutional Animal Care and Use Committee of Jinan University,China approved this study(approval No.IACUS-20181008-03)on October 8,2018.展开更多
Objective: To study protein-protein interaction between heterogeneous nuclear ribonucleoprotein H(hn RNP H) and Dengue virus(DENV) proteins. Methods: DENV proteins were screened against the host hn RNP H protein, in o...Objective: To study protein-protein interaction between heterogeneous nuclear ribonucleoprotein H(hn RNP H) and Dengue virus(DENV) proteins. Methods: DENV proteins were screened against the host hn RNP H protein, in order to identify the host-viral protein-protein interactions in DENV infected THP-1 cells by co-immunoprecipitation. The co-localization of the interacting proteins was further confirmed by immunofluorescence microscopy. Results: The host protein hn RNP H was found to interact with DENV nonstructural 1 protein and help the virus to multiply in the cell. Conclusions: The non-structural 1 glycoprotein is a key modulator of host immune response and is also involved in viral replication. Therefore, disruption of this key interaction between hn RNP H and DENV nonstructural 1 could be an important therapeutic strategy for management of DENV infection.展开更多
Soybean cyst nematode(SCN)Heterodera glycines is considered as the major constraint to soybean production.Gm SHMT08 at Rhg4 locus on chromosome 08,encoding a serine hydroxylmethyltransferase,is a major gene underlying...Soybean cyst nematode(SCN)Heterodera glycines is considered as the major constraint to soybean production.Gm SHMT08 at Rhg4 locus on chromosome 08,encoding a serine hydroxylmethyltransferase,is a major gene underlying resistance against H.glycines in Peking-type soybeans.However,the molecular mechanism underpinning this resistance is less well characterized,and whether Gm SHMT08 could interact with proteins in H.glycines remains unclear.In this study,yeast two-hybrid screening was conducted using Gm SHMT08 as a bait protein,and a fragment of a 70-kDa heat shock protein(Hg HSP70)was screened from H.glycines that exhibited interaction with Gm SHMT08.This interaction was verified by both GST pull-down and bimolecular fluorescence complementation assays.Our finding reveals Hg HSP70 could be applied as a potential candidate gene for further exploring the mechanism on Gm SHMT08-mediated resistance against SCN H.glycines.展开更多
Ustilaginoidea virens,which causes rice false smut(RFS),is one of the most detrimental rice fungal diseases and poses a severe threat to rice production and quality.Effectors in U.virens often act as a group of essent...Ustilaginoidea virens,which causes rice false smut(RFS),is one of the most detrimental rice fungal diseases and poses a severe threat to rice production and quality.Effectors in U.virens often act as a group of essential virulence factors that play crucial roles in the interaction between host and the pathogen.Thus,the functions of individual effectors in U.virens need to be further explored.Here,we found a small secreted hypersensitive response-inducing protein UVI_02019870 was highly conserved in fungi.Furthermore,we performed Y2H and BiFC assay to demonstrated UVI_02019870 interacted with OsCPL1,which was predicted as a chloroplast precursor to regulate chloroplast signaling pathways.Our data provide a theory for gaining an insight into the molecular mechanisms underlying the UVI_02019870 virulence function.展开更多
Fragile X-related protein 1（FXR1P） is a member of the FXR gene family,which also includes fragile X mental retardation protein and fragile X-related protein 2（FXR2P）.To understand the functions of FXR1P,we screene...Fragile X-related protein 1（FXR1P） is a member of the FXR gene family,which also includes fragile X mental retardation protein and fragile X-related protein 2（FXR2P）.To understand the functions of FXR1P,we screened FXR1P-interacting proteins using a yeast two-hybrid system.FXR1P was fused to pGBKT7 and used as the bait to screen a human fetal brain cDNA library.This screening revealed 10 FXR1P-interacting proteins including FTH1.FTH1 encodes Homo sapiens ferritin,heavy polypeptide 1.The interaction between FXR1P and FTH1 was confirmed by retesting in yeast using both a β-galactosidase assay and growth studies on selective media.A co-immunoprecipitation assay in mammalian cells further confirmed the FXR1P/FTH1 interaction.Moreover,the results revealed that FTH1 colocalized with FXR1P in the cytoplasm around the nucleus in mammalian cells.The present findings suggest that FXR1P plays an important role in iron metabolism in the brain by interacting with FTH1.This provides clues for elucidating the relationship between FXR1P function and fragile X syndrome.展开更多
Ranaviruses are harmful viruses that infect amphibians, fish, and reptiles, and have caused particularly devastating declines in amphibian populations. One particular type of ranavirus, called Frog Virus 3 (FV3), has ...Ranaviruses are harmful viruses that infect amphibians, fish, and reptiles, and have caused particularly devastating declines in amphibian populations. One particular type of ranavirus, called Frog Virus 3 (FV3), has been extensively studied due to its prevalence and impact on amphibians. Previous research has primarily focused on the virus’s genes, but little attention has been given to the non-coding regions of its genome. This article reviews recent studies that reveal the ability of ranaviruses, including FV3, to encode microRNA (miRNA), a type of regulatory RNA. These viral miRNAs play a crucial role in suppressing frog immune genes, modulating the virus-host interaction, and promoting viral infection. Understanding how ranaviruses use miRNAs to control disease progression is essential for addressing the health threat they pose to wildlife and ecosystems.展开更多
Recent studies in Arabidopsis have revealed that some vq motif-containing proteins physically interact with WRKY transcription factors; however, their specific biological functions are still poorly understood. In this...Recent studies in Arabidopsis have revealed that some vq motif-containing proteins physically interact with WRKY transcription factors; however, their specific biological functions are still poorly understood. In this study, we confirmed the interaction between VQ1o and WRKY8, and show that VQ1o and WRKY8 formed a complex in the plant cell nucleus. Yeast two-hybrid analysis showed that the middle region of WRKY8 and the vq motif of vqlo are critical for their interaction, and that this interaction promotes the DNA-binding activity of WRKY8. Further investigation revealed that the VqlO protein was exclusively localized in the nucleus, and VQ1o was predominantly expressed in siliques, vQ1o expression was strongly responsive to the necrotrophic fungal pathogen, Botrytis cinerea and defense-relatedhormones. Phenotypic analysis showed that disruption of VQlo increased mutant plants susceptibility to the fungal pathogen B. cinerea, whereas constitutive-expres- sion of VQlo enhanced resistance to B. cinerea. Consis- tent with these findings, expression of the defenserelated PLANT DEFENSIN1.2 （PDFt2） gene was decreased in vqlo mutant plants, after B. cinerea infection, but increased in vQ1o-overexpressing transgenic plants. Taken together, our findings provide evidence that VQlo physically interacts with WRKY8 and positively regulates plant basal resistance against the necrotrophic fungal pathogen B. cinerea.展开更多
Plant interphase cortical microtubules(cMTs)mediate anisotropic cell expansion in response to environmental and developmental cues.In Arabidopsis thaliana,KATANIN 1(KTN1),the p60 catalytic subunit of the conserved MT-...Plant interphase cortical microtubules(cMTs)mediate anisotropic cell expansion in response to environmental and developmental cues.In Arabidopsis thaliana,KATANIN 1(KTN1),the p60 catalytic subunit of the conserved MT-severing enzyme katanin,is essential for cMT ordering and anisotropic cell expansion.However,the regulation of KTN1-mediated cMT severing and ordering remains unclear.In this work,we report that the Arabidopsis IQ67 DOMAIN(IQD)family gene ABNORMAL SHOOT 6(ABS6)encodes a MT-associated protein.Overexpression of ABS6 leads to elongated cotyledons,directional pavement cell expansion,and highly ordered transverse cMT arrays.Genetic suppressor analysis revealed that ABS6-mediated cMT ordering is dependent on KTN1 and SHADE AVOIDANCE 4(SAV4).Live imaging of cMT dynamics showed that both ABS6 and SAV4 function as positive regulators of cMT severing.Furthermore,ABS6 directly interacts with KTN1 and SAV4 and promotes their recruitment to the cMTs.Finally,analysis of loss-of-function mutant combinations showed that ABS6,SAV4,and KTN1 work together to ensure the robust ethylene response in the apical hook of dark-grown seedlings.Together,our findings establish ABS6 and SAV4 as positive regulators of cMT severing and ordering,and highlight the role of cMT dynamics in fine-tuning differential growth in plants.展开更多
Chloroplast genes are transcribed by the plastidencoded RNA polymerase（PEP） or nucleus-encoded RNA polymerase. FRUCTOKINASE-LIKE PROTEINS（FLNs） are phosphofructokinase-B（Pfk B）-type carbohydrate kinases that act...Chloroplast genes are transcribed by the plastidencoded RNA polymerase（PEP） or nucleus-encoded RNA polymerase. FRUCTOKINASE-LIKE PROTEINS（FLNs） are phosphofructokinase-B（Pfk B）-type carbohydrate kinases that act as part of the PEP complex; however, the molecular mechanisms underlying FLN activity in rice remain elusive.Previously, we identified and characterized a heat-stress sensitive albino（hsa_1） mutant in rice. Map-based cloning revealed that HSA_1 encodes a putative OsFLN_2. Here, we further demonstrated that knockdown or knockout of the OsFLN_1, a close homolog of HSA_1/OsFLN_2, considerably inhibits chloroplast biogenesis and the fln_1 knockout mutants, created by clustered regularly interspaced short palindromic repeats（CRISPR） and CRISPR-associate protein_9, exhibit severe albino phenotype and seedling lethality. Moreover, OsFLN_1 localizes to the chloroplast.Yeast two-hybrid, pull-down and bimolecular fluorescencecomplementation experiments revealed that OsFLN_1 and HSA_1/OsFLN_2 interact with THIOREDOXINZ（OsTRXz） to regulate chloroplast development. In agreement with this,knockout of OsTRXz resulted in a similar albino and seedling lethality phenotype to that of the fln_1 mutants. Quantitative reverse transcription polymerase chain reaction and immunoblot analysis revealed that the transcription and translation of PEP-dependent genes were strongly inhibited in fln_1 and trxz mutants, indicating that loss of OsFLN_1, HSA_1/OsFLN_2, or OsTRXz function perturbs the stability of the transcriptionally active chromosome complex and PEP activity. These results show that OsFLN_1 and HSA_1/OsFLN_2 contribute to chloroplast biogenesis and plant growth.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
Dear Editor, NCC （Na-Cl cotransporter） is a cotransporter mainly dis- tributed in the distal tubule of the kidney, functioning to reabsorb sodium and chloride ions from the tubular fluid into the cells of the renal ...Dear Editor, NCC （Na-Cl cotransporter） is a cotransporter mainly dis- tributed in the distal tubule of the kidney, functioning to reabsorb sodium and chloride ions from the tubular fluid into the cells of the renal distal convoluted tubule. It is a transmembrane protein belonging to the SLC12 cotransporter family of electro-neutral cation-coupled chloride cotransporters, which is closely related to hypertension （Gamba, 2005）. A loss of NCC function can cause Gitelman syndrome, a disease characterized by low blood pressure,展开更多
Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in dis...Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in disease. Identification of bioactive materials capable of altering the abundances of these species both safely and effectively is a major goal in microbiome research. Many traditional Chinese medicines (TCMs) have been reported to affect the composition of the gut microbiome. Here, we summarize studies that have used TCMs to alter the gut microbiome and discuss the response relationship between TCMs and gut microbial species. Methods: We searched the PubMed, Web of Science, and Knowledge Network databases using the terms “traditional Chinese medicine,” “gut microbiome,” and specific system disease names (endocrine, immune, nervous, cardiovascular, and digestive). Studies were excluded if irrelevant or if the experimental procedures were unclear. Results: TCMs have been reported to affect a wide range of gut microbial taxa spanning major phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobiota, Actinobacteria, and Fusobacteria. In all, 54 TCMs including compounds and extracts have been tested in rodents and 30 have been examined in human trials. Almost all studies have reported positive results in regulating the gut microbiome as well as modulating corresponding phenotypes, spanning diseases of the endocrine, immune, nervous, cardiovascular, and digestive systems. Gut species, including Akkermansia, Bacteroides, Fusobacterium, Faecalibacterium, and E. coli, were found to be regulated by 19 TCMs. A network was constructed to visualize the interactions between TCMs and these taxa. Conclusion: There exists a complex and close relationship between intestinal microflora and diseases. Sufficient experimental data and studies have proved that the imbalance of intestinal microflora affects health by mediating metabolism, immune regulation, inflammation and signal transduction. Many characteristic alterations of intestinal microflora are positively correlated with diseases, so intestinal microflora has become a potential risk index and treatment target for many diseases. Many TCMs affect the relative abundances of microbial species in the gut, and therefore may be useful for modulating the gut microbiome. This review provides a reference for prioritizing candidate TCMs from the enormous repertoire of such medicines to test which specific gut microbes are targeted.展开更多
Studies of wave-current interactions are vital for the safe design of structures.Regular waves in the presence of uniform,linear shear,and quadratic shear currents are explored by the High-Level Green-Naghdi model in ...Studies of wave-current interactions are vital for the safe design of structures.Regular waves in the presence of uniform,linear shear,and quadratic shear currents are explored by the High-Level Green-Naghdi model in this paper.The five-point central difference method is used for spatial discretization,and the fourth-order Adams predictor-corrector scheme is employed for marching in time.The domain-decomposition method is applied for the wave-current generation and absorption.The effects of currents on the wave profile and velocity field are examined under two conditions:the same velocity of currents at the still-water level and the constant flow volume of currents.Wave profiles and velocity fields demonstrate substantial differences in three types of currents owing to the diverse vertical distribution of current velocity and vorticity.Then,loads on small-scale vertical cylinders subjected to regular waves and three types of background currents with the same flow volume are investigated.The maximum load intensity and load fluctuation amplitude in uniform,linear shear,and quadratic shear currents increase sequentially.The stretched superposition method overestimates the maximum load intensity and load fluctuation amplitude in opposing currents and underestimates these values in following currents.The stretched superposition method obtains a poor approximation for strong nonlinear waves,particularly in the case of the opposing quadratic shear current.展开更多
Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other field...Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other fields.Nevertheless,due to the tendency of1,4-benzenedicarboxylic acid(BDC)to rotate within the framework,MOFs composed of it exhibit significant non-radiative energy dissipation and thus impair the emissive properties.In this study,efficient luminescence of MIL-140A nanocrystals(NCs)with BDC rotors as ligands is achieved by pressure treatment strategy.Pressure treatment effectively modulates the pore structure of the framework,enhancing the interactions between the N,N-dimethylformamide vip molecules and the BDC ligands.The enhanced host-vip interaction contributes to the structural rigidity of the MOF,thereby suppressing the rotation-induced excited-state energy loss.As a result,the pressure-treated MIL-140A NCs displayed bright blue-light emission,with the photoluminescence quantum yield increasing from an initial 6.8%to 69.2%.This study developed an effective strategy to improve the luminescence performance of rotor ligand MOFs,offers a new avenue for the rational design and synthesis of MOFs with superior luminescent properties.展开更多
基金supported by the grants from the National Natural Science Foundation of China(82404638)the Xingdian Talent Plan of Yunnan Province(XDYC-QNRC-2023-0427 and XDYC-YLXZ-2022-0025)the Natural Science Foundation of Yunnan Province(202101BD070001-034,202101BD070001-049,202201AT070267,and 202201AU070183).
文摘Tumor necrosis factor-α(TNF-α)is a key player in the pathogenesis of rheumatoid arthritis(RA)and considered a promising target for therapeutic drug development.Activation of the nuclear factor-kappa B(NF-κB)pathway upon TNF-αbinding to its receptor is crucial for progression of RA.Stephanine(SA),an isoquinoline aporphine-type alkaloid recently identified in Stephania plants,exhibits anti-inflammatory properties,but its underlying mechanisms of action are unknown at present.In this study,we explored whether SA could ameliorate RA through inhibition of the NF-κB signaling pathway in association with TNF-αactivity.Our experiments revealed a binding affinity(K_(D))of SA for TNF-αof 2.934×10^(-6)mol/L.Additionally,SA at a concentration of 10μmol/L effectively hindered the binding of TNF-αto its receptors tumor necrosis factor receptor 1(TNFR1)and TNFR2.In vitro,SA prevented TNF-α-induced death of L929 cells and blocked NF-κB activation triggered by TNF-αin 293-TNF-αresponsive,as well as human fibroblast-like synoviocytes(HFLS)and human RA fibroblast-like synoviocytes(MH7A)cell lines.Furthermore,in a collagen-induced arthritis(CIA)mouse model,SA alleviated the symptoms of RA through suppression of NF-κB signaling.Our collective findings support the therapeutic efficacy of SA,a natural compound targeting TNF-α,in the management of RA.
基金supported by grants from the National Natural Science Foundation of China (Nos. 31302106, 31260616, and 31602035)the National Key Research and Development Program of China (Nos. 2016YFD0500901 and 2017YFD0500903)
文摘Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed animals.The non-structural protein 3D plays an important role in FMDV replication and pathogenesis.However,the interaction partners of 3D,and the effects of those interactions on FMDV replication,remain incompletely elucidated.In the present study,using the yeast two-hybrid system,we identified a porcine cell protein,DEAD-box RNA helicase 1(DDX1),which interacted with FMDV 3D.The DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay(IFA)in porcine kidney 15(PK-15)cells.DDX1 was reported to either inhibit or facilitate viral replication and regulate host innate immune responses.However,the roles of DDX1 during FMDV infection remain unclear.Our results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent manner.In addition,DDX1 stimulated IFN-p activation in FMDV-infected cells.Together,our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.
基金supported by the National Natural Science Foundation of China (No. 81601762)the National Science and Technology Major Project of Infectious Diseases (No. 2017ZX10304402)+1 种基金the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2017ZX09101005-005-003)the Scientific Research Foundation of State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics (No. 2016ZY005)
文摘Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.
文摘Objective.In order to demonstrate the binding of HBV X protein (HBX) with the general transcription factor TFIIB. Methods.In vitro glutathion S transferase (GST) resin Pull Down assay and Far Western Blotting assay, in vivo Co immunoprecipition assay were used. Results.The X199(51 99) domain of HBX is reponsible for HBX binding to TFIIB. While the d10 domain (125 295) of TFIIB is required for TFIIB binding to HBX. When the two basic amino acids(K) at position 178 and 189 of TFIIB were substituted by neutral amino acids(L), the binding of TFIIBK178L and K189L to HBX was siginificantly reduced. When the the basic amino acids were substituted by the acidic amino acids(E),the binding of TFIIB K178E and K189E to HBX were almost lost. In vitro results of HBX binding to TFIIB were further confirmed by in vivo co immunoprecipitation assay. Our results also indicated that the Woodchuck hepatitis virus X protein (WHX) interacts with TFIIB. Conclusion.These results suggested that the communication between HBX and general transcription factor TFIIB is one of the mechanisms which account for its transcriptional transactivation.
基金supported by a grant from the Chinese National Natural Science Foundation(Nos.30270682 and 30770211)to X.Wangsupported in part by a Monsanto Fellowship to the Peking-Yale Joint Center,USA
文摘The COP9 signalosome （CSN） is a multiprotein complex which participates in diverse cellular and developmental processes. CSN1, one of the subunits of CSN, is essential for assembly of the multiprotein complex via PCI （proteasome, COP9 signalosome and initiation factor 3） domain in the C-terminal half of CSN 1. However, the role of the N-terminal domain （NTD） of CSN 1, which is critical for the function of CSN, is not completely understood. Using a yeast two-hybrid （Y2H） screen, we found that the NTD of CSN1 interacts with TSK-associating protein 1 （TSA1）, a reported CaZ＋-binding protein. The interaction between CSN1 and TSA1 was confirmed by co-immunoprecipitation in Arabidopsis. tsal mutants exhibited a short hypocotyl phenotype in darkness but were similar to wild-type Arabidopsis under white light, which suggested that TSA1 might regulate Arabidopsis hypocotyl development in the dark. Furthermore, the expression of TSA1 was significantly lower in a csnl null mutant （fus6）, while CSN1 expression did not change in a tsal mutant with weak TSAI expression. Together, these findings suggest a functional relationship between TSAI and CSN1 in seedling development.
基金This project was supported by the National Natural Science Foundation of China(No.30670809)PLA National Science Fund for Distinguished Young Scholars Grant(No.06J017).
文摘Objective：It has been shown that LRP16 is an estrogen-induced gene through its receptor α（ERα）. Although there is evidence demonstrating that inhibition of LRP16 gene expression in MCF-7 human breast cancer cells partially attenuates its estrogen-responsiveness, the underlying molecular mechanism is still unclear. Here, the effect of LRP16 expression on the ERα signaling transduction was investigated. Methods： Cotransfection assays were used to measure the effect of LRP16 on ERα-mediated transcriptional activity. GST-pulldown and immunoprecipitation （ColP） assays were employed to investigate the physical interaction of LRP16 and ERα. The mammalian two-hybrid method was used to map the functional interaction region. Results： the results of cotransfection assays demonstrated that the transcriptional activities of ERα were enhanced in α LRP16 dose-dependent manner in MCF-7 in the presence of estrogen, however, it was abolished in the absence of E2 in MCF-7 cells. The physical interaction of LRP16 and ERα proteins was confirmed by GST-pulldown in vitro and ColP in vivo assays, which was enhanced by E2 but not dependent on its presence. Furthermore, the results of the mammalian two-hybrid assays indicated that the binding region of ERα to LRP16 located at the A/B AF-1 functional domain and E2 stimulated the binding of LRP16 to the full-length ERα molecule but not to the A/B region alone. Conclusion： These results support a role for estrogenically regulated LRP16 as an ERα coactivator, providing a positive feedback regulatory loop for ERα signal transduction. Based on this function of LRP16, we propose that ERα-positive breast cancer patients with high expression of LRP16 might benefit from targeting LRP16 therapy.
基金This work was supported by the National Natural Science Foundation of China,Nos.31900691(to GWZ),81771331(to HSL)and 81971165(to WW)the National Basic Research Program of China(973 Program),No.2014CB542205(to WW)+5 种基金the Natural Science Foundation of Guangdong Province of China,No.2017A030313595(to HSL)the Science and Technology Program of Guangzhou,China,No.201707010370(to HSL)Project of Educational Commission of Guangdong Province of China,No.2018KQNCX013(to ZSJ)the Fundamental Research Funds for the Central Universities Project,China,No.21618304(to GWZ)Guangdong Provincial Key Research and Development Program“Precision Medicine and Stem Cell”Major Science and Technology Project,China,No.3242001(to WW)China Postdoctoral Science Foundation,No.2019M653292(to ZSJ).
文摘Cytoskeletal microtubule rearrangement and movement are crucial in the repair of spinal cord injury.Spastin plays an important role in the regulation of microtubule severing.Both spastin and collapsin response mediator proteins can regulate neurite growth and branching;however,whether spastin interacts with collapsin response mediator protein 3(CRMP3)during this process remains unclear,as is the mechanism by which CRMP3 participates in the repair of spinal cord injury.In this study,we used a proteomics approach to identify key proteins associated with spinal cord injury repair.We then employed liquid chromatography-mass spectrometry to identify proteins that were able to interact with glutathione S-transferase-spastin.Then,co-immunoprecipitation and staining approaches were used to evaluate potential interactions between spastin and CRMP3.Finally,we co-transfected primary hippocampal neurons with CRMP3 and spastin to evaluate their role in neurite outgrowth.Mass spectrometry identified the role of CRMP3 in the spinal cord injury repair process.Liquid chromatography-mass spectrometry pulldown assays identified three CRMP3 peptides that were able to interact with spastin.CRMP3 and spastin were co-expressed in the spinal cord and were able to interact with one another in vitro and in vivo.Lastly,CRMP3 overexpression was able to enhance the ability of spastin to promote neurite growth and branching.Therefore,our results confirm that spastin and CRMP3 play roles in spinal cord injury repair by regulating neurite growth and branching.These proteins may therefore be novel targets for spinal cord injury repair.The Institutional Animal Care and Use Committee of Jinan University,China approved this study(approval No.IACUS-20181008-03)on October 8,2018.
基金supported by the Defence Institute of Physiology and Allied SciencesDefence Research and Development Organization+1 种基金Ministry of DefenceIndia in the form of TASK-177
文摘Objective: To study protein-protein interaction between heterogeneous nuclear ribonucleoprotein H(hn RNP H) and Dengue virus(DENV) proteins. Methods: DENV proteins were screened against the host hn RNP H protein, in order to identify the host-viral protein-protein interactions in DENV infected THP-1 cells by co-immunoprecipitation. The co-localization of the interacting proteins was further confirmed by immunofluorescence microscopy. Results: The host protein hn RNP H was found to interact with DENV nonstructural 1 protein and help the virus to multiply in the cell. Conclusions: The non-structural 1 glycoprotein is a key modulator of host immune response and is also involved in viral replication. Therefore, disruption of this key interaction between hn RNP H and DENV nonstructural 1 could be an important therapeutic strategy for management of DENV infection.
基金supported by the National Natural Science Foundation of China(31972248)the Agricultural Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences,China(ASTIP-02IPP-04)。
文摘Soybean cyst nematode(SCN)Heterodera glycines is considered as the major constraint to soybean production.Gm SHMT08 at Rhg4 locus on chromosome 08,encoding a serine hydroxylmethyltransferase,is a major gene underlying resistance against H.glycines in Peking-type soybeans.However,the molecular mechanism underpinning this resistance is less well characterized,and whether Gm SHMT08 could interact with proteins in H.glycines remains unclear.In this study,yeast two-hybrid screening was conducted using Gm SHMT08 as a bait protein,and a fragment of a 70-kDa heat shock protein(Hg HSP70)was screened from H.glycines that exhibited interaction with Gm SHMT08.This interaction was verified by both GST pull-down and bimolecular fluorescence complementation assays.Our finding reveals Hg HSP70 could be applied as a potential candidate gene for further exploring the mechanism on Gm SHMT08-mediated resistance against SCN H.glycines.
基金This work is supported by the earmarked fund for China Agriculture Research System(CARS-01).
文摘Ustilaginoidea virens,which causes rice false smut(RFS),is one of the most detrimental rice fungal diseases and poses a severe threat to rice production and quality.Effectors in U.virens often act as a group of essential virulence factors that play crucial roles in the interaction between host and the pathogen.Thus,the functions of individual effectors in U.virens need to be further explored.Here,we found a small secreted hypersensitive response-inducing protein UVI_02019870 was highly conserved in fungi.Furthermore,we performed Y2H and BiFC assay to demonstrated UVI_02019870 interacted with OsCPL1,which was predicted as a chloroplast precursor to regulate chloroplast signaling pathways.Our data provide a theory for gaining an insight into the molecular mechanisms underlying the UVI_02019870 virulence function.
基金the National Natural Science Foundation of China, No. 30370795
文摘Fragile X-related protein 1（FXR1P） is a member of the FXR gene family,which also includes fragile X mental retardation protein and fragile X-related protein 2（FXR2P）.To understand the functions of FXR1P,we screened FXR1P-interacting proteins using a yeast two-hybrid system.FXR1P was fused to pGBKT7 and used as the bait to screen a human fetal brain cDNA library.This screening revealed 10 FXR1P-interacting proteins including FTH1.FTH1 encodes Homo sapiens ferritin,heavy polypeptide 1.The interaction between FXR1P and FTH1 was confirmed by retesting in yeast using both a β-galactosidase assay and growth studies on selective media.A co-immunoprecipitation assay in mammalian cells further confirmed the FXR1P/FTH1 interaction.Moreover,the results revealed that FTH1 colocalized with FXR1P in the cytoplasm around the nucleus in mammalian cells.The present findings suggest that FXR1P plays an important role in iron metabolism in the brain by interacting with FTH1.This provides clues for elucidating the relationship between FXR1P function and fragile X syndrome.
文摘Ranaviruses are harmful viruses that infect amphibians, fish, and reptiles, and have caused particularly devastating declines in amphibian populations. One particular type of ranavirus, called Frog Virus 3 (FV3), has been extensively studied due to its prevalence and impact on amphibians. Previous research has primarily focused on the virus’s genes, but little attention has been given to the non-coding regions of its genome. This article reviews recent studies that reveal the ability of ranaviruses, including FV3, to encode microRNA (miRNA), a type of regulatory RNA. These viral miRNAs play a crucial role in suppressing frog immune genes, modulating the virus-host interaction, and promoting viral infection. Understanding how ranaviruses use miRNAs to control disease progression is essential for addressing the health threat they pose to wildlife and ecosystems.
基金supported by the National Natural Science Foundation of China(31671274,91417307)the Innovative Team of Yunnan Province(2014HC017)
文摘Recent studies in Arabidopsis have revealed that some vq motif-containing proteins physically interact with WRKY transcription factors; however, their specific biological functions are still poorly understood. In this study, we confirmed the interaction between VQ1o and WRKY8, and show that VQ1o and WRKY8 formed a complex in the plant cell nucleus. Yeast two-hybrid analysis showed that the middle region of WRKY8 and the vq motif of vqlo are critical for their interaction, and that this interaction promotes the DNA-binding activity of WRKY8. Further investigation revealed that the VqlO protein was exclusively localized in the nucleus, and VQ1o was predominantly expressed in siliques, vQ1o expression was strongly responsive to the necrotrophic fungal pathogen, Botrytis cinerea and defense-relatedhormones. Phenotypic analysis showed that disruption of VQlo increased mutant plants susceptibility to the fungal pathogen B. cinerea, whereas constitutive-expres- sion of VQlo enhanced resistance to B. cinerea. Consis- tent with these findings, expression of the defenserelated PLANT DEFENSIN1.2 （PDFt2） gene was decreased in vqlo mutant plants, after B. cinerea infection, but increased in vQ1o-overexpressing transgenic plants. Taken together, our findings provide evidence that VQlo physically interacts with WRKY8 and positively regulates plant basal resistance against the necrotrophic fungal pathogen B. cinerea.
基金the Teaching and Research Core Facility at the College of Life Sciences,NWAFU for support in this worksupported by grants from the National Natural Science Foundation of China(31770205 and 31970186 to X.L.,31870268 to F.Y.)。
文摘Plant interphase cortical microtubules(cMTs)mediate anisotropic cell expansion in response to environmental and developmental cues.In Arabidopsis thaliana,KATANIN 1(KTN1),the p60 catalytic subunit of the conserved MT-severing enzyme katanin,is essential for cMT ordering and anisotropic cell expansion.However,the regulation of KTN1-mediated cMT severing and ordering remains unclear.In this work,we report that the Arabidopsis IQ67 DOMAIN(IQD)family gene ABNORMAL SHOOT 6(ABS6)encodes a MT-associated protein.Overexpression of ABS6 leads to elongated cotyledons,directional pavement cell expansion,and highly ordered transverse cMT arrays.Genetic suppressor analysis revealed that ABS6-mediated cMT ordering is dependent on KTN1 and SHADE AVOIDANCE 4(SAV4).Live imaging of cMT dynamics showed that both ABS6 and SAV4 function as positive regulators of cMT severing.Furthermore,ABS6 directly interacts with KTN1 and SAV4 and promotes their recruitment to the cMTs.Finally,analysis of loss-of-function mutant combinations showed that ABS6,SAV4,and KTN1 work together to ensure the robust ethylene response in the apical hook of dark-grown seedlings.Together,our findings establish ABS6 and SAV4 as positive regulators of cMT severing and ordering,and highlight the role of cMT dynamics in fine-tuning differential growth in plants.
基金supported by National Natural Science Foundation of China (31371606, 31601284, 31661143006)The Transgenic Plant Research and Commercialization Project of the Ministry of Agriculture of China (2016ZX08001003-002)+2 种基金Zhejiang Province Outstanding Youth Fund (LR16C130001)The Collaborative Innovation Project of the Chinese Academy of Agricultural Sciences (Y2016XT05)State Key Laboratory of Rice Biology Research Project (2017ZZKT10103)
文摘Chloroplast genes are transcribed by the plastidencoded RNA polymerase（PEP） or nucleus-encoded RNA polymerase. FRUCTOKINASE-LIKE PROTEINS（FLNs） are phosphofructokinase-B（Pfk B）-type carbohydrate kinases that act as part of the PEP complex; however, the molecular mechanisms underlying FLN activity in rice remain elusive.Previously, we identified and characterized a heat-stress sensitive albino（hsa_1） mutant in rice. Map-based cloning revealed that HSA_1 encodes a putative OsFLN_2. Here, we further demonstrated that knockdown or knockout of the OsFLN_1, a close homolog of HSA_1/OsFLN_2, considerably inhibits chloroplast biogenesis and the fln_1 knockout mutants, created by clustered regularly interspaced short palindromic repeats（CRISPR） and CRISPR-associate protein_9, exhibit severe albino phenotype and seedling lethality. Moreover, OsFLN_1 localizes to the chloroplast.Yeast two-hybrid, pull-down and bimolecular fluorescencecomplementation experiments revealed that OsFLN_1 and HSA_1/OsFLN_2 interact with THIOREDOXINZ（OsTRXz） to regulate chloroplast development. In agreement with this,knockout of OsTRXz resulted in a similar albino and seedling lethality phenotype to that of the fln_1 mutants. Quantitative reverse transcription polymerase chain reaction and immunoblot analysis revealed that the transcription and translation of PEP-dependent genes were strongly inhibited in fln_1 and trxz mutants, indicating that loss of OsFLN_1, HSA_1/OsFLN_2, or OsTRXz function perturbs the stability of the transcriptionally active chromosome complex and PEP activity. These results show that OsFLN_1 and HSA_1/OsFLN_2 contribute to chloroplast biogenesis and plant growth.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
基金supported by the National Natural Science Foundation of China(81200513)Qianjiang Talents Project of Technology Office of Zhejiang Province(2011R10049)Wenzhou Science&Technology Bureau(H20110014)
文摘Dear Editor, NCC （Na-Cl cotransporter） is a cotransporter mainly dis- tributed in the distal tubule of the kidney, functioning to reabsorb sodium and chloride ions from the tubular fluid into the cells of the renal distal convoluted tubule. It is a transmembrane protein belonging to the SLC12 cotransporter family of electro-neutral cation-coupled chloride cotransporters, which is closely related to hypertension （Gamba, 2005）. A loss of NCC function can cause Gitelman syndrome, a disease characterized by low blood pressure,
基金funding by National Natural Science Foundation of China(No.82174492)National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Project(N o.ZJJBGS2024002-1).
文摘Background: The human gut microbiome is an important target for disease treatment and prevention. Various microbial species within the complex ecosystem of the microbiome have been shown to play important roles in disease. Identification of bioactive materials capable of altering the abundances of these species both safely and effectively is a major goal in microbiome research. Many traditional Chinese medicines (TCMs) have been reported to affect the composition of the gut microbiome. Here, we summarize studies that have used TCMs to alter the gut microbiome and discuss the response relationship between TCMs and gut microbial species. Methods: We searched the PubMed, Web of Science, and Knowledge Network databases using the terms “traditional Chinese medicine,” “gut microbiome,” and specific system disease names (endocrine, immune, nervous, cardiovascular, and digestive). Studies were excluded if irrelevant or if the experimental procedures were unclear. Results: TCMs have been reported to affect a wide range of gut microbial taxa spanning major phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobiota, Actinobacteria, and Fusobacteria. In all, 54 TCMs including compounds and extracts have been tested in rodents and 30 have been examined in human trials. Almost all studies have reported positive results in regulating the gut microbiome as well as modulating corresponding phenotypes, spanning diseases of the endocrine, immune, nervous, cardiovascular, and digestive systems. Gut species, including Akkermansia, Bacteroides, Fusobacterium, Faecalibacterium, and E. coli, were found to be regulated by 19 TCMs. A network was constructed to visualize the interactions between TCMs and these taxa. Conclusion: There exists a complex and close relationship between intestinal microflora and diseases. Sufficient experimental data and studies have proved that the imbalance of intestinal microflora affects health by mediating metabolism, immune regulation, inflammation and signal transduction. Many characteristic alterations of intestinal microflora are positively correlated with diseases, so intestinal microflora has become a potential risk index and treatment target for many diseases. Many TCMs affect the relative abundances of microbial species in the gut, and therefore may be useful for modulating the gut microbiome. This review provides a reference for prioritizing candidate TCMs from the enormous repertoire of such medicines to test which specific gut microbes are targeted.
基金Supported by the Development and Application Project of Ship CAE Software.
文摘Studies of wave-current interactions are vital for the safe design of structures.Regular waves in the presence of uniform,linear shear,and quadratic shear currents are explored by the High-Level Green-Naghdi model in this paper.The five-point central difference method is used for spatial discretization,and the fourth-order Adams predictor-corrector scheme is employed for marching in time.The domain-decomposition method is applied for the wave-current generation and absorption.The effects of currents on the wave profile and velocity field are examined under two conditions:the same velocity of currents at the still-water level and the constant flow volume of currents.Wave profiles and velocity fields demonstrate substantial differences in three types of currents owing to the diverse vertical distribution of current velocity and vorticity.Then,loads on small-scale vertical cylinders subjected to regular waves and three types of background currents with the same flow volume are investigated.The maximum load intensity and load fluctuation amplitude in uniform,linear shear,and quadratic shear currents increase sequentially.The stretched superposition method overestimates the maximum load intensity and load fluctuation amplitude in opposing currents and underestimates these values in following currents.The stretched superposition method obtains a poor approximation for strong nonlinear waves,particularly in the case of the opposing quadratic shear current.
基金supported by the National Key R&D Program of China(Grant No.2023YFA1406200)the National Natural Science Foundation of China(No.12274177 and 12304261)the China Postdoctoral Science Foundation(No.2024M751076)。
文摘Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other fields.Nevertheless,due to the tendency of1,4-benzenedicarboxylic acid(BDC)to rotate within the framework,MOFs composed of it exhibit significant non-radiative energy dissipation and thus impair the emissive properties.In this study,efficient luminescence of MIL-140A nanocrystals(NCs)with BDC rotors as ligands is achieved by pressure treatment strategy.Pressure treatment effectively modulates the pore structure of the framework,enhancing the interactions between the N,N-dimethylformamide vip molecules and the BDC ligands.The enhanced host-vip interaction contributes to the structural rigidity of the MOF,thereby suppressing the rotation-induced excited-state energy loss.As a result,the pressure-treated MIL-140A NCs displayed bright blue-light emission,with the photoluminescence quantum yield increasing from an initial 6.8%to 69.2%.This study developed an effective strategy to improve the luminescence performance of rotor ligand MOFs,offers a new avenue for the rational design and synthesis of MOFs with superior luminescent properties.
