Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease rem...Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout(Srgap2+/–) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes(Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/– mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.展开更多
Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerati...Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.展开更多
Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether ...Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether and how food processing techniques reduce allergenicity.We here discuss the impacts of food processing technologies on the modification of physicochemical,structural,and immunogenic properties of allergenic proteins.Detection techniques for characterizing changes in these properties of food allergens are summarized.Food processing helps to reduce allergenicity by aggregating or denaturing proteins,which masks,modifies,or destroys antigenic epitopes,whereas,it cannot eliminate allergenicity completely,and sometimes even improves allergenicity by exposing new epitopes.Moreover,most food processing techniques have been tested on purified food allergens rather than food products due to potential interference of other food components.We provide guidance for further development of processing operations that can decrease the allergenicity of allergenic food proteins without negatively impacting the nutritional profile.展开更多
BACKGROUND Transcatheter arterial embolisation(TACE)is the primary treatment for intermediate-stage hepatocellular carcinoma(HCC)patients while some HCC cases have shown resistance to TACE.AIM To investigate the key g...BACKGROUND Transcatheter arterial embolisation(TACE)is the primary treatment for intermediate-stage hepatocellular carcinoma(HCC)patients while some HCC cases have shown resistance to TACE.AIM To investigate the key genes and potential mechanisms correlated with TACE refractoriness in HCC.METHODS The microarray datasets of TACE-treated HCC tissues,HCC and non-HCC tissues were collected by searching multiple public databases.The respective differentially expressed genes(DEGs)were attained via limma R package.Weighted gene co-expression network analysis was employed for identifying the significant modules related to TACE non-response.TACE refractoriness-related genes were obtained by intersecting up-regulated TACE-associated and HCC-associated DEGs together with the genes in significant modules related to TACE nonresponse.The key genes expression in the above two pairs of samples was compared respectively via Wilcoxon tests and standard mean differences model.The prognostic value of the key genes was evaluated by Kaplan-Meier curve.Multivariate analysis was utilised to investigate the independent prognostic factor in key genes.Single-cell RNA(scRNA)sequencing analysis was conducted to explore the cell types in HCC.TACE refractoriness-related genes activity was calculated via AUCell packages.The CellChat R package was used for the investigation of the cell–cell communication between the identified cell types.RESULTS HCC tissues of TACE non-responders(n=66)and TACE responders(n=81),HCC(n=3941)and non-HCC(n=3443)tissues were obtained.The five key genes,DLG associated protein 5(DLGAP5),Kinesin family member 20A(KIF20A),Assembly factor for spindle microtubules(ASPM),Kinesin family member 11(KIF11)and TPX2 microtubule nucleation factor(TPX2)in TACE refractoriness-related genes,were identified.The five key genes were all up-regulated in the TACE non-responders group and the HCC group.High expression of the five key genes predicted poor prognosis in HCC.Among the key genes,TPX2 was an independent prognostic factor.Four cell types,hepatocytes,embryonic stem cells,T cells and B cells,were identified in the HCC tissues.The TACE refractoriness-related genes expressed primarily in hepatocytes and embryonic stem cells.Hepatocytes,as the providers of ligands,had the strongest interaction with embryonic stem cells that provided receptors.CONCLUSION Five key genes(DLGAP5,KIF20A,ASPM,KIF11 and TPX2)were identified as promoting refractory TACE.Hepatocytes and embryonic stem cells were likely to boost TACE refractoriness.展开更多
BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained...BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.展开更多
BACKGROUND Emerging research suggests that microRNAs(miRNAs)play an important role in the development of hepatocellular carcinoma(HCC).A comprehensive analysis of recent research concerning miRNAs in HCC development c...BACKGROUND Emerging research suggests that microRNAs(miRNAs)play an important role in the development of hepatocellular carcinoma(HCC).A comprehensive analysis of recent research concerning miRNAs in HCC development could provide researchers with a valuable reference for further studies.AIM To make a comprehensive analysis of recent studies concerning miRNAs in HCC.METHODS All relevant publications were retrieved from the Web of Science Core Collection database.Bibliometrix software,VOSviewer software and CiteSpace software were used to visually analyze the distribution by time,countries,institutions,journals,and authors,as well as the keywords,burst keywords and thematic map.RESULTS A total of 9426 publications on this topic were found worldwide.According to the keywords analysis,we found that the studies of miRNAs focused on their expression level,effects,and mechanisms on the biological behaviour of HCC.Keywords bursting analysis showed that in the early years(2013–2017),“micro-RNA expression”,“gene expression”,“expression profile”,“functional polymorphism”,“circulating microRNA”,“susceptibility”and“mir 21”started to attract attention.In the latest phase(2018–2022),the hot topics turned to“sorafenib resistance”,“tumor microenvironment”and so on.CONCLUSION This study provides a comprehensive overview of the role of miRNAs in HCC development based on bibliometric analysis.The hotspots in this field focus on miRNAs expression level,effects,and mechanisms on the biological behavior of HCC.The frontiers turned to sorafenib resistance,tumor microenvironment and so on.展开更多
After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astr...After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.展开更多
Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relations...Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.展开更多
Background:Oral squamous cell carcinoma(OSCC)is a common malignant tumor.Recently,Laminin Gamma 2(LAMC2)has been shown to be abnormally expressed in OSCC;however,how LAMC2 signaling contributes to the occurrence and d...Background:Oral squamous cell carcinoma(OSCC)is a common malignant tumor.Recently,Laminin Gamma 2(LAMC2)has been shown to be abnormally expressed in OSCC;however,how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored.This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC.Methods:To explore the mechanism by which LAMC2 is highly expressed in OSCC,we used small interfering RNA(siRNA)to knock down LAMC2 to further observe the changes in the signaling pathway.Furthermore,we used cell proliferation assays,Transwell invasion assays,and wound-healing assays to observe the changes in OSCC proliferation,invasion,and metastasis.RFP-LC3 was used to detect the level of autophagy intensity.A cell line-derived xenograft(CDX)model was used to detect the effect of LAMC2 on tumor growth in vivo.Results:This study found that the level of autophagy was correlated with the biological behavior of OSCC.The downregulation of LAMC2 activated autophagy and inhibited OSCC proliferation,invasion,and metastasis via inhibiting the PI3K/AKT/mTOR pathway.Moreover,autophagy has a dual effect on OSCC,and the synergistic downregulation of LAMC2 and autophagy can inhibit OSCC metastasis,invasion,and proliferation via the PI3K/AKT/mTOR pathway.Conclusions:LAMC2 interacts with autophagy to regulate OSCC metastasis,invasion,and proliferation via the PI3K/AKT/mTOR pathway.LAMC2 down-regulation can synergistically modulate autophagy to inhibit OSCC migration,invasion,and proliferation.展开更多
“A Craftsman Must Sharpen His Tools to Do His Job,”said Confucius.Nuclear detection and readout techniques are the foundation of particle physics,nuclear physics,and particle astrophysics to reveal the nature of the...“A Craftsman Must Sharpen His Tools to Do His Job,”said Confucius.Nuclear detection and readout techniques are the foundation of particle physics,nuclear physics,and particle astrophysics to reveal the nature of the universe.Also,they are being increasingly used in other disciplines like nuclear power generation,life sciences,environmental sciences,medical sciences,etc.The article reviews the short history,recent development,and trend of nuclear detection and readout techniques,covering Semiconductor Detector,Gaseous Detector,Scintillation Detector,Cherenkov Detector,Transition Radiation Detector,and Readout Techniques.By explaining the principle and using examples,we hope to help the interested reader underst and this research field and bring exciting information to the community.展开更多
As the first safety barrier of nuclear reactors,zirconium alloy cladding tubes have attracted extensive attention because of its good mechanical properties.The strength and ductility of zirconium alloy are of great si...As the first safety barrier of nuclear reactors,zirconium alloy cladding tubes have attracted extensive attention because of its good mechanical properties.The strength and ductility of zirconium alloy are of great significance to the service process of cladding tubes,while brittle hydrides precipitate and thus deteriorate the overall performance.Based on the cohesive finite element method,the effects of cohesive strength,interfacial characteristics,and hydrides geometric characteristics on the strength and ductility of two-phase material(zirconium alloy with hydrides)are numerically simulated.The results show that the fracture behavior is significantly affected by the cohesive strength and that the overall strength and ductility are sensitive to the cohesive strength of the zirconium alloy.Furthermore,the interface is revealed to have prominent effects on the overall fracture behavior.When the cohesive strength and fracture energy of the interface are higher than those of the hydride phase,fracture initiates in the hydrides,which is consistent with the experimental phenomena.In addition,it is found that the number density and arrangement of hydrides play important roles in the overall strength and ductility.Our simulation provides theoretical support for the performance analysis of hydrogenated zirconium alloys during nuclear reactor operation.展开更多
Aqueous zinc ion batteries(ZIBs) are attracting considerable attentions for practical energy storage because of their low cost and high safety.Nevertheless,the traditional manganese oxide cathode materials suffer from...Aqueous zinc ion batteries(ZIBs) are attracting considerable attentions for practical energy storage because of their low cost and high safety.Nevertheless,the traditional manganese oxide cathode materials suffer from the low intrinsic electronic conductivity,sluggish ions diffusion kinetics,and structural collapse,hindering their large-scale application.Herein,we successfully developed a latent amorphous Mn_(1.8)Fe_(1.2)O_(4) hollow nanocube(a-H-MnFeO) cathode material derived from Prussian blue analogue precursor.The amorphous nature endows the cathode with lower diffusion barrier and narrower band gap compared with crystalline counterpart,resulting in the superior Zn^(2+) ions and electrons transport kinetics.Hollow structure can furnish abundant surface sites and suppress the structural collapse during the repeated charge/discharge processes.By virtue of the multiple advantageous features,the a-H-MnFeO cathode exhibits exceptional electrochemical performance,in terms of high capacity,excellent rate capability,and prolonged cycle life.This strategy will pave the way for the structural design of emerging cathode materials.展开更多
With the current revolution in Shipping 4.0, a tremendous amount of data is accumulated during vessel operations. Dataquality (DQ) is becoming more and more important for the further digitalization and effective decis...With the current revolution in Shipping 4.0, a tremendous amount of data is accumulated during vessel operations. Dataquality (DQ) is becoming more and more important for the further digitalization and effective decision-making in shippingindustry. In this study, a practical DQ assessment method for raw data in vessel operations is proposed. In this method,specific data categories and data dimensions are developed based on engineering practice and existing literature. Concretevalidation rules are then formed, which can be used to properly divide raw datasets. Afterwards, a scoring method is usedfor the assessment of the data quality. Three levels, namely good, warning and alarm, are adopted to reflect the final dataquality. The root causes of bad data quality could be revealed once the internal dependency among rules has been built,which will facilitate the further improvement of DQ in practice. A case study based on the datasets from a Danish shippingcompany is conducted, where the DQ variation is monitored, assessed and compared. The results indicate that theproposed method is effective to help shipping industry improve the quality of raw data in practice. This innovationresearch can facilitate shipping industry to set a solid foundation at the early stage of their digitalization journeys.展开更多
Knowledge of the raindrop size distribution(DSD)is crucial for disaster prevention and mitigation.The recordbreaking rainfall in the summer of 2020 caused some of the worst flooding ever experienced in China.This stud...Knowledge of the raindrop size distribution(DSD)is crucial for disaster prevention and mitigation.The recordbreaking rainfall in the summer of 2020 caused some of the worst flooding ever experienced in China.This study uses 96 Parsivel disdrometers and eight-year Global Precipitation Measurement(GPM)satellite observations to reveal the microphysical aspects of the disastrous rainfall during its northward migration over East China.The results show that the nearly twice as heavy rainfall in Jiangsu Province compared to Fujian Province can be attributed to the earlier-than-average northward jump of the summer monsoon rainband to the Yangtze-Huaihe River valley.The persistent heavy monsoon rainfall showed similar near-maritime DSD characteristics,with a higher concentration of small raindrops than the surrounding climatic regimes.During the northward movement of the rainband,the DSD variables and composite spectra between the pre-summer rainfall in Fujian and mei-yu rainfall in Jiangsu exhibited inherent similarities with slight regional variations.These are associated with similar statistical vertical precipitation structures for both convective and stratiform rain in these regions/periods.The vertical profiles of radar reflectivity and DSD parameters are typical of monsoonal rainfall features,implying the competition between coalescence,breakup,and accretion of vital warm rain processes.This study attributes the anomalously long duration of the mei-yu season for the record-breaking rainfall and reveals inherent homogeneous rainfall microphysics during the northward movement of the summer monsoon rainband.The conclusion is statistically robust and would be helpful for accurate precipitation estimation and model parameterization of summer monsoon rainfall over East China.展开更多
The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be cr...The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be credited in the acknowledgments.展开更多
Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the ac...Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis.In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay,plaque reduction assay,and fluorescence observation.RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection.In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1.Results:An active compound was isolated and elucidated as mangiferin.Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration(IC_(50))of 64.0 mg/L.Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage(8 h).UL12,UL42,and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group(P<0.01).Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintainingΔΨm induced by HSV-1 in Vero cells.The expression of inflammatory factors TNF-α,IL-1β,and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group(P<0.05),the levels of these inflammatory factors dropped after treatment with mangiferin.Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α,IL-1β,and IL-6.The relative protection rate of HSV-1-infected mice could reach up to55.5%when the concentration of mangiferin was 4 g/kg.Conclusions:Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.展开更多
Flow softening behavior of a homogenized Mg-7Gd-4Y-1Nd-0.5Zr alloy under compression to a final strain of∼1.8 at elevated temperatures of 450∼550℃ and a constant strain rate of 2s^(−1) has been investigated by opti...Flow softening behavior of a homogenized Mg-7Gd-4Y-1Nd-0.5Zr alloy under compression to a final strain of∼1.8 at elevated temperatures of 450∼550℃ and a constant strain rate of 2s^(−1) has been investigated by optical microscopy,scanning electron microscopy,electron back-scattered diffraction and transmission electron microscopy.The results show that true stress first rises to the peak point and then drops to the bottom value and increases again with further increasing strain at each temperature.Twinning dynamic recrystallization(DRX)and continuous DRX contribute to the formation of new fine grains at temperatures 450∼475℃ when the restoration is caused by both DRX and texture change due to extension twinning,resulting in the larger softening degrees compared with the softening effects owing to continuous DRX and discontinuous DRX at 500∼550℃ when twinning activation is suppressed.500℃ is the transition temperature denoting a significant decline in the contribution of twinning and TDRX to the strain with increasing temperature.The cuboid-shape phase exists in both homogenized and compressed samples,while the compositions are varied.展开更多
基金supported by the Notional Natural Science Foundation of China,Nos.81770918 (to ZLC),31871383 (to TL)the Natural Science Foundation of Zhejiang Province,No.LY16H120006 (to ZLC)the Departmental Funds from Wenzhou Medical University,No.89214018 (to ZLC)。
文摘Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout(Srgap2+/–) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes(Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/– mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.
基金supported by the National Natural Science Foundation of China,No.82171336(to XX)。
文摘Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.
基金supported by the National Natural Science Foundation of China (32102605)the Agricultural Science and Technology Innovation Program under Grant (CAAS-ASTIP-2020IAR)the Earmarked Fund for CARS (CARS-44)。
文摘Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether and how food processing techniques reduce allergenicity.We here discuss the impacts of food processing technologies on the modification of physicochemical,structural,and immunogenic properties of allergenic proteins.Detection techniques for characterizing changes in these properties of food allergens are summarized.Food processing helps to reduce allergenicity by aggregating or denaturing proteins,which masks,modifies,or destroys antigenic epitopes,whereas,it cannot eliminate allergenicity completely,and sometimes even improves allergenicity by exposing new epitopes.Moreover,most food processing techniques have been tested on purified food allergens rather than food products due to potential interference of other food components.We provide guidance for further development of processing operations that can decrease the allergenicity of allergenic food proteins without negatively impacting the nutritional profile.
基金Guangxi Higher Education Undergraduate Teaching Reform Project,No.2021JGA142Guangxi Educational Science Planning Key Project,No.2022ZJY2791+1 种基金Guangxi Medical University Education and Teaching Reform Project,No.2021XJGA02Guangxi Zhuang Autonomous Region Health Commission Self-financed Scientific Research Project,No.Z20201147.
文摘BACKGROUND Transcatheter arterial embolisation(TACE)is the primary treatment for intermediate-stage hepatocellular carcinoma(HCC)patients while some HCC cases have shown resistance to TACE.AIM To investigate the key genes and potential mechanisms correlated with TACE refractoriness in HCC.METHODS The microarray datasets of TACE-treated HCC tissues,HCC and non-HCC tissues were collected by searching multiple public databases.The respective differentially expressed genes(DEGs)were attained via limma R package.Weighted gene co-expression network analysis was employed for identifying the significant modules related to TACE non-response.TACE refractoriness-related genes were obtained by intersecting up-regulated TACE-associated and HCC-associated DEGs together with the genes in significant modules related to TACE nonresponse.The key genes expression in the above two pairs of samples was compared respectively via Wilcoxon tests and standard mean differences model.The prognostic value of the key genes was evaluated by Kaplan-Meier curve.Multivariate analysis was utilised to investigate the independent prognostic factor in key genes.Single-cell RNA(scRNA)sequencing analysis was conducted to explore the cell types in HCC.TACE refractoriness-related genes activity was calculated via AUCell packages.The CellChat R package was used for the investigation of the cell–cell communication between the identified cell types.RESULTS HCC tissues of TACE non-responders(n=66)and TACE responders(n=81),HCC(n=3941)and non-HCC(n=3443)tissues were obtained.The five key genes,DLG associated protein 5(DLGAP5),Kinesin family member 20A(KIF20A),Assembly factor for spindle microtubules(ASPM),Kinesin family member 11(KIF11)and TPX2 microtubule nucleation factor(TPX2)in TACE refractoriness-related genes,were identified.The five key genes were all up-regulated in the TACE non-responders group and the HCC group.High expression of the five key genes predicted poor prognosis in HCC.Among the key genes,TPX2 was an independent prognostic factor.Four cell types,hepatocytes,embryonic stem cells,T cells and B cells,were identified in the HCC tissues.The TACE refractoriness-related genes expressed primarily in hepatocytes and embryonic stem cells.Hepatocytes,as the providers of ligands,had the strongest interaction with embryonic stem cells that provided receptors.CONCLUSION Five key genes(DLGAP5,KIF20A,ASPM,KIF11 and TPX2)were identified as promoting refractory TACE.Hepatocytes and embryonic stem cells were likely to boost TACE refractoriness.
基金Supported by National Natural Science Foundation of China,No.82260785.
文摘BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.
基金Guangxi Zhuang Autonomous Region Health Commission Self-Financed Scientific Research Project,No.Z20201174Innovation Project of Guangxi Graduate Education,No.YCBZ2023110+2 种基金Guangxi Higher Education Undergraduate Teaching Reform Project,No.2022JGA146Guangxi Educational Science Planning Key Project,No.2022ZJY2791Guangxi Medical High-level Key Talents Training"139"Program(2020).
文摘BACKGROUND Emerging research suggests that microRNAs(miRNAs)play an important role in the development of hepatocellular carcinoma(HCC).A comprehensive analysis of recent research concerning miRNAs in HCC development could provide researchers with a valuable reference for further studies.AIM To make a comprehensive analysis of recent studies concerning miRNAs in HCC.METHODS All relevant publications were retrieved from the Web of Science Core Collection database.Bibliometrix software,VOSviewer software and CiteSpace software were used to visually analyze the distribution by time,countries,institutions,journals,and authors,as well as the keywords,burst keywords and thematic map.RESULTS A total of 9426 publications on this topic were found worldwide.According to the keywords analysis,we found that the studies of miRNAs focused on their expression level,effects,and mechanisms on the biological behaviour of HCC.Keywords bursting analysis showed that in the early years(2013–2017),“micro-RNA expression”,“gene expression”,“expression profile”,“functional polymorphism”,“circulating microRNA”,“susceptibility”and“mir 21”started to attract attention.In the latest phase(2018–2022),the hot topics turned to“sorafenib resistance”,“tumor microenvironment”and so on.CONCLUSION This study provides a comprehensive overview of the role of miRNAs in HCC development based on bibliometric analysis.The hotspots in this field focus on miRNAs expression level,effects,and mechanisms on the biological behavior of HCC.The frontiers turned to sorafenib resistance,tumor microenvironment and so on.
基金supported by the National Natural Science Foundation of China,Nos.82101455(to RYY),31872773(to GC),82001168(to JYP)the Key Research and Development Program(Social Development)of Jiangsu Province,No.BE2020667(to GC)+3 种基金the Foundation of Jiangsu Province,333 Project High-level Talents",No.BRA2020076(to GC)the Nantong Civic Science and Technology Project of China,No.JC2020028(to RYY)the Natural Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.
基金supported by the National Natural Science Foundation of China,Nos. 81971006 (to DSG), 82101263 (to CXT)Jiangsu Province Science Foundation for Youths,No. BK20210903 (to CXT)+2 种基金Research Foundation for Talented Scholars of Xuzhou Medical University,No. RC20552114 (to CXT)Science&Technology Program of Xuzhou,No. KC19016 (to JC)Project of Xuzhou Medical University,No. 2018KJ06 (to JC)。
文摘Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.
基金This work was supported by the National Natural Science Foundation of China(Grant Numbers 31971106,BWS21L013,21WS09002,JK20211A010213).
文摘Background:Oral squamous cell carcinoma(OSCC)is a common malignant tumor.Recently,Laminin Gamma 2(LAMC2)has been shown to be abnormally expressed in OSCC;however,how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored.This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC.Methods:To explore the mechanism by which LAMC2 is highly expressed in OSCC,we used small interfering RNA(siRNA)to knock down LAMC2 to further observe the changes in the signaling pathway.Furthermore,we used cell proliferation assays,Transwell invasion assays,and wound-healing assays to observe the changes in OSCC proliferation,invasion,and metastasis.RFP-LC3 was used to detect the level of autophagy intensity.A cell line-derived xenograft(CDX)model was used to detect the effect of LAMC2 on tumor growth in vivo.Results:This study found that the level of autophagy was correlated with the biological behavior of OSCC.The downregulation of LAMC2 activated autophagy and inhibited OSCC proliferation,invasion,and metastasis via inhibiting the PI3K/AKT/mTOR pathway.Moreover,autophagy has a dual effect on OSCC,and the synergistic downregulation of LAMC2 and autophagy can inhibit OSCC metastasis,invasion,and proliferation via the PI3K/AKT/mTOR pathway.Conclusions:LAMC2 interacts with autophagy to regulate OSCC metastasis,invasion,and proliferation via the PI3K/AKT/mTOR pathway.LAMC2 down-regulation can synergistically modulate autophagy to inhibit OSCC migration,invasion,and proliferation.
基金supported by the National Natural Science Foundation of China(No.12222512,U2032209,12075045,12335011,1875097,11975257,62074146,11975115,12205374,12305210,11975292,12005276,12005278,12375193,12227805,12235012,12375191,12005279)the National Key Research and Development Program of China(2021YFA1601300)+13 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(XDB34000000)the CAS Pioneer Hundred Talent Programthe CAS“Light of West China”Programthe Natural Science Foundation of Liaoning Province(No.101300261)the Dalian Science and Technology Innovation Fund(2023JJ12GX013)the Special Projects of the Central Government in Guidance of Local Science and Technology Development(Research and development of three-dimensional prospecting technology based on Cosmic-ray muons)(YDZX20216200001297)the Science and Technology Planning Project of Gansu(20JR10RA645)the Lanzhou University Talent Cooperation Research Funds sponsored by both Lanzhou City(561121203)the Gansu provincial science and technology plan projects for talents(054000029)the Beijing Natural Science Foundation(No.1232033)the Beijing Hope Run Special Fund of Cancer Foundation of China(No.LC2021B23)the Guangdong Major Project of Basic and Applied Basic Research(No.2020B0301030008)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.GJJSTD20210009)the Youth Innovation Promotion Association CAS(2021450)。
文摘“A Craftsman Must Sharpen His Tools to Do His Job,”said Confucius.Nuclear detection and readout techniques are the foundation of particle physics,nuclear physics,and particle astrophysics to reveal the nature of the universe.Also,they are being increasingly used in other disciplines like nuclear power generation,life sciences,environmental sciences,medical sciences,etc.The article reviews the short history,recent development,and trend of nuclear detection and readout techniques,covering Semiconductor Detector,Gaseous Detector,Scintillation Detector,Cherenkov Detector,Transition Radiation Detector,and Readout Techniques.By explaining the principle and using examples,we hope to help the interested reader underst and this research field and bring exciting information to the community.
基金Supported by National Key Research and Development Plan of China(Grant No.2018YFC0808800)National Natural Science Foundation of China(Grant No.51875398)China Postdoctoral Science Foundation(Grant No.2021M693240).
文摘As the first safety barrier of nuclear reactors,zirconium alloy cladding tubes have attracted extensive attention because of its good mechanical properties.The strength and ductility of zirconium alloy are of great significance to the service process of cladding tubes,while brittle hydrides precipitate and thus deteriorate the overall performance.Based on the cohesive finite element method,the effects of cohesive strength,interfacial characteristics,and hydrides geometric characteristics on the strength and ductility of two-phase material(zirconium alloy with hydrides)are numerically simulated.The results show that the fracture behavior is significantly affected by the cohesive strength and that the overall strength and ductility are sensitive to the cohesive strength of the zirconium alloy.Furthermore,the interface is revealed to have prominent effects on the overall fracture behavior.When the cohesive strength and fracture energy of the interface are higher than those of the hydride phase,fracture initiates in the hydrides,which is consistent with the experimental phenomena.In addition,it is found that the number density and arrangement of hydrides play important roles in the overall strength and ductility.Our simulation provides theoretical support for the performance analysis of hydrogenated zirconium alloys during nuclear reactor operation.
基金funding supported by the National Natural Science Foundation of China (52101246)the Fundamental Research Funds for the Central Universities+1 种基金the Natural Science Foundation of Heilongjiang Province, China (YQ2022B006)the funding supported by the Natural Science Foundation of Anhui Province (2208085MB21)。
文摘Aqueous zinc ion batteries(ZIBs) are attracting considerable attentions for practical energy storage because of their low cost and high safety.Nevertheless,the traditional manganese oxide cathode materials suffer from the low intrinsic electronic conductivity,sluggish ions diffusion kinetics,and structural collapse,hindering their large-scale application.Herein,we successfully developed a latent amorphous Mn_(1.8)Fe_(1.2)O_(4) hollow nanocube(a-H-MnFeO) cathode material derived from Prussian blue analogue precursor.The amorphous nature endows the cathode with lower diffusion barrier and narrower band gap compared with crystalline counterpart,resulting in the superior Zn^(2+) ions and electrons transport kinetics.Hollow structure can furnish abundant surface sites and suppress the structural collapse during the repeated charge/discharge processes.By virtue of the multiple advantageous features,the a-H-MnFeO cathode exhibits exceptional electrochemical performance,in terms of high capacity,excellent rate capability,and prolonged cycle life.This strategy will pave the way for the structural design of emerging cathode materials.
基金Danish Blue Innoship project which is partly funded by the Innovation Fund Denmark under File No.155-2014-10the Danish Maritime Fund+4 种基金the Orient’s FundShipping Lab project“Digital vessel operation”the Innovation Fund Denmark(IFD)under File No.8090-00063Bthe Lauritzen Fondenthe Orient’s Fond。
文摘With the current revolution in Shipping 4.0, a tremendous amount of data is accumulated during vessel operations. Dataquality (DQ) is becoming more and more important for the further digitalization and effective decision-making in shippingindustry. In this study, a practical DQ assessment method for raw data in vessel operations is proposed. In this method,specific data categories and data dimensions are developed based on engineering practice and existing literature. Concretevalidation rules are then formed, which can be used to properly divide raw datasets. Afterwards, a scoring method is usedfor the assessment of the data quality. Three levels, namely good, warning and alarm, are adopted to reflect the final dataquality. The root causes of bad data quality could be revealed once the internal dependency among rules has been built,which will facilitate the further improvement of DQ in practice. A case study based on the datasets from a Danish shippingcompany is conducted, where the DQ variation is monitored, assessed and compared. The results indicate that theproposed method is effective to help shipping industry improve the quality of raw data in practice. This innovationresearch can facilitate shipping industry to set a solid foundation at the early stage of their digitalization journeys.
基金supported by the National Natural Science Foundation of China(Grant Nos.41905021,42005009).
文摘Knowledge of the raindrop size distribution(DSD)is crucial for disaster prevention and mitigation.The recordbreaking rainfall in the summer of 2020 caused some of the worst flooding ever experienced in China.This study uses 96 Parsivel disdrometers and eight-year Global Precipitation Measurement(GPM)satellite observations to reveal the microphysical aspects of the disastrous rainfall during its northward migration over East China.The results show that the nearly twice as heavy rainfall in Jiangsu Province compared to Fujian Province can be attributed to the earlier-than-average northward jump of the summer monsoon rainband to the Yangtze-Huaihe River valley.The persistent heavy monsoon rainfall showed similar near-maritime DSD characteristics,with a higher concentration of small raindrops than the surrounding climatic regimes.During the northward movement of the rainband,the DSD variables and composite spectra between the pre-summer rainfall in Fujian and mei-yu rainfall in Jiangsu exhibited inherent similarities with slight regional variations.These are associated with similar statistical vertical precipitation structures for both convective and stratiform rain in these regions/periods.The vertical profiles of radar reflectivity and DSD parameters are typical of monsoonal rainfall features,implying the competition between coalescence,breakup,and accretion of vital warm rain processes.This study attributes the anomalously long duration of the mei-yu season for the record-breaking rainfall and reveals inherent homogeneous rainfall microphysics during the northward movement of the summer monsoon rainband.The conclusion is statistically robust and would be helpful for accurate precipitation estimation and model parameterization of summer monsoon rainfall over East China.
文摘The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be credited in the acknowledgments.
基金supported by Project of Zhejiang Basic Public Benefit Research of Zhejiang Province (NO.LGF22Y145002)。
文摘Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis.In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay,plaque reduction assay,and fluorescence observation.RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection.In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1.Results:An active compound was isolated and elucidated as mangiferin.Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration(IC_(50))of 64.0 mg/L.Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage(8 h).UL12,UL42,and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group(P<0.01).Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintainingΔΨm induced by HSV-1 in Vero cells.The expression of inflammatory factors TNF-α,IL-1β,and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group(P<0.05),the levels of these inflammatory factors dropped after treatment with mangiferin.Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α,IL-1β,and IL-6.The relative protection rate of HSV-1-infected mice could reach up to55.5%when the concentration of mangiferin was 4 g/kg.Conclusions:Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.
基金This work was supported by the Changsha University Talent Introduction Project(50800-92808)the Excellent youth project of Hunan Provincial Department of Education(19B055,18B418,19C0156)the Natural Science Foundation of Hunan Province of China(2020JJ4645).
文摘Flow softening behavior of a homogenized Mg-7Gd-4Y-1Nd-0.5Zr alloy under compression to a final strain of∼1.8 at elevated temperatures of 450∼550℃ and a constant strain rate of 2s^(−1) has been investigated by optical microscopy,scanning electron microscopy,electron back-scattered diffraction and transmission electron microscopy.The results show that true stress first rises to the peak point and then drops to the bottom value and increases again with further increasing strain at each temperature.Twinning dynamic recrystallization(DRX)and continuous DRX contribute to the formation of new fine grains at temperatures 450∼475℃ when the restoration is caused by both DRX and texture change due to extension twinning,resulting in the larger softening degrees compared with the softening effects owing to continuous DRX and discontinuous DRX at 500∼550℃ when twinning activation is suppressed.500℃ is the transition temperature denoting a significant decline in the contribution of twinning and TDRX to the strain with increasing temperature.The cuboid-shape phase exists in both homogenized and compressed samples,while the compositions are varied.
