AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
The bromodomain-containing protein 9(BRD9)is a core subunit of mammalian SWI/SNF chromatin remodeling complex termed ncBAF.BRD9 has emerged as a potential target for anticancer drugs,particularly in the treatment of a...The bromodomain-containing protein 9(BRD9)is a core subunit of mammalian SWI/SNF chromatin remodeling complex termed ncBAF.BRD9 has emerged as a potential target for anticancer drugs,particularly in the treatment of acute myeloid leukemia(AML).Herein,we reported 10m(Y22073)and 10t as new BRD9 selective bromodomain inhibitors.Crystallographic studies revealed that the key active imidazolyl group discovered from structure-activity relationship(SAR)can induce Phe163 flipping and significantly enhance the cellular potency of the compounds,making 10m the first BRD9 selective inhibitor with significant cellular activity against AML cells.We also validated the critical role of imidazolyl groups by modifying existing BRD9 inhibitors.The representative compounds 10m and 10t demonstrated potent binding affinity,outstanding selectivity toward BRD9 bromodomain,and significantly inhibited the proliferation of AML cell lines.10m also showed good metabolic stability,solubility and pharmacokinetic properties.Additionally,oral administration of compounds 10m and 10t exhibited potent anti-tumor efficacy in the MV4-11 xenograft mouse model.The potent,selective,and orally available BRD9 bromodomain inhibitors may address the challenges of weak cellular activity and limited phenotypic efficacy faced by BRD9 inhibitors,and serve as new lead compounds for the development of anticancer agents for the treatment of AML.展开更多
BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therape...BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therapeutic options for NECs remain limited,contributing to the poor prognosis of patients.Immunotherapy has emerged as a promising treatment strategy and demonstrated the potential to partially improve the survival and prognosis of patients with NECs.Nevertheless,the unique clinical response termed pseudoprogression(PsP)has garnered considerable attention in the context of immunotherapy.CASE SUMMARY Presented here is a case of NEC recurrence five and a half months after radical gastric surgery.The 45-year-old male patient underwent combination treatment involving a PD-1 blocker and tyrosine kinase inhibitors and encountered two instances of PsP during treatment.The patient ultimately achieved a durable treatment response without altering his treatment regimens,resulting in a substantial therapeutic benefit.CONCLUSION This case report aimed to provide the authors’experience with the diagnosis of PsP and treatment strategies for PsP in ongoing immunotherapy.展开更多
Tropical cyclones(TCs)are complex and powerful weather systems,and accurately forecasting their path,structure,and intensity remains a critical focus and challenge in meteorological research.In this paper,we propose a...Tropical cyclones(TCs)are complex and powerful weather systems,and accurately forecasting their path,structure,and intensity remains a critical focus and challenge in meteorological research.In this paper,we propose an Attention Spatio-Temporal predictive Generative Adversarial Network(AST-GAN)model for predicting the temporal and spatial distribution of TCs.The model forecasts the spatial distribution of TC wind speeds for the next 15 hours at 3-hour intervals,emphasizing the cyclone's center,high wind-speed areas,and its asymmetric structure.To effectively capture spatiotemporal feature transfer at different time steps,we employ a channel attention mechanism for feature selection,enhancing model performance and reducing parameter redundancy.We utilized High-Resolution Weather Research and Forecasting(HWRF)data to train our model,allowing it to assimilate a wide range of TC motion patterns.The model is versatile and can be applied to various complex scenarios,such as multiple TCs moving simultaneously or TCs approaching landfall.Our proposed model demonstrates superior forecasting performance,achieving a root-mean-square error(RMSE)of 0.71 m s^(-1)for overall wind speed and 2.74 m s^(-1)for maximum wind speed when benchmarked against ground truth data from HWRF.Furthermore,the model underwent optimization and independent testing using ERA5reanalysis data,showcasing its stability and scalability.After fine-tuning on the ERA5 dataset,the model achieved an RMSE of 1.33 m s^(-1)for wind speed and 1.75 m s^(-1)for maximum wind speed.The AST-GAN model outperforms other state-of-the-art models in RMSE on both the HWRF and ERA5 datasets,maintaining its superior performance and demonstrating its effectiveness for spatiotemporal prediction of TCs.展开更多
Sea ice and snow are the most sensitive and important crucial components of the global climate system,affecting the global climate by modulating the energy exchange between the ocean and the atmosphere.The sea near Zh...Sea ice and snow are the most sensitive and important crucial components of the global climate system,affecting the global climate by modulating the energy exchange between the ocean and the atmosphere.The sea near Zhongshan Station in Antarctica is covered by landfast sea ice,with snow depth influenced by both thermal factors and wind.This region frequently experiences katabatic winds and cyclones from the westerlies,leading to frequent snow blowing events that redistribute the snow and affects its depth,subsequently impacting the thermodynamic growth of sea ice.This study utilized the one-dimensional thermodynamic model ICEPACK to simulate landfast sea ice thickness and snow depth near Zhongshan Station in 2016.Two parameterization schemes for snow blowing,the Bulk scheme,and the ITDrdg(ITD/ridges)scheme are evaluated for their impact on snow depth.The results show that simulations using snow blowing schemes more closely align with observed results,with the ITDrdg scheme providing more accurate simulations,evidenced by root mean square errors of less than 10 cm for both snow depth and sea ice thickness.Snow blowing also impacts the thermodynamic growth of sea ice,particularly bottom growth.The sea ice bottom increases by 9.0 cm using the ITDrdg scheme compared to simulations without the snow blowing,accounting for 12.5%of total sea ice bottom growth.Furthermore,snow blowing process also influences snow ice formation,highlighting its primary role in affecting snow depth.Continued field observations of snow blowing are necessary to evaluate and improve parameterization schemes.展开更多
全基因组复制在动植物中普遍存在,被认为是促进物种进化的重要动力之一。作为蕨类植物的单种科物种,翼盖蕨(Didymochlaena trancatula)是真水龙骨类I的基部类群,在蕨类中具有独特的演化地位。本研究基于高通量测序,通过同义替换率(Ks)...全基因组复制在动植物中普遍存在,被认为是促进物种进化的重要动力之一。作为蕨类植物的单种科物种,翼盖蕨(Didymochlaena trancatula)是真水龙骨类I的基部类群,在蕨类中具有独特的演化地位。本研究基于高通量测序,通过同义替换率(Ks)分析、相对定年分析揭示翼盖蕨的全基因组复制发生情况。Ks分析表明,翼盖蕨至少经历了两次全基因组复制事件,其中一次发生于59–62 million years ago (Mya),另一次发生于90–94 Mya,这两次全基因组复制事件分别和白垩纪第三纪的Cretaceous-Tertiary(C-T)大灭绝事件以及翼盖蕨的物种分化时间相吻合。进一步对两次全基因组复制保留的基因进行功能注释和富集分析,结果显示与转录及代谢调控相关的基因优势被保留。翼盖蕨的全基因组复制事件可能促进了该物种的分化及其对极端环境的适应性。展开更多
Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is ...Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is also active in traumatic brain injury.In this study,we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury.Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function.In addition,in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice,the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased,and the total number of dendritic spines was increased.Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis,and inhibiting this process could be a new strategy for treating traumatic brain injury.展开更多
Objective:To observe the regulatory effects of RhoA/ROCK pathway on the apoptosis of cardiac myocyte induced by anoxia and its mechanism.Methods:The model of cardiac myocyte anoxia was established.The beat pulsations ...Objective:To observe the regulatory effects of RhoA/ROCK pathway on the apoptosis of cardiac myocyte induced by anoxia and its mechanism.Methods:The model of cardiac myocyte anoxia was established.The beat pulsations and apoptosis rales after 1 h,3 h,6 h,9 h and 12 h of anoxia were recorded and the expressions of RhoA,ROCK1/2,p-PI3 K,p-AKT and caspae-3 were detected,too.The apoptosis and the expressions of related proteins were detected after RNAi of RhoA and the inhibition of ROCK by Y-27632.Results:The beat pulsations after 1 h,3 h,6 h.9h and 12 h decreased gradually but the apoptosis rates increased gradually,and the expressions of RhoA,ROCK1/2,p-P13 K,p-AKT and caspase-3 were increasing along with the increasing duration of anoxia.The apoptotic rales after 1 h,3 h,6 h.9 h and 12 h of anoxia were(4.36±0.98)%,(8.36±2.12)%,(15.32±3.62)%,(18.68±4.83)%and(24.56±6.22)%.respectively and decreased more significantly than control group in different time points of anoxia(P<0.05).and the expressions of RhoA,ROCK1/2,p-PI3 K,p-AKT and caspase-3 decreased significantly(P<0.05).The apoptosis rate and the expressions of RhoA,ROCK1/2,p-PI3 K,p-AKT and caspase-3 decreased significantly(P<0.05) after the inhibition of ROCK by Y-27632(P<0.05).Conclusions:RhoA/ROCK pathway plays a critical role in the regulation of the apoptosis of cardiac myocyte induced by anoxia,which may be accompanied by regulating the activity of PI3K/AKT/Caspase-3 pathway.展开更多
Ferns and lycophytes have remarkably large genomes.However,little is known about how their genome size evolved in fern lineages.To explore the origins and evolution of chromosome numbers and genome size in ferns,we us...Ferns and lycophytes have remarkably large genomes.However,little is known about how their genome size evolved in fern lineages.To explore the origins and evolution of chromosome numbers and genome size in ferns,we used flow cytometry to measure the genomes of 240 species(255 samples)of extant ferns and lycophytes comprising 27 families and 72 genera,of which 228 species(242 samples)represent new reports.We analyzed correlations among genome size,spore size,chromosomal features,phylogeny,and habitat type preference within a phylogenetic framework.We also applied ANOVA and multinomial logistic regression analysis to preference of habitat type and genome size.Using the phylogeny,we conducted ancestral character reconstruction for habitat types and tested whether genome size changes simultaneously with shifts in habitat preference.We found that 2 C values had weak phylogenetic signal,whereas the base number of chromosomes(x)had a strong phylogenetic signal.Furthermore,our analyses revealed a positive correlation between genome size and chromosome traits,indicating that the base number of chromosomes(x),chromosome size,and polyploidization may be primary contributors to genome expansion in ferns and lycophytes.Genome sizes in different habitat types varied significantly and were significantly correlated with habitat types;specifically,multinomial logistic regression indicated that species with larger 2 C values were more likely to be epiphytes.Terrestrial habitat is inferred to be ancestral for both extant ferns and lycophytes,whereas transitions to other habitat types occurred as the major clades emerged.Shifts in habitat types appear be followed by periods of genomic stability.Based on these results,we inferred that habitat type changes and multiple whole-genome duplications have contributed to the formation of large genomes of ferns and their allies during their evolutionary history.展开更多
Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely ...Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely unknown.We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19.We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome,RNA,chromatin immunoprecipitation and high-throughput chromosome conformation capture(Hi-C)sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis.Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with correlation found between three-dimensional(3D)structural change and gene expression.Importantly,HPV integration divided one topologically associated domain(TAD)into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106,with a decrease in PEG3 expression and an increase in CCDC106 expression.This expression dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same HPV-CCDC106 integration.In summary,we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling.Thus,this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis.展开更多
AIM: To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. METHODS: Colonization of BIFICO strains ...AIM: To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. METHODS: Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-kappa B and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. RESULTS: We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifido-bacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori -induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-alpha, IL-1 beta, IL-10, IL-6, G-CSF and MIP-2 (P < 0.05). These results led us to hypothesize that BIFICO treatment would diminish the H. pylori-induced inflammatory response in gastric mucosal epithelial cells in vitro via the NF-kappa B and MAPK signaling pathways. Indeed, we observed a decrease in the expression of the NF-kappa B subunit p65 and in the phosphorylation of I kappa B-alpha, ERK and p38. Moreover, there was a significant decrease in the production of IL-8, TNF-alpha, G-CSF and GM-CSF (P < 0.05), and the increased expression of TLR2, TLR4 and MyD88 induced by H. pylori in the stomach was also significantly reduced following BIFICO treatment (P < 0.05). CONCLUSION: Our results suggest that the probiotic cocktail BIFICO can ameliorate H. pylori-induced gastritis by inhibiting the inflammatory response in gastric epithelial cells.展开更多
In recent years,research on meditation as an important alternative therapy has developed rapidly and been widely applied in clinical medicine.Mechanism studies of meditation have also developed progressively,showing t...In recent years,research on meditation as an important alternative therapy has developed rapidly and been widely applied in clinical medicine.Mechanism studies of meditation have also developed progressively,showing that meditation has great impact on brain structure and function,and epigenetic and telomere regulation.In line with this,the application of meditation has gradually been expanded to mental illness,most often applied for major depressive disorders and substance-related and addictive disorders.The focus of this paper is to illustrate the biological mechanisms of meditation and its application in mental disorders.展开更多
Rare earth garnet(R_(3)Fe_(5)O_(12),RIG)single crystals are the most ideal magneto-optical medium for optical isolators for wavelength longer than 1.1μm,which has been commercially used in optical fiber communication...Rare earth garnet(R_(3)Fe_(5)O_(12),RIG)single crystals are the most ideal magneto-optical medium for optical isolators for wavelength longer than 1.1μm,which has been commercially used in optical fiber communications.However,it is still a great challenge to grow large size RIG single crystals.In this work,highquality Y3 Fe5 O12(YIG)and Bi_(0.9)Tb_(2.1)Fe_(5)O_(12)(Bi:TIG)single crystals were successfully grown by the flux-Bridgman method for the first time.The as-grown crystals up to 20 mm in diameter was obtained using the PbO-B_(2)O_(3)flux.The transmittance of YIG crystals is over 75%in the region of 1100-2500 nm.TIG crystals also have good transmittance in the range of 1100-1700 nm,and show typical Tb absorption from 1700 to 2500 nm.The specific Faraday rotations of YIG and Bi_(0.9)Tb_(2.1)Fe_(5)O_(12) crystals are 185(°)/cm and-1250(°)/cm at 1550 nm,which are comparable to the commercial RIG crystals grown by LPE method.The present results indicate that flux-Bridgman method shows great potential to grow large size and high-quality RIG magneto-optical crystals.展开更多
Cryptic species are commonly misidentified because of high morphological similarities to other species.One group of plants that may harbor large numbers of cryptic species is the quillworts(Isoetes spp.),an ancient aq...Cryptic species are commonly misidentified because of high morphological similarities to other species.One group of plants that may harbor large numbers of cryptic species is the quillworts(Isoetes spp.),an ancient aquatic plant lineage.Although over 350 species of Isoetes have been reported globally,only ten species have been recorded in China.The aim of this study is to better understand Isoetes species diversity in China.For this purpose,we systematically explored the phylogeny and evolution of Isoetes using complete chloroplast genome(plastome)data,spore morphology,chromosome number,genetic structure,and haplotypes of almost all Chinese Isoetes populations.We identified three ploidy levels of Isoetes in Chinaddiploid(2n=22),tetraploid(2n=44),and hexaploid(2n=66).We also found four megaspore and microspore ornamentation types in diploids,six in tetraploids,and three in hexaploids.Phylogenetic analyses confirmed that I.hypsophila as the ancestral group of the genus and revealed that Isoetes diploids,tetraploids,and hexaploids do not form monophyletic clades.Most individual species possess a single genetic structure;however,several samples have conflicting positions on the phylogenetic tree based on SNPs and the tree based on plastome data.All 36 samples shared 22 haplotypes.Divergence time analysis showed that I.hypsophila diverged in the early Eocene(~48.05 Ma),and most other Isoetes species diverged 3-20 Ma.Additionally,different species of Isoetes were found to inhabit different water systems and environments along the Yangtze River.These findings provide new insights into the relationships among Isoetes species in China,where highly similar morphologic populations may harbor many cryptic species.展开更多
BACKGROUND Pseudomonas aeruginosa(P.aeruginosa)is an important cause of nosocomial infections,and contributes to high morbidity and mortality,especially in intensive care units.P.aeruginosa is considered a'critica...BACKGROUND Pseudomonas aeruginosa(P.aeruginosa)is an important cause of nosocomial infections,and contributes to high morbidity and mortality,especially in intensive care units.P.aeruginosa is considered a'critical'category bacterial pathogen by the World Health Organization to encourage an urgent need for research and development of new antibiotics against its infections.AIM To investigate the effectiveness of baicalin combined with tobramycin therapy as a potential treatment method for carbapenem-resistant P.aeruginosa(CRPA)infections.METHODS Polymerase chain reaction(PCR)and RT-PCR were used to detect the expression levels of drug-resistant genes(including VIM,IMP and OprD2)and biofilmrelated genes(including algD,pslA and lasR)in CRPA that confer resistance to tobramycin,baicalin and tobramycin combined with baicalin(0,1/8,1/4,1/2 and 1MIC).RESULTS There was a correlation between biofilm formation and the expression of biofilmrelated genes.In addition,VIM,IMP,OprD2,algD,pslA and lasR that confer biofilm production under different concentrations in CRPA were significantly correlated.The synergistic effect of baicalin combined with tobramycin was a significant down-regulation of VIM,IMP,algD,pslA and lasR.CONCLUSION Baicalin combined with tobramycin therapy can be an effective treatment method for patients with CRPA infection.展开更多
Netrin-1 is currently one of the most highly studied axon guidance factors. Netrin-1 is widely expressed in the embryonic central nervous system, and together with the deleted in colorectal cancer and uncoordinated lo...Netrin-1 is currently one of the most highly studied axon guidance factors. Netrin-1 is widely expressed in the embryonic central nervous system, and together with the deleted in colorectal cancer and uncoordinated locomotion-5 homolog B receptors, netrin-1 plays a guiding role in the construction of neural conduction pathways and the directional migration of neuronal cells. In this study, we established a rat middle cerebral artery ischemia reperfusion model using the intraluminal thread technique. Immunofluorescence microscopy showed that the expression of netrin-1 and deleted in colorectal cancer in the ischemic penumbra was upregulated at 1 day after reperfusion, reached a peak at 14 days, and decreased at 21 days. There was no obvious change in the expression of uncoordinated locomotion-5 homolog B during this time period. Double immunofluorescence labeling revealed that netrin-1 was expressed in neuronal cells and around small vessels, but not in astrocytes and microglia, while deleted in colorectal cancer was localized in the cell membranes and protrusions of neurons and astrocytes. Our experimental findings indicate that netrin-1 may be involved in post-ischemic repair and neuronal protection via deleted in colorectal cancer receptors.展开更多
Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and...Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.展开更多
TiNi alloys with high content Ni(52-55 at.%)are perfectly suitable for preparing wear-and corrosionresistant parts that service on the space station,spacecraft,and submarine,because of their superior superelasticity,h...TiNi alloys with high content Ni(52-55 at.%)are perfectly suitable for preparing wear-and corrosionresistant parts that service on the space station,spacecraft,and submarine,because of their superior superelasticity,high strength,and hardwearing.However,the fabrication of complicated Ni-rich TiNi parts by the traditional machining method often faces problems of poor precision,low efficiency,and high cost.In this work,we succeed in preparing an excellent Ti_(47)Ni_(53) alloy by selective laser melting(SLM),and thus,open a new way for the efficient and precise formation of complicated Ni-rich TiNi parts with superelasticity and hardwearing.An optimized processing window for compact parts without defects is reported.The elaborately fabricated Ti_(47)Ni_(53) alloy exhibited a breaking strain of 11%,a breaking stress of 2.0 GPa,a superelastic strain of 9%,and a better hardwearing than that of casting and quenched Ti_(47)Ni_(53) alloy.Besides,the microstructure,phase transformation,and deformation,as well as their influence mechanisms are investigated by in situ transmission electron microscope(TEM)and high-energy X-ray diffraction(HE-XRD).The results obtained are of significance for both fundamental research and technological applications of SLM-fabricated high Ni content TiNi alloys.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
基金supported in part by grants from the National Key R&D Program of China(Nos.2022YFE0210600 and 2019YFE0123700)the National Natural Science Foundation of China(Nos.22307116 and 82173745)+4 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2024A1515012186,China)the Science and Technology Program of Guangzhou(No.2025A04J4520,China)Guangdong Province Grant for Belt and Road Joint Laboratory(No.2022B1212050004,China)the Youth Innovation Promotion Association CAS(No.2023372,China)the Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences(Nos.GIBHBRP24-03 and GIBHBRP24-04,China).
文摘The bromodomain-containing protein 9(BRD9)is a core subunit of mammalian SWI/SNF chromatin remodeling complex termed ncBAF.BRD9 has emerged as a potential target for anticancer drugs,particularly in the treatment of acute myeloid leukemia(AML).Herein,we reported 10m(Y22073)and 10t as new BRD9 selective bromodomain inhibitors.Crystallographic studies revealed that the key active imidazolyl group discovered from structure-activity relationship(SAR)can induce Phe163 flipping and significantly enhance the cellular potency of the compounds,making 10m the first BRD9 selective inhibitor with significant cellular activity against AML cells.We also validated the critical role of imidazolyl groups by modifying existing BRD9 inhibitors.The representative compounds 10m and 10t demonstrated potent binding affinity,outstanding selectivity toward BRD9 bromodomain,and significantly inhibited the proliferation of AML cell lines.10m also showed good metabolic stability,solubility and pharmacokinetic properties.Additionally,oral administration of compounds 10m and 10t exhibited potent anti-tumor efficacy in the MV4-11 xenograft mouse model.The potent,selective,and orally available BRD9 bromodomain inhibitors may address the challenges of weak cellular activity and limited phenotypic efficacy faced by BRD9 inhibitors,and serve as new lead compounds for the development of anticancer agents for the treatment of AML.
基金Wu Jieping Medical Foundation,No.320.6750.2021-02-113.
文摘BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therapeutic options for NECs remain limited,contributing to the poor prognosis of patients.Immunotherapy has emerged as a promising treatment strategy and demonstrated the potential to partially improve the survival and prognosis of patients with NECs.Nevertheless,the unique clinical response termed pseudoprogression(PsP)has garnered considerable attention in the context of immunotherapy.CASE SUMMARY Presented here is a case of NEC recurrence five and a half months after radical gastric surgery.The 45-year-old male patient underwent combination treatment involving a PD-1 blocker and tyrosine kinase inhibitors and encountered two instances of PsP during treatment.The patient ultimately achieved a durable treatment response without altering his treatment regimens,resulting in a substantial therapeutic benefit.CONCLUSION This case report aimed to provide the authors’experience with the diagnosis of PsP and treatment strategies for PsP in ongoing immunotherapy.
基金supported by the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(NO.SML2021SP201)the National Natural Science Foundation of China(Grant No.42306200 and 42306216)+2 种基金the National Key Research and Development Program of China(Grant No.2023YFC3008100)the Innovation Group Project of the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(Grant No.311021004)the Oceanic Interdisciplinary Program of Shanghai Jiao Tong University(Project No.SL2021ZD203)。
文摘Tropical cyclones(TCs)are complex and powerful weather systems,and accurately forecasting their path,structure,and intensity remains a critical focus and challenge in meteorological research.In this paper,we propose an Attention Spatio-Temporal predictive Generative Adversarial Network(AST-GAN)model for predicting the temporal and spatial distribution of TCs.The model forecasts the spatial distribution of TC wind speeds for the next 15 hours at 3-hour intervals,emphasizing the cyclone's center,high wind-speed areas,and its asymmetric structure.To effectively capture spatiotemporal feature transfer at different time steps,we employ a channel attention mechanism for feature selection,enhancing model performance and reducing parameter redundancy.We utilized High-Resolution Weather Research and Forecasting(HWRF)data to train our model,allowing it to assimilate a wide range of TC motion patterns.The model is versatile and can be applied to various complex scenarios,such as multiple TCs moving simultaneously or TCs approaching landfall.Our proposed model demonstrates superior forecasting performance,achieving a root-mean-square error(RMSE)of 0.71 m s^(-1)for overall wind speed and 2.74 m s^(-1)for maximum wind speed when benchmarked against ground truth data from HWRF.Furthermore,the model underwent optimization and independent testing using ERA5reanalysis data,showcasing its stability and scalability.After fine-tuning on the ERA5 dataset,the model achieved an RMSE of 1.33 m s^(-1)for wind speed and 1.75 m s^(-1)for maximum wind speed.The AST-GAN model outperforms other state-of-the-art models in RMSE on both the HWRF and ERA5 datasets,maintaining its superior performance and demonstrating its effectiveness for spatiotemporal prediction of TCs.
基金The National Natural Science Foundation of China under contract Nos 42306255 and 41976217the National Key R&D Program of China under contract No.2018YFA0605903。
文摘Sea ice and snow are the most sensitive and important crucial components of the global climate system,affecting the global climate by modulating the energy exchange between the ocean and the atmosphere.The sea near Zhongshan Station in Antarctica is covered by landfast sea ice,with snow depth influenced by both thermal factors and wind.This region frequently experiences katabatic winds and cyclones from the westerlies,leading to frequent snow blowing events that redistribute the snow and affects its depth,subsequently impacting the thermodynamic growth of sea ice.This study utilized the one-dimensional thermodynamic model ICEPACK to simulate landfast sea ice thickness and snow depth near Zhongshan Station in 2016.Two parameterization schemes for snow blowing,the Bulk scheme,and the ITDrdg(ITD/ridges)scheme are evaluated for their impact on snow depth.The results show that simulations using snow blowing schemes more closely align with observed results,with the ITDrdg scheme providing more accurate simulations,evidenced by root mean square errors of less than 10 cm for both snow depth and sea ice thickness.Snow blowing also impacts the thermodynamic growth of sea ice,particularly bottom growth.The sea ice bottom increases by 9.0 cm using the ITDrdg scheme compared to simulations without the snow blowing,accounting for 12.5%of total sea ice bottom growth.Furthermore,snow blowing process also influences snow ice formation,highlighting its primary role in affecting snow depth.Continued field observations of snow blowing are necessary to evaluate and improve parameterization schemes.
文摘全基因组复制在动植物中普遍存在,被认为是促进物种进化的重要动力之一。作为蕨类植物的单种科物种,翼盖蕨(Didymochlaena trancatula)是真水龙骨类I的基部类群,在蕨类中具有独特的演化地位。本研究基于高通量测序,通过同义替换率(Ks)分析、相对定年分析揭示翼盖蕨的全基因组复制发生情况。Ks分析表明,翼盖蕨至少经历了两次全基因组复制事件,其中一次发生于59–62 million years ago (Mya),另一次发生于90–94 Mya,这两次全基因组复制事件分别和白垩纪第三纪的Cretaceous-Tertiary(C-T)大灭绝事件以及翼盖蕨的物种分化时间相吻合。进一步对两次全基因组复制保留的基因进行功能注释和富集分析,结果显示与转录及代谢调控相关的基因优势被保留。翼盖蕨的全基因组复制事件可能促进了该物种的分化及其对极端环境的适应性。
基金supported by the National Key R&D Program of China,No.2019YFA0112000(to YHT)the National Natural Science Foundation of China,Nos.82071284(to YHT),81974179(to ZJZ)+4 种基金Shanghai Rising-Star Program,No.21QA1405200(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)the Notional Research Foundation of Korea,Nos.2020M3E5D9079912(to WSC),2021R1A2C3005704(to WSC),2022M3E5E8081188(to WSC)the Korea Health Technology R&D Project,No.HU20C0290(to WSC)。
文摘Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is also active in traumatic brain injury.In this study,we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury.Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function.In addition,in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice,the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased,and the total number of dendritic spines was increased.Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis,and inhibiting this process could be a new strategy for treating traumatic brain injury.
基金supported by the Science Foundation of Wuhan University(Grant No:201255M152)
文摘Objective:To observe the regulatory effects of RhoA/ROCK pathway on the apoptosis of cardiac myocyte induced by anoxia and its mechanism.Methods:The model of cardiac myocyte anoxia was established.The beat pulsations and apoptosis rales after 1 h,3 h,6 h,9 h and 12 h of anoxia were recorded and the expressions of RhoA,ROCK1/2,p-PI3 K,p-AKT and caspae-3 were detected,too.The apoptosis and the expressions of related proteins were detected after RNAi of RhoA and the inhibition of ROCK by Y-27632.Results:The beat pulsations after 1 h,3 h,6 h.9h and 12 h decreased gradually but the apoptosis rates increased gradually,and the expressions of RhoA,ROCK1/2,p-P13 K,p-AKT and caspase-3 were increasing along with the increasing duration of anoxia.The apoptotic rales after 1 h,3 h,6 h.9 h and 12 h of anoxia were(4.36±0.98)%,(8.36±2.12)%,(15.32±3.62)%,(18.68±4.83)%and(24.56±6.22)%.respectively and decreased more significantly than control group in different time points of anoxia(P<0.05).and the expressions of RhoA,ROCK1/2,p-PI3 K,p-AKT and caspase-3 decreased significantly(P<0.05).The apoptosis rate and the expressions of RhoA,ROCK1/2,p-PI3 K,p-AKT and caspase-3 decreased significantly(P<0.05) after the inhibition of ROCK by Y-27632(P<0.05).Conclusions:RhoA/ROCK pathway plays a critical role in the regulation of the apoptosis of cardiac myocyte induced by anoxia,which may be accompanied by regulating the activity of PI3K/AKT/Caspase-3 pathway.
基金the National Natural Science Foundation of China(grant number 31870188,31800174,31700172,41571056)to Wang,Shen,Wang and XingShanghai Landscaping and City Appearance Administrative Bureau of China,Scientific Research Grants(G182411)to Yan+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(grant number XDA13020603,XDA13020500)to Chen and JianGuangdong Natural Science Foundation(grant number 2015A030308015)to Wang。
文摘Ferns and lycophytes have remarkably large genomes.However,little is known about how their genome size evolved in fern lineages.To explore the origins and evolution of chromosome numbers and genome size in ferns,we used flow cytometry to measure the genomes of 240 species(255 samples)of extant ferns and lycophytes comprising 27 families and 72 genera,of which 228 species(242 samples)represent new reports.We analyzed correlations among genome size,spore size,chromosomal features,phylogeny,and habitat type preference within a phylogenetic framework.We also applied ANOVA and multinomial logistic regression analysis to preference of habitat type and genome size.Using the phylogeny,we conducted ancestral character reconstruction for habitat types and tested whether genome size changes simultaneously with shifts in habitat preference.We found that 2 C values had weak phylogenetic signal,whereas the base number of chromosomes(x)had a strong phylogenetic signal.Furthermore,our analyses revealed a positive correlation between genome size and chromosome traits,indicating that the base number of chromosomes(x),chromosome size,and polyploidization may be primary contributors to genome expansion in ferns and lycophytes.Genome sizes in different habitat types varied significantly and were significantly correlated with habitat types;specifically,multinomial logistic regression indicated that species with larger 2 C values were more likely to be epiphytes.Terrestrial habitat is inferred to be ancestral for both extant ferns and lycophytes,whereas transitions to other habitat types occurred as the major clades emerged.Shifts in habitat types appear be followed by periods of genomic stability.Based on these results,we inferred that habitat type changes and multiple whole-genome duplications have contributed to the formation of large genomes of ferns and their allies during their evolutionary history.
基金supported by the National Natural Science Foundation of China(81630060 to P.W.,31771402 to G.L.,81830074 and 81772786 to H.W.,81572569 to G.C.,and 81772775 to J.W.)National Science and Technology Major Project(2019YFC1005202 and 2019YFC1005201 to K.L.,and 2018ZX10301402-002 to Q.G.)the research-oriented clinician funding program of Tongji Medical College,Huazhong University of Science and Technology for P.W
文摘Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely unknown.We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19.We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome,RNA,chromatin immunoprecipitation and high-throughput chromosome conformation capture(Hi-C)sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis.Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with correlation found between three-dimensional(3D)structural change and gene expression.Importantly,HPV integration divided one topologically associated domain(TAD)into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106,with a decrease in PEG3 expression and an increase in CCDC106 expression.This expression dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same HPV-CCDC106 integration.In summary,we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling.Thus,this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis.
基金Supported by National Natural Science Foundation of China,No.81274164Shanghai Manufacture-Education-ResearchMedical Cooperative Project,No 12DZ1930505
文摘AIM: To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. METHODS: Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-kappa B and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. RESULTS: We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifido-bacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori -induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-alpha, IL-1 beta, IL-10, IL-6, G-CSF and MIP-2 (P < 0.05). These results led us to hypothesize that BIFICO treatment would diminish the H. pylori-induced inflammatory response in gastric mucosal epithelial cells in vitro via the NF-kappa B and MAPK signaling pathways. Indeed, we observed a decrease in the expression of the NF-kappa B subunit p65 and in the phosphorylation of I kappa B-alpha, ERK and p38. Moreover, there was a significant decrease in the production of IL-8, TNF-alpha, G-CSF and GM-CSF (P < 0.05), and the increased expression of TLR2, TLR4 and MyD88 induced by H. pylori in the stomach was also significantly reduced following BIFICO treatment (P < 0.05). CONCLUSION: Our results suggest that the probiotic cocktail BIFICO can ameliorate H. pylori-induced gastritis by inhibiting the inflammatory response in gastric epithelial cells.
基金This study was funded by the following fundings:Shanghai Jiao Tong University Medical and Engineering Joint Grant(YG2016ZD06)Shanghai Jiao Tong University Joint Art and Science Funding(14JCRZ05)+1 种基金National Natural Science Foundation of China(81671336)National Key R&D Program of China(2017YFC0909200)。
文摘In recent years,research on meditation as an important alternative therapy has developed rapidly and been widely applied in clinical medicine.Mechanism studies of meditation have also developed progressively,showing that meditation has great impact on brain structure and function,and epigenetic and telomere regulation.In line with this,the application of meditation has gradually been expanded to mental illness,most often applied for major depressive disorders and substance-related and addictive disorders.The focus of this paper is to illustrate the biological mechanisms of meditation and its application in mental disorders.
基金Project supported by State Key Laboratory of Crystal Materials,China(KF1810)Shanghai Municipal Commission of Economy and Informatization,China(GYQJ-2020-1-19)。
文摘Rare earth garnet(R_(3)Fe_(5)O_(12),RIG)single crystals are the most ideal magneto-optical medium for optical isolators for wavelength longer than 1.1μm,which has been commercially used in optical fiber communications.However,it is still a great challenge to grow large size RIG single crystals.In this work,highquality Y3 Fe5 O12(YIG)and Bi_(0.9)Tb_(2.1)Fe_(5)O_(12)(Bi:TIG)single crystals were successfully grown by the flux-Bridgman method for the first time.The as-grown crystals up to 20 mm in diameter was obtained using the PbO-B_(2)O_(3)flux.The transmittance of YIG crystals is over 75%in the region of 1100-2500 nm.TIG crystals also have good transmittance in the range of 1100-1700 nm,and show typical Tb absorption from 1700 to 2500 nm.The specific Faraday rotations of YIG and Bi_(0.9)Tb_(2.1)Fe_(5)O_(12) crystals are 185(°)/cm and-1250(°)/cm at 1550 nm,which are comparable to the commercial RIG crystals grown by LPE method.The present results indicate that flux-Bridgman method shows great potential to grow large size and high-quality RIG magneto-optical crystals.
基金This study was supported by the Key Laboratory of National Forestry and Grassland Administration for Orchid Conservation and Utilization(grant number OC202103)the Harbin Normal University Postgraduate Innovation Project(grant number HSDBSCX2021-01)+1 种基金the National Natural Science Foundation of China General Projects(grant number 32170216)the Hangzhou Science and Technology Development Project(grant number 20201203B113).
文摘Cryptic species are commonly misidentified because of high morphological similarities to other species.One group of plants that may harbor large numbers of cryptic species is the quillworts(Isoetes spp.),an ancient aquatic plant lineage.Although over 350 species of Isoetes have been reported globally,only ten species have been recorded in China.The aim of this study is to better understand Isoetes species diversity in China.For this purpose,we systematically explored the phylogeny and evolution of Isoetes using complete chloroplast genome(plastome)data,spore morphology,chromosome number,genetic structure,and haplotypes of almost all Chinese Isoetes populations.We identified three ploidy levels of Isoetes in Chinaddiploid(2n=22),tetraploid(2n=44),and hexaploid(2n=66).We also found four megaspore and microspore ornamentation types in diploids,six in tetraploids,and three in hexaploids.Phylogenetic analyses confirmed that I.hypsophila as the ancestral group of the genus and revealed that Isoetes diploids,tetraploids,and hexaploids do not form monophyletic clades.Most individual species possess a single genetic structure;however,several samples have conflicting positions on the phylogenetic tree based on SNPs and the tree based on plastome data.All 36 samples shared 22 haplotypes.Divergence time analysis showed that I.hypsophila diverged in the early Eocene(~48.05 Ma),and most other Isoetes species diverged 3-20 Ma.Additionally,different species of Isoetes were found to inhabit different water systems and environments along the Yangtze River.These findings provide new insights into the relationships among Isoetes species in China,where highly similar morphologic populations may harbor many cryptic species.
基金Supported by Jiaxing Science and Technology Planning Project,No.2019AY32006 and No.2020AY30004。
文摘BACKGROUND Pseudomonas aeruginosa(P.aeruginosa)is an important cause of nosocomial infections,and contributes to high morbidity and mortality,especially in intensive care units.P.aeruginosa is considered a'critical'category bacterial pathogen by the World Health Organization to encourage an urgent need for research and development of new antibiotics against its infections.AIM To investigate the effectiveness of baicalin combined with tobramycin therapy as a potential treatment method for carbapenem-resistant P.aeruginosa(CRPA)infections.METHODS Polymerase chain reaction(PCR)and RT-PCR were used to detect the expression levels of drug-resistant genes(including VIM,IMP and OprD2)and biofilmrelated genes(including algD,pslA and lasR)in CRPA that confer resistance to tobramycin,baicalin and tobramycin combined with baicalin(0,1/8,1/4,1/2 and 1MIC).RESULTS There was a correlation between biofilm formation and the expression of biofilmrelated genes.In addition,VIM,IMP,OprD2,algD,pslA and lasR that confer biofilm production under different concentrations in CRPA were significantly correlated.The synergistic effect of baicalin combined with tobramycin was a significant down-regulation of VIM,IMP,algD,pslA and lasR.CONCLUSION Baicalin combined with tobramycin therapy can be an effective treatment method for patients with CRPA infection.
基金supported by the Science and Technology Program of Suzhou Industrial Park in China
文摘Netrin-1 is currently one of the most highly studied axon guidance factors. Netrin-1 is widely expressed in the embryonic central nervous system, and together with the deleted in colorectal cancer and uncoordinated locomotion-5 homolog B receptors, netrin-1 plays a guiding role in the construction of neural conduction pathways and the directional migration of neuronal cells. In this study, we established a rat middle cerebral artery ischemia reperfusion model using the intraluminal thread technique. Immunofluorescence microscopy showed that the expression of netrin-1 and deleted in colorectal cancer in the ischemic penumbra was upregulated at 1 day after reperfusion, reached a peak at 14 days, and decreased at 21 days. There was no obvious change in the expression of uncoordinated locomotion-5 homolog B during this time period. Double immunofluorescence labeling revealed that netrin-1 was expressed in neuronal cells and around small vessels, but not in astrocytes and microglia, while deleted in colorectal cancer was localized in the cell membranes and protrusions of neurons and astrocytes. Our experimental findings indicate that netrin-1 may be involved in post-ischemic repair and neuronal protection via deleted in colorectal cancer receptors.
基金supported by the National Natural Science Foundation of China,Nos.62027812(to HS),81771470(to HS),and 82101608(to YL)Tianjin Postgraduate Research and Innovation Project,No.2020YJSS122(to XD)。
文摘Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.
基金financially supported by the National Key R&D Program of China(No.2018YFB1105100)the NSFC(Nos.51971244 and 51731010)+1 种基金the Advanced Structural Technology Foundation of China(No.2020-JCJQ-JJ-024)supported by the US Department of Energy,Office of Science and thr Office of Basic Energy Science,under Contract No.DE-AC02-06CH11357。
文摘TiNi alloys with high content Ni(52-55 at.%)are perfectly suitable for preparing wear-and corrosionresistant parts that service on the space station,spacecraft,and submarine,because of their superior superelasticity,high strength,and hardwearing.However,the fabrication of complicated Ni-rich TiNi parts by the traditional machining method often faces problems of poor precision,low efficiency,and high cost.In this work,we succeed in preparing an excellent Ti_(47)Ni_(53) alloy by selective laser melting(SLM),and thus,open a new way for the efficient and precise formation of complicated Ni-rich TiNi parts with superelasticity and hardwearing.An optimized processing window for compact parts without defects is reported.The elaborately fabricated Ti_(47)Ni_(53) alloy exhibited a breaking strain of 11%,a breaking stress of 2.0 GPa,a superelastic strain of 9%,and a better hardwearing than that of casting and quenched Ti_(47)Ni_(53) alloy.Besides,the microstructure,phase transformation,and deformation,as well as their influence mechanisms are investigated by in situ transmission electron microscope(TEM)and high-energy X-ray diffraction(HE-XRD).The results obtained are of significance for both fundamental research and technological applications of SLM-fabricated high Ni content TiNi alloys.
