Compared to North American shale composition (NASC), REE contents of sediments from the CC area in the Pacific Ocean are obviously high except that cerium has equal content to that of NASC. Three-valence rare earth el...Compared to North American shale composition (NASC), REE contents of sediments from the CC area in the Pacific Ocean are obviously high except that cerium has equal content to that of NASC. Three-valence rare earth elements were completely enriched in phosphate-phase and cerium in iron-phase. Rare earth elements in the sediments were originally derived from seawater. During lithi- genic and minerogenic processes of metalliferous nodules, three-valence rare earth elements in sediments mobilized and incorporated into sediments as authigenous biogenic-apatite, while cerium had change from Ce3+ to Ce4+ and directly precipitated from seawater and entered metalliferous nodules and caused Ce anomalies in REE pattern in sediments.展开更多
Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB th...Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB through stomach perfusion for 10 d (50 mg/d). Then, RBC-C3bR rate,RBC-IC rate (as the index- es of erythrocyte immunity)and E-rosette forming rate,acidic a-naphthyl acetate esterase positive rate, lymphocyte transformation rate (as the indexes of cellular immunity) of mice were tested. Results RBC-C3Br rate, RBC-IC rat- e,E-rosette forming rate, acidic α-naphthyl acetate esterase positive rate and lymphocyte transformation rate in the Cy-RDAEB group were markedly higher than those in the Cy group (P<0.0l),and returned to the levels of normal group. Conclusion RDAEB is effective in recovering and enhancing cellular and erythrocyte immunity of immuno- suppressed mice.展开更多
Objective:To systemically review the efficacy and safety about the method of enriching qi,activating blood circulation,clearing away dampness and heat combined with western medicine in the therapy of patients with idi...Objective:To systemically review the efficacy and safety about the method of enriching qi,activating blood circulation,clearing away dampness and heat combined with western medicine in the therapy of patients with idiopathy membranous nephropathy(IMN).Methods:We collected the randomized controlled trials(RCTs)of enriching qi,activating blood circulation,clearing away dampness and heat for the treatment of IMN from Pub Med,The Cochrane Library,Medline,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),Wanfang Data and Wiper Databases.Bias of risk of retrieval literature was evaluated according to Cochrane Collaboration standard,and Review Manager 5.3 software was used for statistical analysis.Results:Fourteen trials(836 participants)were included in the meta-analysis.This kind of traditional Chinese method combined with western medicine in the treatment of IMN exerted statistical differences in reducing 24-hour urinary protein[WMD=-0.97,95%CI(-1.30,-0.65),Z=5.86(P<0.00001)]and elevating serum albumin[WMD=3.83,95%CI(2.10,5.57),Z=4.33,P<0.0001],lowering serum cholesterol[WMD=-0.82,95%CI(-1.08,-0.56),Z=6.18,P<0.00001],triglycerides[WMD=-0.39,95%CI(-0.67,-0.11),Z=2.77,P=0.006]and reducing the risk of adverse events[OR=0.29,95%CI[0.16,0.50],Z=4.35,P<0.0001]in the patients with IMN as compared with controls.However,there was no statistically significant difference between the method and controls when combining all trials in serum creatinine[WMD=-5.52,95%CI(-18.06,7.03),Z=0.86,P=0.39],when combining all trials in urea nitrogen[WMD=-0.90,95%CI(-2.22,0.41),Z=1.35,P=0.18].Conclusion:The method of enriching qi,activating blood circulation,clearing away dampness and heat combined with western medicine exerts certain advantages and better safety in treating patients with IMN.However,for the inferiority of the included studies,the conclusion still needs high-quality and large-sample prospective randomized controlled trials to verify.展开更多
[Objectives]To screen out the selenium-enriched Pueraria lobata varieties suitable for cultivation in Guangxi according to the natural selenium-enriching ability of 7 main cultivars.[Methods]Taking 7 main cultivars of...[Objectives]To screen out the selenium-enriched Pueraria lobata varieties suitable for cultivation in Guangxi according to the natural selenium-enriching ability of 7 main cultivars.[Methods]Taking 7 main cultivars of P.lobata in different places as experimental materials,field cultivation was carried out on the selenium-enriched yellow soil in Shanglin County,Nanning City of Guangxi,to study the difference in selenium-enriching ability of different main cultivars and the comparison of selenium content in different parts,as well as the transport mechanism.[Results]Under the condition of soil selenium content of 0.78 mg/kg,the selenium content of the root tubers of the 7 main cultivars all reached the selenium-enrichment standard.The selenium content of a single root tuber of Heping Variety in Teng County,Guangxi was the highest,at 0.061 mg/kg;Guifenge No.1 was the second at 0.055 mg/kg,and the total selenium accumulation per unit area was the largest.The ranking of selenium content in different parts of the same variety was:leaf>vine>head>root tuber.[Conclusions]Guifenge No.1 has the highest yield and the largest total selenium accumulation,so it is the most suitable natural selenium-enriched variety for cultivation.展开更多
Background:To explore active components of Lanbuzheng(Gei herba)and its underlying complex mechanism in treating blood deficiency induced by chemotherapy drug based on network pharmacology and mice experimental valida...Background:To explore active components of Lanbuzheng(Gei herba)and its underlying complex mechanism in treating blood deficiency induced by chemotherapy drug based on network pharmacology and mice experimental validation.Methods:Active components of Lanbuzheng(Gei herba)were screened by Lipinski’s rule of five.Targets acted with active components were predicted by PharmMapper database,and targets whose function associated with blood deficiency were screened by Therapeutic Target Database and UniProt.The networks of component-target and target-pathway were constructed by Cytoscape.The levels of peripheral blood and organ indexes were detected in the animal experiments.Results:One hundred and seventy-three components of Lanbuzheng(Gei herba)were collected,and 60 active components were screened according to the rule of five.According to the degree value of compounds,the top 5 compounds were docosyl trans ferulate,C32 decursin,agrimonolide 6-O-β-D-glucoside,degree=11,173-ethoxyphaeophorbide,and eugenol.Finally,59 targets associated with blood deficiency were obtained and the top 5 targets were MAPK14,TTR,CDK2,AKR1B1 and AR.Based on the interaction network of componenttarget and target-pathway,it’s found that 60 active components could act with 59 targets and 44 pathways for treating blood deficiency.And then,the mice experiments showed that Lanbuzheng(Gei herba)could enrich blood by increasing the levels of red blood cell,white blood cell,hemoglobin,red blood cell specific volume and platelet,and the indexes of liver,thymus and spleen,which validated the treating effect of Lanbuzheng(Gei herba).Conclusion:In this study,a network pharmacology approach and animal experiments were established to explore the nourishing blood effect of Lanbuzheng(Gei herba).The results demonstrated that Lanbuzheng(Gei herba)could improve blood deficiency and provide a theoretical basis for the further research on the in-depth mechanism of Lanbuzheng(Gei herba).展开更多
Selenium is one of essential elements for humans, animals and some kinds of plants.The biological function of selenium shows dual characteristics.The range of selenium content is very narrow between toxic and deficien...Selenium is one of essential elements for humans, animals and some kinds of plants.The biological function of selenium shows dual characteristics.The range of selenium content is very narrow between toxic and deficient concentration.Typical Kashin-Beck endemic areas intimately link with selenium deficiency.In one area,selenium levels展开更多
Background The provision of environmental enrichments to Muscovy ducks could reduce the expression of the aggressive behaviors.The aim of the present study was to evaluate the effects of black soldier fly(BSF)and yell...Background The provision of environmental enrichments to Muscovy ducks could reduce the expression of the aggressive behaviors.The aim of the present study was to evaluate the effects of black soldier fly(BSF)and yellow mealworm(YM)live larva provision on Muscovy duck performance,excreta corticosterone metabolites(ECM),behavior,and blood parameters.Methods A total of 1263-day-old female Muscovy ducklings were allotted to 18 pens(6 replicates/treatment,7 birds/pen)and assigned to 3 experimental treatments:a control group fed commercial feed,and two experimental treatments fed commercial feed plus the 5%(based on the expected daily feed intake,as fed basis)of BSF and YM live larvae(BSF and YM groups,respectively).A two-phase feeding program was applied:starter(from 3 to 31 days of age)and grower-finisher(from 32 to 55 days of age).The live weight,average daily gain,average daily feed intake,and feed conversion ratio were calculated.Larva consumption times were collected,and video recordings were performed during 3 periods(P)each day:the hour before(P1),during(P2),and after(P3)the larva administration.ECM were evaluated at 3,31,and 55-day-old.Finally,the total red and white blood cell counts,serum proteins,lipids,and liver and renal function serum enzymes were evaluated on 12 birds/treatment.Results The experimental treatment did not affect the growth performance of the birds(P>0.05).Larva consumption times were always similar between the two insect species,except at 14–18 days of age,were BSF larvae were consumed faster than YM larvae(P<0.001).The birds showed less walking activity during P2,and preening behavior increased in YM birds during P3.The C birds increased the attack behavior over the weeks(P<0.05).During weeks 1–3 the YM group reduced the attack frequency(P1>P3;P<0.05).Finally,the provision of live BSF and YM larvae significantly reduced the ECM at 55 days of age and the heterophil to lymphocyte ratio(P<0.05).Conclusions Live BSF and YM larva supplementation in Muscovy duck improves duck welfare,without impairing birds'growth performance.展开更多
Following publication of the original article,the authors observed that both Fig.5 and Fig.4 depict the same image.Figure 5 was inaccurately referenced and displayed.The correct Fig.5 is copied below:The original arti...Following publication of the original article,the authors observed that both Fig.5 and Fig.4 depict the same image.Figure 5 was inaccurately referenced and displayed.The correct Fig.5 is copied below:The original article has been updated.展开更多
Lacustrine shale oil and gas are important fields for unconventional exploration and development in China,and organic-rich shale deposition lays down the critical foundation for hydrocarbon generation.There are two se...Lacustrine shale oil and gas are important fields for unconventional exploration and development in China,and organic-rich shale deposition lays down the critical foundation for hydrocarbon generation.There are two sets of shale,the Dongyuemiao and Da’anzhai Members,in the Ziliujing Formation in the Sichuan Basin.To identify the differential enrichment characteristics of organic matter and clarify its controlling factors,geochemical analyses of organic and inorganic geochemical analyses were performed.The results showed that the total organic carbon content of the Dongyuemiao shale(1.36%)is slightly higher than that of the Da’anzhai shale(0.95%).The enrichment of organic matter in the two shales resulted from the comprehensive controls of paleoproductivity,paleoenvironment,and terrigenous input,but different factors have different effects.In addition,driven by climate,the change in the sulfate concentration in the bottom water further led to the different intensities of bacterial sulfate reduction in early diagenesis.This made a great difference regarding organic matter accumulation in the two members.In general,climate may have played a dominant role in organic matter enrichment in the two sets of shale.展开更多
Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulat...Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.展开更多
The boundary element method(BEM)is a popular method for solving acoustic wave propagation problems,especially those in exterior domains,owing to its ease in handling radiation conditions at infinity.However,BEM models...The boundary element method(BEM)is a popular method for solving acoustic wave propagation problems,especially those in exterior domains,owing to its ease in handling radiation conditions at infinity.However,BEM models must meet the requirement of 6–10 elements per wavelength,using the conventional constant,linear,or quadratic elements.Therefore,a large storage size of memory and long solution time are often needed in solving higher-frequency problems.In this work,we propose two new types of enriched elements based on conventional constant boundary elements to improve the computational efficiency of the 2D acoustic BEM.The first one uses a plane wave expansion,which can be used to model scattering problems.The second one uses a special plane wave expansion,which can be used tomodel radiation problems.Five examples are investigated to showthe advantages of the enriched elements.Compared with the conventional constant elements,the new enriched elements can deliver results with the same accuracy and in less computational time.This improvement in the computational efficiency is more evident at higher frequencies(with the nondimensional wave numbers exceeding 100).The paper concludes with the potential of our proposed enriched elements and plans for their further improvement.展开更多
The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based inte...The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.展开更多
Two suites of mafic dykes,T1193-A and T1194-A,outcrop in Gyangze area,southeast Tibet.They are in the area of Comei LIP and have indistinguishable field occurrences with two other dykes in Gyangze,T0902 dyke with 137....Two suites of mafic dykes,T1193-A and T1194-A,outcrop in Gyangze area,southeast Tibet.They are in the area of Comei LIP and have indistinguishable field occurrences with two other dykes in Gyangze,T0902 dyke with 137.7±1.3 Ma zircon age and T0907 dyke with 142±1.4 Ma zircon age reported by Wang YY et al.(2016),indicating coeval formation time.Taking all the four diabase dykes into consideration,two different types,OIB-type and weak enriched-type,can be summarized.The“OIB-type”samples,including T1193-A and T0907 dykes,show OIB-like geochemical features and have initial Sr-Nd isotopic values similar with most mafic products in Comei Large Igneous Provinces(LIP),suggesting that they represent melts directly generated from the Kerguelen mantle plume.The“weak enriched-type”samples,including T1194-A and T0902 dykes,have REEs and trace element patterns showing withinplate affinity but have obvious Nb-Ta-Ti negative anomalies.They show uniform lowerεNd(t)values(−6‒−2)and higher 87Sr/86Sr(t)values(0.706‒0.709)independent of their MgO variation,indicating one enriched mantle source.Considering their closely spatial and temporal relationship with the widespread Comei LIP magmatic products in Tethyan Himalaya,these“weak enriched-type”samples are consistent with mixing of melts from mantle plume and the above ancient Tethyan Himalaya subcontinental lithospheric mantle(SCLM)in different proportions.These weak enriched mafic rocks in Comei LIP form one special rock group and most likely suggest large scale hot mantle plume-continental lithosphere interaction.This process may lead to strong modification of the Tethyan Himalaya lithosphere in the Early Cretaceous.展开更多
BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To in...BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.展开更多
BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be e...BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.展开更多
BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The pre...BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.展开更多
BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.Th...BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.展开更多
CHINA TODAY,THE eight-day-long Spring Festival holiday saw a tourism boom across the country whose blend of pop and traditional culture illumined Lunar Chinese New Year celebrations.Local Beijing authorities attest to...CHINA TODAY,THE eight-day-long Spring Festival holiday saw a tourism boom across the country whose blend of pop and traditional culture illumined Lunar Chinese New Year celebrations.Local Beijing authorities attest to the 100 or more cultural events staged in the capital’s parks during the Spring Festival holiday that enriched its abundantly festive ethos.Temple fairs,enshrining such live folk art activities as calligraphy,lantern-making,shadow-puppetry,and sugar-figurine blowing,in particular drew droves of visitors.展开更多
This study aims to thoroughly investigate the axial power peaking factors (PPF) within the low-enriched uranium (LEU) core of the Ghana Research Reactor-1 (GHARR-1). This study uses advanced simulation tools, like the...This study aims to thoroughly investigate the axial power peaking factors (PPF) within the low-enriched uranium (LEU) core of the Ghana Research Reactor-1 (GHARR-1). This study uses advanced simulation tools, like the MCNPX code for analysing neutron behavior and the PARET/ANL code for understanding power variations, to get a clearer picture of the reactor’s performance. The analysis covers the initial six years of GHARR-1’s operation and includes projections for its whole 60-year lifespan. We closely observed the patterns of both the highest and average PPFs at 21 axial nodes, with measurements taken every ten years. The findings of this study reveal important patterns in power distribution within the core, which are essential for improving the safety regulations and fuel management techniques of the reactor. We provide a meticulous approach, extensive data, and an analysis of the findings, highlighting the significance of continuous monitoring and analysis for proactive management of nuclear reactors. The findings of this study not only enhance our comprehension of nuclear reactor safety but also carry significant ramifications for sustainable energy progress in Ghana and the wider global context. Nuclear engineering is essential in tackling global concerns, such as the demand for clean and dependable energy sources. Research on optimising nuclear reactors, particularly in terms of safety and efficiency, is crucial for the ongoing advancement and acceptance of nuclear energy.展开更多
基金the R&D Project on the Oceanic Metalliferous Nodue during the "Ninth- Five- YearPlan"(No. DY95 ~ 02 ~ 10).
文摘Compared to North American shale composition (NASC), REE contents of sediments from the CC area in the Pacific Ocean are obviously high except that cerium has equal content to that of NASC. Three-valence rare earth elements were completely enriched in phosphate-phase and cerium in iron-phase. Rare earth elements in the sediments were originally derived from seawater. During lithi- genic and minerogenic processes of metalliferous nodules, three-valence rare earth elements in sediments mobilized and incorporated into sediments as authigenous biogenic-apatite, while cerium had change from Ce3+ to Ce4+ and directly precipitated from seawater and entered metalliferous nodules and caused Ce anomalies in REE pattern in sediments.
文摘Objective To investigate the effect of reinforced Decoction of Angelicae Sinensis for enriching blood (RDAEB) on the immunity of immunosuppressed mice induced by cyclophosphamide (Cy). Methods Mice were given RDAEB through stomach perfusion for 10 d (50 mg/d). Then, RBC-C3bR rate,RBC-IC rate (as the index- es of erythrocyte immunity)and E-rosette forming rate,acidic a-naphthyl acetate esterase positive rate, lymphocyte transformation rate (as the indexes of cellular immunity) of mice were tested. Results RBC-C3Br rate, RBC-IC rat- e,E-rosette forming rate, acidic α-naphthyl acetate esterase positive rate and lymphocyte transformation rate in the Cy-RDAEB group were markedly higher than those in the Cy group (P<0.0l),and returned to the levels of normal group. Conclusion RDAEB is effective in recovering and enhancing cellular and erythrocyte immunity of immuno- suppressed mice.
基金Scientific Research Special Project of Capital Health Development in 2018(No.First issues 2018-1-4192)TCM Science and Technology Development Fund of Beijing in 2020(No.JJ-2020-42)。
文摘Objective:To systemically review the efficacy and safety about the method of enriching qi,activating blood circulation,clearing away dampness and heat combined with western medicine in the therapy of patients with idiopathy membranous nephropathy(IMN).Methods:We collected the randomized controlled trials(RCTs)of enriching qi,activating blood circulation,clearing away dampness and heat for the treatment of IMN from Pub Med,The Cochrane Library,Medline,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),Wanfang Data and Wiper Databases.Bias of risk of retrieval literature was evaluated according to Cochrane Collaboration standard,and Review Manager 5.3 software was used for statistical analysis.Results:Fourteen trials(836 participants)were included in the meta-analysis.This kind of traditional Chinese method combined with western medicine in the treatment of IMN exerted statistical differences in reducing 24-hour urinary protein[WMD=-0.97,95%CI(-1.30,-0.65),Z=5.86(P<0.00001)]and elevating serum albumin[WMD=3.83,95%CI(2.10,5.57),Z=4.33,P<0.0001],lowering serum cholesterol[WMD=-0.82,95%CI(-1.08,-0.56),Z=6.18,P<0.00001],triglycerides[WMD=-0.39,95%CI(-0.67,-0.11),Z=2.77,P=0.006]and reducing the risk of adverse events[OR=0.29,95%CI[0.16,0.50],Z=4.35,P<0.0001]in the patients with IMN as compared with controls.However,there was no statistically significant difference between the method and controls when combining all trials in serum creatinine[WMD=-5.52,95%CI(-18.06,7.03),Z=0.86,P=0.39],when combining all trials in urea nitrogen[WMD=-0.90,95%CI(-2.22,0.41),Z=1.35,P=0.18].Conclusion:The method of enriching qi,activating blood circulation,clearing away dampness and heat combined with western medicine exerts certain advantages and better safety in treating patients with IMN.However,for the inferiority of the included studies,the conclusion still needs high-quality and large-sample prospective randomized controlled trials to verify.
基金Key Science and Technology Project of Guangxi(Gui Ke AA17202027-4)Project of Guangxi Teng County Pueraria lobata Experimental Station(Gui TS201431)+1 种基金Special Basic Scientific Research Project of Guangxi Academy of Agricultural Sciences(Gui Nong Ke 2019M16)Special Fund for Basic Scientific Research Project in Chinese Academy of Tropical Agricultural Sciences(1630062020006)。
文摘[Objectives]To screen out the selenium-enriched Pueraria lobata varieties suitable for cultivation in Guangxi according to the natural selenium-enriching ability of 7 main cultivars.[Methods]Taking 7 main cultivars of P.lobata in different places as experimental materials,field cultivation was carried out on the selenium-enriched yellow soil in Shanglin County,Nanning City of Guangxi,to study the difference in selenium-enriching ability of different main cultivars and the comparison of selenium content in different parts,as well as the transport mechanism.[Results]Under the condition of soil selenium content of 0.78 mg/kg,the selenium content of the root tubers of the 7 main cultivars all reached the selenium-enrichment standard.The selenium content of a single root tuber of Heping Variety in Teng County,Guangxi was the highest,at 0.061 mg/kg;Guifenge No.1 was the second at 0.055 mg/kg,and the total selenium accumulation per unit area was the largest.The ranking of selenium content in different parts of the same variety was:leaf>vine>head>root tuber.[Conclusions]Guifenge No.1 has the highest yield and the largest total selenium accumulation,so it is the most suitable natural selenium-enriched variety for cultivation.
基金This study was supported by the National Natural Science Foundation of China(No.81760746 and 81803838)Education Department of Guizhou Province of China(GNYL[2017]006)+3 种基金Provincial Department of Education youth talent support program(qiankehe KY[2017]078)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(2060302)Science and Technology Department of Zunyi City of Zuniyi City of Guizhou Province of China([2016]35,[2016]33)Innovation talent team of Guizhou science and Technology Department(qiankehe platform talents[2020]5007).
文摘Background:To explore active components of Lanbuzheng(Gei herba)and its underlying complex mechanism in treating blood deficiency induced by chemotherapy drug based on network pharmacology and mice experimental validation.Methods:Active components of Lanbuzheng(Gei herba)were screened by Lipinski’s rule of five.Targets acted with active components were predicted by PharmMapper database,and targets whose function associated with blood deficiency were screened by Therapeutic Target Database and UniProt.The networks of component-target and target-pathway were constructed by Cytoscape.The levels of peripheral blood and organ indexes were detected in the animal experiments.Results:One hundred and seventy-three components of Lanbuzheng(Gei herba)were collected,and 60 active components were screened according to the rule of five.According to the degree value of compounds,the top 5 compounds were docosyl trans ferulate,C32 decursin,agrimonolide 6-O-β-D-glucoside,degree=11,173-ethoxyphaeophorbide,and eugenol.Finally,59 targets associated with blood deficiency were obtained and the top 5 targets were MAPK14,TTR,CDK2,AKR1B1 and AR.Based on the interaction network of componenttarget and target-pathway,it’s found that 60 active components could act with 59 targets and 44 pathways for treating blood deficiency.And then,the mice experiments showed that Lanbuzheng(Gei herba)could enrich blood by increasing the levels of red blood cell,white blood cell,hemoglobin,red blood cell specific volume and platelet,and the indexes of liver,thymus and spleen,which validated the treating effect of Lanbuzheng(Gei herba).Conclusion:In this study,a network pharmacology approach and animal experiments were established to explore the nourishing blood effect of Lanbuzheng(Gei herba).The results demonstrated that Lanbuzheng(Gei herba)could improve blood deficiency and provide a theoretical basis for the further research on the in-depth mechanism of Lanbuzheng(Gei herba).
文摘Selenium is one of essential elements for humans, animals and some kinds of plants.The biological function of selenium shows dual characteristics.The range of selenium content is very narrow between toxic and deficient concentration.Typical Kashin-Beck endemic areas intimately link with selenium deficiency.In one area,selenium levels
基金supported by the PRIMA programme under grant agreement No 2015,project SUSTAvian FEEDsupported by the European Unionthe visit by Achille Schiavone(22216/IV/23-Poultry MED project)funded by the Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia in connection with the“Jiménez De La Espada”Regional Programme for Mobility,Collaboration and Knowledge Exchange。
文摘Background The provision of environmental enrichments to Muscovy ducks could reduce the expression of the aggressive behaviors.The aim of the present study was to evaluate the effects of black soldier fly(BSF)and yellow mealworm(YM)live larva provision on Muscovy duck performance,excreta corticosterone metabolites(ECM),behavior,and blood parameters.Methods A total of 1263-day-old female Muscovy ducklings were allotted to 18 pens(6 replicates/treatment,7 birds/pen)and assigned to 3 experimental treatments:a control group fed commercial feed,and two experimental treatments fed commercial feed plus the 5%(based on the expected daily feed intake,as fed basis)of BSF and YM live larvae(BSF and YM groups,respectively).A two-phase feeding program was applied:starter(from 3 to 31 days of age)and grower-finisher(from 32 to 55 days of age).The live weight,average daily gain,average daily feed intake,and feed conversion ratio were calculated.Larva consumption times were collected,and video recordings were performed during 3 periods(P)each day:the hour before(P1),during(P2),and after(P3)the larva administration.ECM were evaluated at 3,31,and 55-day-old.Finally,the total red and white blood cell counts,serum proteins,lipids,and liver and renal function serum enzymes were evaluated on 12 birds/treatment.Results The experimental treatment did not affect the growth performance of the birds(P>0.05).Larva consumption times were always similar between the two insect species,except at 14–18 days of age,were BSF larvae were consumed faster than YM larvae(P<0.001).The birds showed less walking activity during P2,and preening behavior increased in YM birds during P3.The C birds increased the attack behavior over the weeks(P<0.05).During weeks 1–3 the YM group reduced the attack frequency(P1>P3;P<0.05).Finally,the provision of live BSF and YM larvae significantly reduced the ECM at 55 days of age and the heterophil to lymphocyte ratio(P<0.05).Conclusions Live BSF and YM larva supplementation in Muscovy duck improves duck welfare,without impairing birds'growth performance.
文摘Following publication of the original article,the authors observed that both Fig.5 and Fig.4 depict the same image.Figure 5 was inaccurately referenced and displayed.The correct Fig.5 is copied below:The original article has been updated.
基金This work was funded by the National Natural Science Foundation of China(Grant No.42002139 and U20B6001)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA14010404).
文摘Lacustrine shale oil and gas are important fields for unconventional exploration and development in China,and organic-rich shale deposition lays down the critical foundation for hydrocarbon generation.There are two sets of shale,the Dongyuemiao and Da’anzhai Members,in the Ziliujing Formation in the Sichuan Basin.To identify the differential enrichment characteristics of organic matter and clarify its controlling factors,geochemical analyses of organic and inorganic geochemical analyses were performed.The results showed that the total organic carbon content of the Dongyuemiao shale(1.36%)is slightly higher than that of the Da’anzhai shale(0.95%).The enrichment of organic matter in the two shales resulted from the comprehensive controls of paleoproductivity,paleoenvironment,and terrigenous input,but different factors have different effects.In addition,driven by climate,the change in the sulfate concentration in the bottom water further led to the different intensities of bacterial sulfate reduction in early diagenesis.This made a great difference regarding organic matter accumulation in the two members.In general,climate may have played a dominant role in organic matter enrichment in the two sets of shale.
基金supported by a grant from the Massachusetts Alzheimer’s Disease Research Center(5P50 AG 005134)(to SL).
文摘Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.
基金the National Natural Science Foundation of China(https://www.nsfc.gov.cn/,Project No.11972179)the Natural Science Foundation of Guangdong Province(http://gdstc.gd.gov.cn/,No.2020A1515010685)the Department of Education of Guangdong Province(http://edu.gd.gov.cn/,No.2020ZDZX2008).
文摘The boundary element method(BEM)is a popular method for solving acoustic wave propagation problems,especially those in exterior domains,owing to its ease in handling radiation conditions at infinity.However,BEM models must meet the requirement of 6–10 elements per wavelength,using the conventional constant,linear,or quadratic elements.Therefore,a large storage size of memory and long solution time are often needed in solving higher-frequency problems.In this work,we propose two new types of enriched elements based on conventional constant boundary elements to improve the computational efficiency of the 2D acoustic BEM.The first one uses a plane wave expansion,which can be used to model scattering problems.The second one uses a special plane wave expansion,which can be used tomodel radiation problems.Five examples are investigated to showthe advantages of the enriched elements.Compared with the conventional constant elements,the new enriched elements can deliver results with the same accuracy and in less computational time.This improvement in the computational efficiency is more evident at higher frequencies(with the nondimensional wave numbers exceeding 100).The paper concludes with the potential of our proposed enriched elements and plans for their further improvement.
基金supported by the National Natural Science Foundation of China(31972052,32021005,31820103010)the Fundamental Research Funds for the Central Universities(JUSRP22006,JUSRP51501)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.
基金supported by National Science Foundation of China(42102059 and 92055202)the China Geological Survey(DD20221817 and DD20190057)+1 种基金the basic scientific research funding in CAGS(J2204)the Second Tibetan Plateau Scientific Expedition and Research(2019QZKK0702).
文摘Two suites of mafic dykes,T1193-A and T1194-A,outcrop in Gyangze area,southeast Tibet.They are in the area of Comei LIP and have indistinguishable field occurrences with two other dykes in Gyangze,T0902 dyke with 137.7±1.3 Ma zircon age and T0907 dyke with 142±1.4 Ma zircon age reported by Wang YY et al.(2016),indicating coeval formation time.Taking all the four diabase dykes into consideration,two different types,OIB-type and weak enriched-type,can be summarized.The“OIB-type”samples,including T1193-A and T0907 dykes,show OIB-like geochemical features and have initial Sr-Nd isotopic values similar with most mafic products in Comei Large Igneous Provinces(LIP),suggesting that they represent melts directly generated from the Kerguelen mantle plume.The“weak enriched-type”samples,including T1194-A and T0902 dykes,have REEs and trace element patterns showing withinplate affinity but have obvious Nb-Ta-Ti negative anomalies.They show uniform lowerεNd(t)values(−6‒−2)and higher 87Sr/86Sr(t)values(0.706‒0.709)independent of their MgO variation,indicating one enriched mantle source.Considering their closely spatial and temporal relationship with the widespread Comei LIP magmatic products in Tethyan Himalaya,these“weak enriched-type”samples are consistent with mixing of melts from mantle plume and the above ancient Tethyan Himalaya subcontinental lithospheric mantle(SCLM)in different proportions.These weak enriched mafic rocks in Comei LIP form one special rock group and most likely suggest large scale hot mantle plume-continental lithosphere interaction.This process may lead to strong modification of the Tethyan Himalaya lithosphere in the Early Cretaceous.
基金Supported by Ningxia Science and Technology Benefiting People Program,No.2022CMG03064National Natural Science Foundation of China,No.82260879Ningxia Natural Science Foundation,No.2022AAC03144 and 2022AAC02039.
文摘BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.
基金Supported by the 2022 Shaoxing City Health Science and Technology Program(Health Science and Technology Program),No.2022KY050。
文摘BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.
基金Supported by The Guangdong Basic and Applied Basic Research Foundation,No.2023A1515011432The Guangzhou Science and Technology Planning Project,No.2023A04J0627and National Natural Science Foundation of China,No.82004256.
文摘BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.
基金National Key Research and Development Program of China,No.2021YFC2701704the National Clinical Medical Research Center for Geriatric Diseases,"Multicenter RCT"Research Project,No.NCRCG-PLAGH-20230010the Military Logistics Independent Research Project,No.2022HQZZ06.
文摘BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.
文摘CHINA TODAY,THE eight-day-long Spring Festival holiday saw a tourism boom across the country whose blend of pop and traditional culture illumined Lunar Chinese New Year celebrations.Local Beijing authorities attest to the 100 or more cultural events staged in the capital’s parks during the Spring Festival holiday that enriched its abundantly festive ethos.Temple fairs,enshrining such live folk art activities as calligraphy,lantern-making,shadow-puppetry,and sugar-figurine blowing,in particular drew droves of visitors.
文摘This study aims to thoroughly investigate the axial power peaking factors (PPF) within the low-enriched uranium (LEU) core of the Ghana Research Reactor-1 (GHARR-1). This study uses advanced simulation tools, like the MCNPX code for analysing neutron behavior and the PARET/ANL code for understanding power variations, to get a clearer picture of the reactor’s performance. The analysis covers the initial six years of GHARR-1’s operation and includes projections for its whole 60-year lifespan. We closely observed the patterns of both the highest and average PPFs at 21 axial nodes, with measurements taken every ten years. The findings of this study reveal important patterns in power distribution within the core, which are essential for improving the safety regulations and fuel management techniques of the reactor. We provide a meticulous approach, extensive data, and an analysis of the findings, highlighting the significance of continuous monitoring and analysis for proactive management of nuclear reactors. The findings of this study not only enhance our comprehension of nuclear reactor safety but also carry significant ramifications for sustainable energy progress in Ghana and the wider global context. Nuclear engineering is essential in tackling global concerns, such as the demand for clean and dependable energy sources. Research on optimising nuclear reactors, particularly in terms of safety and efficiency, is crucial for the ongoing advancement and acceptance of nuclear energy.