Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-...Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.展开更多
Electronic reconnaissance units commonly utilize an interferometer direction-finding system to measure the incoming direction of radar radiation signals.This approach enables the accurate determination of threat sourc...Electronic reconnaissance units commonly utilize an interferometer direction-finding system to measure the incoming direction of radar radiation signals.This approach enables the accurate determination of threat source locations,which is essential for devising route plans oriented toward flight path generation.When a frequency diverse array(FDA)system is adopted by ground radars,errors are introduced into the angle measurements of the passive direction finding system.To address this issue,this study starts with FDA model establishment and equiphasic surface characteristics analysis and analyzes the principles of FDA deception in identifying one-dimensional single-baseline interferometer directions.Additionally,the Cramer-Rao bounds of the signal carrier frequency estimation error and angle measurement error during the interferometer’s direction finding process are considered.The simulation results verify that the one-dimensional single-baseline interferometer direction finding system can be deceived by the FDA radar,and the FDA with a sine frequency offset exhibits the optimum deception effect.展开更多
Six new lanthanide complexes:[Ln(3,4-DEOBA)3(4,4'-DM-2,2'-bipy)]2·2C_(2)H_(5)OH,[Ln=Dy(1),Eu(2),Tb(3),Sm(4),Ho(5),Gd(6);3,4-DEOBA-=3,4-diethoxybenzoate,4,4'-DM-2,2'-bipy=4,4'-dimethyl-2,2'...Six new lanthanide complexes:[Ln(3,4-DEOBA)3(4,4'-DM-2,2'-bipy)]2·2C_(2)H_(5)OH,[Ln=Dy(1),Eu(2),Tb(3),Sm(4),Ho(5),Gd(6);3,4-DEOBA-=3,4-diethoxybenzoate,4,4'-DM-2,2'-bipy=4,4'-dimethyl-2,2'-bipyridine]were successfully synthesized by the volatilization of the solution at room temperature.The crystal structures of six complexes were determined by single-crystal X-ray diffraction technology.The results showed that the complexes all have a binuclear structure,and the structures contain free ethanol molecules.Moreover,the coordination number of the central metal of each structural unit is eight.Adjacent structural units interact with each other through hydrogen bonds and further expand to form 1D chain-like and 2D planar structures.After conducting a systematic study on the luminescence properties of complexes 1-4,their emission and excitation spectra were obtained.Experimental results indicated that the fluorescence lifetimes of complexes 2 and 3 were 0.807 and 0.845 ms,respectively.The emission spectral data of complexes 1-4 were imported into the CIE chromaticity coordinate system,and their corre sponding luminescent regions cover the yellow light,red light,green light,and orange-red light bands,respectively.Within the temperature range of 299.15-1300 K,the thermal decomposition processes of the six complexes were comprehensively analyzed by using TG-DSC/FTIR/MS technology.The hypothesis of the gradual loss of ligand groups during the decomposition process was verified by detecting the escaped gas,3D infrared spectroscopy,and ion fragment information detected by mass spectrometry.The specific decomposition path is as follows:firstly,free ethanol molecules and neutral ligands are removed,and finally,acidic ligands are released;the final product is the corresponding metal oxide.CCDC:2430420,1;2430422,2;2430419,3;2430424,4;2430421,5;2430423,6.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations...Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.展开更多
The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.A...The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.Accordingly,comprehensive kinetic study by employing thermalgravimetric analysis at various heating rates was presented in this paper.Two main weight loss regions were observed during heating.The initial region corresponded to the dehydration of crystal water,whereas the subsequent region with overlapping peaks involved complex decomposition reactions.The overlapping peaks were separated into two individual reaction peaks and the activation energy of each peak was calculated using isoconversional kinetics methods.The activation energy of peak 1 exhibited a continual increase as the reaction conversion progressed,while that of peak 2 steadily decreased.The optimal kinetic models,identified as belonging to the random nucleation and subsequent growth category,provided valuable insights into the mechanism of the decomposition reactions.Furthermore,the adjustment factor was introduced to reconstruct the kinetic mechanism models,and the reconstructed models described the kinetic mechanism model more accurately for the decomposition reactions.This study enhanced the understanding of the thermochemical behavior and kinetic parameters of the lepidolite sulfation product decomposition reactions,further providing theoretical basis for promoting the selective extraction of lithium.展开更多
AIM:To present an overview of the research on global glaucoma treatment in the last decade in terms of publication year,journals,countries/regions,organizations,references,and keywords,to investigate the current resea...AIM:To present an overview of the research on global glaucoma treatment in the last decade in terms of publication year,journals,countries/regions,organizations,references,and keywords,to investigate the current research international trends and hot topics in this area.METHODS:Bibliometric analysis was conducted on 9128 articles in the Web of Science Core Collection(WoSCC;Clarivate)database.Quantitative and qualitative analysis was employed using VOSviewer(v1.6.18),Pajek(v1.0.0.0),and CiteSpace(v6.1.R2)software.RESULTS:The 9128 papers relating to glaucoma treatment were published from April 2013 to April 2023,of which 7482 articles(82%)were original research articles and 1464(18%)were review articles.The United States(2867)and Johns Hopkins University(166)were the most productive country and institution,respectively,but the University College London had the highest h-index(54).The Journal of Glaucoma was the most productive and Ophthalmology had the highest h-index compared with other journals.The Keywords of interest included treatment surgery,cyclophotocoagulation,minimally invasive glaucoma surgery(MIGS),trabeculectomy,baerveldt,epidemiology,medication adherence,nanoparticle,optical coherence tomography(OCT),gene therapy,and artificial intelligence(AI).Glaucoma surgery appeared as a current research hotspot through the analysis of keywords.CONCLUSION:This study provides insights into the research trends and potential research hotspots in the treatment of glaucoma.This will help researchers to evaluate research policies and to promote international cooperation.展开更多
This paper investigates the reliability of internal marine combustion engines using an integrated approach that combines Fault Tree Analysis(FTA)and Bayesian Networks(BN).FTA provides a structured,top-down method for ...This paper investigates the reliability of internal marine combustion engines using an integrated approach that combines Fault Tree Analysis(FTA)and Bayesian Networks(BN).FTA provides a structured,top-down method for identifying critical failure modes and their root causes,while BN introduces flexibility in probabilistic reasoning,enabling dynamic updates based on new evidence.This dual methodology overcomes the limitations of static FTA models,offering a comprehensive framework for system reliability analysis.Critical failures,including External Leakage(ELU),Failure to Start(FTS),and Overheating(OHE),were identified as key risks.By incorporating redundancy into high-risk components such as pumps and batteries,the likelihood of these failures was significantly reduced.For instance,redundant pumps reduced the probability of ELU by 31.88%,while additional batteries decreased the occurrence of FTS by 36.45%.The results underscore the practical benefits of combining FTA and BN for enhancing system reliability,particularly in maritime applications where operational safety and efficiency are critical.This research provides valuable insights for maintenance planning and highlights the importance of redundancy in critical systems,especially as the industry transitions toward more autonomous vessels.展开更多
To ensure the safe transportation of radioactive materials,numerous countries have established specific standards.For the transfer of fissile materials,it is imperative that the material within the packaging remains i...To ensure the safe transportation of radioactive materials,numerous countries have established specific standards.For the transfer of fissile materials,it is imperative that the material within the packaging remains in a subcritical state during routine,normal,and accidental transport conditions.In the event of an accident,the rods within the storage tank may become rearranged,introducing uncertainty that must be accounted for to ensure that criticality analysis results are conservative.Historically,this uncertainty was addressed overly conservatively due to limited research on non-uniform arrangement scenarios,which proved unsuitable for criticality safety analysis of spent fuel packages.This paper introduced three distinct methods to non-uniformly rearrange fuel rods—Uniform Arrangement by Blocks,Layer-by-Layer Determination,and Birdcage Deformation—and meticulously evaluates the influences of rod rearrangement on the effective multiplication factor of neutrons,k eff,utilizing the Monte Carlo method.Ultimately,this study presents a holistic method capable of encompassing the entire spectrum of potential effects stemming from the rearrangement of fuel rods during rods mispositioning accident.By augmenting the safety margin,this approach proves to be adeptly suited for the criticality safety analysis of nuclear fuel transport containers.展开更多
Industrial waste salts are commonly used to make value-added snow-melting agents to ensure traffic safety in northern China during winter and spring after snowfall.However,heavy metals in industrial waste salts may po...Industrial waste salts are commonly used to make value-added snow-melting agents to ensure traffic safety in northern China during winter and spring after snowfall.However,heavy metals in industrial waste salts may pose certain environmental risks.Snow-melting agents and snow samples were collected and analyzed from highways,arterial roads,footbridges,and other locations in Beijing after the snowstorm in December 2023.It was found that the main component of snow-melting agents was sodium chloride with high concentrations of Cu,Mn,and Zn,which are not regulated in the current policies,despite the recent promotion of environmentally friendly snow-melting agents.The Pb,Zn and Cr contents of some snow samples exceeded the limitation value of surface water quality standards,potentially affecting the soil and water environment near roadsides,although the snow-melting agents comply with relevant standards,which indicates the policy gap in the management of recycled industrial salts.We reviewed and analyzed the relevant standards for snow-melting agents and industrial waste salts proposed nationally and internationally over the past 30 years.Through comparative analysis,we proposed relevant policy recommendations to the existing quality standards of snow-melting agents and the management regulations of industrial waste salts,and the formulation of corresponding usage strategies,aimed at reducing the potential environmental release of heavy metals from the use of snow-melting agents,thereby promoting more sustainable green urban development and environmentally sound waste management.展开更多
Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
The range and angle information of the frequency diverse array(FDA) cannot be exclusively determined at the output of the array because of the range-angle coupled transmit beampattern. The best decoupling approach is ...The range and angle information of the frequency diverse array(FDA) cannot be exclusively determined at the output of the array because of the range-angle coupled transmit beampattern. The best decoupling approach is to form a dot-shaped beampattern rather than the S-shaped beampattern of the basic FDA.Considering the degradation of the output signal-to-interferenceplus-noise ratio(SINR) caused by the coupled beampattern, we propose a dot-shaped beamforming method based on the analyzed overlapping subarray-based using a logarithmic offset and a subarray-based planar FDA using a logarithmically increasing frequency offset, with elements transmitting at multiple frequencies. Several simulation results demonstrate the effectiveness of the proposed method in transmit energy focusing, sidelobe suppression and array resolution.展开更多
文摘Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.
基金supported by the National Natural Science Foundation of China Youth Fund Support Project(61503408)Shaanxi Provincial Association for Science and Technology Youth Talent Support Program Project(20230137)Shaanxi Provincial Natural Science Basic Research Program General Project(2023JCYB509).
文摘Electronic reconnaissance units commonly utilize an interferometer direction-finding system to measure the incoming direction of radar radiation signals.This approach enables the accurate determination of threat source locations,which is essential for devising route plans oriented toward flight path generation.When a frequency diverse array(FDA)system is adopted by ground radars,errors are introduced into the angle measurements of the passive direction finding system.To address this issue,this study starts with FDA model establishment and equiphasic surface characteristics analysis and analyzes the principles of FDA deception in identifying one-dimensional single-baseline interferometer directions.Additionally,the Cramer-Rao bounds of the signal carrier frequency estimation error and angle measurement error during the interferometer’s direction finding process are considered.The simulation results verify that the one-dimensional single-baseline interferometer direction finding system can be deceived by the FDA radar,and the FDA with a sine frequency offset exhibits the optimum deception effect.
文摘Six new lanthanide complexes:[Ln(3,4-DEOBA)3(4,4'-DM-2,2'-bipy)]2·2C_(2)H_(5)OH,[Ln=Dy(1),Eu(2),Tb(3),Sm(4),Ho(5),Gd(6);3,4-DEOBA-=3,4-diethoxybenzoate,4,4'-DM-2,2'-bipy=4,4'-dimethyl-2,2'-bipyridine]were successfully synthesized by the volatilization of the solution at room temperature.The crystal structures of six complexes were determined by single-crystal X-ray diffraction technology.The results showed that the complexes all have a binuclear structure,and the structures contain free ethanol molecules.Moreover,the coordination number of the central metal of each structural unit is eight.Adjacent structural units interact with each other through hydrogen bonds and further expand to form 1D chain-like and 2D planar structures.After conducting a systematic study on the luminescence properties of complexes 1-4,their emission and excitation spectra were obtained.Experimental results indicated that the fluorescence lifetimes of complexes 2 and 3 were 0.807 and 0.845 ms,respectively.The emission spectral data of complexes 1-4 were imported into the CIE chromaticity coordinate system,and their corre sponding luminescent regions cover the yellow light,red light,green light,and orange-red light bands,respectively.Within the temperature range of 299.15-1300 K,the thermal decomposition processes of the six complexes were comprehensively analyzed by using TG-DSC/FTIR/MS technology.The hypothesis of the gradual loss of ligand groups during the decomposition process was verified by detecting the escaped gas,3D infrared spectroscopy,and ion fragment information detected by mass spectrometry.The specific decomposition path is as follows:firstly,free ethanol molecules and neutral ligands are removed,and finally,acidic ligands are released;the final product is the corresponding metal oxide.CCDC:2430420,1;2430422,2;2430419,3;2430424,4;2430421,5;2430423,6.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.
基金financially supported by the National Natural Science Foundation of China(Nos.52034002 and U2202254)the Fundamental Research Funds for the Central Universities,China(No.FRF-TT-19-001)。
文摘The sulfation and decomposition process has proven effective in selectively extracting lithium from lepidolite.It is essential to clarify the thermochemical behavior and kinetic parameters of decomposition reactions.Accordingly,comprehensive kinetic study by employing thermalgravimetric analysis at various heating rates was presented in this paper.Two main weight loss regions were observed during heating.The initial region corresponded to the dehydration of crystal water,whereas the subsequent region with overlapping peaks involved complex decomposition reactions.The overlapping peaks were separated into two individual reaction peaks and the activation energy of each peak was calculated using isoconversional kinetics methods.The activation energy of peak 1 exhibited a continual increase as the reaction conversion progressed,while that of peak 2 steadily decreased.The optimal kinetic models,identified as belonging to the random nucleation and subsequent growth category,provided valuable insights into the mechanism of the decomposition reactions.Furthermore,the adjustment factor was introduced to reconstruct the kinetic mechanism models,and the reconstructed models described the kinetic mechanism model more accurately for the decomposition reactions.This study enhanced the understanding of the thermochemical behavior and kinetic parameters of the lepidolite sulfation product decomposition reactions,further providing theoretical basis for promoting the selective extraction of lithium.
基金Suppotred by Tianjin Key Medical Discipline Construction Project(No.TJYXZDXK-3-004A-2).
文摘AIM:To present an overview of the research on global glaucoma treatment in the last decade in terms of publication year,journals,countries/regions,organizations,references,and keywords,to investigate the current research international trends and hot topics in this area.METHODS:Bibliometric analysis was conducted on 9128 articles in the Web of Science Core Collection(WoSCC;Clarivate)database.Quantitative and qualitative analysis was employed using VOSviewer(v1.6.18),Pajek(v1.0.0.0),and CiteSpace(v6.1.R2)software.RESULTS:The 9128 papers relating to glaucoma treatment were published from April 2013 to April 2023,of which 7482 articles(82%)were original research articles and 1464(18%)were review articles.The United States(2867)and Johns Hopkins University(166)were the most productive country and institution,respectively,but the University College London had the highest h-index(54).The Journal of Glaucoma was the most productive and Ophthalmology had the highest h-index compared with other journals.The Keywords of interest included treatment surgery,cyclophotocoagulation,minimally invasive glaucoma surgery(MIGS),trabeculectomy,baerveldt,epidemiology,medication adherence,nanoparticle,optical coherence tomography(OCT),gene therapy,and artificial intelligence(AI).Glaucoma surgery appeared as a current research hotspot through the analysis of keywords.CONCLUSION:This study provides insights into the research trends and potential research hotspots in the treatment of glaucoma.This will help researchers to evaluate research policies and to promote international cooperation.
基金supported by Istanbul Technical University(Project No.45698)supported through the“Young Researchers’Career Development Project-training of doctoral students”of the Croatian Science Foundation.
文摘This paper investigates the reliability of internal marine combustion engines using an integrated approach that combines Fault Tree Analysis(FTA)and Bayesian Networks(BN).FTA provides a structured,top-down method for identifying critical failure modes and their root causes,while BN introduces flexibility in probabilistic reasoning,enabling dynamic updates based on new evidence.This dual methodology overcomes the limitations of static FTA models,offering a comprehensive framework for system reliability analysis.Critical failures,including External Leakage(ELU),Failure to Start(FTS),and Overheating(OHE),were identified as key risks.By incorporating redundancy into high-risk components such as pumps and batteries,the likelihood of these failures was significantly reduced.For instance,redundant pumps reduced the probability of ELU by 31.88%,while additional batteries decreased the occurrence of FTS by 36.45%.The results underscore the practical benefits of combining FTA and BN for enhancing system reliability,particularly in maritime applications where operational safety and efficiency are critical.This research provides valuable insights for maintenance planning and highlights the importance of redundancy in critical systems,especially as the industry transitions toward more autonomous vessels.
文摘To ensure the safe transportation of radioactive materials,numerous countries have established specific standards.For the transfer of fissile materials,it is imperative that the material within the packaging remains in a subcritical state during routine,normal,and accidental transport conditions.In the event of an accident,the rods within the storage tank may become rearranged,introducing uncertainty that must be accounted for to ensure that criticality analysis results are conservative.Historically,this uncertainty was addressed overly conservatively due to limited research on non-uniform arrangement scenarios,which proved unsuitable for criticality safety analysis of spent fuel packages.This paper introduced three distinct methods to non-uniformly rearrange fuel rods—Uniform Arrangement by Blocks,Layer-by-Layer Determination,and Birdcage Deformation—and meticulously evaluates the influences of rod rearrangement on the effective multiplication factor of neutrons,k eff,utilizing the Monte Carlo method.Ultimately,this study presents a holistic method capable of encompassing the entire spectrum of potential effects stemming from the rearrangement of fuel rods during rods mispositioning accident.By augmenting the safety margin,this approach proves to be adeptly suited for the criticality safety analysis of nuclear fuel transport containers.
基金supported by the National Natural Science Foundation of China(No.22176200)the Industrial Innovation Entrepreneurial Team Project of Ordos 2021.
文摘Industrial waste salts are commonly used to make value-added snow-melting agents to ensure traffic safety in northern China during winter and spring after snowfall.However,heavy metals in industrial waste salts may pose certain environmental risks.Snow-melting agents and snow samples were collected and analyzed from highways,arterial roads,footbridges,and other locations in Beijing after the snowstorm in December 2023.It was found that the main component of snow-melting agents was sodium chloride with high concentrations of Cu,Mn,and Zn,which are not regulated in the current policies,despite the recent promotion of environmentally friendly snow-melting agents.The Pb,Zn and Cr contents of some snow samples exceeded the limitation value of surface water quality standards,potentially affecting the soil and water environment near roadsides,although the snow-melting agents comply with relevant standards,which indicates the policy gap in the management of recycled industrial salts.We reviewed and analyzed the relevant standards for snow-melting agents and industrial waste salts proposed nationally and internationally over the past 30 years.Through comparative analysis,we proposed relevant policy recommendations to the existing quality standards of snow-melting agents and the management regulations of industrial waste salts,and the formulation of corresponding usage strategies,aimed at reducing the potential environmental release of heavy metals from the use of snow-melting agents,thereby promoting more sustainable green urban development and environmentally sound waste management.
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
基金supported by the National Natural Science Foundation of China(61503408)。
文摘The range and angle information of the frequency diverse array(FDA) cannot be exclusively determined at the output of the array because of the range-angle coupled transmit beampattern. The best decoupling approach is to form a dot-shaped beampattern rather than the S-shaped beampattern of the basic FDA.Considering the degradation of the output signal-to-interferenceplus-noise ratio(SINR) caused by the coupled beampattern, we propose a dot-shaped beamforming method based on the analyzed overlapping subarray-based using a logarithmic offset and a subarray-based planar FDA using a logarithmically increasing frequency offset, with elements transmitting at multiple frequencies. Several simulation results demonstrate the effectiveness of the proposed method in transmit energy focusing, sidelobe suppression and array resolution.
