The contamination of heavy metal(loid)s at mining&metallurgical sites has been a major environmental challenge worldwide[1].Typically,large amounts of metal(loid)s-bearing wastes are generated at these sites,such ...The contamination of heavy metal(loid)s at mining&metallurgical sites has been a major environmental challenge worldwide[1].Typically,large amounts of metal(loid)s-bearing wastes are generated at these sites,such as smelting slag,combustion residues,mine tailings,wastewater,and exhaust gas[2].Due to their high mobility in the environment,the released heavy metal(loid)s can easily enter the soil and water environment,posing long-term and widespread threats to ecological and human health[3].展开更多
BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attract...BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.展开更多
Background Examining the health outcomes of veterans who have completed the United States Veterans Health Administration’s(VHA’s)Traumatic Brain Injury(TBI)Screening and Evaluation Program may aid in the refinement ...Background Examining the health outcomes of veterans who have completed the United States Veterans Health Administration’s(VHA’s)Traumatic Brain Injury(TBI)Screening and Evaluation Program may aid in the refinement and improvement of clinical care initiatives within the VHA.This study compared self-reported physical functioning,cardiometabolic health conditions,and health care utilization patterns in Million Veteran Program enrollees with TBI Screening and Evaluation Program data(collected between 2007 and 2019),with the goal of enhancing understanding of potentially modifiable health conditions in this population.Methods In this observational cohort study,veterans(n=16,452)were grouped based on the diagnostic outcome of the TBI Screening and Evaluation Program:1)negative TBI screen(Screen^(-));2)positive TBI screen but no confirmed TBI diagnosis[Screen^(+)/Comprehensive TBI Evaluation(CTBIE)^(-)];or 3)positive TBI screen and confirmed TBI diagnosis(Screen^(+)/CTBIE^(+)).Chi-square tests and analysis of covariance were used to explore group differences in physical functioning,cardiometabolic health conditions,and health care utilization patterns,and logistic regressions were used to examine predictors of Screen^(+/-)and CTBIE^(+/-)group status.Results The results showed that veterans in the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups generally reported poorer levels of physical functioning(P’s<0.001,np2=0.02 to 0.03),higher rates of cardiometabolic health conditions(P’s<0.001,φ=0.14 to 0.52),and increased health care utilization(P’s<0.001,φ=0.14 to>0.5)compared with the Screen-group;however,health outcomes were generally comparable between the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups.Follow-up analyses confirmed that while physical functioning,hypertension,stroke,healthcare utilization,and prescription medication use reliably distinguished between the Screen-and Screen^(+)groups(P’s<0.02,OR’s 0.78 to 3.38),only physical functioning distinguished between the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups(P<0.001,OR 0.99).Conclusions The findings suggest that veterans who screen positive for TBI,regardless of whether they are ultimately diagnosed with TBI,are at greater risk for negative health outcomes,signifying that these veterans represent a vulnerable group that may benefit from increased clinical care and prevention efforts.展开更多
Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This co...Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.展开更多
Classical molecular dynamics(MD)simulation method is employed to study the uniaxial tensile deformation of nanocrystalline magnesium(Mg)of varying grain size levels.The mean grain size of the sample is varied from 6.4...Classical molecular dynamics(MD)simulation method is employed to study the uniaxial tensile deformation of nanocrystalline magnesium(Mg)of varying grain size levels.The mean grain size of the sample is varied from 6.4 nm to 45 nm,with each sample containing about 43 million atoms in the modeling system.The deformation nanomechanics reveals two distinct deformation mechanisms.For larger grain-sized samples,dislocation dominated deformation is observed while,in smaller grain-sized samples,grain boundary-based mechanisms such as grain boundary sliding,grain boundary rotation are observed.The transition of normal and inverse Hall-Petch relation occurs at around lOnm.Dislocation density quantification shows that the dislocation density in the sample drastically reduces with decreasing grain size.Elastic modulus of nanocrystalline Mg with mean grain size above 20 nm remains comparable to that of the coarse-grained polycrystalline bulk,followed by a rapid reduction below that grain size.The present work reveals the nanomechanics of nanocrystalline Mg,facilitating the design and development of Mg-based nanostructured alloys with superior mechanical properties.展开更多
End-to-end repair under no or low tension leads to improved outcomes for transected nerves with short gaps,compared to repairs with a graft.However,grafts are typically used to enable a tension-free repair for moderat...End-to-end repair under no or low tension leads to improved outcomes for transected nerves with short gaps,compared to repairs with a graft.However,grafts are typically used to enable a tension-free repair for moderate to large gaps,as excessive tension can cause repairs to fail and catastrophically impede recovery.In this study,we tested the hypothesis that unloading the repair interface by redistributing tension away from the site of repair is a safe and feasible strategy for end-to-end repair of larger nerve gaps.Further,we tested the hypothesis that such an approach does not adversely affect structural and functional regeneration.In this study,we used a rat sciatic nerve injury model to compare the integrity of repair and several regenerative outcomes following end-to-end repairs of nerve gaps of increasing size.In addition,we proposed the use of a novel implantable device to safely repair end-to-end repair of larger nerve gaps by redistributing tension away from the repair interface.Our data suggest that redistriubution of tension away from the site of repair enables safe end-to-end repair of larger gap sizes.In addition,structural and functional measures of regeneration were equal or enhanced in nerves repaired under tension – with or without a tension redistribution device – compared to tension-free repairs.Provided that repair integrity is maintained,end-to-end repairs under tension should be considered as a reasonable surgical strategy.All animal experiments were performed under the approval of the Institutional Animal Care and Use Committee of University of California,San Diego(Protocol S11274).展开更多
The health value of honey is universally acknowledged from time immemorial.Manuka(Leptospermum scoparium)is a tree,indigenous to New Zealand and South East Australia,and from the myrtle family,Myrtaceae.The honey prod...The health value of honey is universally acknowledged from time immemorial.Manuka(Leptospermum scoparium)is a tree,indigenous to New Zealand and South East Australia,and from the myrtle family,Myrtaceae.The honey produced from its flowers is a uni-floral honey largely produced in New Zealand.It is becoming increasingly popular as a functional food,seen in the aisles of health stores as its displays superior nutritional and phytochemistry profile over other varieties of honey.Examining existing research databases revealed its biological properties ranging from anti-oxidant,anti-inflammatory,anti-bacterial,anti-viral,anti-biotic and wound healing to immune-stimulatory properties.Methylglyoxal is the unique compound in the honey responsible for some of its potent anti-microbial properties.Further,propolis another component of honey contains chiefly flavonoids(i.e.galangin,pinocembrin),phenolic acids and their esters that may also contribute to its immuno-stimulant properties.Recent findings of the biological roles have been discussed with emphasis on the underlying mechanisms.The hurdles associated in its development as a functional food and also nutraceutical with future scopes have also been mentioned.Relevant data published in MEDLINE,Cochrane library,and EMBASE in the past decade have been gathered to formulate this review.展开更多
基金Project(202203021212308)supported by the Fundamental Research Program of Shanxi Province,ChinaProject(HZKY20220508)supported by the Ministry of Education’s“Chunhui Plan”Cooperative Scientific Research Project,China+5 种基金Project(KF-22-16)supported by the Open Fund from the Key Lab of Eco-restoration of Regional Contaminated Environment(Shenyang University)Ministry of Education,ChinaProject(20222020)supported by the Doctoral Foundation of Taiyuan University of Science and Technology,ChinaProject(2022L297)supported by the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi Province,ChinaProject supported by the Startup Funds of San Diego State University,USAProject(202304051001016)supported by the Special Fund for Science and Technology Innovation Teams of Shanxi Province,China。
基金We also gratefully acknowledge the financial support by the National Key Research and Development Program of China and the Natural Science Foundation of Hunan Province(2019 YFC 1803600,2019 YFC 1803500,2019 YFC 1805200,2020 YFC 1807700,2020 YFC 1808300,2021 YFC 2902600,2022 YFC 2904400,2023 YFC 3707700,2024 JJ 1012).Finally,we would like to thank all the authors for their important contributions to this special issue as well as to the advancement of the remediation field.
文摘The contamination of heavy metal(loid)s at mining&metallurgical sites has been a major environmental challenge worldwide[1].Typically,large amounts of metal(loid)s-bearing wastes are generated at these sites,such as smelting slag,combustion residues,mine tailings,wastewater,and exhaust gas[2].Due to their high mobility in the environment,the released heavy metal(loid)s can easily enter the soil and water environment,posing long-term and widespread threats to ecological and human health[3].
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+5 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005and Open Project of Key Laboratory of Dunhuang Medicine and Transformation of Ministry of Education,No.DHYX21-07,No.DHYX22-05,and No.DHYX21-01.
文摘BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.
基金supported by a Career Development Award awarded to Dr. Merritt from the VA Clinical Science Research&Development Service (IK2 CX001952)Dr. Clark received start-up funds from the University of Texas at Austin that further supported this work。
文摘Background Examining the health outcomes of veterans who have completed the United States Veterans Health Administration’s(VHA’s)Traumatic Brain Injury(TBI)Screening and Evaluation Program may aid in the refinement and improvement of clinical care initiatives within the VHA.This study compared self-reported physical functioning,cardiometabolic health conditions,and health care utilization patterns in Million Veteran Program enrollees with TBI Screening and Evaluation Program data(collected between 2007 and 2019),with the goal of enhancing understanding of potentially modifiable health conditions in this population.Methods In this observational cohort study,veterans(n=16,452)were grouped based on the diagnostic outcome of the TBI Screening and Evaluation Program:1)negative TBI screen(Screen^(-));2)positive TBI screen but no confirmed TBI diagnosis[Screen^(+)/Comprehensive TBI Evaluation(CTBIE)^(-)];or 3)positive TBI screen and confirmed TBI diagnosis(Screen^(+)/CTBIE^(+)).Chi-square tests and analysis of covariance were used to explore group differences in physical functioning,cardiometabolic health conditions,and health care utilization patterns,and logistic regressions were used to examine predictors of Screen^(+/-)and CTBIE^(+/-)group status.Results The results showed that veterans in the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups generally reported poorer levels of physical functioning(P’s<0.001,np2=0.02 to 0.03),higher rates of cardiometabolic health conditions(P’s<0.001,φ=0.14 to 0.52),and increased health care utilization(P’s<0.001,φ=0.14 to>0.5)compared with the Screen-group;however,health outcomes were generally comparable between the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups.Follow-up analyses confirmed that while physical functioning,hypertension,stroke,healthcare utilization,and prescription medication use reliably distinguished between the Screen-and Screen^(+)groups(P’s<0.02,OR’s 0.78 to 3.38),only physical functioning distinguished between the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups(P<0.001,OR 0.99).Conclusions The findings suggest that veterans who screen positive for TBI,regardless of whether they are ultimately diagnosed with TBI,are at greater risk for negative health outcomes,signifying that these veterans represent a vulnerable group that may benefit from increased clinical care and prevention efforts.
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+4 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005.
文摘Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.
基金This work was performed under the auspices of startup funds from the San Diego State University(SDSU)the support of the US National Science of Foundation,Division of Materials Research,under Award No.1900876.
文摘Classical molecular dynamics(MD)simulation method is employed to study the uniaxial tensile deformation of nanocrystalline magnesium(Mg)of varying grain size levels.The mean grain size of the sample is varied from 6.4 nm to 45 nm,with each sample containing about 43 million atoms in the modeling system.The deformation nanomechanics reveals two distinct deformation mechanisms.For larger grain-sized samples,dislocation dominated deformation is observed while,in smaller grain-sized samples,grain boundary-based mechanisms such as grain boundary sliding,grain boundary rotation are observed.The transition of normal and inverse Hall-Petch relation occurs at around lOnm.Dislocation density quantification shows that the dislocation density in the sample drastically reduces with decreasing grain size.Elastic modulus of nanocrystalline Mg with mean grain size above 20 nm remains comparable to that of the coarse-grained polycrystalline bulk,followed by a rapid reduction below that grain size.The present work reveals the nanomechanics of nanocrystalline Mg,facilitating the design and development of Mg-based nanostructured alloys with superior mechanical properties.
基金supported by the Department of Veterans Affairs(VA MERIT IRX001471A to SBS)
文摘End-to-end repair under no or low tension leads to improved outcomes for transected nerves with short gaps,compared to repairs with a graft.However,grafts are typically used to enable a tension-free repair for moderate to large gaps,as excessive tension can cause repairs to fail and catastrophically impede recovery.In this study,we tested the hypothesis that unloading the repair interface by redistributing tension away from the site of repair is a safe and feasible strategy for end-to-end repair of larger nerve gaps.Further,we tested the hypothesis that such an approach does not adversely affect structural and functional regeneration.In this study,we used a rat sciatic nerve injury model to compare the integrity of repair and several regenerative outcomes following end-to-end repairs of nerve gaps of increasing size.In addition,we proposed the use of a novel implantable device to safely repair end-to-end repair of larger nerve gaps by redistributing tension away from the repair interface.Our data suggest that redistriubution of tension away from the site of repair enables safe end-to-end repair of larger gap sizes.In addition,structural and functional measures of regeneration were equal or enhanced in nerves repaired under tension – with or without a tension redistribution device – compared to tension-free repairs.Provided that repair integrity is maintained,end-to-end repairs under tension should be considered as a reasonable surgical strategy.All animal experiments were performed under the approval of the Institutional Animal Care and Use Committee of University of California,San Diego(Protocol S11274).
文摘The health value of honey is universally acknowledged from time immemorial.Manuka(Leptospermum scoparium)is a tree,indigenous to New Zealand and South East Australia,and from the myrtle family,Myrtaceae.The honey produced from its flowers is a uni-floral honey largely produced in New Zealand.It is becoming increasingly popular as a functional food,seen in the aisles of health stores as its displays superior nutritional and phytochemistry profile over other varieties of honey.Examining existing research databases revealed its biological properties ranging from anti-oxidant,anti-inflammatory,anti-bacterial,anti-viral,anti-biotic and wound healing to immune-stimulatory properties.Methylglyoxal is the unique compound in the honey responsible for some of its potent anti-microbial properties.Further,propolis another component of honey contains chiefly flavonoids(i.e.galangin,pinocembrin),phenolic acids and their esters that may also contribute to its immuno-stimulant properties.Recent findings of the biological roles have been discussed with emphasis on the underlying mechanisms.The hurdles associated in its development as a functional food and also nutraceutical with future scopes have also been mentioned.Relevant data published in MEDLINE,Cochrane library,and EMBASE in the past decade have been gathered to formulate this review.
