The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
Foot reflexology(FR)is a Chinese-originated and non-invasive complementary therapy increasingly used by functional,alternative and para-medical professionals.Enhance attempts are made to study FR in non-functional org...Foot reflexology(FR)is a Chinese-originated and non-invasive complementary therapy increasingly used by functional,alternative and para-medical professionals.Enhance attempts are made to study FR in non-functional organic conditions.The present invited Editorial discusses the application of FR in autoimmune diseases(AD),highlighting a few successful studies demonstrating symptomatic relief and objective improvements.Despite promising results,the FR domain remains under-investigated and an urgent need to confirm and understand the effect of FR in chronic diseases,including AD,is highly recommended.展开更多
To effectively address the challenge where the speed of tunnel lining construction struggles to match that of tunnel face and inverted arch construction,and to enhance the quality of secondary lining,a new type of ske...To effectively address the challenge where the speed of tunnel lining construction struggles to match that of tunnel face and inverted arch construction,and to enhance the quality of secondary lining,a new type of skeleton-free,traversing secondary lining trolley has been developed.This trolley features a set of gantries paired with two sets of formwork.The formwork adopts a multi-segment hinged and strengthened design,ensuring its own strength can meet the requirements of secondary lining concrete pouring without relying on the support of the gantries.When retracted,the formwork can be transported by the gantries through another set of formwork in the supporting state,enabling early formwork support,effectively accelerating the construction progress of the tunnel’s secondary lining,and extending the maintenance time of the secondary lining with the formwork.Finite element software modeling was used for simulation calculations,and the results indicate that the structural strength,stiffness,and other performance parameters of the new secondary lining trolley meet the design requirements,verifying the rationality of the design.展开更多
The construction of the tunnel face is a critical aspect of tunnel excavation,and its supporting equipment mainly includes drilling jumbos,arch installation trolleys,wet spraying manipulators,and anchor bolt trolleys....The construction of the tunnel face is a critical aspect of tunnel excavation,and its supporting equipment mainly includes drilling jumbos,arch installation trolleys,wet spraying manipulators,and anchor bolt trolleys.To address the issues of high construction costs and the need to replace equipment for different processes,this paper designs an economical and practical multi-functional integrated trolley based on engineering cases.This trolley is suitable for various construction methods such as full-face excavation and benching method,and integrates functions such as drilling and blasting holes,anchor bolt holes,advance grouting holes,pipe roof construction,charging,anchor bolt installation and grouting,and arch mesh installation.It reduces the number of operators,improves the tunnel working environment,lowers construction costs,and enhances construction efficiency.展开更多
With the rapid development of high-speed railway tunnel construction mileage and technology,the construction of the tunnel face is a key part of tunnel construction in high-speed railway tunnel projects.As mechanizati...With the rapid development of high-speed railway tunnel construction mileage and technology,the construction of the tunnel face is a key part of tunnel construction in high-speed railway tunnel projects.As mechanization and intelligence levels continue to increase,supporting equipment mainly includes rock drilling trolleys,arch installation trolleys,wet spraying robots,anchor trolleys,etc.To address the issues of high construction costs and the need to replace equipment for different processes,this paper designs an economical and practical multi-functional integrated trolley for high-speed railway double-track tunnels based on engineering cases.This trolley can adapt to various tunnel face excavation methods such as the full-face method and the bench method,enabling integrated functions such as drilling and blasting holes,anchor holes,advance grouting holes,pipe roof construction,charging,anchor installation and grouting,and arch mesh installation.This reduces the number of operators,improves the working environment of high-speed railway tunnels,lowers construction costs,and enhances construction efficiency.展开更多
As a key national project,a newly built plateau railway features a large proportion of tunnels and high construction difficulty.To reduce the voids in the secondary lining of tunnels and address issues such as ineffec...As a key national project,a newly built plateau railway features a large proportion of tunnels and high construction difficulty.To reduce the voids in the secondary lining of tunnels and address issues such as ineffective vibration of the vault,vault voiding,and the inability to monitor the casting status during tunnel lining construction with ordinary lining trolleys,a new smart lining trolley with large clearance that integrates functions such as vibration,automatic casting,and pressure monitoring has been developed.This was achieved by combining the functional design of the new smart lining trolley,comparing traditional construction techniques,and introducing information-based and intelligent design concepts.Through simulation calculations using finite element software modeling,it is verified that the structural stiffness,strength,and other performance parameters of the smart lining trolley meet the technical design requirements.展开更多
Suboptimal treatment of laryngeal squamous cell carcinoma(LSCC)provides poor survival rate.The poor bioavailability,resistance to cetuximab(Cet),and the instability of small interfering RNA(siRNA)limit their efficacy ...Suboptimal treatment of laryngeal squamous cell carcinoma(LSCC)provides poor survival rate.The poor bioavailability,resistance to cetuximab(Cet),and the instability of small interfering RNA(siRNA)limit their efficacy in LSCC therapy.The present study has been aimed to develop a Cet and focal adhesion kinase(FAK)siRNA(siFAK)co-delivery nanosystem.Zeolitic imidazolate framework-8(ZIF-8),with its large specific surface area and pH-responsive properties,is an ideal delivery carrier allowing controlled drug release in the acidic tumor microenvironment.Therefore,Cet was loaded onto ZIF-8 and encapsulated in a TU177 cell membrane(TCM)after the electrostatic adsorption of siFAK.Fourier transform infrared(FTIR)spectroscopy,transmission electron microscopy(TEM),scanning electron microscopy(SEM),zeta potential,X-ray diffraction,and particle size analyses were deployed to characterize Cet/siFAK@ZIF-8@TCM.TU177 cells and subcutaneously transplanted tumor-bearing nude mice were used to evaluate the intracellular uptake,cytotoxicity,in vivo biocompatibility,biodistribution,biosafety,pH responsiveness,and anti-LSCC efficacy of Cet/siFAK@ZIF-8@TCM.After ZIF-8@TCM were loaded with Cet and siFAK,alterations in their physical and crystal structures,particle size,and zeta potential were observed.Meanwhile,the co-delivery system increased the loading of Cet through the electrostatic adsorption of siFAK to Cet-loaded ZIF-8.The intracellular uptake of Cet/siFAK@ZIF-8@TCM also protected siFAK from degradation,effectively decreasing the messenger RNA(mRNA)and protein expression levels of FAK in LSCC cells.The ZIF-8@TCM nanosystem for co-delivery of Cet and siFAK exhibited pH-responsiveness and tumor-targeting capabilities,thereby exerting anti-LSCC effects.Co-delivery of Cet and siFAK via the pH-responsive ZIF-8@TCM system enabled the targeted release of the chemotherapeutic and gene,in turn maximizing their anti-LSCC effect while ensuring biosafety.展开更多
Increasing human activity is altering the struc-ture of forests,which affects the composition of communi-ties,including birds.However,little is known about the key forest structure variables that determine the richnes...Increasing human activity is altering the struc-ture of forests,which affects the composition of communi-ties,including birds.However,little is known about the key forest structure variables that determine the richness of bird communities in European temperate oak forests.We,there-fore,aimed to identify key variables in these habitats that could contribute to the design of management strategies for forest conservation by surveying 11 oak-dominated forest sites throughout the mid-mountain range of Hungary at 86 survey points to reveal the role of different compositional and structural variables for forest stands that influence the breeding bird assemblages in the forests at the functional group and individual species levels.Based on decision tree modelling,our results showed that the density of trees larger than 30 cm DBH was an overall important variable,indi-cating that large-diameter trees were essential to provide diverse bird communities.The total abundance of birds,the foliage-gleaners,primary and secondary cavity nest-ers,residents,and five specific bird species were related to the density of high trunk diameter trees.The abundance of shrub nesters was negatively influenced by a high density of trees over 10 cm DBH.The density of the shrub layer positively affected total bird abundance and the abundance of foliage gleaners,secondary cavity nesters and residents.Analysis of the co-dominant tree species showed that the presence of linden,beech,and hornbeam was important in influencing the abundance of various bird species,e.g.,Eur-asian Treecreeper(Certhia familiaris),Marsh Tit(Poecile palustris)and Wood Warbler(Phylloscopus sibilatrix).Our results indicated that large trees,high tree diversity,and dense shrub layer were essential for forest bird communities and are critical targets for protection to maintain diverse and abundant bird communities in oak-dominated forest habitats.展开更多
Numerous clustering algorithms are valuable in pattern recognition in forest vegetation,with new ones continually being proposed.While some are well-known,others are underutilized in vegetation science.This study comp...Numerous clustering algorithms are valuable in pattern recognition in forest vegetation,with new ones continually being proposed.While some are well-known,others are underutilized in vegetation science.This study compares the performance of practical iterative reallocation algorithms with model-based clustering algorithms.The data is from forest vegetation in Virginia(United States),the Hyrcanian Forest(Asia),and European beech forests.Practical iterative reallocation algorithms were applied as non-hierarchical methods and Finite Gaussian mixture modeling was used as a model-based clustering method.Due to limitations on dimensionality in model-based clustering,principal coordinates analysis was employed to reduce the dataset’s dimensions.A log transformation was applied to achieve a normal distribution for the pseudo-species data before calculating the Bray-Curtis dissimilarity.The findings indicate that the reallocation of misclassified objects based on silhouette width(OPTSIL)with Flexible-β(-0.25)had the highest mean among the tested clustering algorithms with Silhouette width 1(REMOS1)with Flexible-β(-0.25)second.However,model-based clustering performed poorly.Based on these results,it is recommended using OPTSIL with Flexible-β(-0.25)and REMOS1 with Flexible-β(-0.25)for forest vegetation classification instead of model-based clustering particularly for heterogeneous datasets common in forest vegetation community data.展开更多
Dear Editor,Lung cancer remains the leading cause of cancer-related deaths[1],with non-small cell lung cancer(NSCLC)accounting for 85%of cases.Prognosis largely depends on the stage at diagnosis[2];stage Ia patients h...Dear Editor,Lung cancer remains the leading cause of cancer-related deaths[1],with non-small cell lung cancer(NSCLC)accounting for 85%of cases.Prognosis largely depends on the stage at diagnosis[2];stage Ia patients have a 5-year survival rate of about 70%,compared to under 20%overall[3].This highlights the need for effective screening.Currently,low-dose computed tomography(LDCT)is the preferred screening method for high-risk individuals,but it is expensive and has a high false-positive rate,often requiring invasive biopsies.Singapore’s 2010 Cancer Screening guidelines do not recommend chest radiography,sputum cytology,or CT for lung cancer screening[4].展开更多
The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research ...The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.展开更多
Topographic complexity supports the maintenance of a high diversity of microhabitats,which may act as important‘safe havens’-or microrefugia-for biodiversity.Microrefugia are sites with specific environmental condit...Topographic complexity supports the maintenance of a high diversity of microhabitats,which may act as important‘safe havens’-or microrefugia-for biodiversity.Microrefugia are sites with specific environmental conditions that facilitate the persistence of species during environmental changes and exhibit unique ecoevolutionary dynamics.However,our knowledge about how topographic complexity and related ecoevolutionary selective forces influence the functional and phylogenetic signatures of species assemblages in microrefugia is very limited.Although the conceptual framework on the systematic integration of plant functional traits into the study of refugia is well established,more empirical studies on functional trait composition and functional diversity in refugia are urgently needed for more effective conservation.Here we analyzed the distribution of various plant functional traits and phylogenetic patterns in microhabitats(south-and north-facing slopes,and bottoms)of 30 large topographic depressions(i.e.doline microrefugia)and microhabitats of the surrounding plateaus in two distant forested karst regions.We found that plant assemblages in the understory of dolines and their surroundings are characterized by unique functional values and combinations of traits.Doline bottoms had the highest functional diversity among doline microhabitats and supported plant assemblages with considerably different trait compositions from the plateaus.Bottoms also had the highest phylogenetic diversity.These results suggest that topographic complexity in forested dolines has a significant effect on the distribution of plant functional traits in the understory.High functional and phylogenetic diversity in doline bottoms can have important consequences for the long-term survival of plant populations,highlighting that these microhabitats may provide a higher resilience and support an adaptive community-level response to natural and anthropogenic stressors.Understanding mechanisms that drive the survival of species within microrefugia is required to determine the best conservation and management strategies.展开更多
The authors regret that an error occurred during the preparation of their article:One of the official databases,which was used for functional trait collections,contained an incorrect term–'chametophytes'–for...The authors regret that an error occurred during the preparation of their article:One of the official databases,which was used for functional trait collections,contained an incorrect term–'chametophytes'–for the life form category'chamaephytes'.Unfortunately,this incorrect term was used throughout the article following the nomenclature of this official database:in one instance in the main text,in Fig.3 and its caption,in Fig.5,and in two instances in the supplementary material.展开更多
目的探索血液筛查结果为HBsAg+&HBV DNA NR的HBV感染的血清学和分子生物学特性。方法通过重复核酸检测、PEG沉降病毒富集联合in-house的巢式PCR和实时荧光定量PCR,对HBsAg+&HBV DNA NR标本进行HBV DNA的确认、抗-HBc和HBsAg定...目的探索血液筛查结果为HBsAg+&HBV DNA NR的HBV感染的血清学和分子生物学特性。方法通过重复核酸检测、PEG沉降病毒富集联合in-house的巢式PCR和实时荧光定量PCR,对HBsAg+&HBV DNA NR标本进行HBV DNA的确认、抗-HBc和HBsAg定量检测,并将HBV序列与对照组HBV慢性感染和隐匿性感染序列进行比对分析。结果2011年1月~2020年12月,共检测标本792195份,筛选出HBsAg+&HBV DNA-标本53份(1∶14947)。获得S序列3份、Pre Core/Core序列4份,确认含有HBV DNA的标本有5份。Core区域发现独特氨基酸替换(P130T、P135Q/S、R151Q、G153S、S155F),可能对病毒包装、复制产生影响。结论血液筛查结果为HBsAg+&HBV DNA NR的血液存在极低水平的HBV DNA;低水平HBV DNA可能与Pre Core/Core区域的某些突变影响病毒复制有关。选择灵敏度更好的HBsAg和HBV DNA检测试剂能够进一步降低HBV经血传播的潜在风险。展开更多
Spontaneous combustion of coal is a problem that affects the mining operation and generates environ-mental,economic,social and geotechnical impacts.This phenomenon has been divided into two pro-cesses:ignition and pro...Spontaneous combustion of coal is a problem that affects the mining operation and generates environ-mental,economic,social and geotechnical impacts.This phenomenon has been divided into two pro-cesses:ignition and propagation.Fire propagation develops in coal seams because of a set of factors such as direction and wind speed,fracturing and temperature.In this work,heat transfer and chemical kinetics are studied from conservation equations of energy and species,respectively,using the software COMSOL Multiphysics to simulate the propagation of fires in coal seams.Two possible scenarios were analyzed that usually occur in the walls of the coal seams,such as fire focus and fire complete screens.It was found that the propagation kinetics of the fire changes depending on the temperature,the fractur-ing of rock mass and the area of fire influence.For temperature values lower than 300℃,there is con-sumption around 250 cm^3/h,values around 700℃,the consumption is 1500 cm^3/h,and for fires of 1200℃ have values of 3000 cm^3/h.Depending on the speed of propagation can vary from 4 to 17cm/day,considering on the level and fracturing of the final wall of the open pit.展开更多
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
文摘Foot reflexology(FR)is a Chinese-originated and non-invasive complementary therapy increasingly used by functional,alternative and para-medical professionals.Enhance attempts are made to study FR in non-functional organic conditions.The present invited Editorial discusses the application of FR in autoimmune diseases(AD),highlighting a few successful studies demonstrating symptomatic relief and objective improvements.Despite promising results,the FR domain remains under-investigated and an urgent need to confirm and understand the effect of FR in chronic diseases,including AD,is highly recommended.
文摘To effectively address the challenge where the speed of tunnel lining construction struggles to match that of tunnel face and inverted arch construction,and to enhance the quality of secondary lining,a new type of skeleton-free,traversing secondary lining trolley has been developed.This trolley features a set of gantries paired with two sets of formwork.The formwork adopts a multi-segment hinged and strengthened design,ensuring its own strength can meet the requirements of secondary lining concrete pouring without relying on the support of the gantries.When retracted,the formwork can be transported by the gantries through another set of formwork in the supporting state,enabling early formwork support,effectively accelerating the construction progress of the tunnel’s secondary lining,and extending the maintenance time of the secondary lining with the formwork.Finite element software modeling was used for simulation calculations,and the results indicate that the structural strength,stiffness,and other performance parameters of the new secondary lining trolley meet the design requirements,verifying the rationality of the design.
文摘The construction of the tunnel face is a critical aspect of tunnel excavation,and its supporting equipment mainly includes drilling jumbos,arch installation trolleys,wet spraying manipulators,and anchor bolt trolleys.To address the issues of high construction costs and the need to replace equipment for different processes,this paper designs an economical and practical multi-functional integrated trolley based on engineering cases.This trolley is suitable for various construction methods such as full-face excavation and benching method,and integrates functions such as drilling and blasting holes,anchor bolt holes,advance grouting holes,pipe roof construction,charging,anchor bolt installation and grouting,and arch mesh installation.It reduces the number of operators,improves the tunnel working environment,lowers construction costs,and enhances construction efficiency.
文摘With the rapid development of high-speed railway tunnel construction mileage and technology,the construction of the tunnel face is a key part of tunnel construction in high-speed railway tunnel projects.As mechanization and intelligence levels continue to increase,supporting equipment mainly includes rock drilling trolleys,arch installation trolleys,wet spraying robots,anchor trolleys,etc.To address the issues of high construction costs and the need to replace equipment for different processes,this paper designs an economical and practical multi-functional integrated trolley for high-speed railway double-track tunnels based on engineering cases.This trolley can adapt to various tunnel face excavation methods such as the full-face method and the bench method,enabling integrated functions such as drilling and blasting holes,anchor holes,advance grouting holes,pipe roof construction,charging,anchor installation and grouting,and arch mesh installation.This reduces the number of operators,improves the working environment of high-speed railway tunnels,lowers construction costs,and enhances construction efficiency.
文摘As a key national project,a newly built plateau railway features a large proportion of tunnels and high construction difficulty.To reduce the voids in the secondary lining of tunnels and address issues such as ineffective vibration of the vault,vault voiding,and the inability to monitor the casting status during tunnel lining construction with ordinary lining trolleys,a new smart lining trolley with large clearance that integrates functions such as vibration,automatic casting,and pressure monitoring has been developed.This was achieved by combining the functional design of the new smart lining trolley,comparing traditional construction techniques,and introducing information-based and intelligent design concepts.Through simulation calculations using finite element software modeling,it is verified that the structural stiffness,strength,and other performance parameters of the smart lining trolley meet the technical design requirements.
文摘Suboptimal treatment of laryngeal squamous cell carcinoma(LSCC)provides poor survival rate.The poor bioavailability,resistance to cetuximab(Cet),and the instability of small interfering RNA(siRNA)limit their efficacy in LSCC therapy.The present study has been aimed to develop a Cet and focal adhesion kinase(FAK)siRNA(siFAK)co-delivery nanosystem.Zeolitic imidazolate framework-8(ZIF-8),with its large specific surface area and pH-responsive properties,is an ideal delivery carrier allowing controlled drug release in the acidic tumor microenvironment.Therefore,Cet was loaded onto ZIF-8 and encapsulated in a TU177 cell membrane(TCM)after the electrostatic adsorption of siFAK.Fourier transform infrared(FTIR)spectroscopy,transmission electron microscopy(TEM),scanning electron microscopy(SEM),zeta potential,X-ray diffraction,and particle size analyses were deployed to characterize Cet/siFAK@ZIF-8@TCM.TU177 cells and subcutaneously transplanted tumor-bearing nude mice were used to evaluate the intracellular uptake,cytotoxicity,in vivo biocompatibility,biodistribution,biosafety,pH responsiveness,and anti-LSCC efficacy of Cet/siFAK@ZIF-8@TCM.After ZIF-8@TCM were loaded with Cet and siFAK,alterations in their physical and crystal structures,particle size,and zeta potential were observed.Meanwhile,the co-delivery system increased the loading of Cet through the electrostatic adsorption of siFAK to Cet-loaded ZIF-8.The intracellular uptake of Cet/siFAK@ZIF-8@TCM also protected siFAK from degradation,effectively decreasing the messenger RNA(mRNA)and protein expression levels of FAK in LSCC cells.The ZIF-8@TCM nanosystem for co-delivery of Cet and siFAK exhibited pH-responsiveness and tumor-targeting capabilities,thereby exerting anti-LSCC effects.Co-delivery of Cet and siFAK via the pH-responsive ZIF-8@TCM system enabled the targeted release of the chemotherapeutic and gene,in turn maximizing their anti-LSCC effect while ensuring biosafety.
基金supported part ia l l y by LIFE4Oak Forests Project LIFE16NAT/IT/000245)the RRF 2.3.121202200008 projectthe MERLiN project funded under the European Commission H2020 Programme(101036337 MERLiN H2020 LC GD 2020)。
文摘Increasing human activity is altering the struc-ture of forests,which affects the composition of communi-ties,including birds.However,little is known about the key forest structure variables that determine the richness of bird communities in European temperate oak forests.We,there-fore,aimed to identify key variables in these habitats that could contribute to the design of management strategies for forest conservation by surveying 11 oak-dominated forest sites throughout the mid-mountain range of Hungary at 86 survey points to reveal the role of different compositional and structural variables for forest stands that influence the breeding bird assemblages in the forests at the functional group and individual species levels.Based on decision tree modelling,our results showed that the density of trees larger than 30 cm DBH was an overall important variable,indi-cating that large-diameter trees were essential to provide diverse bird communities.The total abundance of birds,the foliage-gleaners,primary and secondary cavity nest-ers,residents,and five specific bird species were related to the density of high trunk diameter trees.The abundance of shrub nesters was negatively influenced by a high density of trees over 10 cm DBH.The density of the shrub layer positively affected total bird abundance and the abundance of foliage gleaners,secondary cavity nesters and residents.Analysis of the co-dominant tree species showed that the presence of linden,beech,and hornbeam was important in influencing the abundance of various bird species,e.g.,Eur-asian Treecreeper(Certhia familiaris),Marsh Tit(Poecile palustris)and Wood Warbler(Phylloscopus sibilatrix).Our results indicated that large trees,high tree diversity,and dense shrub layer were essential for forest bird communities and are critical targets for protection to maintain diverse and abundant bird communities in oak-dominated forest habitats.
基金financially supported by the vice chancellor for research and technology of Urmia University
文摘Numerous clustering algorithms are valuable in pattern recognition in forest vegetation,with new ones continually being proposed.While some are well-known,others are underutilized in vegetation science.This study compares the performance of practical iterative reallocation algorithms with model-based clustering algorithms.The data is from forest vegetation in Virginia(United States),the Hyrcanian Forest(Asia),and European beech forests.Practical iterative reallocation algorithms were applied as non-hierarchical methods and Finite Gaussian mixture modeling was used as a model-based clustering method.Due to limitations on dimensionality in model-based clustering,principal coordinates analysis was employed to reduce the dataset’s dimensions.A log transformation was applied to achieve a normal distribution for the pseudo-species data before calculating the Bray-Curtis dissimilarity.The findings indicate that the reallocation of misclassified objects based on silhouette width(OPTSIL)with Flexible-β(-0.25)had the highest mean among the tested clustering algorithms with Silhouette width 1(REMOS1)with Flexible-β(-0.25)second.However,model-based clustering performed poorly.Based on these results,it is recommended using OPTSIL with Flexible-β(-0.25)and REMOS1 with Flexible-β(-0.25)for forest vegetation classification instead of model-based clustering particularly for heterogeneous datasets common in forest vegetation community data.
基金supported by the Singapore Ministry of Health’s National Medical Research Council(NMRC/STaR/MOH-00070900,CIRG/MOH-00006400)the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiatives(to Boon Cher Goh)the NUS Centre for Cancer Research(N2CR),Cancer Programme under Translational Research Programmes(TRPs),Yong Loo Lin School of Medicine,NUS(NUHSRO/2020/122/MSC/07/Cancer)(to Lingzhi Wang and Boon Cher Goh).
文摘Dear Editor,Lung cancer remains the leading cause of cancer-related deaths[1],with non-small cell lung cancer(NSCLC)accounting for 85%of cases.Prognosis largely depends on the stage at diagnosis[2];stage Ia patients have a 5-year survival rate of about 70%,compared to under 20%overall[3].This highlights the need for effective screening.Currently,low-dose computed tomography(LDCT)is the preferred screening method for high-risk individuals,but it is expensive and has a high false-positive rate,often requiring invasive biopsies.Singapore’s 2010 Cancer Screening guidelines do not recommend chest radiography,sputum cytology,or CT for lung cancer screening[4].
基金supported by the Department of Biotechnology(DBT),Government of India(BT/556/NE/U-Excel/).
文摘The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.
基金funded by the National Research,Development and Innovation Office(NKFIH FK 142428 grant)The contribution of Z.B.was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences and by the New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research,Development and Innovation Fund(ÚNKP-23-5-SZTE-697)+2 种基金K.F.was supported by the New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research,Development and Innovation Fund(ÚNKP-23-3-SZTE-441)C.T.was supported by the NKFIH K 146137 grantA.E-V.was supported by the long-term research development project of the Czech Academy of Sciences(RVO 67985939).
文摘Topographic complexity supports the maintenance of a high diversity of microhabitats,which may act as important‘safe havens’-or microrefugia-for biodiversity.Microrefugia are sites with specific environmental conditions that facilitate the persistence of species during environmental changes and exhibit unique ecoevolutionary dynamics.However,our knowledge about how topographic complexity and related ecoevolutionary selective forces influence the functional and phylogenetic signatures of species assemblages in microrefugia is very limited.Although the conceptual framework on the systematic integration of plant functional traits into the study of refugia is well established,more empirical studies on functional trait composition and functional diversity in refugia are urgently needed for more effective conservation.Here we analyzed the distribution of various plant functional traits and phylogenetic patterns in microhabitats(south-and north-facing slopes,and bottoms)of 30 large topographic depressions(i.e.doline microrefugia)and microhabitats of the surrounding plateaus in two distant forested karst regions.We found that plant assemblages in the understory of dolines and their surroundings are characterized by unique functional values and combinations of traits.Doline bottoms had the highest functional diversity among doline microhabitats and supported plant assemblages with considerably different trait compositions from the plateaus.Bottoms also had the highest phylogenetic diversity.These results suggest that topographic complexity in forested dolines has a significant effect on the distribution of plant functional traits in the understory.High functional and phylogenetic diversity in doline bottoms can have important consequences for the long-term survival of plant populations,highlighting that these microhabitats may provide a higher resilience and support an adaptive community-level response to natural and anthropogenic stressors.Understanding mechanisms that drive the survival of species within microrefugia is required to determine the best conservation and management strategies.
文摘The authors regret that an error occurred during the preparation of their article:One of the official databases,which was used for functional trait collections,contained an incorrect term–'chametophytes'–for the life form category'chamaephytes'.Unfortunately,this incorrect term was used throughout the article following the nomenclature of this official database:in one instance in the main text,in Fig.3 and its caption,in Fig.5,and in two instances in the supplementary material.
文摘目的探索血液筛查结果为HBsAg+&HBV DNA NR的HBV感染的血清学和分子生物学特性。方法通过重复核酸检测、PEG沉降病毒富集联合in-house的巢式PCR和实时荧光定量PCR,对HBsAg+&HBV DNA NR标本进行HBV DNA的确认、抗-HBc和HBsAg定量检测,并将HBV序列与对照组HBV慢性感染和隐匿性感染序列进行比对分析。结果2011年1月~2020年12月,共检测标本792195份,筛选出HBsAg+&HBV DNA-标本53份(1∶14947)。获得S序列3份、Pre Core/Core序列4份,确认含有HBV DNA的标本有5份。Core区域发现独特氨基酸替换(P130T、P135Q/S、R151Q、G153S、S155F),可能对病毒包装、复制产生影响。结论血液筛查结果为HBsAg+&HBV DNA NR的血液存在极低水平的HBV DNA;低水平HBV DNA可能与Pre Core/Core区域的某些突变影响病毒复制有关。选择灵敏度更好的HBsAg和HBV DNA检测试剂能够进一步降低HBV经血传播的潜在风险。
基金CIMEX Mineral Institute of the National University of Colombia for the trust and support provided for the development of this researchthe Cerrejón company for financing this project
文摘Spontaneous combustion of coal is a problem that affects the mining operation and generates environ-mental,economic,social and geotechnical impacts.This phenomenon has been divided into two pro-cesses:ignition and propagation.Fire propagation develops in coal seams because of a set of factors such as direction and wind speed,fracturing and temperature.In this work,heat transfer and chemical kinetics are studied from conservation equations of energy and species,respectively,using the software COMSOL Multiphysics to simulate the propagation of fires in coal seams.Two possible scenarios were analyzed that usually occur in the walls of the coal seams,such as fire focus and fire complete screens.It was found that the propagation kinetics of the fire changes depending on the temperature,the fractur-ing of rock mass and the area of fire influence.For temperature values lower than 300℃,there is con-sumption around 250 cm^3/h,values around 700℃,the consumption is 1500 cm^3/h,and for fires of 1200℃ have values of 3000 cm^3/h.Depending on the speed of propagation can vary from 4 to 17cm/day,considering on the level and fracturing of the final wall of the open pit.
