Climate has changed sufficiently over the last 150 years and forced out upper treeline advance at the most studied sites around the world.The rate of advance has been extremely variable–from tens to hundreds meters i...Climate has changed sufficiently over the last 150 years and forced out upper treeline advance at the most studied sites around the world.The rate of advance has been extremely variable–from tens to hundreds meters in altitude.This is because the degree at which tree frontal populations respond to climate change depends on the complex interaction of biological and physical factors.The resulting stand pattern is the consequence of the interaction between dispersal and survival functions.A few publications have addressed the question of how this pattern is generated.In order to understand how the spatial structure of tree stands was formed at the upper limit of their distribution in the Ural Mountains,we assessed the distance and direction of dispersal of offspring from maternal individuals.We found that in frontal Larix sibirica Ledeb.populations,‘effective’dispersal of offspring ranges from 3 to 758 m(with a median of 20–33 m in open forest and 219 m in single-tree tundra in the Polar Urals and 107 m in open forest in the Northern Urals).We revealed that most of the offspring effectively dispersed not only in the direction of the prevailing winds,but also in the opposite direction up the slope,and the distance can reach 500–760 m.The data obtained can be used to develop an individual-based model which is capable of simulating in detail the dynamics of tree stands at the upper limit of their growth and reliably predicting the future position and pattern of treeline ecotone as growth conditions continue to improve in the face of observed climate change.展开更多
A philosophy for the design of novel,lightweight,multi-layered armor,referred to as Composite Armor Philosophy(CAP),which can adapt to the passive protection of light-,medium-,and heavy-armored vehicles,is presented i...A philosophy for the design of novel,lightweight,multi-layered armor,referred to as Composite Armor Philosophy(CAP),which can adapt to the passive protection of light-,medium-,and heavy-armored vehicles,is presented in this study.CAP can serve as a guiding principle to assist designers in comprehending the distinct roles fulfilled by each component.The CAP proposal comprises four functional layers,organized in a suggested hierarchy of materials.Particularly notable is the inclusion of a ceramic-composite principle,representing an advanced and innovative solution in the field of armor design.This paper showcases real-world defense industry applications,offering case studies that demonstrate the effectiveness of this advanced approach.CAP represents a significant milestone in the history of passive protection,marking an evolutionary leap in the field.This philosophical approach provides designers with a powerful toolset with which to enhance the protection capabilities of military vehicles,making them more resilient and better equipped to meet the challenges of modern warfare.展开更多
BACKGROUND The etiology of pancreatic cancer remains unclear. This limits the possibility of prevention and effective treatment. Hepatitis B virus(HBV) is responsible for the development of different types of cancer, ...BACKGROUND The etiology of pancreatic cancer remains unclear. This limits the possibility of prevention and effective treatment. Hepatitis B virus(HBV) is responsible for the development of different types of cancer, but its role in pancreatic cancer is still being discussed.AIM To assess the prevalence of previous HBV infection and to identify viral biomarkers in patients with pancreatic ductal adenocarcinoma(PDAC) to support the role of the virus in etiology of this cancer.METHODS The data of 130 hepatitis B surface antigen-negative subjects were available for the final analysis,including 60 patients with PDAC confirmed by cytology or histology and 70 sex-and age-matched controls. All the participants were tested for HBV biomarkers in blood [antibody to hepatitis B core antigen(anti-HBc), antibody to hepatitis B surface antigen(anti-HBs) and HBV DNA], and for those with PDAC, biomarkers in resected pancreatic tissues were tested(HBV DNA, HBV pregenomic RNA and covalently closed circular DNA). We performed immunohistochemistry staining of pancreatic tissues for hepatitis B virus X antigen and Ki-67 protein. Non-parametric statistics were used for the analysis.RESULTS Anti-HBc was detected in 18/60(30%) patients with PDAC and in 9/70(13%) participants in the control group(P = 0.029). Accordingly, the odds of PDAC in anti-HBc-positive subjects were higher compared to those with no previous HBV infection(odds ratio: 2.905, 95% confidence interval: 1.191-7.084, standard error 0.455). HBV DNA was detected in 8 cases of PDAC and in 6 of them in the pancreatic tumor tissue samples only(all patients were anti-HBc positive). Blood HBV DNA was negative in all subjects of the control group with positive results of the serum anti-HBc test. Among 9 patients with PDAC, 5 revealed signs of replicative competence of the virus(covalently closed circular DNA with or without pregenomic RNA) in the pancreatic tumor tissue samples. Hepatitis B virus X antigen expression and active cell proliferation was revealed by immunohistochemistry in 4 patients with PDAC in the pancreatic tumor tissue samples.CONCLUSION We found significantly higher risks of PDAC in anti-HBc-positive patients. Detection of viral replication and hepatitis B virus X protein expression in the tumor tissue prove involvement of HBV infection in pancreatic cancer development.展开更多
BACKGROUND Hepatitis B virus(HBV)is a known carcinogen that may be involved in pancreatic cancer development.Detection of HBV biomarkers[especially expression of HBV regulatory X protein(HBx)]within the tumor tissue m...BACKGROUND Hepatitis B virus(HBV)is a known carcinogen that may be involved in pancreatic cancer development.Detection of HBV biomarkers[especially expression of HBV regulatory X protein(HBx)]within the tumor tissue may provide direct support for this.However,there is still a lack of such reports,particularly in non-endemic regions for HBV infection.Here we present two cases of patients with pancreatic ductal adenocarcinoma,without a history of viral hepatitis,in whom the markers of HBV infection were detected in blood and in the resected pancreatic tissue.CASE SUMMARY The results of examination of two patients with pancreatic cancer,who gave informed consent for participation and publication,were the source for this study.Besides standards of care,special examination to reveal occult HBV infection was performed.This included blood tests for HBsAg,anti-HBc,anti-HBs,HBV DNA,and pancreatic tissue examinations with polymerase chain reaction for HBV DNA,pregenomic HBV RNA(pgRNA HBV),and covalently closed circular DNA HBV(cccDNA)and immunohistochemistry staining for HBxAg and Ki-67.Both subjects were operated on due to pancreatic ductal adenocarcinoma and serum HBsAg was not detected.However,in both of them anti-HBc antibodies were detected in blood,although HBV DNA was not found.Examination of the resected pancreatic tissue gave positive results for HBV DNA,expression of HBx,and active cellular proliferation by Ki-67 index in both cases.However,HBV pgRNA and cccDNA were detected only in case 1.CONCLUSION These cases may reflect potential involvement of HBV infection in the development of pancreatic cancer.展开更多
Gliomas are solid brain tumors composed of tumor cells and recruited heterogenic stromal components.The study of the interactions between the perivascular niche and its surrounding cells is of great value in unravelin...Gliomas are solid brain tumors composed of tumor cells and recruited heterogenic stromal components.The study of the interactions between the perivascular niche and its surrounding cells is of great value in unraveling mechanisms of drug resistance in malignant gliomas.In this study,we isolated the stromal diploid cell population from oligodendroglioma and a mixed population of tumor aneuploid and stromal diploid cells from astrocytoma specimens.The stromal cells expressed neural stem/progenitor and mesenchymal markers showing the same discordant phenotype that is typical for glioma cells.Moreover,some of the stromal cells expressed CD133.For the first time,we demonstrated that this type of stromal cells had the typical myofibroblastic phenotype as theα-SMA+cells formedα-SMA fibers and exhibited the specific function to deposit extracellular matrix(ECM)proteins at least in vitro.Immunofluorescent analysis showed diffuse or focalα-SMA staining in the cytoplasm of the astrocytoma-derived,A172,T98G,and U251MG glioma cells.We could suggest thatα-SMA may be one of the main molecules,bearing protective functions.Possible mechanisms and consequences ofα-SMA disruptions in gliomas are discussed.展开更多
The prevention of blindness from glaucoma requires multiple treatments to lower intraocular pressure.Here,human contact lenses are modified with highly porous metal-organic frameworks with sustained release of brimonid...The prevention of blindness from glaucoma requires multiple treatments to lower intraocular pressure.Here,human contact lenses are modified with highly porous metal-organic frameworks with sustained release of brimonidine for prolonged glaucoma treatment.Various metal-organic frameworks were screened for their attachment to lenses,loading with brimonidine,and drug-release properties.Opti-mized therapeutic ocular lenses conjugated with MIL-101(Cr)frameworks maintain optical transparency and power.Coating of lenses with MIL-101(Cr)nanoparticles reduced brimonidine washout with tears and ensured a gradual and localized release of the drug into the eyeball through the cornea.The hybrid lenses provided a 4.5-fold better decrease in eye pressure,compared by area under the curve(AUC)value to a commercially available brimonidine tartrate solution.Therapeutic lenses did not induce any notable eye irritation or corneal damage in vivo.The newly devel-oped hybrid lenses are expected to provide a robust platform for the therapy and prevention of various ocular diseases.展开更多
Knowledge graphs(KGs)express relationships between entity pairs,and many real-life problems can be formulated as knowledge graph reasoning(KGR).Conventional approaches to KGR have achieved promising performance but st...Knowledge graphs(KGs)express relationships between entity pairs,and many real-life problems can be formulated as knowledge graph reasoning(KGR).Conventional approaches to KGR have achieved promising performance but still have some drawbacks.On the one hand,most KGR methods focus only on one phase of the KG lifecycle,such as KG completion or refinement,while ignoring reasoning over other stages,such as KG extraction.On the other hand,traditional KGR methods,broadly categorized as symbolic and neural,are unable to balance both scalability and interpretability.To resolve these two problems,we take a more comprehensive perspective of KGR with regard to the whole KG lifecycle,including KG extraction,completion,and refinement,which correspond to three subtasks:knowledge extraction,relational reasoning,and inconsistency checking.In addition,we propose the implementation of KGR using a novel neural symbolic framework,with regard to both scalability and interpretability.Experimental results demonstrate that our proposed methods outperform traditional neural symbolic models.展开更多
Bioengineered scaffolds are crucial components in artificial tissue construction.In general,these scaffolds provide inert three-dimensional(3D)surfaces supporting cell growth.However,some scaffolds can affect the phen...Bioengineered scaffolds are crucial components in artificial tissue construction.In general,these scaffolds provide inert three-dimensional(3D)surfaces supporting cell growth.However,some scaffolds can affect the phenotype of cultured cells,especially,adherent stromal cells,such as fibroblasts.Here we report on unique properties of 3D fibroin/gelatin materials,which may rapidly induce expression of adhesion molecules,such as ICAM-1 and VCAM-1,in cultured primary murine embryonic fibroblasts(MEFs).In contrast,two-dimensional(2D)fibroin/gelatin films did not show significant effects on gene expression profiles in fibroblasts as compared to 3D culture conditions.Interestingly,TNF expression was induced in MEFs cultured in 3D fibroin/gelatin scaffolds,while genetic or pharmacological TNF ablation resulted in diminished ICAM-1 and VCAM-1 expression by these cells.Using selective MAPK inhibitors,we uncovered critical contribution of JNK to 3D-induced upregulation of these adhesion molecules.Moreover,we observed ICAM-1/VCAM-1-dependent adhesion of lymphocytes to fibroblasts cultured in 3D fibroin/gelatin scaffolds,but not on 2D fibroin/gelatin films,suggesting functional reprogramming in stromal cells,when exposed to 3D environment.Finally,we observed significant infiltration of lymphocytes into 3D fibroin/gelatin,but not into collagen scaffolds in vivo upon subcapsular kidney implantation in mice.Together our data highlight the important features of fibroin/gelatin scaffolds,when they are produced as 3D sponges rather than 2D films,which should be considered when using these materials for tissue engineering.展开更多
Dear Editor,Chromosomal translocations result from the interchange of geneticmaterial between non-homologous chromosomes.Chromosomal translocations are formed by erroneous repair of double-stranded breaks(DSBs)via non...Dear Editor,Chromosomal translocations result from the interchange of geneticmaterial between non-homologous chromosomes.Chromosomal translocations are formed by erroneous repair of double-stranded breaks(DSBs)via non-homologous end joining(NHEJ)[1].Some genotoxic drugs produce DSBs and thus present a major risk factor for the development of oncogenic chromosomal translocations.The risk factors that interfere with translocationprone DSB repair,once DSBs are already formed,are obscure,and potential effects of drugs on translocation formation during this step have never been explored.展开更多
基金supported by the Russian Center for Scientific Information under grant RFBR–21–54–12016 for the sampling and treating of collected materialsby the Russian Scientific Foundation under grant RSF-24–14-00206 for data analysis and preparation of the manuscript.
文摘Climate has changed sufficiently over the last 150 years and forced out upper treeline advance at the most studied sites around the world.The rate of advance has been extremely variable–from tens to hundreds meters in altitude.This is because the degree at which tree frontal populations respond to climate change depends on the complex interaction of biological and physical factors.The resulting stand pattern is the consequence of the interaction between dispersal and survival functions.A few publications have addressed the question of how this pattern is generated.In order to understand how the spatial structure of tree stands was formed at the upper limit of their distribution in the Ural Mountains,we assessed the distance and direction of dispersal of offspring from maternal individuals.We found that in frontal Larix sibirica Ledeb.populations,‘effective’dispersal of offspring ranges from 3 to 758 m(with a median of 20–33 m in open forest and 219 m in single-tree tundra in the Polar Urals and 107 m in open forest in the Northern Urals).We revealed that most of the offspring effectively dispersed not only in the direction of the prevailing winds,but also in the opposite direction up the slope,and the distance can reach 500–760 m.The data obtained can be used to develop an individual-based model which is capable of simulating in detail the dynamics of tree stands at the upper limit of their growth and reliably predicting the future position and pattern of treeline ecotone as growth conditions continue to improve in the face of observed climate change.
基金co-financed by the European Regional Development Fund of the European UnionGreek national funds through the Operational Program Competitiveness,Entrepreneurship and Innovation,under the call RESEARCH-CREATE-INNOVATE(project code:T1EDK-04429)。
文摘A philosophy for the design of novel,lightweight,multi-layered armor,referred to as Composite Armor Philosophy(CAP),which can adapt to the passive protection of light-,medium-,and heavy-armored vehicles,is presented in this study.CAP can serve as a guiding principle to assist designers in comprehending the distinct roles fulfilled by each component.The CAP proposal comprises four functional layers,organized in a suggested hierarchy of materials.Particularly notable is the inclusion of a ceramic-composite principle,representing an advanced and innovative solution in the field of armor design.This paper showcases real-world defense industry applications,offering case studies that demonstrate the effectiveness of this advanced approach.CAP represents a significant milestone in the history of passive protection,marking an evolutionary leap in the field.This philosophical approach provides designers with a powerful toolset with which to enhance the protection capabilities of military vehicles,making them more resilient and better equipped to meet the challenges of modern warfare.
基金Supported by Ministry of Science and Higher Education of Russian Federation,No. FGMF-2022-0005Russian Science Foundation,No. 20-15-00373Moscow Healthcare Department,No. AAAA-A18-118021590196-1。
文摘BACKGROUND The etiology of pancreatic cancer remains unclear. This limits the possibility of prevention and effective treatment. Hepatitis B virus(HBV) is responsible for the development of different types of cancer, but its role in pancreatic cancer is still being discussed.AIM To assess the prevalence of previous HBV infection and to identify viral biomarkers in patients with pancreatic ductal adenocarcinoma(PDAC) to support the role of the virus in etiology of this cancer.METHODS The data of 130 hepatitis B surface antigen-negative subjects were available for the final analysis,including 60 patients with PDAC confirmed by cytology or histology and 70 sex-and age-matched controls. All the participants were tested for HBV biomarkers in blood [antibody to hepatitis B core antigen(anti-HBc), antibody to hepatitis B surface antigen(anti-HBs) and HBV DNA], and for those with PDAC, biomarkers in resected pancreatic tissues were tested(HBV DNA, HBV pregenomic RNA and covalently closed circular DNA). We performed immunohistochemistry staining of pancreatic tissues for hepatitis B virus X antigen and Ki-67 protein. Non-parametric statistics were used for the analysis.RESULTS Anti-HBc was detected in 18/60(30%) patients with PDAC and in 9/70(13%) participants in the control group(P = 0.029). Accordingly, the odds of PDAC in anti-HBc-positive subjects were higher compared to those with no previous HBV infection(odds ratio: 2.905, 95% confidence interval: 1.191-7.084, standard error 0.455). HBV DNA was detected in 8 cases of PDAC and in 6 of them in the pancreatic tumor tissue samples only(all patients were anti-HBc positive). Blood HBV DNA was negative in all subjects of the control group with positive results of the serum anti-HBc test. Among 9 patients with PDAC, 5 revealed signs of replicative competence of the virus(covalently closed circular DNA with or without pregenomic RNA) in the pancreatic tumor tissue samples. Hepatitis B virus X antigen expression and active cell proliferation was revealed by immunohistochemistry in 4 patients with PDAC in the pancreatic tumor tissue samples.CONCLUSION We found significantly higher risks of PDAC in anti-HBc-positive patients. Detection of viral replication and hepatitis B virus X protein expression in the tumor tissue prove involvement of HBV infection in pancreatic cancer development.
基金the Ministry of Science and Higher Education,No.FGMF-2022-0005the Russian Science Foundation,No.20-15-00373and the Moscow Healthcare Department,No.AAAA-A18-118021590196-1.
文摘BACKGROUND Hepatitis B virus(HBV)is a known carcinogen that may be involved in pancreatic cancer development.Detection of HBV biomarkers[especially expression of HBV regulatory X protein(HBx)]within the tumor tissue may provide direct support for this.However,there is still a lack of such reports,particularly in non-endemic regions for HBV infection.Here we present two cases of patients with pancreatic ductal adenocarcinoma,without a history of viral hepatitis,in whom the markers of HBV infection were detected in blood and in the resected pancreatic tissue.CASE SUMMARY The results of examination of two patients with pancreatic cancer,who gave informed consent for participation and publication,were the source for this study.Besides standards of care,special examination to reveal occult HBV infection was performed.This included blood tests for HBsAg,anti-HBc,anti-HBs,HBV DNA,and pancreatic tissue examinations with polymerase chain reaction for HBV DNA,pregenomic HBV RNA(pgRNA HBV),and covalently closed circular DNA HBV(cccDNA)and immunohistochemistry staining for HBxAg and Ki-67.Both subjects were operated on due to pancreatic ductal adenocarcinoma and serum HBsAg was not detected.However,in both of them anti-HBc antibodies were detected in blood,although HBV DNA was not found.Examination of the resected pancreatic tissue gave positive results for HBV DNA,expression of HBx,and active cellular proliferation by Ki-67 index in both cases.However,HBV pgRNA and cccDNA were detected only in case 1.CONCLUSION These cases may reflect potential involvement of HBV infection in the development of pancreatic cancer.
基金The design of this study and analysis of data were financially supported by the grants from Russian Science Foundation(No.18-75-10076)and by RFBR(No.19-315-51035).
文摘Gliomas are solid brain tumors composed of tumor cells and recruited heterogenic stromal components.The study of the interactions between the perivascular niche and its surrounding cells is of great value in unraveling mechanisms of drug resistance in malignant gliomas.In this study,we isolated the stromal diploid cell population from oligodendroglioma and a mixed population of tumor aneuploid and stromal diploid cells from astrocytoma specimens.The stromal cells expressed neural stem/progenitor and mesenchymal markers showing the same discordant phenotype that is typical for glioma cells.Moreover,some of the stromal cells expressed CD133.For the first time,we demonstrated that this type of stromal cells had the typical myofibroblastic phenotype as theα-SMA+cells formedα-SMA fibers and exhibited the specific function to deposit extracellular matrix(ECM)proteins at least in vitro.Immunofluorescent analysis showed diffuse or focalα-SMA staining in the cytoplasm of the astrocytoma-derived,A172,T98G,and U251MG glioma cells.We could suggest thatα-SMA may be one of the main molecules,bearing protective functions.Possible mechanisms and consequences ofα-SMA disruptions in gliomas are discussed.
基金Ministry of Science and Higher Education of the Russian Federation,Grant/Award Number:075-15-2024-536。
文摘The prevention of blindness from glaucoma requires multiple treatments to lower intraocular pressure.Here,human contact lenses are modified with highly porous metal-organic frameworks with sustained release of brimonidine for prolonged glaucoma treatment.Various metal-organic frameworks were screened for their attachment to lenses,loading with brimonidine,and drug-release properties.Opti-mized therapeutic ocular lenses conjugated with MIL-101(Cr)frameworks maintain optical transparency and power.Coating of lenses with MIL-101(Cr)nanoparticles reduced brimonidine washout with tears and ensured a gradual and localized release of the drug into the eyeball through the cornea.The hybrid lenses provided a 4.5-fold better decrease in eye pressure,compared by area under the curve(AUC)value to a commercially available brimonidine tartrate solution.Therapeutic lenses did not induce any notable eye irritation or corneal damage in vivo.The newly devel-oped hybrid lenses are expected to provide a robust platform for the therapy and prevention of various ocular diseases.
基金funded by National Natural Science Foundation of China(Grant no.91846204 and U19B2027)National Key Research and Development Program of China(Grant no.2018YFB1402800).
文摘Knowledge graphs(KGs)express relationships between entity pairs,and many real-life problems can be formulated as knowledge graph reasoning(KGR).Conventional approaches to KGR have achieved promising performance but still have some drawbacks.On the one hand,most KGR methods focus only on one phase of the KG lifecycle,such as KG completion or refinement,while ignoring reasoning over other stages,such as KG extraction.On the other hand,traditional KGR methods,broadly categorized as symbolic and neural,are unable to balance both scalability and interpretability.To resolve these two problems,we take a more comprehensive perspective of KGR with regard to the whole KG lifecycle,including KG extraction,completion,and refinement,which correspond to three subtasks:knowledge extraction,relational reasoning,and inconsistency checking.In addition,we propose the implementation of KGR using a novel neural symbolic framework,with regard to both scalability and interpretability.Experimental results demonstrate that our proposed methods outperform traditional neural symbolic models.
基金This work was supported by the Russian Science Foundation grant#19-75-30032Genotyping of mice and primary cell cultures was supported by grant 075-15-2019-1660 from the Ministry of Science and Higher Education of the Russian Federation.Generation of TNF KO and IL-6 KO MEFs was supported by the Russian Foundation for Basic Research grant#19-04-01094.
文摘Bioengineered scaffolds are crucial components in artificial tissue construction.In general,these scaffolds provide inert three-dimensional(3D)surfaces supporting cell growth.However,some scaffolds can affect the phenotype of cultured cells,especially,adherent stromal cells,such as fibroblasts.Here we report on unique properties of 3D fibroin/gelatin materials,which may rapidly induce expression of adhesion molecules,such as ICAM-1 and VCAM-1,in cultured primary murine embryonic fibroblasts(MEFs).In contrast,two-dimensional(2D)fibroin/gelatin films did not show significant effects on gene expression profiles in fibroblasts as compared to 3D culture conditions.Interestingly,TNF expression was induced in MEFs cultured in 3D fibroin/gelatin scaffolds,while genetic or pharmacological TNF ablation resulted in diminished ICAM-1 and VCAM-1 expression by these cells.Using selective MAPK inhibitors,we uncovered critical contribution of JNK to 3D-induced upregulation of these adhesion molecules.Moreover,we observed ICAM-1/VCAM-1-dependent adhesion of lymphocytes to fibroblasts cultured in 3D fibroin/gelatin scaffolds,but not on 2D fibroin/gelatin films,suggesting functional reprogramming in stromal cells,when exposed to 3D environment.Finally,we observed significant infiltration of lymphocytes into 3D fibroin/gelatin,but not into collagen scaffolds in vivo upon subcapsular kidney implantation in mice.Together our data highlight the important features of fibroin/gelatin scaffolds,when they are produced as 3D sponges rather than 2D films,which should be considered when using these materials for tissue engineering.
基金Cancéropole IdF,the Koltzov Institute of Developmental Biology,Russian Academy of Sciences Government basic research programs(0088-2021-0007)the Ministry of Science and Higher Education grants(075-15-2021-1075 to YV and 075-15-2021-1062 and 075-15-2021-1060 to MR)+1 种基金Russian Foundation for Basic Research(19-54-16002)the Interdisciplinary Scientific and Educational School of Moscow University≪Molecular Technologies of the Living Systems and Synthetic Biology≫to MR.AS was supported by the Travel Grant from Boehringer Ingelheim Fonds in 2018.
文摘Dear Editor,Chromosomal translocations result from the interchange of geneticmaterial between non-homologous chromosomes.Chromosomal translocations are formed by erroneous repair of double-stranded breaks(DSBs)via non-homologous end joining(NHEJ)[1].Some genotoxic drugs produce DSBs and thus present a major risk factor for the development of oncogenic chromosomal translocations.The risk factors that interfere with translocationprone DSB repair,once DSBs are already formed,are obscure,and potential effects of drugs on translocation formation during this step have never been explored.