The existence of solutions for singular nonlinear two point boundary value problems subject to Sturm Liouville boundary conditions with p Laplacian operators is studied by the method of upper and lower solution...The existence of solutions for singular nonlinear two point boundary value problems subject to Sturm Liouville boundary conditions with p Laplacian operators is studied by the method of upper and lower solutions. The proof is based on an application of Schauder’s fixed point theorem to a modified problem whose solutions are that of the original one. At the same time, Arzela Ascoli theorem is used to prove that the defined operator N is a compact map.展开更多
The existence of multiple positive solutions for a class of higher order p Laplacian boundary value problem is studied. By means of the Leggett Williams fixed point theorem in cones, existence criteria which e...The existence of multiple positive solutions for a class of higher order p Laplacian boundary value problem is studied. By means of the Leggett Williams fixed point theorem in cones, existence criteria which ensure the existence of at least three positive solutions of the boundary value problem are established.展开更多
BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
The Meishan section of China has been confirmed as the ＂Global Stratotype Section and Point＂ of the P/T boundary. In the section, the authors found several types of iron grains, including pyrite, pure iron grains an...The Meishan section of China has been confirmed as the ＂Global Stratotype Section and Point＂ of the P/T boundary. In the section, the authors found several types of iron grains, including pyrite, pure iron grains and goethite. From the research of macro minerals, it is easy to find that the grains rich in iron appear from the bottom of the event layer of the section. In other words, it is probably residue of the geochemical catastrophe of that time. Therefore, it is important to trace the source of these iron grains and their relationships, which probably provides evidence for volcanic eruption or impact-volcanoes and has directive significance to the crisis during the P/T transitional period. Through the study of the characterization and relationships of these iron grains, the authors make a preliminary discussion on the P/T mass extinction.展开更多
The present note is concerned with two connected and highly important fundamental questions of physics and cosmology, namely if E8E8 Lie symmetry group describes the universe and where cosmic dark energy comes from. F...The present note is concerned with two connected and highly important fundamental questions of physics and cosmology, namely if E8E8 Lie symmetry group describes the universe and where cosmic dark energy comes from. Furthermore, we reason following Wheeler, Hartle and Hawking that since the boundary of a boundary is an empty set which models the quantum wave of the cosmos, then it follows that dark energy is a fundamental physical phenomenon associated with the boundary of the holographic boundary. This leads directly to a clopen universe which is its own Penrose tiling-like multiverse with energy density in full agreement with COBE, WMAP and Type 1a supernova cosmic measurements.展开更多
The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma（OSCC） and adjacent tissues to establish a molecular surgical boundary and provide a cancer progr...The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma（OSCC） and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T（cancer）, P1（0–0.5 cm）, P2（0.5–1 cm）, P3（1–1.5 cm） and P4（1.5–2 cm） groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21CIP1/WAF1, e IF4 E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining.Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21CIP1/WAF1 expression displayed an opposite trend. e IF4 E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression.展开更多
Two-dimensional tidal open boundary conditions of the M2 constituent in the Bohai and Yellow Seas(BYS) have been estimated by assimilating T/P altimeter data.During inversion,independent point(IP) strategy was used,in...Two-dimensional tidal open boundary conditions of the M2 constituent in the Bohai and Yellow Seas(BYS) have been estimated by assimilating T/P altimeter data.During inversion,independent point(IP) strategy was used,in which several IPs on the open boundary is assumed,values at these IPs can be optimized with an adjoint method,and those at other grid points are determined by linearly interpolating the values at IPs.The reasonability and feasibility of the model are tested by ideal twin experiments.In the practical experiment(PE) after assimilation,the cost function may reach 1% or less of its initial value.Mean absolute errors in amplitude and phase can be less than 5 cm and 5°,respectively,and the obtained co-chart can show the character of the M2 constituent in the BYS.The results of the PE indicate that using only two IPs on the open boundary can yield better simulated results.展开更多
In this paper, we consider the existence of three nontrivial solutions for a discrete non-linear multiparameter periodic problem involving the p-Laplacian. By using the similar method for the Dirichlet boundary value ...In this paper, we consider the existence of three nontrivial solutions for a discrete non-linear multiparameter periodic problem involving the p-Laplacian. By using the similar method for the Dirichlet boundary value problems in [C. Bonanno and P. Candito, Appl. Anal., 88（4） （2009）, pp. 605-616], we construct two new strong maximum principles and obtain that the boundary value problem has three positive solutions for λ and μ in some suitable intervals. The approaches we use are the critical point theory.展开更多
文摘The existence of solutions for singular nonlinear two point boundary value problems subject to Sturm Liouville boundary conditions with p Laplacian operators is studied by the method of upper and lower solutions. The proof is based on an application of Schauder’s fixed point theorem to a modified problem whose solutions are that of the original one. At the same time, Arzela Ascoli theorem is used to prove that the defined operator N is a compact map.
文摘The existence of multiple positive solutions for a class of higher order p Laplacian boundary value problem is studied. By means of the Leggett Williams fixed point theorem in cones, existence criteria which ensure the existence of at least three positive solutions of the boundary value problem are established.
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
基金This research was supported by the National Natural Science Foundation of China （Nos. 40232025 40072055+1 种基金 40572020） the Research Fund for the Doctoral Program of Higher Education （No. 20040290005）.
文摘The Meishan section of China has been confirmed as the ＂Global Stratotype Section and Point＂ of the P/T boundary. In the section, the authors found several types of iron grains, including pyrite, pure iron grains and goethite. From the research of macro minerals, it is easy to find that the grains rich in iron appear from the bottom of the event layer of the section. In other words, it is probably residue of the geochemical catastrophe of that time. Therefore, it is important to trace the source of these iron grains and their relationships, which probably provides evidence for volcanic eruption or impact-volcanoes and has directive significance to the crisis during the P/T transitional period. Through the study of the characterization and relationships of these iron grains, the authors make a preliminary discussion on the P/T mass extinction.
文摘The present note is concerned with two connected and highly important fundamental questions of physics and cosmology, namely if E8E8 Lie symmetry group describes the universe and where cosmic dark energy comes from. Furthermore, we reason following Wheeler, Hartle and Hawking that since the boundary of a boundary is an empty set which models the quantum wave of the cosmos, then it follows that dark energy is a fundamental physical phenomenon associated with the boundary of the holographic boundary. This leads directly to a clopen universe which is its own Penrose tiling-like multiverse with energy density in full agreement with COBE, WMAP and Type 1a supernova cosmic measurements.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81001209 and 81172578)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 81321002)
文摘The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma（OSCC） and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T（cancer）, P1（0–0.5 cm）, P2（0.5–1 cm）, P3（1–1.5 cm） and P4（1.5–2 cm） groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21CIP1/WAF1, e IF4 E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining.Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21CIP1/WAF1 expression displayed an opposite trend. e IF4 E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression.
基金Supported by the State Ministry of Science and Technology of China (Nos.2007AA09Z118,2008AA09A402)the National Natural Science Foundation of China(No.41076006)the Ministry of Education's 111 Project(No.B07036)
文摘Two-dimensional tidal open boundary conditions of the M2 constituent in the Bohai and Yellow Seas(BYS) have been estimated by assimilating T/P altimeter data.During inversion,independent point(IP) strategy was used,in which several IPs on the open boundary is assumed,values at these IPs can be optimized with an adjoint method,and those at other grid points are determined by linearly interpolating the values at IPs.The reasonability and feasibility of the model are tested by ideal twin experiments.In the practical experiment(PE) after assimilation,the cost function may reach 1% or less of its initial value.Mean absolute errors in amplitude and phase can be less than 5 cm and 5°,respectively,and the obtained co-chart can show the character of the M2 constituent in the BYS.The results of the PE indicate that using only two IPs on the open boundary can yield better simulated results.
基金Supported by NSFC(11326127,11101335)NWNULKQN-11-23the Fundamental Research Funds for the Gansu Universities
文摘In this paper, we consider the existence of three nontrivial solutions for a discrete non-linear multiparameter periodic problem involving the p-Laplacian. By using the similar method for the Dirichlet boundary value problems in [C. Bonanno and P. Candito, Appl. Anal., 88（4） （2009）, pp. 605-616], we construct two new strong maximum principles and obtain that the boundary value problem has three positive solutions for λ and μ in some suitable intervals. The approaches we use are the critical point theory.
