Brazil has become one of the top producers and exporters of food, fibre, and bionergy in the world.The expansion of livestock and soybean production in the Amazon basin appears to be independent of the sugarcane expan...Brazil has become one of the top producers and exporters of food, fibre, and bionergy in the world.The expansion of livestock and soybean production in the Amazon basin appears to be independent of the sugarcane expansion in southeastern Brazil whereas the impact of sugarcane expansion over areas of soybean plantation in previous Cerrado biome is still unknown. However, the expansion of sugarcane production in the state of S?o Paulohas been shown to cause an increase in the local abundance of rodents and result in the emergence of infectious diseases such as hantaviruses and leptospirosis in humans. In addition, with an increase in the use of agrochemicals there will be an increase in euthrophication of watercourses and soil pollution. Considering that S?o Paulo has a population of approximately 40 million people, these local impacts are relevant. Environmental law should be improved and enforced in Brazil to ensure that sugarcane production is not only economically profitable but also environmentally responsible.展开更多
Objective:Nutraceutical products are widely used for their claimed therapeutic benefits.However,falsified or adulterated nutraceuticals present a major health threat to consumers.This study investigates the pharmaceut...Objective:Nutraceutical products are widely used for their claimed therapeutic benefits.However,falsified or adulterated nutraceuticals present a major health threat to consumers.This study investigates the pharmaceutical quality,safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100%natural.Methods:Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography(HPLC).The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy(NIR)and Se De M.The cytotoxic effects of these products on HepG2 cells were determined through cell proliferation(XTT)and lactate dehydrogenase(LDH)cytotoxicity assays.Lastly,the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release analysis.Results:HPLC analysis detected the presence of sildenafil citrate,a vasodilator,and the active ingredient in Viagra and Revatio,in all batches of the products we analyzed.Amount of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different batches.NIR assessment showed inter-and intra-batch heterogeneity in product composition.Results of the XTT and LDH assays showed significant cytotoxic effects of the analyzed products.XTT analysis revealed that the viability of HepG2 treated with tested products varied from 27.57%to 41.43%.Interestingly,the male enhancement products also showed anti-inflammatory effects.Conclusion:Despite their labeling as 100%natural,all products tested in this study contained levels of sildenafil citrate,which was not reported on the packaging.There was a lack of pharmaceutical uniformity among products of the same batch and across different batches.Additionally,the products we tested had cytotoxic effects.These study findings highlight the adulteration,poor quality and hazard of these nutraceuticals.Therefore,strict regulation of these products and standardization of the definition of nutraceuticals are urgently needed.Further,these falsely advertised products should be withdrawn from the market due to potential adverse effects on the health of their consumers.展开更多
Alzheimer’s disease(AD)and associated cognitive dysfunction are major healthcare challenges globally.Various mechanisms of pathogenesis and signaling molecules have been studied for their plausible role in disease in...Alzheimer’s disease(AD)and associated cognitive dysfunction are major healthcare challenges globally.Various mechanisms of pathogenesis and signaling molecules have been studied for their plausible role in disease initiation and progression.Neuroinflammation has been considered a major hallmark of AD.Amyloid beta(Ab),hyperphosphorylated tau protein,and formed neurofibrillary tangles(NFT)are positively correlated with neuroinflammation.Microglial activation was found to be a key contributor to neuroinflammation,AD pathogenesis,and progression.The mechanism of microglial activation has been studied in detail,and looking into its pivotal role in disease etiology,various drugs have been developed,and many are in the clinical phases of development.These drugs either inhibit the microglial activation or neuroinflammatory event postmicroglial activation.Considering these facts,in the present study,we herein discuss the mechanism of microglial activation and the mechanism of neuroinflammation related to microglial activation and dementia.Here we also discussed the various drugs that either act at tau protein or mitigate neuroinflammation,along with their status in clinical trials.In brief,this review provides an in-depth mechanism of microglial activation and updates on drugs that can inhibit this activation,leading to significant anti-Alzheimer effect and mitigation of cognitive dysfunction.展开更多
This study proposes a segmented approach to analyzing diabetes risk factors using the dataset diabete_custom.xlsx(150 individuals,14 medical and behavioral variables).The combination of KMeans with logistic regression...This study proposes a segmented approach to analyzing diabetes risk factors using the dataset diabete_custom.xlsx(150 individuals,14 medical and behavioral variables).The combination of KMeans with logistic regression and KMeans with decision tree enabled the definition of three clusters corresponding to low,moderate,and high risk,while identifying key variables such as blood glucose,BMI,and heredity.The hybrid models improve accuracy and interpretability compared to KMeans alone,with the decision tree being slightly more effective in unbalanced clusters.These findings provide a foundation for personalized interventions,including targeted screening,glycemic and nutritional monitoring,physical activity,and educational campaigns tailored to each risk profile.展开更多
Despite significant advances in targeted therapies and immunotherapies,non-small cell lung cancer(NSCLC)continues to present a global health challenge,with a modest five-year survival rate of 28%,largely due to the em...Despite significant advances in targeted therapies and immunotherapies,non-small cell lung cancer(NSCLC)continues to present a global health challenge,with a modest five-year survival rate of 28%,largely due to the emergence of treatment-resistant and metastatic tumors.In response,we synthesized a novel bioactive compound,ethyl 6-chlorocoumarin-3-carboxylyl L-theanine(TClC),which significantly inhibited NSCLC growth,epithelial mesenchymal transition(EMT),migration,and invasion in vitro and tumor growth and metastasis in vivo without inducing toxicity.TClC disrupts autocrine loops that promote tumor progression,particularly in stem-like CD133-positive NSCLC(CD133+LC)cells,which are pivotal in tumor metastasis.Through targeted molecular assays,we identified direct binding targets of TClC,including Akt,NF-κB,β-catenin,EZH2,and PD-L1.This interaction not only suppresses the expression of oncogenic factors and cancer stem cell markers but also downregulates the expression of a multidrug resistance transporter,underscoring the compound’s poly-pharmacological potential.These results position TClC as a promising candidate for NSCLC treatment,signaling a new era in the development of cancer therapies that directly target multiple critical cancer pathways.展开更多
In this work,we are concerned with numerical approximation of the gyroaverage operators arising in plasma physics to take into account the effects of the finite Larmor radius corrections.Several methods are proposed i...In this work,we are concerned with numerical approximation of the gyroaverage operators arising in plasma physics to take into account the effects of the finite Larmor radius corrections.Several methods are proposed in the space configuration and compared to the reference spectral method.We then investigate the influence of the different approximations considering the coupling with some guiding-center models available in the literature.展开更多
In this report,a charge preserving numerical resolution of the 1D VlasovAmp`ere equation is achieved,with a forward Semi-Lagrangian method introduced in[10].The Vlasov equation belongs to the kinetic way of simulating...In this report,a charge preserving numerical resolution of the 1D VlasovAmp`ere equation is achieved,with a forward Semi-Lagrangian method introduced in[10].The Vlasov equation belongs to the kinetic way of simulating plasmas evolution,and is coupled with the Poisson’s equation,or equivalently under charge conservation,the Amp`ere’s one,which self-consistently rules the electric field evolution.In order to ensure having proper physical solutions,it is necessary that the scheme preserves charge numerically.B-spline deposition will be used for the interpolation step.The solving of the characteristics will be made with a Runge-Kutta 2 method and with a Cauchy-Kovalevsky procedure.展开更多
We study the number of solutions N（B,F） of the diophantine equation n1n2 = n3n4,where 1 ≤ n1≤B, 1≤ n3 ≤B, n2, n4 ∈ F and F C [1, B] is a factor closed set. We study more particularly the case when F = {m = p1^...We study the number of solutions N（B,F） of the diophantine equation n1n2 = n3n4,where 1 ≤ n1≤B, 1≤ n3 ≤B, n2, n4 ∈ F and F C [1, B] is a factor closed set. We study more particularly the case when F = {m = p1^ε1…pk^εk ,εj∈ {0, 1}, 1≤ j ≤ k}, p1,… ,pk being distinct prime numbers.展开更多
In this paper,we study high order discretization methods for solving the Maxwell equations on hybrid triangle-quad meshes.We have developed high order finite edge element methods coupled with different high order time...In this paper,we study high order discretization methods for solving the Maxwell equations on hybrid triangle-quad meshes.We have developed high order finite edge element methods coupled with different high order time schemes and we compare results and efficiency for several schemes.We introduce in particular a class of simple high order low dissipation time schemes based on a modified Taylor expansion.展开更多
The current study aimed to explore the hypothesis that probiotic bacteria are significantly involved in the control of obesity using Wistar rats as the test group by feeding high fat diets(HFD)induced obesity.A total ...The current study aimed to explore the hypothesis that probiotic bacteria are significantly involved in the control of obesity using Wistar rats as the test group by feeding high fat diets(HFD)induced obesity.A total of four groups of rats were considered viz.,normal pellet diet fed(NC),HFD fed(DC),HFD fed rats treated with probiotic fermented milk with soy protein isolate(SPI)and whey protein concentrate(WPC)(T1),HFD fed rats treated with probiotic fermented milk without WPC and SPI(T2).Body weight,abdominal fat weight,liver weight,serum Alanine aminotransferase level,and alkaline phosphatase level significantly(p<0.05)decreased after giving daily probiotic milk product supplementation with@2 ml per day for continuous 4 weeks.Whereas,C-reactive protein and Aspartate aminotransferase levels were not altered to a significant extent.The histology of the liver from the disease model group showed large lipid vacuoles deposited in the parenchyma cells.Product T2 confirmed fewer micro vesicular fatty changes and the appearance of T2 was better than T1.Overall,the in vivo study results indicated that the probiotic fermented milk exerted a better anti-obesity effect.展开更多
The reduction of Hamiltonian systems aims to build smaller reduced models,valid over a certain range of time and parameters,in order to reduce computing time.By maintaining the Hamiltonian structure in the reduced mod...The reduction of Hamiltonian systems aims to build smaller reduced models,valid over a certain range of time and parameters,in order to reduce computing time.By maintaining the Hamiltonian structure in the reduced model,certain longterm stability properties can be preserved.In this paper,we propose a non-linear reduction method for models coming from the spatial discretization of partial differential equations:it is based on convolutional auto-encoders and Hamiltonian neural networks.Their training is coupled in order to learn the encoder-decoder operators and the reduced dynamics simultaneously.Several test cases on non-linear wave dynamics show that the method has better reduction properties than standard linear Hamiltonian reduction methods.展开更多
基金financed by FAPESP-Biota Program(Proc.No.2006/60954-4)CNPq(Proc.No.557872/2008-1).
文摘Brazil has become one of the top producers and exporters of food, fibre, and bionergy in the world.The expansion of livestock and soybean production in the Amazon basin appears to be independent of the sugarcane expansion in southeastern Brazil whereas the impact of sugarcane expansion over areas of soybean plantation in previous Cerrado biome is still unknown. However, the expansion of sugarcane production in the state of S?o Paulohas been shown to cause an increase in the local abundance of rodents and result in the emergence of infectious diseases such as hantaviruses and leptospirosis in humans. In addition, with an increase in the use of agrochemicals there will be an increase in euthrophication of watercourses and soil pollution. Considering that S?o Paulo has a population of approximately 40 million people, these local impacts are relevant. Environmental law should be improved and enforced in Brazil to ensure that sugarcane production is not only economically profitable but also environmentally responsible.
文摘Objective:Nutraceutical products are widely used for their claimed therapeutic benefits.However,falsified or adulterated nutraceuticals present a major health threat to consumers.This study investigates the pharmaceutical quality,safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100%natural.Methods:Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography(HPLC).The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy(NIR)and Se De M.The cytotoxic effects of these products on HepG2 cells were determined through cell proliferation(XTT)and lactate dehydrogenase(LDH)cytotoxicity assays.Lastly,the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release analysis.Results:HPLC analysis detected the presence of sildenafil citrate,a vasodilator,and the active ingredient in Viagra and Revatio,in all batches of the products we analyzed.Amount of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different batches.NIR assessment showed inter-and intra-batch heterogeneity in product composition.Results of the XTT and LDH assays showed significant cytotoxic effects of the analyzed products.XTT analysis revealed that the viability of HepG2 treated with tested products varied from 27.57%to 41.43%.Interestingly,the male enhancement products also showed anti-inflammatory effects.Conclusion:Despite their labeling as 100%natural,all products tested in this study contained levels of sildenafil citrate,which was not reported on the packaging.There was a lack of pharmaceutical uniformity among products of the same batch and across different batches.Additionally,the products we tested had cytotoxic effects.These study findings highlight the adulteration,poor quality and hazard of these nutraceuticals.Therefore,strict regulation of these products and standardization of the definition of nutraceuticals are urgently needed.Further,these falsely advertised products should be withdrawn from the market due to potential adverse effects on the health of their consumers.
文摘Alzheimer’s disease(AD)and associated cognitive dysfunction are major healthcare challenges globally.Various mechanisms of pathogenesis and signaling molecules have been studied for their plausible role in disease initiation and progression.Neuroinflammation has been considered a major hallmark of AD.Amyloid beta(Ab),hyperphosphorylated tau protein,and formed neurofibrillary tangles(NFT)are positively correlated with neuroinflammation.Microglial activation was found to be a key contributor to neuroinflammation,AD pathogenesis,and progression.The mechanism of microglial activation has been studied in detail,and looking into its pivotal role in disease etiology,various drugs have been developed,and many are in the clinical phases of development.These drugs either inhibit the microglial activation or neuroinflammatory event postmicroglial activation.Considering these facts,in the present study,we herein discuss the mechanism of microglial activation and the mechanism of neuroinflammation related to microglial activation and dementia.Here we also discussed the various drugs that either act at tau protein or mitigate neuroinflammation,along with their status in clinical trials.In brief,this review provides an in-depth mechanism of microglial activation and updates on drugs that can inhibit this activation,leading to significant anti-Alzheimer effect and mitigation of cognitive dysfunction.
文摘This study proposes a segmented approach to analyzing diabetes risk factors using the dataset diabete_custom.xlsx(150 individuals,14 medical and behavioral variables).The combination of KMeans with logistic regression and KMeans with decision tree enabled the definition of three clusters corresponding to low,moderate,and high risk,while identifying key variables such as blood glucose,BMI,and heredity.The hybrid models improve accuracy and interpretability compared to KMeans alone,with the decision tree being slightly more effective in unbalanced clusters.These findings provide a foundation for personalized interventions,including targeted screening,glycemic and nutritional monitoring,physical activity,and educational campaigns tailored to each risk profile.
基金supported by the National Key Research and Development Program of China(2017YFB0702600,2017YFB0702602,2017YFB0702602-2)the Shandong Provincial Natural Science Foundation(ZR2019MH076,ZR2022MH291)+3 种基金the Ministry of Science and Technology of the People’s Republic of China(“863 grant”,2012AA020206)the Department of Science and Technology of Shan-dong Province(20092009GG10002087)the National Natural Science Foundation of China(81603024,30973553)the NIH grant R01 CA186100,Wenzhou Institute University of Chinese Academy of Sciences,and Corbett Estate Fund for the Cancer Research(62285-531021-41800,62285-531021-51800,62285-531021-61800,62285-531021-71800).
文摘Despite significant advances in targeted therapies and immunotherapies,non-small cell lung cancer(NSCLC)continues to present a global health challenge,with a modest five-year survival rate of 28%,largely due to the emergence of treatment-resistant and metastatic tumors.In response,we synthesized a novel bioactive compound,ethyl 6-chlorocoumarin-3-carboxylyl L-theanine(TClC),which significantly inhibited NSCLC growth,epithelial mesenchymal transition(EMT),migration,and invasion in vitro and tumor growth and metastasis in vivo without inducing toxicity.TClC disrupts autocrine loops that promote tumor progression,particularly in stem-like CD133-positive NSCLC(CD133+LC)cells,which are pivotal in tumor metastasis.Through targeted molecular assays,we identified direct binding targets of TClC,including Akt,NF-κB,β-catenin,EZH2,and PD-L1.This interaction not only suppresses the expression of oncogenic factors and cancer stem cell markers but also downregulates the expression of a multidrug resistance transporter,underscoring the compound’s poly-pharmacological potential.These results position TClC as a promising candidate for NSCLC treatment,signaling a new era in the development of cancer therapies that directly target multiple critical cancer pathways.
文摘In this work,we are concerned with numerical approximation of the gyroaverage operators arising in plasma physics to take into account the effects of the finite Larmor radius corrections.Several methods are proposed in the space configuration and compared to the reference spectral method.We then investigate the influence of the different approximations considering the coupling with some guiding-center models available in the literature.
文摘In this report,a charge preserving numerical resolution of the 1D VlasovAmp`ere equation is achieved,with a forward Semi-Lagrangian method introduced in[10].The Vlasov equation belongs to the kinetic way of simulating plasmas evolution,and is coupled with the Poisson’s equation,or equivalently under charge conservation,the Amp`ere’s one,which self-consistently rules the electric field evolution.In order to ensure having proper physical solutions,it is necessary that the scheme preserves charge numerically.B-spline deposition will be used for the interpolation step.The solving of the characteristics will be made with a Runge-Kutta 2 method and with a Cauchy-Kovalevsky procedure.
文摘We study the number of solutions N（B,F） of the diophantine equation n1n2 = n3n4,where 1 ≤ n1≤B, 1≤ n3 ≤B, n2, n4 ∈ F and F C [1, B] is a factor closed set. We study more particularly the case when F = {m = p1^ε1…pk^εk ,εj∈ {0, 1}, 1≤ j ≤ k}, p1,… ,pk being distinct prime numbers.
基金This work was partially supported by the Agence Nationale de la Recherche,ANR-06-CIS6-0013.
文摘In this paper,we study high order discretization methods for solving the Maxwell equations on hybrid triangle-quad meshes.We have developed high order finite edge element methods coupled with different high order time schemes and we compare results and efficiency for several schemes.We introduce in particular a class of simple high order low dissipation time schemes based on a modified Taylor expansion.
基金financially supported by the Department of Biotechnology(DBT),Govt.of India project No.BT/PR15969/NER/95/39/2015,Dated 18th October,2016,Agri/2015/02.
文摘The current study aimed to explore the hypothesis that probiotic bacteria are significantly involved in the control of obesity using Wistar rats as the test group by feeding high fat diets(HFD)induced obesity.A total of four groups of rats were considered viz.,normal pellet diet fed(NC),HFD fed(DC),HFD fed rats treated with probiotic fermented milk with soy protein isolate(SPI)and whey protein concentrate(WPC)(T1),HFD fed rats treated with probiotic fermented milk without WPC and SPI(T2).Body weight,abdominal fat weight,liver weight,serum Alanine aminotransferase level,and alkaline phosphatase level significantly(p<0.05)decreased after giving daily probiotic milk product supplementation with@2 ml per day for continuous 4 weeks.Whereas,C-reactive protein and Aspartate aminotransferase levels were not altered to a significant extent.The histology of the liver from the disease model group showed large lipid vacuoles deposited in the parenchyma cells.Product T2 confirmed fewer micro vesicular fatty changes and the appearance of T2 was better than T1.Overall,the in vivo study results indicated that the probiotic fermented milk exerted a better anti-obesity effect.
文摘The reduction of Hamiltonian systems aims to build smaller reduced models,valid over a certain range of time and parameters,in order to reduce computing time.By maintaining the Hamiltonian structure in the reduced model,certain longterm stability properties can be preserved.In this paper,we propose a non-linear reduction method for models coming from the spatial discretization of partial differential equations:it is based on convolutional auto-encoders and Hamiltonian neural networks.Their training is coupled in order to learn the encoder-decoder operators and the reduced dynamics simultaneously.Several test cases on non-linear wave dynamics show that the method has better reduction properties than standard linear Hamiltonian reduction methods.
