The present research investigated a segment of the micro-arthropod populations residing within nests of Messor arenarius ants in the Negev Desert of Israel. The total frequencies of micro-arthropods in the chaff of th...The present research investigated a segment of the micro-arthropod populations residing within nests of Messor arenarius ants in the Negev Desert of Israel. The total frequencies of micro-arthropods in the chaff of those ants’ nests were found to be higher than in the surrounding soil of the same nests. Acari (mites) were observed to be more abundant during the spring season, whereas their presence decreased during the summer months. Springtails (Collembola) were found to follow the Acari pattern, commonly found within the nests of those ants during spring but were absent during summer. Psocoptera order inhabiting soil habitats were infrequently encountered during spring, but their prevalence increased significantly during summer, particularly within the chaff of the ants’ nests, suggesting that chaff is their primary food source in the Negev Desert. Our research suggests that shifts in seasonality have important consequences on the distribution of soil invertebrate communities with implications on nutrient cycling.展开更多
There is currently a massive movement advocating for the enhancement of biomedical research on aging,sometimes referred to as“longevity advocacy”or“longevity activism”[1].The principal argument of the longevity ad...There is currently a massive movement advocating for the enhancement of biomedical research on aging,sometimes referred to as“longevity advocacy”or“longevity activism”[1].The principal argument of the longevity advocacy movement is that the therapies developed by biomedical research of aging should enable us to directly intervene in the aging process and thus prevent multiple aging-related diseases,thereby extending healthy longevity.展开更多
Head and neck squamous cell cancer(HNSCC)is a leading global malignancy.Every year,More than 830000 people are diagnosed with HNSCC globally,with more than 430000 fatalities.HNSCC is a deadly diverse malignancy with m...Head and neck squamous cell cancer(HNSCC)is a leading global malignancy.Every year,More than 830000 people are diagnosed with HNSCC globally,with more than 430000 fatalities.HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics.It originates from the squamous epithelium of the oral cavity,oropharynx,nasopharynx,larynx,and hypopharynx.The most frequently impacted regions are the tongue and larynx.Previous investigations have demonstrated the critical role of host genetic susceptibility in the progression of HNSCC.Despite the advances in our knowledge,the improved survival rate of HNSCC patients over the last 40 years has been limited.Failure to identify the molecular origins of development of HNSCC and the genetic basis of the disease and its biological heterogeneity impedes the development of new therapeutic methods.These results indicate a need to identify more genetic factors underlying this complex disease,which can be better used in early detection and prevention strategies.The lack of reliable animal models to investigate the underlying molecular processes is one of the most significant barriers to understanding HNSCC tumors.In this report,we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes(e.g.Smad 4 and P53 genes)to identify genetic factors affecting the development of this complex disease using genome-wide association studies,epigenetics,micro RNA,long noncoding RNA,lnc RNA,histone modifications,methylation,phosphorylation,and proteomics.展开更多
Hydrogen production via water electrolysis defines the novel energy vector for achieving a sustainable society.However,the true progress of the given technology is hindered by the sluggish and complex hydrogen evoluti...Hydrogen production via water electrolysis defines the novel energy vector for achieving a sustainable society.However,the true progress of the given technology is hindered by the sluggish and complex hydrogen evolution reaction(HER)occurring at the cathodic side of the system where overpriced and scarce Pt-based electrocatalysts are usually employed.Therefore,efficient platinum group metals(PGMs)-free electrocatalysts to carry out HER with accelerated kinetics are urgently demanded.In this scenario,molybdenum disulfide(MoS_(2))owing to efficacious structural attributes and optimum hydrogen-binding free energy(ΔG_(H*))is emerging as a reliable alternative to PGMs.However,the performance of MoS_(2)-based electrocatalysts is still far away from the benchmark performance.The HER activity of MoS_(2)can be improved by engineering the structural parameters i.e.,doping,defects inducement,modulating the electronic structure,stabilizing the 1 T phase,creating nanocomposites,and altering the morphologies using appropriate fabrication pathways.Here,we have comprehensively reviewed the majority of the scientific endeavors published in recent years to uplift the HER activity of MoS_(2)-based electrocatalysts using different methods.Advancements in the major fabrication strategies including hydrothermal synthesis methods,chemical vapor deposition,exfoliation techniques,plasma treatments,chemical methodologies,etc.to tune the structural parameters and hence their ultimate influence on the electrocatalytic activity in acidic and/or alkaline media have been thoroughly discussed.This study can provide encyclopedic insights about the fabrication routes that have been pursued to improve the HER performance of MoS_(2)-based electrocatalysts.展开更多
The electrocatalytic CO_(2) reduction in aqueous solution mainly involves bond cleavage and formation between C,H and O,and it is highly desirable to expand the bond formation reaction of C with other atoms to obtain ...The electrocatalytic CO_(2) reduction in aqueous solution mainly involves bond cleavage and formation between C,H and O,and it is highly desirable to expand the bond formation reaction of C with other atoms to obtain novel and valuable chemicals.The electrochemical synthesis of N-containing organic chemicals in electrocatalytic CO_(2) reduction via introducing N sources is an effective strategy to expand the product scope,since chemicals con-taining C–N bonds(e.g.amides and amines)are important reactants/products for medicine,agriculture and in-dustry.This article focuses on the research progress of C–N coupling from CO_(2) and inorganic nitrogenous species in aqueous solution.Firstly,the reaction pathways related to the reaction intermediates for urea,formamide,acetamide,methylamine and ethylamine are highlighted.Then,the electrocatalytic performance of different catalysts for these several N-containing products are summarized and classified.Finally,the challenges and op-portunities are analyzed,aiming to provide general insights into future research directions for electrocatalytic C–N coupling.展开更多
Objective: Hemp seed oil is perfect for most skin types;it moisturizes skin and protects it from inflammation, oxidation, and other causes of aging. The problem is that the Hemp oil-based products do not penetrate the...Objective: Hemp seed oil is perfect for most skin types;it moisturizes skin and protects it from inflammation, oxidation, and other causes of aging. The problem is that the Hemp oil-based products do not penetrate the skin;they remain on the skin’s surface. Recently researchers have been trying to prepare nano emulsions of hemp oil to facilitate its permeation to deep skin layers. In all techniques used today, surfactants are added to the emulsification process. These surfactants may cause unwanted skin side effects. In the present study, we prepare micronized Hemp (m-Hemp) without using any surfactants in the micronization process, thus avoiding the side effects associated with surfactant addition. Methods & Results: Particles size of m-Hemp was evaluated using electron microscopy. Various sizes of m-Hemp were found, the smallest being 100 nm in diameter. The antioxidation properties of m-Hemp were measured using the Electron Spin Resonance (ESR) technique and were found to be enhanced. Skin topography and morphology following a cream containing m-Hemp treatment were visualized by Optical Profilometry and ESEM respectively. The results show a marked improvement in skin topography in all measured parameters. In addition, human keratinocytes (HaCaT) were exposed to inflammatory conditions and were then treated using Hemp. As a result, one of the key inflammatory factors (IL-2) was significantly reduced after treatment with m-Hemp (p ≤ 0.0001). The skin penetration of the cream containing m-Hemp was tested on human skin using the IMOPE (Iterative Multi-plane Optical Property Extraction) system. The results indicate that m-Hemp penetrates both the stratum corneum and the deep epidermal layers towards the dermis. Conclusion: The new cream prepared with micronized Hemp shows significant anti-inflammatory and antioxidative effects and demonstrates the entrance of m-Hemp to the skin epidermal layer.展开更多
Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction (AR). The mechanisms of these m...Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction (AR). The mechanisms of these modifications are not well characterized though protein kinases were shown to be involved in the regulation of intracellular Ca2+ during both capacitation and the AR. In the present review, we summarize some of the signaling events that are involved in capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase (PI3K) is phosphorylated/activated via a protein kinase A (PKA)-dependent cascade, and downregulated by protein kinase C a (PKCa). PKCa is active at the beginning of capacitation, resulting in PI3K inactivation. During capacitation, PKCa as well as PP172 is degraded by a PKA-dependent mechanism, allowing the activation of PI3K. The activation of PKA during capacitation depends mainly on cyclic adenosine monophosphate (cAMP) produced by the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads to an increase in actin polymerization, an essential process for the development of hyperactivated motility, which is necessary for successful fertilization. Actin polymerization is mediated by PIP2 in two ways: first, PIP2 acts as a cofactor for phospholipase D (PLD) activation, and second, as a molecule that binds and inhibits actin-severing proteins such as gelsolin. Tyrosine phosphorylation of gelsolin during capacitation by Src family kinase (SFK) is also important for its inactivation. Prior to the AR, gelsolin is released from PIP2 and undergoes dephosphorylation/activation, resulting in fast F-actin depolymerization, leading to the AR.展开更多
Alzheimer’s disease is an incurable chronic neurodegenerative disorder and the leading cause of dementia,imposing a growing economic burden upon society.The disease progression is associated with gradual deposition o...Alzheimer’s disease is an incurable chronic neurodegenerative disorder and the leading cause of dementia,imposing a growing economic burden upon society.The disease progression is associated with gradual deposition of amyloid plaques and the formation of neurofibrillary tangles within the brain parenchyma,yet severe dementia is the culminating phase of the enduring pathology.Converging evidence suggests that Alzheimer’s disease-related cognitive decline is the outcome of an extremely complex and persistent pathophysiological process.The disease is characterized by distinctive abnormalities apparent at systemic,histological,macromolecular,and biochemical levels.Moreover,besides the well-defined and self-evident characteristic profuse neurofibrillary tangles,dystrophic neurites,and amyloid-beta deposits,the Alzheimer’s disease-associated pathology includes neuroinflammation,substantial neuronal loss,apoptosis,extensive DNA damage,considerable mitochondrial malfunction,compromised energy metabolism,and chronic oxidative stress.Likewise,distinctive metabolic dysfunction has been named a leading cause and a hallmark of Alzheimer’s disease that is apparent decades prior to disease manifestation.State-of-theart metabolomics studies demonstrate that altered branched-chain amino acids(BCAAs)metabolism accompanies Alzheimer’s disease development.Lower plasma valine levels are correlated with accelerated cognitive decline,and,conversely,an increase in valine concentration is associated with reduced risk of Alzheimer’s disease.Additionally,a clear BCAAs-related metabolic signature has been identified in subjects with obesity,diabetes,and atherosclerosis.Also,arginine metabolism is dramatically altered in Alzheimer’s disease human brains and animal models.Accordingly,a potential role of the urea cycle in the Alzheimer’s disease development has been hypothesized,and preclinical studies utilizing intervention in the urea cycle and/or BCAAs metabolism have demonstrated clinical potential.Continual failures to offer a competent treatment strategy directed against amyloid-beta or Tau proteins-related lesions,which could face all challenges of the multifaceted Alzheimer’s disease pathology,led to the hypothesis that hyperphosphorylated Tau and deposited amyloid-beta proteins are just hallmarks or epiphenomena,but not the ultimate causes of Alzheimer’s disease.Therefore,approaches targeting amyloid-beta or Tau are not adequate to cure the disease.Accordingly,the modern scientific vision of Alzheimer’s disease etiology and pathogenesis must reach beyond the hallmarks,and look for alternative strategies and areas of research.展开更多
The prolongation of life expectancy and the drastic reduction of fertility rate are the primary cause of an agingworld. It is projected that the elderly (above 65) will increase within the next 25 years by 82% , where...The prolongation of life expectancy and the drastic reduction of fertility rate are the primary cause of an agingworld. It is projected that the elderly (above 65) will increase within the next 25 years by 82% , whereas the new bornonly by 3% . Despite the enormous medical progress during the past few decades, the last years of life are still accom-panied by increasing ill health and disability. The ability to maintain active and independent living for as long as possi-ble is a crucial factor for aging in health and dignity. Therefore, the promotion of healthy aging and the prevention ofdisability in men, must assume a central role in medical research and medical practice as well as in the formulation ofnational health and social policies. Effective programs promoting health and aging will ensure a more efficient use ofhealth and social services and improve the quality of life in older persons by enabling them to remain independent andproductive. The most important and drastic gender differences in aging are related to organs and or systems dependantor influenced by reproductive hormones. In distinction to the course of reproductive aging in women, with the rapid de-cline in sex hormones and expressed by the cessation of menses, aging men experience a slow and continuous decline ofhormones. This decline in endocrine function involves; A decrease of testosterone, dehydroepiandrosterone (DHEA),oestrogens, thyroid stimulating hormone (TSH), growth hormone (GH), insulin-like growth factor-1 (IGF-1), andmelatonin. This decrease is concomitant with an increase of LH and FSH. In addition sex hormone binding globulin's(SHBG) increase with age resulting in further lowering the concentrations of free biologically active androgens. Inter-ventions such as hormone replacement therapy may prevent, delay or alleviate the debilitating conditions which may re-sult from secondary partial endocrine deficiency. Primary and secondary preventive strategies such as the promotion of asafe environment, healthy lifestyle including proper nutrition, appropriate exercise, avoidance of smoking, avoidanceof drug and alcohol abuses, if done effectively, should result in a significant reduction of the health and social costs,reduce pain and suffering, increase the quality of life of the elderly and enable them to remain productive and contributeto the well-being of society. In light of this, public awareness of medical knowledge needs to be increased and basic,clinical, socio-economic and epidemiological research intensified. (Asian J Androl 2001 Sep; 3; 161 - 168)展开更多
To bind and fertilize the egg, the spermatozoon should undergo few biochemical and motility changes in the female reproductive tract collectively called capacitation. The capacitated spermatozoon binds to the egg zona...To bind and fertilize the egg, the spermatozoon should undergo few biochemical and motility changes in the female reproductive tract collectively called capacitation. The capacitated spermatozoon binds to the egg zona pellucida, and then undergoes the acmsome reaction (AR), which allows its penetration into the egg. The mechanisms regulating sperm capacitation and the AR are not completely understood. In the present review, we summarize some data regarding the role and regulation of the epidermal growth factor receptor (EGFR) in these processes. In the capacitation process, the EGFR is partially activated by protein kinase A (PKA), resulting in phospholipase D (PLD) activation and actin polymerization. Protein kinase C alpha (PKCα), which is already activated at the beginning of the capacitation, also participates in PLD activation. Further activation of the EGFR at the end of the capacitation enhances intracellular Ca2+ concentration leading to F-actin breakdown and allows the AR to take place. Under in vivoconditions, the EGFR can be directly activated by its known ligand epidermal growth factor (EGF), and indirectly by activating PKA or by transactivation mediated by G protein-coupled receptors (GPCRs) activation or by ouabain. Under physiological conditions, sperm PKA is activated mainly by bicarbonate, which activates the soluble adenylyl cyclase to produce cyclic adenosine monophosphate (cAMP), the activator of PKA. The GPCR activators angiotensin II or Ivsoohosphatidic acid, as well as ouabain and EGF are phvsioloeical comoonents oresent in the female reoroductive tract.展开更多
Nonalcoholic fatty liver disease(NAFLD)has becomeone of the most common causes of liver disease worldwide and has been recognized as a major health burden.The prevalence of NAFLD has grown proportionallywith the rise ...Nonalcoholic fatty liver disease(NAFLD)has becomeone of the most common causes of liver disease worldwide and has been recognized as a major health burden.The prevalence of NAFLD has grown proportionallywith the rise in obesity,sedentary lifestyle,unhealthydietary pattern,and metabolic syndrome.Currently,there is no drug therapy that can be formulated fortreating NAFLD.A combination of dietary modificationsand increased physical activity remains the mainstayof NAFLD management.It is hard to maintain thismode of management;however,it seems to havesignificant long-term benefits.Furthermore,NAFLDpatients,whether obese or not,should be educatedthat a healthy diet and physical activity have benefitsbeyond weight reduction.Further large controlled randomized trials are needed in order to identify the bestdietary regimen and physical activity in the management of NAFLD patients.This review highlights the roleof diet and lifestyle modifications in the managementof NAFLD,and focuses on human studies regarding dietary modifications and physical activity.展开更多
在陆上的系统的土壤生物不均匀的在时空被散布,并且经常聚集了。在土壤环境的时间空间的补缀被认为为土壤生物多样性的维护关键,提供紧与资源划分交织的多样的微产地。“到帮助的一个规模单位”的决心理解生态的过程在最近的年里成为...在陆上的系统的土壤生物不均匀的在时空被散布,并且经常聚集了。在土壤环境的时间空间的补缀被认为为土壤生物多样性的维护关键,提供紧与资源划分交织的多样的微产地。“到帮助的一个规模单位”的决心理解生态的过程在最近的年里成为了重要、很可争辩的问题之一。一个现场考古工作在一个荒芜的生态系统在北 Negev 荒芜的高地,在 biogeochemical 变量上决定好规模的风景补丁潮湿异质的影响的以色列和微生物引起的活动连接被执行。结果证明我们把有影响的性质归因于的土壤潮湿的时间空间的补缀,在土壤潮湿可获得性与减少被发现成为更多的异种遗传因子(从 8.2~0.4 g kg ? 1 )向热,干旱期,随着变异系数( CV )变化等于66.9%。有机物( OM )和全部的可溶的氮( TSN )的时间空间的分发被发现到一致地相对在整个湿季节(冬季和春天)被散布,随向干旱期的相对高的异质的增加(从0.25%~2.17%为 OM ,并且从 0~10.2 mg kg ? 1 为 TSN )与为 OM 和 TSN 的47.4%和99.7%的 CV 分别地。不同时间空间的风景模式为 Ca 被获得(CV =44.6%) , K (CV =34.4%) ,并且 Na (CV =92%) 在整个学习时期的离子。 CO2 进化( CV =48.6%)被发现具有更低的异质(在 2 和 39 g CO2-C g 之间变化? 1 干土 h ? 1 )在潮湿的季节,例如,冬季和春天,与Na+的异质和 TSN 和有机物的底层满足的高结合的呼吸的更低的价值,并且与在干旱期的更多的同质(在 1 和 50 g CO2-C g 之间变化? 1 干土 h ? 1 )。我们的结果阐明影响的荒芜的系统产地的异质和复杂性玷污生物区系活动。展开更多
文摘The present research investigated a segment of the micro-arthropod populations residing within nests of Messor arenarius ants in the Negev Desert of Israel. The total frequencies of micro-arthropods in the chaff of those ants’ nests were found to be higher than in the surrounding soil of the same nests. Acari (mites) were observed to be more abundant during the spring season, whereas their presence decreased during the summer months. Springtails (Collembola) were found to follow the Acari pattern, commonly found within the nests of those ants during spring but were absent during summer. Psocoptera order inhabiting soil habitats were infrequently encountered during spring, but their prevalence increased significantly during summer, particularly within the chaff of the ants’ nests, suggesting that chaff is their primary food source in the Negev Desert. Our research suggests that shifts in seasonality have important consequences on the distribution of soil invertebrate communities with implications on nutrient cycling.
文摘There is currently a massive movement advocating for the enhancement of biomedical research on aging,sometimes referred to as“longevity advocacy”or“longevity activism”[1].The principal argument of the longevity advocacy movement is that the therapies developed by biomedical research of aging should enable us to directly intervene in the aging process and thus prevent multiple aging-related diseases,thereby extending healthy longevity.
基金supported by a core fund from Tel Aviv University and the Department of Oral and Maxillofacial Surgery,Baruch Padeh Medical Center,Poriya,Israel。
文摘Head and neck squamous cell cancer(HNSCC)is a leading global malignancy.Every year,More than 830000 people are diagnosed with HNSCC globally,with more than 430000 fatalities.HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics.It originates from the squamous epithelium of the oral cavity,oropharynx,nasopharynx,larynx,and hypopharynx.The most frequently impacted regions are the tongue and larynx.Previous investigations have demonstrated the critical role of host genetic susceptibility in the progression of HNSCC.Despite the advances in our knowledge,the improved survival rate of HNSCC patients over the last 40 years has been limited.Failure to identify the molecular origins of development of HNSCC and the genetic basis of the disease and its biological heterogeneity impedes the development of new therapeutic methods.These results indicate a need to identify more genetic factors underlying this complex disease,which can be better used in early detection and prevention strategies.The lack of reliable animal models to investigate the underlying molecular processes is one of the most significant barriers to understanding HNSCC tumors.In this report,we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes(e.g.Smad 4 and P53 genes)to identify genetic factors affecting the development of this complex disease using genome-wide association studies,epigenetics,micro RNA,long noncoding RNA,lnc RNA,histone modifications,methylation,phosphorylation,and proteomics.
基金the Italian Ministry of University and Research(MUR)through the“Rita Levi Montalcini 2018”Fellowship(Grant number PGR18MAZLI)ENEA–UNIMIB PNRR agreement(Attività1.1.3 del PNRR POR H2)+1 种基金the Ministry of Science and Technology(State of Israel)and the Ministry of Foreign Affairs and International Cooperation–Directorate General for Cultural and Economic Promotion and Innovation(Italian Republic),respectively,within the bilateral project Italy-Israel(WE-CAT)the Italian ministry MUR for funding through the FISR 2019 project AMPERE(FISR2019_01294)。
文摘Hydrogen production via water electrolysis defines the novel energy vector for achieving a sustainable society.However,the true progress of the given technology is hindered by the sluggish and complex hydrogen evolution reaction(HER)occurring at the cathodic side of the system where overpriced and scarce Pt-based electrocatalysts are usually employed.Therefore,efficient platinum group metals(PGMs)-free electrocatalysts to carry out HER with accelerated kinetics are urgently demanded.In this scenario,molybdenum disulfide(MoS_(2))owing to efficacious structural attributes and optimum hydrogen-binding free energy(ΔG_(H*))is emerging as a reliable alternative to PGMs.However,the performance of MoS_(2)-based electrocatalysts is still far away from the benchmark performance.The HER activity of MoS_(2)can be improved by engineering the structural parameters i.e.,doping,defects inducement,modulating the electronic structure,stabilizing the 1 T phase,creating nanocomposites,and altering the morphologies using appropriate fabrication pathways.Here,we have comprehensively reviewed the majority of the scientific endeavors published in recent years to uplift the HER activity of MoS_(2)-based electrocatalysts using different methods.Advancements in the major fabrication strategies including hydrothermal synthesis methods,chemical vapor deposition,exfoliation techniques,plasma treatments,chemical methodologies,etc.to tune the structural parameters and hence their ultimate influence on the electrocatalytic activity in acidic and/or alkaline media have been thoroughly discussed.This study can provide encyclopedic insights about the fabrication routes that have been pursued to improve the HER performance of MoS_(2)-based electrocatalysts.
基金financially supported by National Natural Science Foundation of China(22072051,22122202,21972051).
文摘The electrocatalytic CO_(2) reduction in aqueous solution mainly involves bond cleavage and formation between C,H and O,and it is highly desirable to expand the bond formation reaction of C with other atoms to obtain novel and valuable chemicals.The electrochemical synthesis of N-containing organic chemicals in electrocatalytic CO_(2) reduction via introducing N sources is an effective strategy to expand the product scope,since chemicals con-taining C–N bonds(e.g.amides and amines)are important reactants/products for medicine,agriculture and in-dustry.This article focuses on the research progress of C–N coupling from CO_(2) and inorganic nitrogenous species in aqueous solution.Firstly,the reaction pathways related to the reaction intermediates for urea,formamide,acetamide,methylamine and ethylamine are highlighted.Then,the electrocatalytic performance of different catalysts for these several N-containing products are summarized and classified.Finally,the challenges and op-portunities are analyzed,aiming to provide general insights into future research directions for electrocatalytic C–N coupling.
文摘Objective: Hemp seed oil is perfect for most skin types;it moisturizes skin and protects it from inflammation, oxidation, and other causes of aging. The problem is that the Hemp oil-based products do not penetrate the skin;they remain on the skin’s surface. Recently researchers have been trying to prepare nano emulsions of hemp oil to facilitate its permeation to deep skin layers. In all techniques used today, surfactants are added to the emulsification process. These surfactants may cause unwanted skin side effects. In the present study, we prepare micronized Hemp (m-Hemp) without using any surfactants in the micronization process, thus avoiding the side effects associated with surfactant addition. Methods & Results: Particles size of m-Hemp was evaluated using electron microscopy. Various sizes of m-Hemp were found, the smallest being 100 nm in diameter. The antioxidation properties of m-Hemp were measured using the Electron Spin Resonance (ESR) technique and were found to be enhanced. Skin topography and morphology following a cream containing m-Hemp treatment were visualized by Optical Profilometry and ESEM respectively. The results show a marked improvement in skin topography in all measured parameters. In addition, human keratinocytes (HaCaT) were exposed to inflammatory conditions and were then treated using Hemp. As a result, one of the key inflammatory factors (IL-2) was significantly reduced after treatment with m-Hemp (p ≤ 0.0001). The skin penetration of the cream containing m-Hemp was tested on human skin using the IMOPE (Iterative Multi-plane Optical Property Extraction) system. The results indicate that m-Hemp penetrates both the stratum corneum and the deep epidermal layers towards the dermis. Conclusion: The new cream prepared with micronized Hemp shows significant anti-inflammatory and antioxidative effects and demonstrates the entrance of m-Hemp to the skin epidermal layer.
文摘Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction (AR). The mechanisms of these modifications are not well characterized though protein kinases were shown to be involved in the regulation of intracellular Ca2+ during both capacitation and the AR. In the present review, we summarize some of the signaling events that are involved in capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase (PI3K) is phosphorylated/activated via a protein kinase A (PKA)-dependent cascade, and downregulated by protein kinase C a (PKCa). PKCa is active at the beginning of capacitation, resulting in PI3K inactivation. During capacitation, PKCa as well as PP172 is degraded by a PKA-dependent mechanism, allowing the activation of PI3K. The activation of PKA during capacitation depends mainly on cyclic adenosine monophosphate (cAMP) produced by the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads to an increase in actin polymerization, an essential process for the development of hyperactivated motility, which is necessary for successful fertilization. Actin polymerization is mediated by PIP2 in two ways: first, PIP2 acts as a cofactor for phospholipase D (PLD) activation, and second, as a molecule that binds and inhibits actin-severing proteins such as gelsolin. Tyrosine phosphorylation of gelsolin during capacitation by Src family kinase (SFK) is also important for its inactivation. Prior to the AR, gelsolin is released from PIP2 and undergoes dephosphorylation/activation, resulting in fast F-actin depolymerization, leading to the AR.
基金supported by a Marie Curie CIG Grant 322113a Leir Foundation Grant+1 种基金a Ginzburg Family Foundation Granta Katz Foundation Grant to AOS
文摘Alzheimer’s disease is an incurable chronic neurodegenerative disorder and the leading cause of dementia,imposing a growing economic burden upon society.The disease progression is associated with gradual deposition of amyloid plaques and the formation of neurofibrillary tangles within the brain parenchyma,yet severe dementia is the culminating phase of the enduring pathology.Converging evidence suggests that Alzheimer’s disease-related cognitive decline is the outcome of an extremely complex and persistent pathophysiological process.The disease is characterized by distinctive abnormalities apparent at systemic,histological,macromolecular,and biochemical levels.Moreover,besides the well-defined and self-evident characteristic profuse neurofibrillary tangles,dystrophic neurites,and amyloid-beta deposits,the Alzheimer’s disease-associated pathology includes neuroinflammation,substantial neuronal loss,apoptosis,extensive DNA damage,considerable mitochondrial malfunction,compromised energy metabolism,and chronic oxidative stress.Likewise,distinctive metabolic dysfunction has been named a leading cause and a hallmark of Alzheimer’s disease that is apparent decades prior to disease manifestation.State-of-theart metabolomics studies demonstrate that altered branched-chain amino acids(BCAAs)metabolism accompanies Alzheimer’s disease development.Lower plasma valine levels are correlated with accelerated cognitive decline,and,conversely,an increase in valine concentration is associated with reduced risk of Alzheimer’s disease.Additionally,a clear BCAAs-related metabolic signature has been identified in subjects with obesity,diabetes,and atherosclerosis.Also,arginine metabolism is dramatically altered in Alzheimer’s disease human brains and animal models.Accordingly,a potential role of the urea cycle in the Alzheimer’s disease development has been hypothesized,and preclinical studies utilizing intervention in the urea cycle and/or BCAAs metabolism have demonstrated clinical potential.Continual failures to offer a competent treatment strategy directed against amyloid-beta or Tau proteins-related lesions,which could face all challenges of the multifaceted Alzheimer’s disease pathology,led to the hypothesis that hyperphosphorylated Tau and deposited amyloid-beta proteins are just hallmarks or epiphenomena,but not the ultimate causes of Alzheimer’s disease.Therefore,approaches targeting amyloid-beta or Tau are not adequate to cure the disease.Accordingly,the modern scientific vision of Alzheimer’s disease etiology and pathogenesis must reach beyond the hallmarks,and look for alternative strategies and areas of research.
文摘The prolongation of life expectancy and the drastic reduction of fertility rate are the primary cause of an agingworld. It is projected that the elderly (above 65) will increase within the next 25 years by 82% , whereas the new bornonly by 3% . Despite the enormous medical progress during the past few decades, the last years of life are still accom-panied by increasing ill health and disability. The ability to maintain active and independent living for as long as possi-ble is a crucial factor for aging in health and dignity. Therefore, the promotion of healthy aging and the prevention ofdisability in men, must assume a central role in medical research and medical practice as well as in the formulation ofnational health and social policies. Effective programs promoting health and aging will ensure a more efficient use ofhealth and social services and improve the quality of life in older persons by enabling them to remain independent andproductive. The most important and drastic gender differences in aging are related to organs and or systems dependantor influenced by reproductive hormones. In distinction to the course of reproductive aging in women, with the rapid de-cline in sex hormones and expressed by the cessation of menses, aging men experience a slow and continuous decline ofhormones. This decline in endocrine function involves; A decrease of testosterone, dehydroepiandrosterone (DHEA),oestrogens, thyroid stimulating hormone (TSH), growth hormone (GH), insulin-like growth factor-1 (IGF-1), andmelatonin. This decrease is concomitant with an increase of LH and FSH. In addition sex hormone binding globulin's(SHBG) increase with age resulting in further lowering the concentrations of free biologically active androgens. Inter-ventions such as hormone replacement therapy may prevent, delay or alleviate the debilitating conditions which may re-sult from secondary partial endocrine deficiency. Primary and secondary preventive strategies such as the promotion of asafe environment, healthy lifestyle including proper nutrition, appropriate exercise, avoidance of smoking, avoidanceof drug and alcohol abuses, if done effectively, should result in a significant reduction of the health and social costs,reduce pain and suffering, increase the quality of life of the elderly and enable them to remain productive and contributeto the well-being of society. In light of this, public awareness of medical knowledge needs to be increased and basic,clinical, socio-economic and epidemiological research intensified. (Asian J Androl 2001 Sep; 3; 161 - 168)
文摘To bind and fertilize the egg, the spermatozoon should undergo few biochemical and motility changes in the female reproductive tract collectively called capacitation. The capacitated spermatozoon binds to the egg zona pellucida, and then undergoes the acmsome reaction (AR), which allows its penetration into the egg. The mechanisms regulating sperm capacitation and the AR are not completely understood. In the present review, we summarize some data regarding the role and regulation of the epidermal growth factor receptor (EGFR) in these processes. In the capacitation process, the EGFR is partially activated by protein kinase A (PKA), resulting in phospholipase D (PLD) activation and actin polymerization. Protein kinase C alpha (PKCα), which is already activated at the beginning of the capacitation, also participates in PLD activation. Further activation of the EGFR at the end of the capacitation enhances intracellular Ca2+ concentration leading to F-actin breakdown and allows the AR to take place. Under in vivoconditions, the EGFR can be directly activated by its known ligand epidermal growth factor (EGF), and indirectly by activating PKA or by transactivation mediated by G protein-coupled receptors (GPCRs) activation or by ouabain. Under physiological conditions, sperm PKA is activated mainly by bicarbonate, which activates the soluble adenylyl cyclase to produce cyclic adenosine monophosphate (cAMP), the activator of PKA. The GPCR activators angiotensin II or Ivsoohosphatidic acid, as well as ouabain and EGF are phvsioloeical comoonents oresent in the female reoroductive tract.
文摘Nonalcoholic fatty liver disease(NAFLD)has becomeone of the most common causes of liver disease worldwide and has been recognized as a major health burden.The prevalence of NAFLD has grown proportionallywith the rise in obesity,sedentary lifestyle,unhealthydietary pattern,and metabolic syndrome.Currently,there is no drug therapy that can be formulated fortreating NAFLD.A combination of dietary modificationsand increased physical activity remains the mainstayof NAFLD management.It is hard to maintain thismode of management;however,it seems to havesignificant long-term benefits.Furthermore,NAFLDpatients,whether obese or not,should be educatedthat a healthy diet and physical activity have benefitsbeyond weight reduction.Further large controlled randomized trials are needed in order to identify the bestdietary regimen and physical activity in the management of NAFLD patients.This review highlights the roleof diet and lifestyle modifications in the managementof NAFLD,and focuses on human studies regarding dietary modifications and physical activity.
文摘在陆上的系统的土壤生物不均匀的在时空被散布,并且经常聚集了。在土壤环境的时间空间的补缀被认为为土壤生物多样性的维护关键,提供紧与资源划分交织的多样的微产地。“到帮助的一个规模单位”的决心理解生态的过程在最近的年里成为了重要、很可争辩的问题之一。一个现场考古工作在一个荒芜的生态系统在北 Negev 荒芜的高地,在 biogeochemical 变量上决定好规模的风景补丁潮湿异质的影响的以色列和微生物引起的活动连接被执行。结果证明我们把有影响的性质归因于的土壤潮湿的时间空间的补缀,在土壤潮湿可获得性与减少被发现成为更多的异种遗传因子(从 8.2~0.4 g kg ? 1 )向热,干旱期,随着变异系数( CV )变化等于66.9%。有机物( OM )和全部的可溶的氮( TSN )的时间空间的分发被发现到一致地相对在整个湿季节(冬季和春天)被散布,随向干旱期的相对高的异质的增加(从0.25%~2.17%为 OM ,并且从 0~10.2 mg kg ? 1 为 TSN )与为 OM 和 TSN 的47.4%和99.7%的 CV 分别地。不同时间空间的风景模式为 Ca 被获得(CV =44.6%) , K (CV =34.4%) ,并且 Na (CV =92%) 在整个学习时期的离子。 CO2 进化( CV =48.6%)被发现具有更低的异质(在 2 和 39 g CO2-C g 之间变化? 1 干土 h ? 1 )在潮湿的季节,例如,冬季和春天,与Na+的异质和 TSN 和有机物的底层满足的高结合的呼吸的更低的价值,并且与在干旱期的更多的同质(在 1 和 50 g CO2-C g 之间变化? 1 干土 h ? 1 )。我们的结果阐明影响的荒芜的系统产地的异质和复杂性玷污生物区系活动。