Interplay between microglia and environmental risk factors in Alzheimer's disease

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

Responding of zooplankton to environmental factor changes in the Changjiang River estuarine regions in spring-summer from 2016 to 2020

The estuarine areas are under frequent influence from freshwater intrusion and ocean currents,in which zooplankton species are diversified and variable as they are sensitive to physio-chemical variations in water.Therefore,understanding the relationships between zooplankton and environmental factors help us know the water quality.To achieve co-existence with species in similar ecological group or habit,they could inevitably alter themselves to fit the ecology and adjust the function according to the competitive exclusion in ecological theory.However,information of the co-existence of dominant species in the Changjiang(Yangtze)River estuary(CRE)and adjacent waters remains scarce.We explored the relationships between dominant zooplankton and environmental factors in the study region in spring-summer from 2016 to 2020,involving particularly the composition of dominant species,ecological groups,their relationships with environmental factors,and co-existence of important species,using the non-multidimensional scale analysis(nMDS)method and redundancy analysis.Results show that Labidocera euchaeta and Tortanus vermiculus were dominant species in the study scope.The turnover rate of dominant zooplankton was greater(>50%)in spring while the species number was higher in summer.The dominant species were estuarine,offshore,and eurytopic based on the adaptation to salinity.In spring,the ecological groups were dominated by estuarine species,while in summer by estuarine and offshore species.In addition,the nMDS showed that the dominant species in the same ecological group were more dispersed and not prominently clustered;the dominant species were staggered among different ecological groups.The temperature,salinity,pH,dissolved oxygen,and chlorophyll a were the main environmental factors on the distribution of the dominant species in spring,while in summer were dissolved oxygen,temperature,salinity,and pH.The domination of medusae of Nemopsis bachei and Pleurobrachia globosa in zooplankton community in spring,and the continuous decrease in abundance of L.euchaeta reflected the effects of local climate change.The temperature and salinity changes in different years and the subsequent response of zooplankton reflected the influence of freshwater intrusion and/or ocean currents.Zooplankton in similar ecological habits exhibited the competitive exclusion in terms of co-existence.

Effects of inorganic nutrients and environmental factors on the removal of n-propylbenzene and isopropylbenzene in seawater by cryptophytes Rhinomonas reticulata S6A

To effectively remove n-propylbenzene(n-PBZ)and isopropylbenzene(i-PBZ)leaked into seawater using Rhinomonas reticulata S6A(a newly isolated marine microalga),the effects of three inorganic nutrients and four environmental factors on their degradation were determined after 7 d of inoculation.Results show that NaNO_(3) at 300 mg/L caused a higher removal efficiency of both n-PBZ and i-PBZ(44.79%and 39.26%),while for NaH_(2) PO_(4)·H_(2) O,greater removal rates of two PBZs(47.30%and 42.23%)were achieved at 30 and 20 mg/L,respectively.NaHCO_(3) supplementation(500-750 mg/L)resulted in a large reduction(43.67%-45.04%)in i-PBZ concentration.The change in seawater pH(from 6 to 9)did not affect the elimination of n-PBZ and i-PBZ.The most suitable salinity and temperature were 30 and 25-30℃,respectively,leading to the PBZs removal of~40%.Light intensity exhibited significant influence on elimination of PBZs,and the maximum removal efficiencies of 56.07%(n-PBZ)and 55.00%(i-PBZ)were recorded under 200 and 600μmol/(m^(2)·s),respectively.In addition,the microalga could still remove PBZs when it failed to grow well due to darkness,strong light,low temperature,or low salinity,which might mean that good growth of alga is not always a necessary condition for PBZs removal.Therefore,attention should be paid to the suitability of nutrient levels and environmental conditions(excluding pH)in seawater when using microalgae for bioremediating PBZs-contaminated seawater.

Variation Characteristics of Root Traits of Different Alfalfa Cultivars under Saline-Alkaline Stress and their Relationship with Soil Environmental Factors

Soil salinization is the main factor that threatens the growth and development of plants and limits the increase of yield.It is of great significance to study the key soil environmental factors affecting plant root traits to reveal the adaptation strategies of plants to saline-alkaline-stressed soil environments.In this study,the root biomass,root morphological parameters and root mineral nutrient content of two alfalfa cultivars with different sensitivities to alkaline stress were analyzed with black soil as the control group and the mixed saline-alkaline soil with a ratio of 7:3 between black soil and saline-alkaline soil as the saline-alkaline treatment group.At the same time,the correlation analysis of soil salinity indexes,soil nutrient indexes and the activities of key enzymes involved in soil carbon,nitrogen and phosphorus cycles was carried out.The results showed that compared with the control group,the pH,EC,and urease(URE)of the soil surrounding the roots of two alfalfa cultivars were significantly increased,while soil total nitrogen(TN),total phosphorus(TP),organic carbon(SOC),andα-glucosidase activity(AGC)were significantly decreased under saline-alkaline stress.There was no significant difference in root biomass and root morphological parameters of saline-alkaline tolerant cultivar GN under saline-alkaline stress.The number of root tips(RT),root surface area(RS)and root volume(RV)of AG were reduced by 61.16%,44.54%,and 45.31%,respectively,compared with control group.The ratios of K^(+)/Na^(+),Ca^(2+)/Na^(+)and Mg^(2+)/Na^(+)of GN were significantly higher than those of AG(p<0.05).The root fresh weight(RFW)and dry weight(RDW),root length(RL),RV and RT of alfalfa were positively regulated by soil SOC and TN,but negatively regulated by soil pH,EC,and URE(p<0.01).Root Ca^(2+)/Na+ratio was significantly positively correlated with soil TN,TP and SOC(p<0.01).The absorption of Mg and Ca ions in roots is significantly negatively regulated by soilβ-glucosidase activity(BGC)and acid phosphatase activity(APC)(p<0.05).This study improved knowledge of the relationship between root traits and soil environmental factors and offered a theoretical framework for elucidating how plant roots adapt to saline-alkaline stressed soil environments.

The coupling control of biological precursors and environmental factors onβ-carotane enrichment in alkaline lacustrine source rocks:A case study from the Fengcheng formation in the western Junggar Basin,NW China

The organic-rich mudstones and dolostones of the Permian Fengcheng Formation(Fm.)are typically alkaline lacustrine source rocks,which are typified by impressively abundantβ-carotane.Abundant β-carotane has been well acknowledged as an effective indicator of biological sources or depositional environments.However,the specific biological sources of β-carotane and the coupling control of biological sources and environmental factors on the enrichment of β-carotane in the Fengcheng Fm.remains obscure.Based on a comprehensive investigation of the bulk,molecular geochemistry,and organic petrology of sedimentary rocks and the biochemistry of phytoplankton in modern alkaline lakes,we proposed a new understanding of the biological precursors of β-carotane and elucidated the enrichment mechanism of β-carotane in the Fengcheng Fm.The results show that the biological precursors crucially control the enrichment of β-carotane in the Fengcheng Fm.The haloalkaliphilic cyanobacteria are the primary biological sources of β-carotane,which is suggested by a good positive correlation between the 2-methylhopane index,7-+8-methyl heptadecanes/C_(max),C_(29%),and β-carotane/C_(max)in sedimentary rocks and the predominance of cyanobacteria with abundantβ-carotene in modern alkaline lakes.The enrichment of β-carotane requires the reducing condition,and the paleoredox state that affects the enrichment of β-carotane appears to have a threshold.The paleoclimate conditions do not considerably impact the enrichment of β-carotane,but they have some influence on the water's paleosalinity by affecting evaporation and precipitation.While it does not directly affect the enrichment of β-carotane in the Fengcheng Fm.,paleosalinity does have an impact on the cyanobacterial precursor supply and the preservation conditions.

Ecological environmental quality evaluation and driving factor analysis of the Lijiang River Basin,based on Google Earth Engine

For regional ecological management,it is important to evaluate the quality of ecosystems and analyze the underlying causes of ecological changes.Using the Google Earth Engine(GEE)platform,the remote sensing ecological index(RSEI)was calculated for the Lijiang River Basin in Guangxi Zhuang Autonomous Region for 1991,2001,2011,and 2021.Spatial autocorrelation analysis was employed to investigate spatiotemporal variations in the ecological environmental quality of the Lijiang River Basin.Furthermore,geographic detectors were used to quantitatively analyze influencing factors and their interaction effects on ecological environmental quality.The results verified that:1)From 1991 to 2021,the ecological environmental quality of the Lijiang River Basin demonstrated significant improvement.The area with good and excellent ecological environmental quality in proportion increased by 19.69%(3406.57 km^(2)),while the area with fair and poor ecological environmental quality in proportion decreased by 10.76%(1860.36 km^(2)).2)Spatially,the ecological environmental quality of the Lijiang River Basin exhibited a pattern of low quality in the central region and high quality in the periphery.Specifically,poor ecological environmental quality characterized the Guilin urban area,Pingle County,and Lingchuan County.3)From 1991 to 2021,a significant positive spatial correlation was observed in ecological environmental quality of the Lijiang River Basin.Areas with high-high agglomeration were predominantly forests and grasslands,indicating good ecological environmental quality,whereas areas with low-low agglomeration were dominated by cultivated land and construction land,indicating poor ecological environmental quality.4)Annual average precipitation and temperature exerted the most significant influence on the ecological environmental quality of the basin,and their interactions with other factors had the great influence.This study aimed to enhance understanding of the evolution of the ecological environment in the Lijiang River Basin of Guangxi Zhuang Autonomous Region and provide scientific guidance for decision-making and management related to ecology in the region.

Disinfection Byproducts and Their Precursors in Drinking Water Sources:Origins,Influencing Factors,and Environmental Insights

Tracing the contamination origins in water sources and identifying the impacts of natural and human processes are essential for ecological safety and public health.However,current analysis approaches are not ideal,as they tend to be laborious,time-consuming,or technically difficult.Disinfection byproducts(DBPs)are a family of well-known secondary pollutants formed by the reactions of chemical disinfectants with DBP precursors during water disinfection treatment.Since DBP precursors have various origins(e.g.,natural,domestic,industrial,and agricultural sources),and since the formation of DBPs from different precursors in the presence of specific disinfectants is distinctive,we argue that DBPs and DBP precursors can serve as alternative indicators to assess the contamination in water sources and identify pollution origins.After providing a retrospective of the origins of DBPs and DBP precursors,as well as the specific formation patterns of DBPs from different precursors,this article presents an overview of the impacts of various natural and anthropogenic factors on DBPs and DBP precursors in drinking water sources.In practice,the DBPs(i.e.,their concentration and speciation)originally present in source water and the DBP precursors determined using DBP formation potential tests—in which water samples are dosed with a stoichiometric excess of specific disinfectants in order to maximize DBP formation under certain reaction conditions—can be considered as alternative metrics.When jointly used with other water quality parameters(e.g.,dissolved organic carbon,dissolved organic nitrogen,fluorescence,and molecular weight distribution)and specific contaminants of emerging concern(e.g.,certain pharmaceuticals and personal care products),DBPs and DBP precursors in drinking water sources can provide a more comprehensive picture of water pollution for better managing water resources and ensuring human health.

Analysis of the Factors That Cause Environmental Degradation of Lake Santa Maria Tasi Tolu Dili Timor-Leste

This research aims to understand more closely the damage to the lake environment and the factors that cause pollution in Lake Santa Maria are the first factor of increasing urbanization, the use of the land around the lake as a place to live, the absence of maximum control from the local government this case, the Dili municipal authority. Types of solid waste consist of iron from car accidents, motorcycles, used building materials, plastic, used drink bottles and clothes, mosquito nets, food scraps from household waste, as well as old fishing nets from residents. In addition, household waste such as bath and bath, dishwashing, detergents, and waste from tempeh and tofu factories, including burnt oil from cars and motorcycles, are thrown into the lake. Municipal waste management is based on environmental standards to determine the quality of waste management in Dili Municipality. It is possible to identify the composition of waste and waste, as well as predict its environmental impact. Human (Anthropic) factors Domestic Liquid Waste, Domestic Solid Waste: Composed of organic and inorganic waste. Synthetic Waste, Disposal of Used Oil, Disposal of Domestic Animal Waste, Shallow Drains and Septic Tanks, Mountain Garbage, Garbage Thrown by Visitors, Natural Factors, Climate change, Prolonged drought, Low rainfall, El Niño and La Niña factors, Wind speed, Heat (high daily temperature pressure), Greater water evaporation, Dry wind. The occurrence of contamination necessarily implies an ecological imbalance. The impact introduced by residual compounds and waste that may be associated with the toxicity.

Tree mycorrhizal associations determine how biodiversity,large trees,and environmental factors drive aboveground carbon stock in temperate forests

Biodiversity,large trees,and environmental conditions such as climate and soil have important effects on forest carbon stocks.However,recent studies in temperate forests suggest that the relative importance of these factors depends on tree mycorrhizal associations,whereby large-tree effects may be driven by ectomycorrhizal(EM)trees,diversity effects may be driven by arbuscular mycorrhizal(AM)trees,and environment effects may depend on differential climate and soil preferences of AM and EM trees.To test this hypothesis,we used forest-inventory data consisting of over 80,000 trees from 631 temperate-forest plots(30 m×30 m)across Northeast China to examine how biodiversity(species diversity and ecological uniqueness),large trees(top 1%of tree diameters),and environmental factors(climate and soil nutrients)differently regulate aboveground carbon stocks of AM trees,EM trees,and AM and EM trees combined(i.e.total aboveground carbon stock).We found that large trees had a positive effect on both AM and EM tree carbon stocks.However,biodiversity and environmental factors had opposite effects on AM vs.EM tree carbon stocks.Specifically,the two components of biodiversity had positive effects on AM tree carbon stocks,but negative effects on EM tree carbon stocks.Environmental heterogeneity(mean annual temperature and soil nutrients)also exhibited contrasting effects on AM and EM tree carbon stocks.Consequently,for the total carbon stock,the positive large-tree effect far surpasses the diversity and environment effect.This is mainly because when integrating AM and EM tree carbon stock into total carbon stock,the opposite diversity-effect(also environment-effect)on AM vs.EM tree carbon stock counteracts each other while the consistent positive large-tree effect on AM and EM tree carbon stock is amplified.In summary,this study emphasized a mycorrhizal viewpoint to better understand the determinants of overarching aboveground carbon profile across regional forests.

The IDD Transcription Factors:Their Functions in Plant Development and Environmental Response

INDETERMINATE-DOMAIN proteins(IDDs)are a plant-specific transcription factor family characterized by a conserved ID domain with four zinc finger motifs.Previous studies have demonstrated that IDDs coordinate a diversity of physiological processes and functions in plant growth and development,including floral transition,plant architecture,seed and root development,and hormone signaling.In this review,we especially summarized the latest knowledge on the functions and working models of IDD members in Arabidopsis,rice,and maize,particularly focusing on their role in the regulatory network of biotic and abiotic environmental responses,such as gravity,temperature,water,and pathogens.Understanding these mechanisms underlying the function of IDD proteins in these processes is important for improving crop yields by manipulating their activity.Overall,the review offers valuable insights into the functions and mechanisms of IDD proteins in plants,providing a foundation for further research and potential applications in agriculture.

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

Functions of nuclear factor Y in nervous system development,function and health

Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and enhancers.Over the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently regeneration.However,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains elusive.In this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.

The effects of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents:a meta-analysis

Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase brain-derived neurotrophic factor levels in children and adolescents, the effects of specific types of exercise on brain-derived neurotrophic factor levels are still controversial. To address this issue, we used meta-analytic methods to quantitatively evaluate, analyze, and integrate relevant studies. Our goals were to formulate general conclusions regarding the use of exercise interventions, explore the physiological mechanisms by which exercise improves brain health and cognitive ability in children and adolescents, and provide a reliable foundation for follow-up research. We used the Pub Med, Web of Science, Science Direct, Springer, Wiley Online Library, Weipu, Wanfang, and China National Knowledge Infrastructure databases to search for randomized controlled trials examining the influences of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents. The extracted data were analyzed using Review Manager 5.3. According to the inclusion criteria, we assessed randomized controlled trials in which the samples were mainly children and adolescents, and the outcome indicators were measured before and after the intervention. We excluded animal experiments, studies that lacked a control group, and those that did not report quantitative results. The mean difference(MD;before versus after intervention) was used to evaluate the effect of exercise on brain-derived neurotrophic factor levels in children and adolescents. Overall, 531 participants(60 children and 471 adolescents, 10.9–16.1 years) were included from 13 randomized controlled trials. Heterogeneity was evaluated using the Q statistic and I^(2) test provided by Review Manager software. The meta-analysis showed that there was no heterogeneity among the studies(P = 0.67, I^(2) = 0.00%). The combined effect of the interventions was significant(MD = 2.88, 95% CI: 1.53–4.22, P < 0.0001), indicating that the brain-derived neurotrophic factor levels of the children and adolescents in the exercise group were significantly higher than those in the control group. In conclusion, different types of exercise interventions significantly increased brain-derived neurotrophic factor levels in children and adolescents. However, because of the small sample size of this meta-analysis, more high-quality research is needed to verify our conclusions. This metaanalysis was registered at PROSPERO(registration ID: CRD42023439408).

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.

Impacts of Environmental Factors on the Structure Characteristics of Avian Community in Shanghai Woodlots in Spring

From March to May, 2004, we selected 8 typical parks or green lands in Shanghai downtown as the study sites to conduct a ornithological research. During this study, total 55 species of birds were recorded, which included 31 resident and 24 migratory species. With statistics methodology, we analyzed the avian communities with 10 major environmental factors covering the park area, water percentage, vegetation species, canopy cover, shrub cover, grass cover, hill number, location condition, human quantity, path width, the study results indicated that: (1) the following 7 environmental factors were important to impact the structures of the avian community, they were park area, vegetation species, shrub coverage, grass coverage, hill number, location condition of the parks and path width; (2) the avian community of theses urban parks tended to deteriorate in the bird number and diversity; the man-made lake which was currently promoted in the park designing and planning process would not be good to attract the birds.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Grey Relational Analysis between Chlorophyll a and Environmental Factors in ShaHu Lake

[Objective] The aim was to explore effects of environmental factors on the content of Chlorophyll a in ShaHu Lake.[Method] Based on the data in Shahu Lake from November in 2007 to September in 2008,the relationship between chlorophyll a and environmental factors like water temperature,pH,secchi-depth （SD）,total nitrogen,total phosphorus and potassium permanganate index was studied by grey relational analysis method.[Result] The main environmental factors affecting the content of Chlorophyll a in ShaHu Lake were in order of water temperature potassium permanganate index 〉total nitrogen 〉pH〉 total phosphorus 〉SD.[Conclusion] The research provides reference for the control of eutrophication and the reasonable development and utilization of Shahu Lake.