A comparative study of the anti-fatigue activity of extracts from different parts of Cistanche tubulosa(Schenk)Wight

Objective:To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa(Schenk)Wight(C.tubulosa,Rou Cong Rong),focusing on central and exercise-induced fatigue in mice.This study investigated the pharmacological effects of the total oligosaccharides,polysaccharides,and phenylethanoid glycosides(CPhGs)extracted from C.tubulosa.Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue.The mice were treated with different extracts of C.tubulosa,and their effects were assessed using behavioral tests to measure exercise capacity,learning,and memory function.Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels,liver and muscle glycogen storage,and various fatigue-related biomarkers.Results: This study found that treatment with C.tubulosa extract improved exercise capacity,learning,and memory in mice.Total oligosaccharides from C.tubulosa enhanced adrenocorticotropic hormone,cholinesterase,and thyroid-stimulating hormone levels,reduced cortisol levels in central fatigue models,and ameliorated biochemical markers of exercise-induced fatigue,including lowering lactic acid,blood urea nitrogen,and malondialdehyde levels.Among the tested extracts,the total oligosaccharides showed the most comprehensive anti-fatigue effects.Conclusion: The anti-fatigue effects of C.tubulosa,particularly those of its total oligosaccharides,are pronounced in both central and exercise-induced fatigue.These effects are mediated by the regulation of neurotransmitter levels,enhancement of glycogen storage,and improvement of antioxidant enzyme activity,suggesting potential therapeutic benefits in fatigue-related conditions.

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.

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.

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.

Anti-fatigue effects of salidroside in mice

Objective： To study the anti-fatigue effects of salidroside in mice. Methods： Totally 120 normal male Kunming mice were randomized into 5 groups （4 salidroside intervention groups and the control group） based on body weight. The control group was given distilled water and the 4 intervention groups were given various doses of salidroside （60, 180, 360, 720 mg/kg） for 15 consecutive days, respectively. The levels of lactate, serum urea nitrogen, muscle and liver glycogen, the longest swimming time and hemoglobin were determined before and after swimming test. Results： Different doses of salidroside significantly lengthened the swimming time and increased the contents of hemoglobin and muscle and liver glycogen, while reducing that of lactate in blood significantly compared with control group, especially in the 180 mg/kg salidroside group. Conclusion： Salidroside has noticeable anti-fatigue effect on mice. These effects were dose-dependent, and the strongest effect on most biomarkers was seen with an intermediate dose.

Anti-Fatigue Effect of Blended <i>Camellia oleifera Abel</i>Tea Oil and Ge-132 in Mice

Nowadays, people are busier and busier for working and living, and suffer a lot of pressure on their body or mind. Therefore, people are prone to have fatigue activity and decrease their working efficiency and happiness. It was reported that fatigue is a common symptom in the community, with up to half of the general population complaining of fatigue. More and more researchers devoted themselves to studying natural active ingredients in organism as the anti-fatigue drugs to release fatigue symptom. However, these natural ingredients were difficult to obtain from plants, animals and microorganisms by separating and purifying. In addition, some active substances have many side effects. In our study, we employed tea seed oil as main ingredients blended with bis-(carboxyethylgermanium) sesquioxide (Ge-132) to investigate the effects of anti-fatigue on mice by administrating mice with low dose, intermediate dose and high dose of tea seed oil complex for 0, 2 or 4 weeks. The specific tests of studying effects of anti-fatigue were body weight, weight-loaded force swimming, blood urea nitrogen, blood lactic acid and hepaticglycogen. And the results showed that appropriate level of tea seed oil complex could decrease the body weight and prolong the weight-loaded swimming time, and had an active effect on the bloodurea nitrogen, hepatic glycogen and blood lactic acid level mice, which significantly embodied the anti-fatigue activity of tea seed oil complex.

Evaluation of silymarin extract from Silybum marianum in mice: anti-fatigue activity

Silymarin has been used for centuries for its hepatoprotective properties. The specific objective of this study was to evaluate the anti-fatigue properties of silymarin. The silymarin was administered orally at doses of 50, 100, and 200 mg/kg for 4 weeks;the fatigue level and exercise performance were evaluated using exhaustive swimming time and pole-climbing time, as well as levels of plasma lactate, ammonia, glucose, creatine kinase(CK), serum urea nitrogen(SUN), blood lactic acid(BLA), muscle glycogen(MG), and liver glycogen(LG) contents after an intensive swimming session. The results demonstrated that silymarin treatment decreased the BLA and SUN levels while increased the LG and MG levels. In addition, silymarin decreased plasma lactate and ammonia levels and CK activity after swimming test, this is related to the mechanism that increases energy storage(as glycogen) and release(as blood glucose), and decreases plasma levels of lactate, ammonia, and CK. The observation of the skeletal muscle structures of mice also confirmed that skeletal muscles became more damaged in the control group compared with the silymarin-treated mice after prolonged endurance exercise. Therefore, it is reasonable to infer that silymarin may bear potential pharmacological effects in combating fatigue.

Present Situation of the Anti-Fatigue Processing of High-Strength Steel Internal Thread Based on Cold Extrusion Technology:A Review

The adoption of cold-extrusion forming for internal thread net forming becomes an important component of anti-fatigue processing with the development of internal thread processing towards high performance, low cost and low energy consumption. It has vast application foreground in the field of aviation, spaceflight, high speed train and etc. The internal thread processing and anti-fatigue manufacture technology are summarized. In terms of the perspective of processing quality and fatigue serving life, the advantages and disadvantages of the processing methods from are compared. The internal thread cold-extrusion processing technology is investigated for the purpose of improving the anti-fatigue serving life of internal thread. The superiorities of the plastic deformation law and surface integrity of the metal layer in the course of cold extrusion for improving its stability and economy are summed up. The proposed research forecasts the develop- ment tendency of the internal thread anti-fatigue manufacturing technology.

The study of Gongshisong＇ s anti-fatigue active site sifting

Aim To investigate the influence of the Gongshisong extract of different extraction parts on mice sports fatigue index. Method The mice were randomly divided into blank group, model group, the Gongshisong extract group （petroleum ether, chloroform, ethyl acetate, n-butanol, the aqueous layer） and the positive control group. The mice in different groups were fed with corresponding Gongshisong extract liquid 2.5 g kg^-1 d^-1 once per day for consecutively 7 days. The blank group and model group were given 1% sodium carboxymethyl cellulose so- lution, the positive control group was administered with Rhodiola 0.59 g · kg^-1· d^-1 After the last administered each group of mice were determined of weihgt-loading swimming time, liver glycogen and muscle glycogen content, and urea nitrogen, lactic acid and creatine kinase in 90min mice after swimming content in blood. Result Com- pared with the blank group, the petroleum ether extract of Gongshisong could significantly prolong the swimming time of mice （P 〈 0.05）, enhancing the mice muscle glycogen reserves （P 〈 0.05）, and reduce the level of urea nitrogen and creatine kinase in mice after swimming （P 〈 0.05）. Butanol extraction liquid of Gongshisong can ob- viously prolong the swimming time of mice （P 〈 0.05）, increasing the reserves of glycogen in mice （P 〈 0.05）, decreasing the level of urea nitrogen in mice and blood lactate after swimming （P 〈 0.05 ）. Water extract of Gong- shisong could significantly prolong the swimming time of mice （P 〈 0.05） , increasing muscle glycogen storage （P 〈0.05）, reducing the level of blood lactic acid in mice after swimming （P 〈 0.05）. Ethyl acetate extract of Gongshisong could significantly prolong the swimming time of mice （P 〈 0.05） , and increase the reserves of glyco- gen in mice （P 〈0. 05）. Conclusion Comprehensive analysis, the petroleum ether, n-butanol and water site of Gongshisong is better anti fatigue active site.

Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning

BACKGROUND Intensive care unit-acquired weakness(ICU-AW)is a common complication that significantly impacts the patient's recovery process,even leading to adverse outcomes.Currently,there is a lack of effective preventive measures.AIM To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment.METHODS Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission.Relevant data from the initial 14 d of ICU stay,such as age,comorbidities,sedative dosage,vasopressor dosage,duration of mechanical ventilation,length of ICU stay,and rehabilitation therapy,were gathered.The relationships between these variables and ICU-AW were examined.Utilizing iterative machine learning techniques,a multilayer perceptron neural network model was developed,and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve.RESULTS Within the ICU-AW group,age,duration of mechanical ventilation,lorazepam dosage,adrenaline dosage,and length of ICU stay were significantly higher than in the non-ICU-AW group.Additionally,sepsis,multiple organ dysfunction syndrome,hypoalbuminemia,acute heart failure,respiratory failure,acute kidney injury,anemia,stress-related gastrointestinal bleeding,shock,hypertension,coronary artery disease,malignant tumors,and rehabilitation therapy ratios were significantly higher in the ICU-AW group,demonstrating statistical significance.The most influential factors contributing to ICU-AW were identified as the length of ICU stay(100.0%)and the duration of mechanical ventilation(54.9%).The neural network model predicted ICU-AW with an area under the curve of 0.941,sensitivity of 92.2%,and specificity of 82.7%.CONCLUSION The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation.A primary preventive strategy,when feasible,involves minimizing both ICU stay and mechanical ventilation duration.

Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin receptor.Therefore,while,based on the current knowledge,the tropomyosin receptor kinase B receptor agonists do not seem to have the potential to reve rse the disease pathology per se,promoting brainderived neurotrophic factor/tro pomyosin receptor kinase B signaling still has a very high therapeutic relevance.

The Preparation Technology Research and Composition Analysis of Anti-fatigue Yikangshu Granules

[Objectives]To optimize the preparation technology of Yikangshu granule,an anti-fatigue health food.[Methods]The process was studied from three aspects(raw material extraction,excipient selection and forming process),and then it was verified in pilot production,and the content of the three components of the product was determined.[Results]The optimum production process of the formula granules was as follows:raw materials were extracted(adding 1∶9 water,extracting twice,2.5 h each time);vacuum concentration;adding excipients and mixing after vacuum drying,crushing and sieving;granulation of 75%ethanol sifted by a 20-mesh sieve;drying at 60℃,sifting through 14-mesh,and packaging.The average content of products obtained was as follows:crude polysaccharides(3204 mg/100 g),total saponins(2295 mg/100 g),astragaloside A(21 mg/100 g).[Conclusions]The optimized preparation technology is stable and feasible,and has a quality that can be controlled,which can provide a reference for the development of health food in food industry.

Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

The roles of macrophage migration inhibitory factor in retinal diseases

Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.

Spatial-temporal differentiation and influencing factors of rural settlements in mountainous areas: an example of Liangshan Yi Autonomous Prefecture, Southwestern China

Rural settlement is the basic spatial unit for compact communities in rural area. Scientific exploration of spatial-temporal differentiation and its influencing factors is the premise of spatial layout rationalization. Based on land use data of Liangshan Yi Autonomous Prefecture(hereinafter referred to as Liangshan Prefecture) in Sichuan Province, China from 1980 to 2020, compactness index, fractal dimension, imbalance index, location entropy and the optimal parameters-based geographical detector(OPGD) model are used to analyze the spatial-temporal evolution of the morphological characteristics of rural settlements, and to explore the influence of natural geographical factors, socioeconomic factors, and policy factors on the spatial differentiation of rural settlements. The results show that:(1) From 1980 to 2020, the rural settlements area in Liangshan Prefecture increased by 15.96 km^(2). In space, the rural settlements are generally distributed in a local aggregation, dense in the middle and sparse around the periphery. In 2015, the spatial density and expansion index of rural settlements reached the peak.(2) From 1980 to 2020, the compactness index decreased from 0.7636 to 0.7496, the fractal dimension increased from 1.0283 to 1.0314, and the fragmentation index decreased from 0.1183 to 0.1047. The spatial morphological structure of rural settlements tended to be loose, the shape contour tended to be complex, the degree of fragmentation decreased, and the spatial distribution was significantly imbalanced.(3) The results of OPGD detection in 2015 show that the influence of each factor is slope(0.2371) > traffic accessibility(0.2098) > population(0.1403) > regional GDP(0.1325) > elevation(0.0987) > poverty alleviation(0). The results of OPGD detection in 2020 show that the influence of each factor is slope(0.2339) > traffic accessibility(0.2198) > population(0.1432) > regional GDP(0.1219) > poverty alleviation(0.0992) > elevation(0.093). Natural geographical factors(slope and elevation) are the basic factors affecting the spatial distribution of rural settlements, and rural settlements are widely distributed in the river valley plain and the second half mountain area. Socioeconomic factors(traffic accessibility, population, and regional GDP) have a greater impact on the spatial distribution of rural settlements, which is an important factor affecting the spatial distribution of rural settlements. Policy factors such as poverty alleviation relocation have an indispensable impact on the spatial distribution of rural settlements. The research results can provide decisionmaking basis for the spatial arrangement of rural settlements in Liangshan Prefecture, and optimize the implementation of rural revitalization policies.

Anti-fatigue Effect of Water Extract from Centella asiatica(L.)Urban on Mice

[Objectives]To study the anti-fatigue effect of water extract from Centella asiatica(L.)Urban on mice.[Methods]After intragastric administration of low,medium and high concentration of water extract from Centella asiatica(L.)Urban for 14 d,the rotarod time and the content of serum lactic acid in mice were determined,respectively.[Results]Compared with the control group,the rotarod time of mice in the low and medium concentration groups was significantly prolonged(P<0.05),but there was no significant difference between the control group and the high concentration group;the content of serum lactic acid in the medium concentration group was significantly lower than that in the control group(P<0.01),but there was no significant difference between low concentration group and high concentration group and the control group.[Conclusions]A certain concentration of water extract from Centella asiatica(L.)Urban had a good anti-fatigue effect.