Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

Blood glucose-lowering activity of protocatechuic acid is mediated by inhibiting a-glucosidase

α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.

Different responses of two adjacent artificial beaches to Typhoon Hato in Zhuhai,China

Major differences in beach erosion between two neighboring artificial beaches Xiangluwan Beach(XL beach)and Meiliwan Beach(ML beach)in Zhuhai,China,were studied after Super Typhoon Hato.In this study,a fully nonlinear Boussinesq wave model(FUNWAVE)-Total Variation Diminishing(TVD)was used to distinguish the main impact factors,their relative contributions,and the hydrodynamic mechanisms underlying the different beach responses.Results show that compared to the ML beach,the main reason for the relatively weak erosion on Xiangluwan(XL)beach was the smaller beach berm height(accounting for approximately 75.9%of the erosion response).Regarding the beach with a higher berm,the stronger wave-induced undertow flow,along with the higher sediment concentration,led to a higher offshore sediment transport flux,resulting in more severe erosion relative to the beach with a smaller berm height.The second most important reason explaining the weak erosion on XL beach was the absence of seawalls(accounting for approximately 17.9%of the erosion response).Wave reflection induced by the seawall could cause higher suspended sediment concentration,resulting in a toe scouring near the seawall.The offshore submerged breakwater protected XL beach slightly(accounting for approximately 6.1%of the erosion response).Due to the higher water level induced by storm surge,most of the wave energy could penetrate through the submerged breakwater.The effect of the larger berm width of XL beach was negligible.Compared to the beach with a larger berm width,the erosion/deposition regions in the beach with a narrower berm width showed shoreward migration,without significant changes in the erosion/deposition extent.Despite of this,the larger berm width could reduce the wave energy reaching the shoreline.This study of the storm stability of artificial beaches may be applied to beach restoration design.

Protective effects of peptide KSPLY derived from Hericium erinaceus on H_(2)O_(2)-induced oxidative damage in HepG2 cells

Reactive oxygen species(ROS)-induced oxidative damage is strongly associated with the pathogenesis of chronic diseases,and natural antioxidant peptides have good abilities of scavenging ROS.The antioxidant activity of peptide Lys-Ser-Pro-Leu-Tyr(KSPLY)derived from Hericium erinaceus remains unclear.In the present study,the antioxidant effect and mechanism of KSPLY on H_(2)O_(2)-induced oxidative damage in HepG2 cells were investigated.The results indicated that KSPLY exhibited the antioxidant capacity in H_(2)O_(2)-induced HepG2 cells by enhancing superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT)activities.In comparison with the H_(2)O_(2)-treated damage group,the apoptosis rate,ROS level,and malondialdehyde(MDA)content of HepG2 cells treated with KSPLY were significantly decreased.The H.erinaceus-derived peptide KSPLY pretreatment promoted the expression of detoxification and antioxidant enzymes via the Keap1/Nrf2 signal pathway,thereby inhibiting the generation of ROS and MDA.In conclusion,the H.erinaceus-derived peptide KSPLY effectively protected HepG2 cells against H_(2)O_(2)-induced oxidative damage,and it provided a theoretical basis for the further development of new natural antioxidants.

Dynamic geomorphology and storm response characteristics of the promontory-straight beach-a case of Gulei Beach, Fujian

As one of the main areas of tropical storm action in the northwestern Pacific Ocean,South China experiences several typhoons each year,and coastal erosion is a problem,making the area a natural testing ground for studying the dynamic geomorphological processes and storm response of promontory-straight coasts.This study is based on three years of topographic data and remote sensing imagery of Gulei Beach and uses topographic profile morphology,single width erosion-accretion and mean change,combined with the Coastsat model to quantify the seasonal and interannual variability and storm response of the beach and to explain the evolution of shoreline change and beach dynamics geomorphology in the last decade.Gulei Beach has been in a state of overall erosion and local accretion for a long time,with relatively obvious cyclical changes;seasonal changes are also obvious,which are mainly characterized by summer accretion and winter erosion,with accretion at the top of the bay and accretion and erosion on the north and south sides of the bay corner,respectively;the seasonal erosion-accretion volume of the beach profile ranges from-80 m3/m to 95.52 m3/m,and the interannual erosion-accretion volume ranges from-69.09 m3/m to 87.31 m3/m.The response of beaches to typhoons with different paths varies greatly depending on the length,slope,orientation and scale of beach development.The large and gently developing Futou beach is less responsive to storms,while the less developed headlands in the southern Gulei Peninsula are more susceptible to disturbance by external factors and respond more strongly to typhoons.Storm distance is more influential than storm intensity.Under the influence of human activities,obvious erosion hotspots develop during normal weather,but storm processes produce redistribution of beach material patterns,and erosion hotspots disappear after storms.The results of this study enrich the theory of beach dynamics geomorphology and provide technical support for disaster prevention and mitigation,as well as ecological restoration of coastal zones.

Typhoon vs. cold wave: a comparative assessment of geomorphic response and boulder displacement using RFID technology

Extreme storm events in coastal zones play significant roles in shaping the morphology of boulder beaches.However,boulder displacement and the geomorphological evolution of boulder beaches driven by different extreme storm events,especially typhoon events,remain poorly understood.Thus,boulder displacement and the geomorphic response on a boulder beach in Fujian,southeastern China,were explored before,during and after a cold wave event(Dec.1–7,2020)and before and after Typhoon In-Fa(Jul.19–27,2021),a large tropical storm.This was achieved by tracking 42 tagged boulders distributed in the intertidal and supratidal zones using Radio Frequency Identification(RFID)and topographic surveys using real-time kinematic techniques,respectively.The results showed obvious disparities in boulder displacement in different geomorphic zones due to cold wave and typhoon events that were mainly characterized by migration magnitude,range,direction,and mode of transport.The typhoon event led to rapid and substantial changes in the overall morphology of the boulder beach,while the cold wave event impacted the intertidal morphology of the boulder beach to only a small extent.The surrounding structure of boulders,beach slope and beach elevation had a combined dominant effect on boulder displacement under the same extreme event.Hydrodynamic factors(effective wave energy fluxes,incident wave direction,storm surge and water level)had dominant effects on boulder displacement during different extreme events.In terms of a single event,the magnitude of the boulder displacement driven by the typhoon was much greater than that driven by the cold wave.However,considering the frequency and duration of cold waves in winter,the impact of multiple consecutive cold waves on the geomorphology of the boulder beach cannot be ignored in this study area.Alternating and repeated interactions between these two processes constitute the complete geomorphic evolution of the boulder beach.This study contributes to improved predictions of the morphodynamic response of boulder beaches to future storms,especially large tropical storms,and facilitates better coastal management.

Sediment source-to-sink process variations of sandy-muddy transitional beaches and their morphological indications

The clay mineralogy of 28 sandy-muddy transitional beach(SMT-Beach)sediments and surrounding mountain river sediments along the coasts of southeastern China was systematically investigated to reveal the sediment source-to-sink process variations of such beaches and their morphological indications.The results show that the clay mineral assemblages of these SMT-Beaches mainly comprise of almost equal illite(~30%),kaolinite(~28%),chlorite(~22%),and smectite(~20%)contents.From the surrounding mountain rivers to the SMT-Beaches,clay mineral assemblages show distinct spatial changes characterized by a large decrease(~40%)in kaolinite,whereas the other three clay minerals present relative increases,especially clear for smectite.The muddy sediment sources of SMT-Beaches inferred from the clay mineralogy are mainly derived from nearby mountain rivers coupled with long-distance transport and penetration of the Changjiang River.The sandy sediments of these beaches are predominantly sourced from nearby mountain rivers,the weathering products of surrounding rocks in both mainland and island environments,and erosion of the“Old Red Sand”and“Red Soil Platform”.However,the sandy sediment sources of the SMT-Beaches are largely reduced because of the remarkable decrease in the river fluvial supply associated with intensive human activities such as dam construction and coastal reclamation.Subsequently,the sandy sections of SMT-Beaches present clear erosion and have revealed by both time series remote sensing images and a compilation of published literature.In contrast,the muddy sediment supply of SMT-Beaches is temporarily stable and relatively constant,resulting in the landward migration of the mudflats with relative transgression or accumulation.These findings highlight that the natural evolution processes of SMT-Beaches have been greatly reshaped by intensive human activities.

Nourishment and disaster mitigation efficiency of feeding sand on the dry section of a dissipative beach

To explore the nourishment effect and disaster reduction efficiency of a fully dissipative dry beach under the impact of storms,this paper uses the measured topography and hydrodynamic data to establish a one-dimensional numerical model of the XBeach beach profile.By numerically modeling the change in the nourished profile for different dry beach widths under normal waves and storm conditions and the recovery process of the profile after the storm,the degree of response in dry beach nourishment for the fully dissipative beach is analyzed.The results show that under normal wave conditions,the response of the nourished dry beach is obvious.Sediment on the dry beach erodes heavily,and the shoreline moves landward over a long distance.With the increase in the width and size of the dry beach,the wave height at the bottom of the backshore profile decreases,the wave height attenuation rate increases continuously,and the wave elimination effect is remarkable.When the storm incident wave intensifies,the wave height attenuation rate of the nourished dry beach decreases,indicating that the smaller the storm intensity is,the more significant the wave reduction effect of the nourished dry beach is.At the same time,different profile arrangements of nourished dry beaches suffer from different degrees of erosion under storm conditions,with significant changes in profile morphology.With intensified storm action,the intensity of sediment erosion in the nourished dry beach increases,the nourishment is weakened,and the recovery effect of the profile after the storm is not obvious.The results of the numerical modeling highlight that the dry beach nourishment method can resist storms to a certain extent,but the overall effect is relatively limited.

Variation in cross-shore wind speeds influenced by the morphology of nourished beach

The cross-shore variation in wind speeds influenced by beach nourishment,especially the dramatic changes at the nourished berm,is important for understanding the aeolian sand transport processes that occur after beach nourishment,which will contribute to better beach nourishment project design on windy coasts.In this paper,the influencing factors and potential mechanism of wind speed variation at the edge of a nourished berm were studied.Field observations,together with the Duna model,were used to study the cross-shore wind speed distribution for different nourishment schemes.The results show that the nourished berm elevation and beachface slope are the main factors controlling the increase in wind speed at the berm edge.When the upper beach slope is constant,the wind speed at the berm edge has a positive linear correlation with the berm elevation.When the berm elevation remains constant,the wind speed at the berm edge is also proportional to the upper beach slope.Considering the coupling effects of nourished berm elevation and beachface slope,a model for predicting the wind speed amplification rate at the nourished berm edge was established,and the underlying coupling mechanism was illustrated.

Effect of fence opening configurations on dune development

Fences have been widely used in coastal protection engineering for their low cost,simple deployment,and easy integration with ecosystems.The effects of fence porosity and height on dune development have been investigated while not much attention has been paid to the effects of fence opening configurations,such as opening size and geometry,and porosity distributions.In this study,we deployed eight fences with same height and similar porosity,but different opening configurations on a sandy beach in Pingtan,Fujian Province.Results indicate that there is a similar two-dune-one-trough pattern for all fences at the beginning of dune development,and opening size,orientation,and geometry,and porosity distribution control the leeward dune peak locations.Fences with small openings and non-uniform porosity have high trapping efficiency,and upper denser porosity may be the optimal design as these fences have the highest trapping efficiency and capacity.The conclusions from this study can provide guidance on practical fence design.

Protolith ages and timing of peak and retrograde metamorphism of the high-pressure granulites in the Shandong Peninsula,eastern North China Craton

High-pressure （HP） granulites widely occur as enclaves within tonalite-trondhjemite- granodiorite （TTG） gneisses of the Early Precambrian metamorphic basement in the Shandong Peninsula, southeast part of the North China Craton （NCC）. Based on cathodoluminescence （CL）, laser Raman spec- troscopy and in-situ U-Pb dating, we characterize the zircons from the HP granulites and group them into three main types： inherited （magmatic） zircon, HP metamorphic zircon and retrograde zircon. The inher- ited zircons with clear or weakly defined magmatic zoning contain inclusions of apatites, and 207pb/206pb ages of 2915--2890 Ma and 2763--2510 Ma, correlating with two magmatic events in the Archaean base- ment. The homogeneous HP metamorphic zircons contain index minerals of high-pressure metamor- phism including garnet, clinopyroxene, plagioclase, quartz, rutile and apatite, and yield 207pb/2066pb ages between 1900 and 1850 Ma, marking the timing of peak HP granulite facies metamorphism. The retrograde zircons contain inclusions of orthopyroxene, plagioclase, quartz, apatite and amphibole, and yield the youngest 207pb/206pb ages of 1840-1820 Ma among the three groups, which we correlate to the medium to low-pressure granulite facies retrograde metamorphism. The data presented in this study suggest subduction of Meso- and Neoarchean magmatic protoliths to lower crust depths where they were subjected to HP granulite facies metamorphism during Palaeoproterozoic （1900-1850 Ma）. Subse- quently, the HP granulites were exhumated to upper crust levels, and were ovel-printed by medium to low-pressure granulite and amphibolite facies retrograde event at ca. 1840--820 Ma.

Fiscal Expenditure and Income Gap between Urban and Rural Residents: An Empirical Study Based on Malmquist Index and Spatial Econometrics

Based on the analysis methods of non-parametric Malmquist index and spatial econometrics as well as the provincial panel data in 2007-2010, this paper estimates the efficiency of fiscal expenditure from local governments in china in terms of reducing the income gap between urban and rural residents for the first time and evaluates the spatial correlation and heterogeneity of this efficiency. The results have shown that the fiscal expenditure of most provinces is of low efficiency in reducing the income gap between urban and rural residents, and the expenditure efficiency of local governments is not relevant to their levels of economic development. Besides, the efficiency on reducing the urban-rural income gap between different regions of China has a tendency of convergence. But this is mainly reflected inside the regional economic belt. There is significant difference between the efficiency of each economic belt. The central region has the highest efficiency in a rising trend, the western region has the lowest efficiency in a downward trend, while the eastern region is relatively stable.

Review of Researches on Agricultural Industry Chain at Home and Abroad

Management of agricultural industry chain is the main form of modern agricultural industrialization. Integration and optimization of agricultural chain have great significance in deepening the reform in the countryside,quickening the development of agricultural modernization and establishing new system of agricultural management. Based on the theory sources and contents of agricultural chain as well as the current researches at home and abroad,this paper hackles and concludes information technology,logistics management and food safety and quality in foreign agricultural chain as well as the organization model,operation mechanism,integration and optimization,promotion and extension,financing and risk prevention,influencing factors as well as performance evaluation in domestic agricultural chain and offers relevant review in order to provide further reference for future researches.

Behavioral and Electrophysiological Responses to Caffeine of Helicoverpa armigera Larvae and H. assulta Larvae

The dual-choices tests of behavioral test were used to study the gustatory behavioral responses to caffeine of Helicoverpa armigera larvae and H. assulta larvae. Electrophysiological responses were studied by electrophysiological tip recording. Behavioral experiments showed that caffeine was a feeding deterrent for both larvae, but it showed a stronger feeding deterring effect on the oligophagous H. assulta . The electrophysiological tip-recording results showed that both H. armigera larvae and H. assulta larvae had one caffeine-sensitive feeding deterrent neuron at the medial sensilla, and the electrophysiological pulse response of H. assulta larvae was significantly stronger than that of H. armigera larvae. Therefore, caffeine had a stronger feeding deterring effect on the oligophagous H. assulta than the polyphagous H. armigera . The difference in behavioral effect was closely related to the sensitivity of to caffeine the feeding deterrent neurons at the medial sensilla.

Clinical observation of colon carcinoma treated with Boerning capsules plus FOLFOX4 regimen

Objective:To evaluate the effects and adverse reactions of Boerning capsules plus FOLFOX4 regimen in clinical treatment for colon carcinoma.Methods:Total patients with colon carcinoma were randomly divided into two groups from January 2005 to May 2006:group A(45 patients)were received Boerning capsules plus FOLFOX4 regimen treatment,and group B(49 patients)were received FOLFOX4 regimen treatment only.Results:Boerning capsules could obviously improve the life quality of the colon carcinoma patients.The weight gain in group A was higher than that of group B.No significant existed in the body immune function changes(T cell subgroup).But it could ameliorate the adverse reactions which induced by the chemotherapy.Conclusion:Boerning capsules can improve the life quality of the colon carcinoma patients and ame- liorate the symptoms and sign which induced by the chemotherapy.

Study on Growth of China's Agricultural Industrial Chain from the Perspective of Large Scale

The growth of agricultural industrial chain is the result of market demand,fund,technology,industrial development and policy guidance. At present,separate and small peasant operating model has become one of the important factors restricting the growth of agricultural industrial chain. From growth mechanism of agricultural industrial chain and actual conditions of China,this paper analyzed actual factors restricting the growth of agricultural industrial chain,and held that it is required to break system bottleneck of large scale agricultural production,match management conditions of large scale agricultural production,and orient towards large scale organization,large scale service,large scale industrial distribution,and large scale chain.

Probabilistic Fatigue Life Framework of Notched Specimens Based on the Weibull Distribution Under Multiaxial Loading

In engineering applications,the notch effect and size effect significantly influence the evaluation of fatigue performance in components,necessitating special attention in life prediction.This study proposes a new probabilistic model,based on the theory of critical distance(TCD),to predict fatigue life,with the aim of quantitatively assessing the impact of notch effect and size effect.The stress distribution on the critical plane is first characterized using a sixth-order multinomial function,and the relative stress gradient function is utilized to calculate the value of the critical distance.Furthermore,the effect of the ratio of shear strain to normal strain on fatigue life under multiaxial loading is considered.Additionally,the integration of the Weibull distribution into the TCD is employed for conducting probabilistic modeling of fatigue life.Finally,fatigue experiments are conducted on notched specimens of Q355D steel,demonstrating that the life prediction results under 50%survival probability are superior to the traditional TCD method.

缺口件多轴疲劳寿命预估新方法

局部应力应变法(LSSM)以危险点处的局部应力应变历程进行寿命评价,忽略了非比例附加强化及缺口附近应力梯度对疲劳损伤的影响.论文通过分析裂纹萌生面(临界面)上剪应力和正应力分布状态,提出一种计算缺口件多轴疲劳损伤影响区的数学计算方法,建立考虑法向正/剪应力梯度与非比例附加强化效应的寿命预估模型.首先,基于能量法和临界面理论,借助坐标变换原理将应变能密度最大的材料平面定义为临界面,建立确定裂纹萌生方向的计算方法.其次,以临界面上特定路径为积分方向,将缺口件三维问题转化为线性问题,简化计算过程.综合考虑峰值应力和等效应力场强对多轴疲劳寿命的贡献度,建立表征缺口件多轴疲劳损伤演化过程的损伤参量.最后,通过TC4合金和Q345钢多轴疲劳试验验证论文模型的可行性和精确度,并与LSSM法、FS模型、SWT模型进行对比分析.

Electrostatic self-assembly of 2D/2D CoWO_(4)/g-C_(3)N_(4)p-n heterojunction for improved photocatalytic hydrogen evolution:Built-in electric field modulated charge separation and mechanism unveiling

Two-dimensional(2D)semiconductor heterojunctions are considered as an effective strategy to achieve fast separation of photoinduced carriers.Herein,a novel CoWO_(4)/g-C_(3)N_(4)(CWO/CN)p–n junction was synthesized using an electrostatic selfassembly method.The constructed 2D/2D p–n heterostructure had a rich hetero-interface,increased charge density,and fast separation efficiency of photoinduced carriers.The in-situ Kelvin probe force microscopy confirmed that the separation pathway of photoinduced carriers through the interface obeyed an II-scheme charge transfer mechanism.Experimental results and density functional theory calculations indicated the differences of work function between CWO and CN induced the generation of built-in electric field,ensuring an efficient separation and transfer process of photoinduced carriers.Under the optimized conditions,the CWO/CN heterojunction displayed enhanced photocatalytic H_(2)generation activity under full spectrum and visible lights irradiation,respectively.Our study provides a novel approach to design 2D/2D hetero-structured photocatalysts based on p–n type semiconductor for photocatalytic H_(2)generation.

Method for Predicting the Fatigue Life of Geometrically Discontinuous Structures Under Combined Bending and Torsion

The fatigue damage model based on theory of damage mechanics is capable of predicting the fatigue life under multiaxial loading. Meanwhile, the application of critical plane method in the prediction of multiaxial fatigue life has made certain progress. According to the law of thermodynamics, a new damage evolution equation is developed in the present study to predict the fatigue life of geometrically discontinuous structure under tension-torsion loading based on damage mechanics and the critical plane method. The essence of this approach is tha t the st rain parame ter of the uniaxial nonlinear fatigue damage model is replaced with the equivalent strain, which consists of the releva nt parame ters of the critical plane. However, it is difficult to calculate the stress-strain status and the critical plane position of geometrically dis? continuous structure by theoretical methods because of the existence of stress concentration and the multiaxial nonproportional characteristics. Therefore, a new numerical simulation method is proposed to determine the critical plane of geometrically discontinuous structure under multiaxial loading by means of the finite element method and MATLAB software. The fatigue life of notched specimens subjected to combined bending and torsion is predicted using the proposed met hod, and the result is compared with t hose from the experimen ts and the Manson-Cfiffin law. The comparisons show that the proposed method is superior to the Manson-Coffin law and is capable of reproducing the experimental results reasonably when the geometry of the structure is complex. It completely meets the needs of engineering practice.