Navigating the pathways:TAR-DNA-binding-protein-43 aggregation,axonal transport,and local synthesis in amyotrophic lateral sclerosis pathology

Neurons are highly polarized cells with axons reaching over a meter long in adult humans.To survive and maintain their proper function,neurons depend on specific mechanisms that regulate spatiotemporal signaling and metabolic events,which need to be carried out at the right place,time,and intensity.Such mechanisms include axonal transport,local synthesis,and liquid-liquid phase separations.Alterations and malfunctions in these processes are correlated to neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS).

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Evolution of mechanical properties,localized corrosion resistance and microstructure of a high purity Al-Zn-Mg-Cu alloy during non-isothermal aging

The evolution of mechanical properties,localized corrosion resistance of a high purity Al-Zn-Mg-Cu alloy during non-isothermal aging(NIA)was investigated by hardness test,electrical conductivity test,tensile test,intergranular corrosion test,exfoliation corrosion test,slow strain rate tensile test and electrochemical test,and the mechanism has been discussed based on microstructure examination by optical microscopy,electron back scattered diffraction,scanning electron microscopy and scanning transmission electron microscopy.The NIA treatment includes a heating stage from 40℃to 180℃with a rate of 20℃/h and a cooling stage from 180℃to 40℃with a rate of 10℃/h.The results show that the hardness and strength increase rapidly during the heating stage of NIA since the increasing temperature favors the nucleation and the growth of strengthening precipitates and promotes the transformation of Guinier-Preston(GPI)zones toη'phase.During the cooling stage,the sizes ofη'phase increase with a little change in the number density,leading to a further slight increase of the hardness and strength.As NIA proceeds,the corroded morphology in the alloy changes from a layering feature to a wavy feature,the maximum corrosion depth decreases,and the reason has been analyzed based on the microstructural and microchemical feature of precipitates at grain boundaries and subgrain boundaries.

The Impacts of Flood and Local Communities’ Coping Strategies along the River Gambia

Flood disasters as Climate change hazards are common in developing countries, particularly in communities along the river Gambia. Local communities, for instance, had their local coping strategies that enabled them to stay in their communities even amid these ordeals, and climate change disaster threats. This work strives to understand flood impacts and the local peoples’ adaptation or coping strategies along the River Gambia basin. A community-based cross-sectional research study of 422 research participants of which 294 are males (69.7%) and females 128 (30.3%), and a focus group discussion of 10 groups which comprised 5 female groups and 5 male groups respectively found that 98.6% of the households experienced floods in their community, and 70.6% experienced flood in their houses, 2.1% have impending flood information and 88.4% do not know evacuation centres. The majority of the households had some local coping strategies, but they acknowledged their insufficient effectiveness. The result also shows that the impact of floods on farmlands, roads, buildings, and livestock was greatly felt. Coping strategies such as sandbags, raised elevations, contour bonds, dikes, and buildings on highlands were all found to be common mechanisms the local people used. The study opines that floods affect communities, but the effects vary depending on individual assets.

Studying the co-evolution of information diffusion,vaccination behavior and disease transmission in multilayer networks with local and global effects

Today,with the rapid development of the internet,a large amount of information often accompanies the rapid transmission of disease outbreaks,and increasing numbers of scholars are studying the relationship between information and the disease transmission process using complex networks.In fact,the disease transmission process is very complex.Besides this information,there will often be individual behavioral measures and other factors to consider.Most of the previous research has aimed to establish a two-layer network model to consider the impact of information on the transmission process of disease,rarely divided into information and behavior,respectively.To carry out a more in-depth analysis of the disease transmission process and the intrinsic influencing mechanism,this paper divides information and behavior into two layers and proposes the establishment of a complex network to study the dynamic co-evolution of information diffusion,vaccination behavior,and disease transmission.This is achieved by considering four influential relationships between adjacent layers in multilayer networks.In the information layer,the diffusion process of negative information is described,and the feedback effects of local and global vaccination are considered.In the behavioral layer,an individual's vaccination behavior is described,and the probability of an individual receiving a vaccination is influenced by two factors:the influence of negative information,and the influence of local and global disease severity.In the disease layer,individual susceptibility is considered to be influenced by vaccination behavior.The state transition equations are derived using the micro Markov chain approach(MMCA),and disease prevalence thresholds are obtained.It is demonstrated through simulation experiments that the negative information diffusion is less influenced by local vaccination behavior,and is mainly influenced by global vaccination behavior;vaccination behavior is mainly influenced by local disease conditions,and is less influenced by global disease conditions;the disease transmission threshold increases with the increasing vaccination rate;and the scale of disease transmission increases with the increasing negative information diffusion rate and decreases with the increasing vaccination rate.Finally,it is found that when individual vaccination behavior considers both the influence of negative information and disease,it can increase the disease transmission threshold and reduce the scale of disease transmission.Therefore,we should resist the diffusion of negative information,increase vaccination proportions,and take appropriate protective measures in time.

Improving the utility of locally differentially private protocols for longitudinal and multidimensional frequency estimates

This paper investigates the problem of collecting multidimensional data throughout time(i.e.,longitudinal studies)for the fundamental task of frequency estimation under Local Differential Privacy(LDP)guarantees.Contrary to frequency estimation of a single attribute,the multidimensional aspect demands particular attention to the privacy budget.Besides,when collecting user statistics longitudinally,privacy progressively degrades.Indeed,the“multiple”settings in combination(i.e.,many attributes and several collections throughout time)impose several challenges,for which this paper proposes the first solution for frequency estimates under LDP.To tackle these issues,we extend the analysis of three state-of-the-art LDP protocols(Generalized Randomized Response–GRR,Optimized Unary Encoding–OUE,and Symmetric Unary Encoding–SUE)for both longitudinal and multidimensional data collections.While the known literature uses OUE and SUE for two rounds of sanitization(a.k.a.memoization),i.e.,L-OUE and L-SUE,respectively,we analytically and experimentally show that starting with OUE and then with SUE provides higher data utility(i.e.,L-OSUE).Also,for attributes with small domain sizes,we propose Longitudinal GRR(L-GRR),which provides higher utility than the other protocols based on unary encoding.Last,we also propose a new solution named Adaptive LDP for LOngitudinal and Multidimensional FREquency Estimates(ALLOMFREE),which randomly samples a single attribute to be sent with the whole privacy budget and adaptively selects the optimal protocol,i.e.,either L-GRR or L-OSUE.As shown in the results,ALLOMFREE consistently and considerably outperforms the state-of-the-art L-SUE and L-OUE protocols in the quality of the frequency estimates.

Local existence and uniqueness of the incompressible Navier-Stokes-Landau-Lifshitz equations with the Dzyaloshinskii-Moriya interaction and V-flow term

In this paper,we prove that there exists a unique local solution for the Cauchy problem of a system of the incompressible Navier-Stokes-Landau-Lifshitz equations with the Dzyaloshinskii-Moriya interaction and V-flow term inR^(2) and R^(3).Our methods rely upon approximating the system with a perturbed parabolic system and parallel transport.

Spatial Analysis of the Aging Population and Socio-economic Factors of China:Global and Local Perspectives

Population aging has become an inevitable trend and exerted profound influences on socio-economic development in China.In this study,we utilized data from national population census and statistical yearbooks in 2010 and 2020 to explore spatio-temporal patterns of aging population and its coupling correlations with socio-economic factors from both global and local perspectives.The results from Local Indicators of Spatial Association(LISA)uncover notable spatial disparities in aging population rates,with higher rates concentrated in the eastern regions and lower rates in the western areas of the Chinese mainland.The results from the global correlation analysis with the changes in aging population rates show significant positive correlations with government interventions and industrial structures,but negatively correlated with economic development,social consumption,and medical facilities.From a local perspective,a Geographically Weighted(GW)correlation analysis is employed to uncover local correlations between aging trends and socio-economic factors.The insights gained from this technique not only underscore the complexity and diversity of economic implications stemming from population aging,but also provide invaluable guidance for crafting region-specific economic policies tailored to various stages of population aging.

Local existence and uniqueness of solutions to the evolutionary model for magnetoviscoelasticity

In this paper,we prove the local existence and uniqueness of solutions to the evolutionary model for magnetoviscoelasticity in R^(2),R^(3).This model consists of an incompressible Navier-Stokes,a regularized system for the evolution of the deformation gradient and the Landau-Lifshitz-Gilbert system for the dynamics of the mag-netization.Our approach depends on approximating the system with a sequence of perturbed systems.

Radiative heat transfer analysis of a concave porous fin under the local thermal non-equilibrium condition:application of the clique polynomial method and physics-informed neural networks

The heat transfer through a concave permeable fin is analyzed by the local thermal non-equilibrium(LTNE)model.The governing dimensional temperature equations for the solid and fluid phases of the porous extended surface are modeled,and then are nondimensionalized by suitable dimensionless terms.Further,the obtained nondimensional equations are solved by the clique polynomial method(CPM).The effects of several dimensionless parameters on the fin's thermal profiles are shown by graphical illustrations.Additionally,the current study implements deep neural structures to solve physics-governed coupled equations,and the best-suited hyperparameters are attained by comparison with various network combinations.The results of the CPM and physicsinformed neural network(PINN)exhibit good agreement,signifying that both methods effectively solve the thermal modeling problem.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer

BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Efficacy evaluation and survival analysis of the combination of oxaliplatin plus Teysuno (SOX) with immune checkpoint inhibitors in the conversion therapy of locally advanced gastric cancer

Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.

Value and Measures of Integrating Local Red Culture into the Ideological and Political Course of Environmental Disciplines under the OBE Concept

Based on output-oriented education,the OBE(Outcome-Based Education)concept integrates local red culture into the ideological and political course of environmental disciplines,and is an important part of training applied talents of environmental disciplines in the new era.This educational model makes an innovation on the traditional educational and teaching concepts and centers on students.This paper analyzes the value of integrating local red culture into the ideological and political course under the OBE concept,and puts forward an effective implementation path.

Principles for Designing New Types of Housing for a Strong and Resilient Local Economy in the Republic of Congo

The Congolese population is organised into households, which are thus headed by a chief who ensures the social well-being, development and integration into working life of the individuals in his charge. This study examines the functional principles of new housing design as an instrument for transforming the (current) failing economy into a strong and resilient one. Accordingly, a literature review of the practice of designing and building housing in human settlements in the Congo revealed the state of the art on this subject. An analysis of the existing housing stock from a demographic, social and economic point of view made it possible to identify the most common household sizes and numbers, as well as the lifestyle processes that determine the need for developed space. To this end, the experimental method was used to propose configuration plans for various new types of dwelling. To this end, the study highlighted the link between people’s standard of living and the effectiveness of their involvement in the local economy. To achieve the aims of the National Development Plan (NDP), particular attention must be paid to solving the housing problem. The existing housing stock actively contributes to the problems associated with unemployment and insecurity. Functional principles for the design of new types of housing have been developed. Four model types are proposed in line with the demographic structure of the population, their socio-economic characteristics and their lifestyle.

An Analysis of the Path of Ethnic Unity and Progress Education under Academy-Based Education: Taking Ningxia University as an Example

Academy-based education is an active exploration and effective attempt to reform higher education and talent cultivation systems in the new era.This article aims to deeply analyze the characteristics and advantages of academy-based education.Combining the theoretical connotation and practical needs of ethnic unity and progress education and taking Ningxia University as an example,it explores the construction and implementation path of ethnic unity and progress education under academy-based education.It promotes communication and integration between students of different ethnic groups,enhances ethnic identity and national consciousness,and promotes the high-quality development of ethnic unity and progress cause.

An Investigation on the Application of Online and Offline Hybrid Teaching in Local Anatomy Course of Acupuncture and Moxibustion Specialty

The purpose of this paper is to explore the application of online and offline blended teaching in local anatomy courses of acupuncture specialty.It introduces the concept and characteristics of blended teaching mode and analyzes the respective advantages of online and offline teaching as well as the advantages and application prospects of blended teaching mode.The teaching status quo of local anatomy courses in acupuncture and moxibustion is analyzed,pointing out the problems of the traditional teaching mode and the application prospect of the blended teaching mode.In the practical part,the preparation and design of online teaching resources,the design of offline practical teaching sessions,and the evaluation methods of teaching effect are introduced in detail.This study aims to provide new teaching modes and ideas for teaching acupuncture and moxibustion and promote the improvement of teaching quality.

A study of the effect of local scour on the flow field near the spur dike

The flow field near a spur dike such as down flow and horseshoe vortex system(HVS)are susceptible to the topographic changes in the local scouring process,resulting in variation of the sediment transport with time.In this study,large eddy simulations with fixed-bed at different scouring stages were conducted to investigate the changes in flow field.The results imply that the bed deformation leads to an increase in flow rate per unit area,which represent the capability of sediment transportation by water,in the scour hole.Moreover,the intensity of turbulent kinetic energy and bimodal motion near the sand bed induced by the HVS were also varied.However,the peak moments between the two sediment transport mechanisms were different.Hence,understanding the complex feedback mechanism between topography and flow field is essential for the local scour problem.

Local Knowledge on the Influence of Land Use/Cover Changes and Conservation Threats on Avian Community in the Kilombero Wetlands, Tanzania

Local knowledge of the history and ecology of wetland ecosystems is very useful in wetland resources management, especially when other historical ecological information is not available and can be integrated with scientific knowledge to introduce better management of resources. The aims of this paper were to assess existing local knowledge on land use/cover changes in the Kilombero wetlands, thereafter investigate local knowledge on its effect on avian population in the wetland and identify factors influencing local knowledge on such changes in the study area. Random sampling was used to obtain representative sample population for this study. Structured questionnaire and focus group discussions were used to extract information from local people in six villages. Study results from multi-response analysis showed that natural forests had been converted into cropland and bushed grassland, grassland to crop land, grassland to grazed land, forest to settlement and grassland to settlement. Land use change was singled out as primary cause of decrease in avian community in the wetland. Threats to the conservation of avian species were identified as livestock grazing, drought, use of poison, traps and bush meat hunting for food. Age and education level were seen as determinants of household’s knowledge on the ecological changes. This pool of existing knowledge is important among wetland users and stakeholders in order to generate conservation strategies of the wetland ecosystem.

Numerical study on local scour characteristics around submarine pipelines in the Yellow River Delta silty sandy soil under waves and currents

Due to their high reliability and cost-efficiency,submarine pipelines are widely used in offshore oil and gas resource engineering.Due to the interaction of waves,currents,seabed,and pipeline structures,the soil around submarine pipelines is prone to local scour,severely affecting their operational safety.With the Yellow River Delta as the research area and based on the renormalized group(RNG)k-εturbulence model and Stokes fifth-order wave theory,this study solves the Navier-Stokes(N-S)equation using the finite difference method.The volume of fluid(VOF)method is used to describe the fluid-free surface,and a threedimensional numerical model of currents and waves-submarine pipeline-silty sandy seabed is established.The rationality of the numerical model is verified using a self-built waveflow flume.On this basis,in this study,the local scour development and characteristics of submarine pipelines in the Yellow River Delta silty sandy seabed in the prototype environment are explored and the influence of the presence of pipelines on hydrodynamic features such as surrounding flow field,shear stress,and turbulence intensity is analyzed.The results indicate that(1)local scour around submarine pipelines can be divided into three stages:rapid scour,slow scour,and stable scour.The maximum scour depth occurs directly below the pipeline,and the shape of the scour pits is asymmetric.(2)As the water depth decreases and the pipeline suspension height increases,the scour becomes more intense.(3)When currents go through a pipeline,a clear stagnation point is formed in front of the pipeline,and the flow velocity is positively correlated with the depth of scour.This study can provide a valuable reference for the protection of submarine pipelines in this area.