Anopheles gambiae larvicidal and adulticidal potential of Phyllanthus amarus(Schumach and Thonn,1827)obtained from different localities of Nigeria

Objective:To screen phytochemicals in ethanolic leaf extracts of Phyllanthus amarus collected from three different geographical zones in Nigeria and evaluate their effects on larva and adult of Anopheles gambiae.Methods:The sample extracts of Phyllanthus amarus prepared with ethanol solvent were tested against Anopheles gambiae at two important developmental stages of its life cycle using slightly modified WHO protocols.Results:Alkaloids,saponins,tannins,flavonoids,glycosides,phenols,and terpenes were detected in each extract.Among these samples,the extract from northwest exhibited the highest larvicidal activity(LC50=263.02 ppm),followed by southeast and southwest extracts(LC50=288.40 and 295.12 ppm,respectively after 48 h),while the extract from southwest exhibited the highest adulticidal activity(LC50=275.42 ppm),followed by northwest and southeast extract(LC50=301.99 and 316.22 ppm,respectively after 24 h).A 50%larva mortality was almost attained at 600 ppm after 48 h duration of exposure to the northwest extract.Conclusions:The tested samples possess strong larvicidal and adulticidal property against Anopheles gambiae which depends on their chemical composition and localities of collection.Further studies are needed to explore the insecticidal activity against a wider range of mosquito species,and to identify active ingredient(s)of the extract responsible for such activity.

Hierarchy of Rural Localities in the Niakhar Area (Fatick, Senegal)

Although the study of the hierarchy of localities presents an important social and economic stake, studies focused on the hierarchy of rural localities are relatively weak, especially in Africa. It is important to highlight the hierarchy of rural areas in order to reveal poles that can support sustainable growth. Our main objective is to study the hierarchy of rural localities in the Niakhar area, using a geographic approach. The data come from the Niakhar demographic, epidemiological and environmental observatory database and the Niakhar Atlas project of the French Research Institute for Development (IRD). The net flow method, the primacy index, the median population threshold method and the measurement of the correlation between level of centrality and population size are used to analyze the data. Our study allowed us to determine the main types of centrality and to establish the hierarchy of rural localities in the Niakhar zone. It also highlighted the strong correlation between the rank of localities and the size of the population of the latter. The main contribution of our work is to have highlighted, in order, the structuring localities of the rural space of the Niakhar area, by combining several indicators of centrality.

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).

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

Positioning localities from spatial assertions based on Voronoi neighboring

With the rapid development of Internet,much spatial information contained in non-structured or semi-structured documents is available on the World Wide Web.In such documents,localities are always textually described using spatial relationships and named places,instead of numerical coordinates.Hence,extracting positional information from locality descriptions is an important task.In this paper,we bridge two aspects of locality descriptions,namely generating locality descriptions and positioning localities,and provide a method to compute probability density according to the selection probability of a reference object to describe the position of the target object.Refinement operation on uncertainty field is used to deal with locality description involving multiple reference objects.Three metrics are introduced to measure the results of positioning localities.We choose the mixed selection probability function based on Euclidean distance and Voronoi stolen-area to compute probability density function.Finally,we use three cases to demonstrate the proposed methods.

Point Cloud Classification Using Content-Based Transformer via Clustering in Feature Space

Recently, there have been some attempts of Transformer in 3D point cloud classification. In order to reduce computations, most existing methods focus on local spatial attention,but ignore their content and fail to establish relationships between distant but relevant points. To overcome the limitation of local spatial attention, we propose a point content-based Transformer architecture, called PointConT for short. It exploits the locality of points in the feature space(content-based), which clusters the sampled points with similar features into the same class and computes the self-attention within each class, thus enabling an effective trade-off between capturing long-range dependencies and computational complexity. We further introduce an inception feature aggregator for point cloud classification, which uses parallel structures to aggregate high-frequency and low-frequency information in each branch separately. Extensive experiments show that our PointConT model achieves a remarkable performance on point cloud shape classification. Especially, our method exhibits 90.3% Top-1 accuracy on the hardest setting of ScanObjectN N. Source code of this paper is available at https://github.com/yahuiliu99/PointC onT.

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.

Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

A Study on the Transmission Dynamics of the Omicron Variant of COVID-19 Using Nonlinear Mathematical Models

This research examines the transmission dynamics of the Omicron variant of COVID-19 using SEIQIcRVW and SQIRV models,considering the delay in converting susceptible individuals into infected ones.The significant delays eventually resulted in the pandemic’s containment.To ensure the safety of the host population,this concept integrates quarantine and the COVID-19 vaccine.We investigate the stability of the proposed models.The fundamental reproduction number influences stability conditions.According to our findings,asymptomatic cases considerably impact the prevalence of Omicron infection in the community.The real data of the Omicron variant from Chennai,Tamil Nadu,India,is used to validate the outputs.

Multi-Material Topology Optimization for Spatial-Varying Porous Structures

This paper aims to propose a topology optimization method on generating porous structures comprising multiple materials.The mathematical optimization formulation is established under the constraints of individual volume fraction of constituent phase or total mass,as well as the local volume fraction of all phases.The original optimization problem with numerous constraints is converted into a box-constrained optimization problem by incorporating all constraints to the augmented Lagrangian function,avoiding the parameter dependence in the conventional aggregation process.Furthermore,the local volume percentage can be precisely satisfied.The effects including the globalmass bound,the influence radius and local volume percentage on final designs are exploited through numerical examples.The numerical results also reveal that porous structures keep a balance between the bulk design and periodic design in terms of the resulting compliance.All results,including those for irregular structures andmultiple volume fraction constraints,demonstrate that the proposedmethod can provide an efficient solution for multiple material infill structures.

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.

Scheme Based on Multi-Level Patch Attention and Lesion Localization for Diabetic Retinopathy Grading

Early screening of diabetes retinopathy(DR)plays an important role in preventing irreversible blindness.Existing research has failed to fully explore effective DR lesion information in fundus maps.Besides,traditional attention schemes have not considered the impact of lesion type differences on grading,resulting in unreasonable extraction of important lesion features.Therefore,this paper proposes a DR diagnosis scheme that integrates a multi-level patch attention generator(MPAG)and a lesion localization module(LLM).Firstly,MPAGis used to predict patches of different sizes and generate a weighted attention map based on the prediction score and the types of lesions contained in the patches,fully considering the impact of lesion type differences on grading,solving the problem that the attention maps of lesions cannot be further refined and then adapted to the final DR diagnosis task.Secondly,the LLM generates a global attention map based on localization.Finally,the weighted attention map and global attention map are weighted with the fundus map to fully explore effective DR lesion information and increase the attention of the classification network to lesion details.This paper demonstrates the effectiveness of the proposed method through extensive experiments on the public DDR dataset,obtaining an accuracy of 0.8064.

Mechanistic investigation on Ag-Cu_(2)O in electrocatalytic CO_(2) to CH_(4) by in situ/operando spectroscopic and theoretical analysis

Silver-copper electrocatalysts have demonstrated effectively catalytic performance in electroreduction CO_(2) toward CH_(4),yet a revealing insight into the reaction pathway and mechanism has remained elusive.Herein,we construct chemically bonded Ag-Cu_(2)O boundaries,in which the complete reduction of Cu_(2)O to Cu has been strongly impeded owing to the presence of surface Ag shell.The interfacial confinement effect helps to maintain Cu^(+)sites at the Ag-Cu_(2)O boundaries.Using in situ/operando spectroscopy and theoretical simulations,it is revealed that CO_(2) is enriched at the Ag-Cu_(2)O boundaries due to the enhanced physisorption and chemisorption to CO_(2),activating CO_(2) to form the stable intermediate^(*)CO.The boundaries between Ag shell and the Cu_(2)O mediate local^(*)CO coverage and promote^(*)CHO intermediate formation,consequently facilitating CO_(2)-to-CH_(4) conversion.This work not only reveals the structure-activity relationships but also offers insights into the reaction mechanism on Ag-Cu catalysts for efficient electrocatalytic CO_(2) reduction.

Construction of a Computational Scheme for the Fuzzy HIV/AIDS Epidemic Model with a Nonlinear Saturated Incidence Rate

This work aimed to construct an epidemic model with fuzzy parameters.Since the classical epidemic model doesnot elaborate on the successful interaction of susceptible and infective people,the constructed fuzzy epidemicmodel discusses the more detailed versions of the interactions between infective and susceptible people.Thenext-generation matrix approach is employed to find the reproduction number of a deterministic model.Thesensitivity analysis and local stability analysis of the systemare also provided.For solving the fuzzy epidemic model,a numerical scheme is constructed which consists of three time levels.The numerical scheme has an advantage overthe existing forward Euler scheme for determining the conditions of getting the positive solution.The establishedscheme also has an advantage over existing non-standard finite difference methods in terms of order of accuracy.The stability of the scheme for the considered fuzzy model is also provided.From the plotted results,it can beobserved that susceptible people decay by rising interaction parameters.

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.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

Cooperative Anti-Jamming and Interference Mitigation for UAV Networks: A Local Altruistic Game Approach

To improve the anti-jamming and interference mitigation ability of the UAV-aided communication systems, this paper investigates the channel selection optimization problem in face of both internal mutual interference and external malicious jamming. A cooperative anti-jamming and interference mitigation method based on local altruistic is proposed to optimize UAVs’ channel selection. Specifically, a Stackelberg game is modeled to formulate the confrontation relationship between UAVs and the jammer. A local altruistic game is modeled with each UAV considering the utilities of both itself and other UAVs. A distributed cooperative anti-jamming and interference mitigation algorithm is proposed to obtain the Stackelberg equilibrium. Finally, the convergence of the proposed algorithm and the impact of the transmission power on the system loss value are analyzed, and the anti-jamming performance of the proposed algorithm can be improved by around 64% compared with the existing algorithms.

Monitoring seismicity in the southern Sichuan Basin using a machine learning workflow

Monitoring seismicity in real time provides significant benefits for timely earthquake warning and analyses.In this study,we propose an automatic workflow based on machine learning(ML)to monitor seismicity in the southern Sichuan Basin of China.This workflow includes coherent event detection,phase picking,and earthquake location using three-component data from a seismic network.By combining Phase Net,we develop an ML-based earthquake location model called Phase Loc,to conduct real-time monitoring of the local seismicity.The approach allows us to use synthetic samples covering the entire study area to train Phase Loc,addressing the problems of insufficient data samples,imbalanced data distribution,and unreliable labels when training with observed data.We apply the trained model to observed data recorded in the southern Sichuan Basin,China,between September 2018 and March 2019.The results show that the average differences in latitude,longitude,and depth are 5.7 km,6.1 km,and 2 km,respectively,compared to the reference catalog.Phase Loc combines all available phase information to make fast and reliable predictions,even if only a few phases are detected and picked.The proposed workflow may help real-time seismic monitoring in other regions as well.