The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug development.However,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted therapies.Furthermore,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

Commentary on"Speed and surface steepness affect internal tibial loading during running"

It is a pleasure to write a commentary on the work of Dr.Hannah Rice and colleagues,l who have advanced our understanding of how the mechanical loading environment of the tibia changes as a function of running grade and speed.It is important that we understand how the tibia is loaded during conditions that an individual is likely to encounter when running as it is these internal loads which we believe are responsible for the development of bone-stress injuries.

Germline Gene-Editing Creates Enhanced Livestock-Technical and Especially Ethical Issues Challenge Its Use in Humans

Using clustered regularly interspaced short palindromic repeats(CRISPR)-based molecular tools,scientists are engineering-as they are also doing with plants.-animals with advantageous traits,like disease resistance and improved food yield.While these innovative techniques could one day be applied in humans,technical hurdles and ethical concerns likely place this possibility far in the future,The enhancements rely on germline gene editing,which alters the genes in a way that passes the changes on to offspring.Ger m-line gene editing differs from the somatic cell gene editing used in the highly promising new treatment recently approved for the human disease sickle cell anemia.

Understanding intrarenal backflow: Intrarenal pressure during ureteroscopy and beyond

The number of ureterorenoscopic procedures for upper urinary tract stone management has increased dramatically during recent years worldwide[1].Developments in flexible ureteroscope and laser technology have made it possible to successfully address larger and more complex stone scenarios retrogradely.On the other hand,this means that more and more patients are exposed to the potential adverse effects of ureteroscopy[2].In general,ureteroscopy is considered a safe procedure.However,serious complications and even deaths do occur,and these events are most likely underreported[3,4].

Developments in the U.S.Republican Party Since the 2020 Election

On November 8,2023,the Republican Party of the United States hosted its third televised debate for the presidential nomination primary in Miami,Florida.Former President Donald Trump,though absent once again,still maintains a lead in all polls and is even considered highly likely to win the Republican nomination for the third time,to fight Biden again and compete for the White House throne.In fact,over the three years since Trump left office,and Biden came to power,the Republican Party did not get rid of the influence of the political philosophy represented by Trump,and the party’s political ecology and policy agenda inevitably by Trump’s personal influence,presenting a subtle and complex political phenomenon as Trump has never left.

Embracing the Year of the Dragon

The Lunar New Year has increasingly become a common festival of people throughout the world.CHINESE people,and people throughout the world,are looking forward to welcoming the Year of the Dragon,which falls on February 10,2024.The Dragon is considered the most auspicious of the 12 signs in the Chinese zodiac and this year is specifically the Year of the Wood Dragon,the first since 1964.According to Lifestyle Asia,“Wood Dragons enjoy fulfilling careers.They’re likely to materialize all their ambitions into actions,coming up with truly revolutionary ideas.”

马尔代夫泛在化教育的演变:实践、挑战和问题

Learning and teaching have been undergoing transformational changes in the past 100 years,each change promising a richer and more meaningful interaction of learners and instructors. Beginning from the limitations of correspondence courses and distance education, remote learning has trended through computerassisted instruction(CAI), e-learning, m-learning, and now ubiquitous or u-learning. Some forms of this type of education have been renamed or repackaged in multiple forms of instruction including hybrid and flexible learning. More recently, u-learning or ubiquitous learning has been gaining currency and approbation.This article outlines the development of education other than face-to-face learning and teaching in the context of the Maldives to disentangle its practices, challenges, and issues. Some of these issues are likely to impact u-learning and its descendent and off-shoot modes.

Leggings: The new fashion staple

Leggings have been a staple in the fashion industry for decades,consistently remaining one of the most popular and versatile items of clothing.They have achieved viral status and continue to be a highly sought-after fashion item,transcending age and cultural barriers.The body-hugging style of leggings has remained in vogue,attracting young people of all ages and backgrounds.With their enduring popularity,it’s likely that leggings will remain a fashion staple for years to come.

Ligand Based Virtual Screening of Molecular Compounds in Drug Discovery Using GCAN Fingerprint and Ensemble Machine Learning Algorithm

The drug development process takes a long time since it requires sorting through a large number of inactive compounds from a large collection of compounds chosen for study and choosing just the most pertinent compounds that can bind to a disease protein.The use of virtual screening in pharmaceutical research is growing in popularity.During the early phases of medication research and development,it is crucial.Chemical compound searches are nowmore narrowly targeted.Because the databases containmore andmore ligands,thismethod needs to be quick and exact.Neural network fingerprints were created more effectively than the well-known Extended Connectivity Fingerprint(ECFP).Only the largest sub-graph is taken into consideration to learn the representation,despite the fact that the conventional graph network generates a better-encoded fingerprint.When using the average or maximum pooling layer,it also contains unrelated data.This article suggested the Graph Convolutional Attention Network(GCAN),a graph neural network with an attention mechanism,to address these problems.Additionally,it makes the nodes or sub-graphs that are used to create the molecular fingerprint more significant.The generated fingerprint is used to classify drugs using ensemble learning.As base classifiers,ensemble stacking is applied to Support Vector Machines(SVM),Random Forest,Nave Bayes,Decision Trees,AdaBoost,and Gradient Boosting.When compared to existing models,the proposed GCAN fingerprint with an ensemble model achieves relatively high accuracy,sensitivity,specificity,and area under the curve.Additionally,it is revealed that our ensemble learning with generated molecular fingerprint yields 91%accuracy,outperforming earlier approaches.

Unfamiliar waveforms spanning from the ST to TP segments only observed in certain limb leads of the standard 12-lead electrocardiogram due to Aslanger’ s sign

Aslanger’s sign,also known as the arterial pulse tapping artifact or electromechanical association artifact,is an electrocardiographic artifact caused by arterial pulsation at the site where the limb leads of the standard 12-lead electrocardiogram near the radial or posterior tibial arteries are positioned,particularly in hyperdynamic states.[1–8]It occurs in every cardiac cycle with a constant coupling interval between the QRS complex and artifact.This synchronization with the underlying heart rhythm makes it less likely to be recognized as an artifact compared to unsynchronized artifacts,such as those caused by limb movement and inadequate contact between the electrode and skin.[1,2,7,8]Almost all reported cases of Aslanger’s sign exhibit an unusual waveform morphology in all 12 leads except one of the standard 12-lead electrocardiogram.This sign is often confused with an electrocardiographic finding commonly observed during acute coronary events.

Large-Scale Energy Storage for Carbon Neutrality

The shift toward a dual-carbon strategy is expected to instigate extensive and profound changes across virtually all economic sectors and aspects of national life in China.The transformation and upgrading of energy systems and related infrastructure are particularly noteworthy.The future of energy supply will likely be dominated by renewable generation.One of the most significant challenges in this future landscape is the fluctuation and variability of wind and solar power,which often lead to a substantial amount of curtailed wind,solar,and hydropower.Such curtailment has shown an increasing trend,becoming a major obstacle to the swift deployment of renewable power generation.This challenge must be addressed to ensure the successful implementation of the dual-carbon strategy and the dominance of renewable energy in the future.

Farmers Reap Right to Repair Agricultural Equipment

A farmer is ready to harvest the winter wheat crop when his combine harvester breaks down.Even if the problem would be relatively simple to remedy,the farmer probably cannot make the repair himself or get help from an independent shop because manufacturers have restricted access to the tools,documentation,and other requirements for fixing their equipment[1].Instead,the farmer will likely have to turn to one of the manufacturer’s dealers,which could mean waiting days or even weeks for a service call from a company technician[2].In the meantime,the farmer’s crop sits unharvested,vulnerable to damage or destruction by bad weather[2].

Fate and toxicity of nanoparticles in aquatic systems

Nanotechnology is a ground-breaking multidisciplinary fi eld across a broad spectrum of basic and applied sciences for producing and applying nano-sized materials for innovative solutions.The use of nanomaterials in industrial applications,medical products,and consumers has increased repeatedly over the last few years,and these applications will likely continue to grow.In an aquatic ecosystem,nanoparticles take entry through a direct route that includes industrial discharge,disposal of wastewater treatment e ffl uents,and indirect runof f from the soil.After reaching the aquatic environment,the nanomaterials are highly af fected by their backdrops and subsequently go through various conversions like agglomeration,aggregation,dissolution,sulfi dation,etc.The fate and the behavior of nanomaterials in the aquatic system not only depend on their physical-chemical properties but also on the pH,temperature,salinity,water hardness,and concentration of natural organic matter present in receiving water.In this review,emphasis has been given to the toxicological properties and potential risks of nanomaterials in terms of factors contributing to their toxicology,bioavailability,and accumulation in aquatic organisms as well as the environment.Furthermore,we summarize the published data on engineered nanoparticles’ef fect on aquatic organisms.The issues related to the accumulation and penetration of nanoparticles in the aquatic organism,their toxic ef fect,and biotransformation along with the food web are also discussed.Since nanomaterials are being increasingly released into aquatic bodies,it is important to pay greater attention to their toxicity and how it af fects the aquatic ecosystem.The nanomaterials are bioavailable to plants,resulting in trophic transfer,and they impact other organisms through biomagnifi cation,as discussed in this review.To close the enormous information gap,extensive research on the interactions and impacts of NPs on dif ferent species belonging to dif ferent trophic levels of the aquatic environment and the destiny of NPs along the food chain of the ecosystem is urgently needed.

The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies

Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.

Editorial:Driving into Future with Reliable,Secure,Efficient and Intelligent MetaVehicles

Welcome to the sixth issue of the IEEE/CAA Journal of Automatica Sinica(JAS)in 2023!In the first issue in 2023,I briefly discussed about MetaVehicles,a technological expression of intelligent vehicles,robotics,AI,blockchain,knowledge automation,networking and communication[1].As the concept of the Metaverse continues to evolve and expand,the range of vehicle entities is diversely enlarged,including passenger vehicles,heavy duty vehicles,rail vehicles,marine vehicles,aerial vehicles,and other types of transportation.The development and use of MetaVehicles are likely to become more sophisticated.Therefore,from a systems and control perspective,new methods of control,estimation and optimization should be developed to achieve the improved vehicular control system stability and reliability in the physical space.

Genetic diversity, population structure, and genome-wide association analysis of ginkgo cultivars

Ginkgo biloba is an economically valuable tree worldwide.The species has nearly become extinct during the Quaternary,which has likely resulted in reduction of its genetic variability.The genetic variability is now conserved in few natural populations in China and a number of cultivars that are,however,derived from a few ancient trees,helping the species survive in China through medieval times.Despite the recent interest in ginkgo,however,detailed knowledge of its genetic diversity,conserved in cultivated trees and cultivars,has remained poor.This limits efficient conservation of its diversity as well as efficient use of the existing germplasm resources.Here we performed genotyping-by-sequencing(GBS)on 102 cultivated germplasms of ginkgo collected to explore their genetic structure,kinship,and inbreeding prediction.For the first time in ginkgo,a genome-wide association analysis study(GWAS)was used to attempt gene mapping of seed traits.The results showed that most of the germplasms did not show any obvious genetic relationship.The size of the ginkgo germplasm population expanded significantly around 1500 years ago during the Sui and Tang dynasties.Classification of seed cultivars based on a phylogenetic perspective does not support the current classification criteria based on phenotype.Twenty-four candidate genes were localized after performing GWAS on the seed traits.Overall,this study reveals the genetic basis of ginkgo seed traits and provides insights into its cultivation history.These findings will facilitate the conservation and utilization of the domesticated germplasms of this living fossil plant.

Raman spectroscopy in crop quality assessment: focusing on sensing secondary metabolites: a review

As a crop quality sensor,Raman spectroscopy has been consistently proposed as one of the most promising and non-destructive methods for qualitative and quantitative analysis of plant substances,because it can measure molecular structures in a short time without requiring pretreatment along with simple usage.The sensitivity of the Raman spectrum to target chemicals depends largely on the wavelength,intensity of the laser power,and exposure time.Especially for plant samples,it is very likely that the peak of the target material is covered by strong fluorescence effects.Therefore,methods using lasers with low energy causing less fluorescence,such as 785 nm or near-infrared,are vigorously discussed.Furthermore,advanced techniques for obtaining more sensitive and clear spectra,like surface-enhanced Raman spectroscopy,time-gated Raman spectroscopy or combination with thin-layer chromatography,are being investigated.Numerous interpretations of plant quality can be represented not only by the measurement conditions but also by the spectral analysis methods.Up to date,there have been attempted to optimize and generalize analysis methods.This review summarizes the state of the art of micro-Raman spectroscopy in crop quality assessment focusing on secondary metabolites,from in vitro to in vivo and even in situ,and suggests future research to achieve universal application.

Conjunctival cyst with apocrine hidrocystoma-like features:a case report

Dear Editor,I am Takafumi Igarashi from Hokkaido University Hospital,Japan.Apocrine hidrocystoma is a benign cystic tumor arising in the apocrine sweat glands proposed by Mehregan^([1])in 1964.It is likely that apocrine hidrocystoma arises in the uvula,ears,chest,and shoulders,as well as the (peri)ocular regions such as the eyelid,and sclera^([2-4]).

The Effect of Self-Investment on Hoarding Tendency of Chinese College Students:Role of Psychological Connections

Because of factors such as energy and time one invests in an object,the stronger the connection,value,and reluc-tance to lose said object individual will have.Hoarding behavior arises when individuals incorporate a strong attachment with themselves to an object.The purpose of this study is to examine the effect of self-investment on hoarding tendency and the roles of possession-self link and liking level in this connection.A hypothetical model of the relationship between self-investment,possession-self link,liking level,and hoarding tendency was tested.A convenience sampling method was used to survey 450 college students in Yunnan Province on either a paper-based or online self-report scale.The data were collected using self-investment,possession-self link,and liking level questionnaires,as well as the Saving Inventory Revised.Results showed positive relationship between the study variables,ranging from 0.37 to 0.87.College students’self-investment had a direct positive pre-dictive effect on hoarding tendency;self-investment,in turn,indirectly predicted hoarding tendency through the mediating effect of possession-self link;and individual liking level of items had a moderating effect for self-invest-ment on the possession-self link.This study shows how self-investment affects the hoarding tendency of college students,and the results of this study also help demonstrate the value of self-investment and possession-self link in optimizing students’hoarding tendency and thus promoting good psychological status.

Cerebrotendinous xanthomatosis presenting with schizophrenia-like disorder:A case report

BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a rare autosomal recessive lipid-storage disorder caused by mutations in CYP27A1.Psychiatric manifestations in CTX are rare and nonspecific,and they often lead to considerable diagnostic and treatment delay.CASE SUMMARY A 33-year-old female patient admitted to the psychiatric ward for presentation of delusions,hallucinations,and behavioral disturbance is reported.The patient presented with cholestasis,cataract,Achilles tendon xanthoma,and cerebellar signs in adulthood and with intellectual disability and learning difficulties in childhood.After the characteristic CTX findings on imaging were obtained,a pathological examination of the Achilles tendon xanthoma was refined.Replacement therapy was then initiated after the diagnosis was clarified by genetic analysis.During hospitalization in the psychiatric ward,the nonspecific psychiatric manifestations of the patient posed difficulty in diagnosis.After the patient’s history of CTX was identified,the patient was diagnosed with organic schizophrenia-like disorder,and psychotic symptoms were controlled by replacement therapy combined with antipsychotic medication.CONCLUSION Psychiatrists should be aware of CTX,its psychiatric manifestations,and clinical features and avoid misdiagnosis of CTX for timely intervention.