Humanization for neurological disease modeling:A roadmap to increase the potential of Drosophila model systems

Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurological and behavioral investiga-tions.However,non-vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies.One reason for this situ-ation is the predominance of gene overexpression(and gene loss-of-function)meth-odologies used when establishing a Drosophila model of a given neurological disease,a strategy that does not recapitulate accurately enough the genetic disease condi-tions.I argue here the need for a systematic humanization approach,whereby the Drosophila orthologs of human disease genes are replaced with the human sequences.This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly.I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application,and consider its importance for subsequent disease modeling and drug discovery in Drosophila.I argue that this paradigm will not only advance our un-derstanding of the molecular etiology of a number of neurological disorders,but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.

Industrial Dehumanization——Viewed from the husband and wife relationship in "Odour of Chrysanthemums"

Lawrence is regarded as one of most accomplished short story writers in twentieth century,with "Odour of Chrysanthemums" one of his early works.Through the death of a miner,the text shows how humanity was ruined by industrial civilization.This essay is intended to unveil the destructive force by analyzing the relationship between the husband and wife.

Challenges of the dialog between humanization of health and medicine for the assistance to woman health in the Brazilian scenario

The present article aims to present, by a bibliographic review, the current challenges of the dialog among fundamental issues referring to humanization as for current public policy in Brazilian scenario. The first one concerns with national health humanization policies and ultimately the humanization of the assistance to the woman’s health, especially at delivery and child birth. Using the hermeneutic dialectic as methodology, it’s understood that having these three facets, dialog consists not only of a great challenge but also of a condition on being put into practice, and expected issues become an effective reality.

Successful Digital Transformation and HRM Humanization

This paper investigates a core role of Human Resource Management(HRM)humanization for successful digital transformation in digital economy.The term“humanization”is applied to an iterative method of human relation development for human resources satisfaction and high results of organizational performance.The author summarized the peculiarities of digitalization in Russian companies in the context of the Russian labor market trends.The paper focuses on factors that determine human potential utilization and development in modern condition.The author grounded linkage between HRM humanization and digital transformation projects effect by three examples of Russian companies.The results let us conclude importance of HRM humanization and define core problems and directions in Russian context.

Humanization in Educational Environments;Aspects Necessary for Living in School Today

While it is true,quality has always been measured through statistics and percentages,often forgetting the training of the whole person.Now,when we talk about issues such as humanism and education supported by technology,we can fall into extremes:it is common to label technology as the provider of all the evils of today’s civilization;or the opposite assumption;to argue that incorporating technologies into education would be the panacea for all the problems it faces and finally,to assume that the subject of the humanities is more typical of actions and attitudes of the past than as a current need,giving vitality to any educational process.However,and fortunately for the educational community,today there are global efforts to make the educational task a human action that minimizes inequities and the abysmal differences that exist in countries like ours.Fernando Reimers says:“Equal educational opportunities must be the priority objective of educational policies,the aim of education must be to contribute to creating just societies”.This requires improving the learning environments of the poor,but not only along the paths that have been started over the last decade.This aspect pointed out by Reimers is precisely the central aspect that all educational action must contemplate;the educational policies that are implemented in our country must guarantee,above all,the construction of a just and egalitarian society,strengthening the cultural wealth that we have,with respect to the diversity of people,their past,their present and especially their future.

基于GRU-DRSN的双通道人体活动识别

人体活动识别(human activity recognizition, HAR)在医疗、军工、智能家居等领域有很大的应用空间。传统机器学习方法特征提取难度较大且精度不高。针对上述问题并结合传感器时序特性,提出了一种融合CBAM(convolutional block attention module)注意力机制的GRU-DRSN双通道并行模型,有效避免了传统串行模型因网络深度加深引起梯度爆炸和消失问题。同时并行结构使得两条支路具有相同的优先级,使用深度残差收缩网络(deep residual shrinkage network, DRSN)提取数据的深层空间特征,同时使用门控循环结构(gated recurrent unit, GRU)学习活动样本在时间序列上的特征,同时进行提取样本不同维度的特征,并通过CBAM模块进行特征的权重分配,最后通过Softmax层进行识别,实现了端对端的人体活动识别。使用公开数据集(wireless sensor data mining, WISDM)进行验证,模型平均精度达到了97.6%,与传统机器学习模型和前人所提神经网络模型相比,有更好的识别效果。

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

From Digital Human Modeling to Human Digital Twin: Framework and Perspectives in Human Factors

The human digital twin(HDT)emerges as a promising human-centric technology in Industry 5.0,but challenges remain in human modeling and simulation.Digital human modeling(DHM)provides solutions for modeling and simulating human physical and cognitive aspects to support ergonomic analysis.However,it has limitations in real-time data usage,personalized services,and timely interaction.The emerging HDT concept offers new possibilities by integrating multi-source data and artificial intelligence for continuous monitoring and assessment.Hence,this paper reviews the evolution from DHM to HDT and proposes a unified HDT framework from a human factors perspective.The framework comprises the physical twin,the virtual twin,and the linkage between these two.The virtual twin integrates human modeling and AI engines to enable model-data-hybrid-enabled simulation.HDT can potentially upgrade traditional ergonomic methods to intelligent services through real-time analysis,timely feedback,and bidirectional interactions.Finally,the future perspectives of HDT for industrial applications as well as technical and social challenges are discussed.In general,this study outlines a human factors perspective on HDT for the first time,which is useful for cross-disciplinary research and human factors innovation to enhance the development of HDT in industry.

Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

Integrins and their potential roles in mammalian pregnancy

Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes.

The relationship between DNA fragmentation and the intensity of morphologically abnormal human spermatozoa

Objective:To determine the relationship between teratozoospermia and sperm DNA fragmentation(SDF)in the human ejaculate.Methods:This retrospective study included 100 normozoospermic men as a control cohort(abnormal forms>14%),210 patients with a high level of abnormal forms(≤4%)and 65 patients presenting with a moderate level of abnormal forms(>4%to≤14%)based on the World Health Organization definitions.Sperm morphology was assessed using bright field microscopy.Sperm DNA fragmentation was assessed using the sperm chromatin dispersion assay.Non-parametric analyses were conducted to examine the relationship between abnormal sperm morphology and sperm DNA fragmentation;receiver operating characteristic(ROC)analyses were conducted to assess sensitivity and specificity of this relationship.Results:A correlation analysis revealed that the higher the proportion of abnormal spermatozoa in the ejaculate,the higher the level of SDF(Spearman's Rho=-0.230;P<0.001).Significant differences in the proportion of SDF were found when all cohorts were compared(P<0.001);these significant differences were also retained when the different cohorts were compared pairwise.ROC analysis showed a moderate but significant predictive value for SDF to differentiate patients with different levels of teratozoospemia.Conclusions:Although analysis of a more continuous range of values for teratozoospermia would help further clarify any causal relationship with SDF,there is clearly a synergistic or coincident affiliation between these variables that needs to be acknowledged by the clinician when interpreting the spermiogram.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of mutidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original Tesearch papers demonstrating the latest advancement of mutidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original researchpapers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.Papers regarding components of food especiallynutrients and non-nutrient bioactive compounds(withputative health benefits)are welcomed.FSHW aims tounveil the correlations between food science and humanhealth through the dissemination of both fundamentaland applied researchoutcomesworldwide.

Assessment of runoff changes in the sub-basin of the upper reaches of the Yangtze River basin, China based on multiple methods

Quantitative assessment of the impact of climate variability and human activities on runoff plays a pivotal role in water resource management and maintaining ecosystem integrity.This study considered six sub-basins in the upper reaches of the Yangtze River basin,China,to reveal the trend of the runoff evolution and clarify the driving factors of the changes during 1956–2020.Linear regression,Mann-Kendall test,and sliding t-test were used to study the trend of the hydrometeorological elements,while cumulative distance level and ordered clustering methods were applied to identify mutation points.The contributions of climate change and human disturbance to runoff changes were quantitatively assessed using three methods,i.e.,the rainfall-runoff relationship method,slope variation method,and variable infiltration capacity(Budyko)hypothesis method.Then,the availability and stability of the three methods were compared.The results showed that the runoff in the upper reaches of the Yangtze River basin exhibited a decreasing trend from 1956 to 2020,with an abrupt change in 1985.For attribution analysis,the runoff series could be divided into two phases,i.e.,1961–1985(baseline period)and 1986–2020(changing period);and it was found that the rainfall-runoff relationship method with precipitation as the representative of climate factors had limited usability compared with the other two methods,while the slope variation and Budyko hypothesis methods had highly consistent results.Different factors showed different effects in the sub-basins of the upper reaches of the Yangtze River basin.Moreover,human disturbance was the main factor that contributed to the runoff changes,accounting for 53.0%–82.0%;and the contribution of climate factors to the runoff change was 17.0%–47.0%,making it the secondary factor,in which precipitation was the most representative climate factor.These results provide insights into how climate and anthropogenic changes synergistically influence the runoff of the upper reaches of the Yangtze River basin.

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

Atmospheric Particulate Matter 2.5(PM_(2.5))Induces Cell Damage and Pruritus in Human Skin

With the accelerated rate of urbanization in recent years,air pollution has become an environmental problem that requires urgent resolution,almost all of the world’s population exposed to pollution on a daily basis.Among the various air pollutants,the excessive dispersion and suspension of particulate matter(PM)in the air.

Core–Shell Microfiber Encapsulation Enables Glycerol‑Free Cryopreservation of RBCs with High Hematocrit

Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in emergencies.High concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinical practice,which results in cytotoxicity and osmotic injuries that must be carefully controlled.However,existing studies on the low-glycerol cryopreservation of RBCs still suffer from the bottleneck of low hematocrit levels,which require relatively large storage space and an extra concentration process before transfusion,making it inconvenient(time-consuming,and also may cause injury and sample lose)for clinical applications.To this end,we develop a novel method for the glycerol-free cryopreservation of human RBCs with a high final hematocrit by using trehalose as the sole cryoprotectant to dehydrate RBCs and using core–shell alginate hydrogel microfibers to enhance heat transfer during cryopreservation.Different from previous studies,we achieve the cryopreservation of human RBCs at high hematocrit(>40%)with high recovery(up to 95%).Additionally,the washed RBCs post-cryopreserved are proved to maintain their morphology,mechanics,and functional properties.This may provide a nontoxic,high-efficiency,and glycerol-free approach for RBC cryopreservation,along with potential clinical transfusion benefits.