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.

Humanβ-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long noncoding RNA TCONS_00014506

BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

Human pluripotent stem cell-derived kidney organoids:Current progress and challenges

Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

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.

Coupling Analysis of Multiple Machine Learning Models for Human Activity Recognition

Artificial intelligence(AI)technology has become integral in the realm of medicine and healthcare,particularly in human activity recognition(HAR)applications such as fitness and rehabilitation tracking.This study introduces a robust coupling analysis framework that integrates four AI-enabled models,combining both machine learning(ML)and deep learning(DL)approaches to evaluate their effectiveness in HAR.The analytical dataset comprises 561 features sourced from the UCI-HAR database,forming the foundation for training the models.Additionally,the MHEALTH database is employed to replicate the modeling process for comparative purposes,while inclusion of the WISDM database,renowned for its challenging features,supports the framework’s resilience and adaptability.The ML-based models employ the methodologies including adaptive neuro-fuzzy inference system(ANFIS),support vector machine(SVM),and random forest(RF),for data training.In contrast,a DL-based model utilizes one-dimensional convolution neural network(1dCNN)to automate feature extraction.Furthermore,the recursive feature elimination(RFE)algorithm,which drives an ML-based estimator to eliminate low-participation features,helps identify the optimal features for enhancing model performance.The best accuracies of the ANFIS,SVM,RF,and 1dCNN models with meticulous featuring process achieve around 90%,96%,91%,and 93%,respectively.Comparative analysis using the MHEALTH dataset showcases the 1dCNN model’s remarkable perfect accuracy(100%),while the RF,SVM,and ANFIS models equipped with selected features achieve accuracies of 99.8%,99.7%,and 96.5%,respectively.Finally,when applied to the WISDM dataset,the DL-based and ML-based models attain accuracies of 91.4%and 87.3%,respectively,aligning with prior research findings.In conclusion,the proposed framework yields HAR models with commendable performance metrics,exhibiting its suitability for integration into the healthcare services system through AI-driven applications.

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.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHWISSN:2213-4530,CN10-1750/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.

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.

Mother-to-Child Transmission of Human Papillomavirus in Burkina Faso

Introduction: Human papillomavirus (HPV) infection is the most widespread sexually transmitted infection in the world. Today, there is growing evidence that HPV can be transmitted early in life, and one potential route is mother-to-child transmission. Data on this route of HPV transmission are scarce in Africa and particularly in Burkina Faso, where no data on the subject are yet available. The aim of our study was to estimate the rate of mother-to-child transmission of HPV infection and to identify circulating genotypes. Methodology: Cervico-uterine samples were collected from 100 full-term pregnant women and, buccal samples were obtained from their newborns at Hopital Saint Camille de Ouagadougou (HOSCO) by the specialist physician. HPV DNA amplification and genotyping were performed by PCR followed by hybridization using the HPV Direct Flow Chips kit, detecting 36 genotypes including 18 high-risk and 18 low-risk. Results: The prevalence of HPV in newborns was 8% (8/100). Six (6) HPV-positive neonates had HPV-positive mothers, while 2 HPV-positive neonates had HPV-negative mothers. The vertical transmission rate was 26.09% (6/23). Mother-newborn genotypes were concordant. However, the genotype profile of the newborns was more restricted than that of the mothers. Conclusion: HPV DNA was found in 8% of newborns in our study. The genotype profile of the mother-newborn pair was concordant. Asymptomatic HPV infection in a pregnant woman could constitute a risk factor for vertical transmission.

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 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 multdisci-plinary subjets 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.Papers regarding components of food especially nutrients and non-nutrient bioactive compounds(with putative health benefits)are welcomed.FSHW aims to unveil the correlations between food science and human health through the dissemination of both fundamental and applied research outcomes worldwide.

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,CN10-1750/TS)publishesoriginal research papers demonstrating the latest advancement of multidisciplinary subjects related to food science and human health.Topies may include but not limited to:nutriology,biochemistry,microbiology,immunology and toxicology.