Synchronization and firing mode transition of two neurons in a bilateral auditory system driven by a high–low frequency signal

The FitzHugh–Nagumo neuron circuit integrates a piezoelectric ceramic to form a piezoelectric sensing neuron,which can capture external sound signals and simulate the auditory neuron system.Two piezoelectric sensing neurons are coupled by a parallel circuit consisting of a Josephson junction and a linear resistor,and a binaural auditory system is established.Considering the non-singleness of external sound sources,the high–low frequency signal is used as the input signal to study the firing mode transition and synchronization of this system.It is found that the angular frequency of the high–low frequency signal is a key factor in determining whether the dynamic behaviors of two coupled neurons are synchronous.When they are in synchronization at a specific angular frequency,the changes in physical parameters of the input signal and the coupling strength between them will not destroy their synchronization.In addition,the firing mode of two coupled auditory neurons in synchronization is affected by the characteristic parameters of the high–low frequency signal rather than the coupling strength.The asynchronous dynamic behavior and variations in firing modes will harm the auditory system.These findings could help determine the causes of hearing loss and devise functional assistive devices for patients.

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.

Impact of Plastic Waste on the Human Health in Low-Income Countries: A Systematic Review

Background: Plastic pollution is the accumulation of waste composed of plastic and its derivatives all over the environment. Whether in the form of visible garbage or microparticles, as it slowly degrades, plastic pollution poses significant threats to terrestrial and aquatic habitats and the wildlife that call them home, whether through ingestion, entanglement or exposure to the chemicals contained in the material. Unfortunately, there is a lack of documentation on the impact of plastic waste on human health in low- and middle-income countries (LMICs). Methods: We searched five electronic databases (PubMed, Embase, Global Health, CINAHL and Web of Science) and gray literature, following the preferred reporting elements for systematic reviews and meta-analyses (PRISMA), for the impact of plastic waste on human health in developing countries. We included quantitative and qualitative studies written in English and French. We assessed the quality of the included articles using the Mixed Methods Appraisal tool (MMAT). Results: A total of 3779 articles were initially identified by searching electronic databases. After eliminating duplicates, 3167 articles were reviewed based on title and abstract, and 26 were selected for full-text review. Only three articles were retained. The three articles dealt with practices likely to lead to oral exposure to plastic chemicals in human health, as well as the level of awareness of participants concerning the possible impact of plastic on human health, namely, the use of plastic baby bottles, the use of microwaves to cook food and reheat precooked food, the use of plastic bottles to store water in the refrigerator, water purifier containers with plastic bodies and plastic lunch boxes, the reuse of plastic bags and the inadequacy of treatment facilities. Conclusion: Plastic waste poses different risks to human health at every stage of its life cycle. Hence, strategies must be adopted to raise public awareness of the dangers of plastic waste to their health. Trial registration: The review protocol is registered in the PROSPERO international prospective register of systematic reviews (ID = CRD42023409087).

Ethics of Human Resources Management in the Cameroonian Health System, Medical Nomadism and the Ineffectiveness of the Fight against High Blood Pressure

Context/objectives: The fight against Chronic Non-Communicable Diseases (NCDs) is a long-term undertaking, which requires available, motivated and well-managed human resources (HR). The administrative management of skills on both qualitative and quantitative levels is one of the essential functions of a health system. To better implement policies of fight against High Blood Pressure (HBP) and other chronic diseases, it is important to establish strategies to retain health personnel. This loyalty requires favorable working conditions and consideration of the contribution-reward couple. Good working conditions are likely to reduce the phenomenon of medical nomadism;conversely, poor HR management can contribute to their exodus towards exotic “green pastures”, thus leading to an additional crisis in the Cameroonian health system. The fight against HBP is a complex, multifaceted and multifactorial reality that requires appropriate management model for all types of resources mainly HR. The main objective of this research is to show the impact of poor management of human resources in Cameroon health system on medical nomadism and the ineffectiveness of the fight against High Blood Pressure. Method: A cross-sectional descriptive survey among five hundred (500) health facilities in the center region of Cameroon has been conducted. A stratified probabilistic technique has been used, and the number of health facilities to be surveyed has been determined using the “sample size estimation table” of Depelteau. The physical questionnaires have been printed and then distributed to data collectors. After data collection, the latter were grouped during processing in Excel sheets. The Chi-square test was used for data with a qualitative value and that of Kolmogorov-Sminorf for data with a quantitative value to assess the normality and reliability of data. The Crochach’s Alpha reliability test allowed us to have a summary of the means and variances and then to search for intragroup correlations between variables. Descriptive analysis was possible with the XLSTAT 2016 software. Results: 43.60% of Health Facilities (HF) managers were unqualified. 82.20% of HF managers have staff in a situation of professional insecurity. They are mainly contractual (49.00), decision-making agents (24.40%), casual agents (08.80). The proportion of unstable personnel is average of 22.00% and very unstable, 12.00%.

Digital Human Rights from the Perspective of System Theory——Concept Definition, Social Function, and Constitutional Basis

The three core issues in the“digital human rights”debate are whether“digital human rights”are possible,necessary,and feasible.Both sides of the debate focus on discovering the value of“digital human rights”to individuals from a semantic level,but ignore the significance of“digital human rights”to the whole society and its subsystems at the level of social structure.By introducing Niklas Luhmann's System Theory,this observation blind spot can be eliminated.Fundamental rights are devoted to directly shaping not a physiological-psychological“individual”as a social environment but a social“person”that can be included by social systems.It is clear that digital human rights are the right to participate in digital communication of a“human”as a“person”,so they are possible in terms of conceptual definition.Digital human rights can help“people”lower the threshold for participation in digital communication,limit the excessive expansion of social systems,and promote the free and complete expression of body and mind,so they are necessary for social functions.There are limitations in the existing two ideas of“incorporating digital human rights into the constitution”.Based on the new construction idea of System Theory of Law,digital human rights as the right to participate in digital communication can be typified into digital communication in social sub-fields such as politics,economy,science,and art.The right to participate constructs a complete digital human rights system,making it feasible on the basis of the constitution.

Combined CNN-LSTM Deep Learning Algorithms for Recognizing Human Physical Activities in Large and Distributed Manners:A Recommendation System

Recognizing human activity(HAR)from data in a smartphone sensor plays an important role in the field of health to prevent chronic diseases.Daily and weekly physical activities are recorded on the smartphone and tell the user whether he is moving well or not.Typically,smartphones and their associated sensing devices operate in distributed and unstable environments.Therefore,collecting their data and extracting useful information is a significant challenge.In this context,the aimof this paper is twofold:The first is to analyze human behavior based on the recognition of physical activities.Using the results of physical activity detection and classification,the second part aims to develop a health recommendation system to notify smartphone users about their healthy physical behavior related to their physical activities.This system is based on the calculation of calories burned by each user during physical activities.In this way,conclusions can be drawn about a person’s physical behavior by estimating the number of calories burned after evaluating data collected daily or even weekly following a series of physical workouts.To identify and classify human behavior our methodology is based on artificial intelligence models specifically deep learning techniques like Long Short-Term Memory(LSTM),stacked LSTM,and bidirectional LSTM.Since human activity data contains both spatial and temporal information,we proposed,in this paper,to use of an architecture allowing the extraction of the two types of information simultaneously.While Convolutional Neural Networks(CNN)has an architecture designed for spatial information,our idea is to combine CNN with LSTM to increase classification accuracy by taking into consideration the extraction of both spatial and temporal data.The results obtained achieved an accuracy of 96%.On the other side,the data learned by these algorithms is prone to error and uncertainty.To overcome this constraint and improve performance(96%),we proposed to use the fusion mechanisms.The last combines deep learning classifiers tomodel non-accurate and ambiguous data to obtain synthetic information to aid in decision-making.The Voting and Dempster-Shafer(DS)approaches are employed.The results showed that fused classifiers based on DS theory outperformed individual classifiers(96%)with the highest accuracy level of 98%.Also,the findings disclosed that participants engaging in physical activities are healthy,showcasing a disparity in the distribution of physical activities between men and women.

Intelligent 3D garment system of the human body based on deep spiking neural network

Background Intelligent garments,a burgeoning class of wearable devices,have extensive applications in domains such as sports training and medical rehabilitation.Nonetheless,existing research in the smart wearables domain predominantly emphasizes sensor functionality and quantity,often skipping crucial aspects related to user experience and interaction.Methods To address this gap,this study introduces a novel real-time 3D interactive system based on intelligent garments.The system utilizes lightweight sensor modules to collect human motion data and introduces a dual-stream fusion network based on pulsed neural units to classify and recognize human movements,thereby achieving real-time interaction between users and sensors.Additionally,the system incorporates 3D human visualization functionality,which visualizes sensor data and recognizes human actions as 3D models in real time,providing accurate and comprehensive visual feedback to help users better understand and analyze the details and features of human motion.This system has significant potential for applications in motion detection,medical monitoring,virtual reality,and other fields.The accurate classification of human actions contributes to the development of personalized training plans and injury prevention strategies.Conclusions This study has substantial implications in the domains of intelligent garments,human motion monitoring,and digital twin visualization.The advancement of this system is expected to propel the progress of wearable technology and foster a deeper comprehension of human motion.

Model-Based Systems Engineering Approach to Design a Human Settlement to Better Serve Displaced People

The challenge of transitioning from temporary humanitarian settlements to more sustainable human settlements is due to a significant increase in the number of forcibly displaced people over recent decades, difficulties in providing social services that meet the required standards, and the prolongation of emergencies. Despite this challenging context, short-term considerations continue to guide their planning and management rather than more integrated, longer-term perspectives, thus preventing viable, sustainable development. Over the years, the design of humanitarian settlements has not been adapted to local contexts and perspectives, nor to the dynamics of urbanization and population growth and data. In addition, the current approach to temporary settlement harms the environment and can strain limited resources. Inefficient land use and ad hoc development models have compounded difficulties and generated new challenges. As a result, living conditions in settlements have deteriorated over the last few decades and continue to pose new challenges. The stakes are such that major shortcomings have emerged along the way, leading to disruption, budget overruns in a context marked by a steady decline in funding. However, some attempts have been made to shift towards more sustainable approaches, but these have mainly focused on vague, sector-oriented themes, failing to consider systematic and integration views. This study is a contribution in addressing these shortcomings by designing a model-driving solution, emphasizing an integrated system conceptualized as a system of systems. This paper proposes a new methodology for designing an integrated and sustainable human settlement model, based on Model-Based Systems Engineering and a Systems Modeling Language to provide valuable insights toward sustainable solutions for displaced populations aligning with the United Nations 2030 agenda for sustainable development.

CPG Human Motion Phase Recognition Algorithm for a Hip Exoskeleton with VSA Actuator

Due to the dynamic stiffness characteristics of human joints, it is easy to cause impact and disturbance on normal movements during exoskeleton assistance. This not only brings strict requirements for exoskeleton control design, but also makes it difficult to improve assistive level. The Variable Stiffness Actuator (VSA), as a physical variable stiffness mechanism, has the characteristics of dynamic stiffness adjustment and high stiffness control bandwidth, which is in line with the stiffness matching experiment. However, there are still few works exploring the assistive human stiffness matching experiment based on VSA. Therefore, this paper designs a hip exoskeleton based on VSA actuator and studies CPG human motion phase recognition algorithm. Firstly, this paper puts forward the requirements of variable stiffness experimental design and the output torque and variable stiffness dynamic response standards based on human lower limb motion parameters. Plate springs are used as elastic elements to establish the mechanical principle of variable stiffness, and a small variable stiffness actuator is designed based on the plate spring. Then the corresponding theoretical dynamic model is established and analyzed. Starting from the CPG phase recognition algorithm, this paper uses perturbation theory to expand the first-order CPG unit, obtains the phase convergence equation and verifies the phase convergence when using hip joint angle as the input signal with the same frequency, and then expands the second-order CPG unit under the premise of circular limit cycle and analyzes the frequency convergence criterion. Afterwards, this paper extracts the plate spring modal from Abaqus and generates the neutral file of the flexible body model to import into Adams, and conducts torque-stiffness one-way loading and reciprocating loading experiments on the variable stiffness mechanism. After that, Simulink is used to verify the validity of the criterion. Finally, based on the above criterions, the signal mean value is removed using feedback structure to complete the phase recognition algorithm for the human hip joint angle signal, and the convergence is verified using actual human walking data on flat ground.

Systematic and Theoretical Unfolding of Research on Xi Jinping’s Discourses on Respecting and Protecting Human Rights

Xi Jinping’s discourses on respecting and protect-ing human rights stand as a shining example of the sinicization and modernization of Marxist human rights theory,embodying profound theoretical,political,practical,and cultural logic.Existing research has conducted comprehensive and systematic theoretical analysis and academic extractions on the following contents:the core essence in-herent in these important discourses,including the“theory of human rights concepts,”the“theory of human rights paths,”the“theory of human rights practices,”the“theory of human rights protection,”and the“theory of human rights governance,”along with their profound theoretical significance,practical significance,and global signifi-cance.In the future,researchers should emphasize efforts on studying the original texts and understanding the original principles.While focusing on the precision of concepts,the scientific nature of the prop-ositions,the maturity of theoretical systems,and the rigor of internal logic related to Xi Jinping’s discourses on respecting and protecting human rights,researchers should also pay attention to constructing a discourse system on human rights from the dimensions of discourse power,discourse cluster,and discourse field.Researchers should be adept at drawing innovative insights into human rights theory from China’s vibrant human rights practices and the vast masses of people.This approach will facilitate the systematic unfolding,academic trans-formation,and innovative development of Xi Jinping’s discourses on respecting and protecting human rights.

Computer Vision-Based Human Body Posture Correction System

With the development of technology and the progress of life,more and more people,regardless of entertainment,learning,or work,cannot do without computer desks and cannot put down their mobile phones.Due to prolonged sitting and often neglecting the importance of posture,incorrect posture can often lead to health problems such as hunchback,lumbar muscle strain,and shoulder and neck pain over time.To address this issue,we designed a computer vision-based human body posture detection system.The system utilizes YOLOv8 technology to accurately locate key points of the human body skeleton,and then analyzes the coordinate positions and depth information of these key points to establish a criterion for distinguishing different postures.With the assistance of an SVM classifier,the system achieves an average recognition rate of 95%.Finally,we successfully deployed the posture detection system on Raspberry Pi hardware and conducted extensive testing.The test results demonstrate that the system can effectively detect various postures and provide real-time reminders to users to correct poor posture,demonstrating good practicality and stability.

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.

Safety evaluation of human umbilical cord-mesenchymal stem cells in type 2 diabetes mellitus treatment:A phase 2 clinical trial

BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.

Injectable collagen scaffold with human umbilical cordderived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage:phase Ⅰ clinical trial

Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December 2020.Patients were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any transplantation.The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation.The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells.Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related encephalomalacia.Severe adve rse events associated with cell transplantation were not observed.Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.

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.

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.

Biological factors controlling starch digestibility in human digestive system

Starch digestion rate and location in the gastrointestinal tract(GIT)are critical for human health.This review aims to present a comprehensive summary on our current understanding of physiological,biochemical,anatomical and geometrical factors of human digestive system that are related to in vivo starch digestibility.It is shown that all digestive compartments including mouth,stomach,small intestine,and large intestine play critical roles in regulating the overall starch digestion process.A proper investigation of starch digestion pattern should thus be based on the consideration of all these compartments.Main biological factors are summarized as oral mastication and salivation,gastric emptying and motility,small intestinal enzymes and motility,large intestinal resistant starch(RS)-microbiota interactions and gut-brain feedback control,as well as glucose adsorption and hormonal feedback control.However,connections among these biological factors in determining starch digestive behaviors remain elusive.This is due to the inherent complexity of human GIT anatomy,motility and biochemical conditions,as well as ethical,financial and technical issues in conducting clinical studies.Much technological and scientific efforts from both clinical studies and in vitro simulation models are required for a better understanding of in vivo starch digestion behaviors.

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.