Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Simulation Analysis of Deformation Control for Magnetic Soft Medical Robots

Dear Editor,This letter presents a biocompatible cross-shaped magnetic soft robot and investigates its deformation mode control strategy through COMSOL modeling and simulation.Magnetic soft robots offer novel avenues for precise treatment within intricate regions of the human body.

How mesenchymal stem cells transform into adipocytes:Overview of the current understanding of adipogenic differentiation

Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes.Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis.However,the mechanism underlying the adipogenic differentiation of MSCs is not fully understood.Here,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation.Finally,the relationship between maladipogenic differentiation and diseases is briefly discussed.We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

Research progress and quality markers prediction analysis of Dysosma versipellis

Dysosma versipellis is the rhizome of Bajiaolian in Berberaceae.It is a unique medicinal plant in China and it was the first to be recorded in Shennong’s Classic of Materia Medica(unknown author,25–220 C.E.).It has complex chemical components as well as complex,pharmacological and toxicological effects are extensive.Based on the recent research progress,the chemical constituents,pharmacological activities and toxicological effects of Dysosma versipellis were summarized.Combined with the core concept of quality markers of traditional Chinese medicine,the prediction and analysis were carried out from the aspects of phytogenetics and the source pathway of specific chemical constituents,traditional medicinal properties,traditional efficacy,chemical composition measurability,blood components,and pharmacokinetics,in order to provide reference for further study of Dysosma versipellis.

Proteomics Study of Benzene Metabolite Hydroquinone Induced Hematotoxicity in K562 Cells

Objective Hydroquinone(HQ),one of the phenolic metabolites of benzene,is widely recognized as an important participant in benzene-induced hematotoxicity.However,there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn’t been fully understood yet.Methods In this study,we treated K562 cells with 40μmol/L HQ for 72 h,examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring(PRM),and performed bioinformatics analysis to identify interaction networks.Results One hundred and eighty-seven upregulated differentially expressed proteins(DEPs)and 279 downregulated DEPs were identified in HQ-exposed K562 cells,which were involved in neutrophilmediated immunity,blood microparticle,and other GO terms,as well as the lysosome,metabolic,cell cycle,and cellular senescence-related pathways.Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways,we constructed the network of protein interactions and determined 6 DEPs(STAT1,STAT3,CASP3,KIT,STAT5B,and VEGFA)as main hub proteins with the most interactions,among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity.Conclusion Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

A core scientific problem in the treatment of central nervous system diseases:newborn neurons

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult neurons.Yet over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or renewed.Herein,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system injury.Central nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem cells.Because of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than neurons.Consequently,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural function.Scientists have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming techniques.Used alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural circuit.Thus can integration re plenish lost neurons after central nervous system injury,by improving the local microenvironment.By regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn neurons.This offers a novel approach for treating central nervous system injury.

Experimental and simulation study on shear stress-induced erythrocyte damage based on vortex oscillator

Background:Shear stress-induced erythrocyte damage,namely hemolysis,is an important problem in the development of blood-contacting medical devices such as mechanical circulatory support devices.Computational fluid dynamics simulation combined with hemolysis prediction models have been widely used to predict hemolysis.With the development of hemolysis prediction models,the new hemolysis prediction model requires more experimental data to verify.In addition,the difference of in vitro blood-shearing device also affect the accuracy of hemolysis prediction.Methods:To address these problems,a new in vitro blood-shearing device(vortex oscillator)was used to further verify the accuracy of the hemolysis prediction models,and to guide the optimal design of blood-contacting medical devices such as mechanical circulatory support devices.Firstly,the flow field information such as wall stress and velocity of the vortex oscillator under different speeds was analyzed.Secondly,different hemolysis prediction models were used to calculate hemolysis,and the predicted data was compared with the experimental data.Results and Conclusion:In this study,the flow field information inside the vortex oscillator at high rotational speeds was systematically investigated,and the prediction of hemolysis was carried out.The results showed that the predicted data of hemolysis was significantly different from the experimental data,which indicated that it was urgent to establish a standardized in vitro blood-shearing platform to provide a reference for accurate hemolysis prediction.

Medical Additive Manufacturing: From a Frontier Technology to the Research and Development of Products

1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)printing.Problems and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common features.For example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of biomedicine.The most widely used materials in biomedicine are biocompatible.Various homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.

Injectable hydrogels for cartilage and bone tissue engineering

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix(ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.

Altered profiles of fecal metabolites correlate with visceral hypersensitivity and may contribute to symptom severity of diarrhea-predominant irritable bowel syndrome

BACKGROUND Fecal metabolites are associated with gut visceral sensitivity,mucosal immune function and intestinal barrier function,all of which have critical roles in the pathogenesis of irritable bowel syndrome(IBS).However,the metabolic profile and pathophysiology of IBS are still unclear.We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea(IBS-D).AIM To investigate the fecal metabolite composition and the role of metabolites in IBSD pathophysiology.METHODS Thirty IBS-D patients and 15 age-and sex-matched healthy controls(HCs)underwent clinical and psychological assessments,including the IBS Symptom Severity System(IBS-SSS),an Italian modified version of the Bowel Disease Questionnaire,the Bristol Stool Form Scale(BSFS),the Hospital Anxiety and Depression Scale,and the Visceral Sensitivity Index.Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator.Fecal metabolites,including amino acids and organic acids,were measured by targeted metabolomics approaches.Correlation analyses between these parameters were performed.RESULTS The patients presented with increased stool water content,more psychological symptoms and increased visceral hypersensitivity compared with the controls.In fecal metabolites,His[IBS-D:0.0642(0.0388,0.1484),HC:0.2636(0.0780,0.3966),P=0.012],Ala[IBS-D:0.5095(0.2826,0.9183),HC:1.0118(0.6135,1.4335),P=0.041],Tyr[IBS-D:0.1024(0.0173,0.4527),HC:0.5665(0.2436,1.3447),P=0.018],Phe[IBS-D:0.1511(0.0775,0.3248),HC:0.3967(0.1388,0.7550),P=0.028],and Trp[IBS-D:0.0323(0.0001,0.0826),HC:0.0834(0.0170,0.1759),P=0.046]were decreased in IBS-D patients,but isohexanoate[IBS-D:0.0127(0.0060,0.0246),HC:0.0070(0.0023,0.0106),P=0.028]was significantly increased.Only Tyr was mildly correlated with BSFS scores in all subjects(r=-0.347,P=0.019).A possible potential biomarker panel was identified to correlate with IBS-SSS score(R2 Adjusted=0.693,P<0.001).In this regression model,the levels of Tyr,Val,hexanoate,fumarate,and pyruvate were significantly associated with the symptom severity of IBS-D.Furthermore,visceral sensation,including abdominal pain and visceral hypersensitivity,was correlated with isovalerate,valerate and isohexanoate.CONCLUSION Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity.

Biocompatibility and Immunotoxicology of the Preclinical Implantation of a Collagen-based Artificial Dermal Regeneration Matrix

Objective Graft rejection, with the possibility of a violent immune response, may be severe and life threatening. Our aim was to thoroughly investigate the biocompatibility and immunotoxicology of collagen-based dermal matrix(DM) before assessment in clinical trials. Methods DM was subcutaneously implanted in BALB/c mice in two doses to induce a potential immune response. The spleen and lymph nodes were assessed for shape, cell number, cell phenotype via flow cytometry, cell activation via CCK8 kit, Annexin V kit, and Ki67 immunostaining. Serum samples were used to measure antibody concentration by enzyme-linked immunosorbent assay. Local inflammation was analyzed by histology and immunohistochemistry staining. Data analysis was performed by one-way ANOVA and non-parametric tests. Results Our data illustrate that the spleen and lymph node sizes were similar between the negative control mice and mice implanted with DM. However, in the high-dose DM(DM-H) group, the total cell populations in the spleen and lymph nodes, T cells and B cells in the spleen had slight increases in prophase, and the low-dose DM(DM-L) group did not display gross abnormities. Moreover, DM-H initiated moderate cell activation and proliferation in the early phase post-immunization, whereas DM-L did not. Neither DM-H nor DM-L implantation noticeably increased IgM and IgG serum concentrations. Examination of the local cellular response revealed only benign cell infiltration and TNF-α expression in slides of DM in the early phase. Conclusion Overall, DM-H may have induced a benign temporary acute immune response post-implantation, whereas DM-L had quite low immunogenicity. Thus, this DM can be regarded as a safe product.

Biomimetic delivery of signals for bone tissue engineering

Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation.Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug's physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.

The Effect of Home-Based Cardiac Rehabilitation on Functional Capacity,Behavior,and Risk Factors in Patients with Acute Coronary Syndrome in China

Aim:To investigate the effect of home-based cardiac rehabilitation on functional capacity,health behavior,and risk factors in patients with acute coronary syndrome in China.Methods:Eighty patients with acute coronary syndrome were enrolled in this prospective randomized controlled study.Patients in the cardiac rehabilitation group(n=52)received home-based cardiac rehabilitation with a heart manual and a home exercise video for 3 months and patients in the control group(n=28)received only routine secondary prevention.The 6-min walk distance,laboratory test results,healthy behavior(questionnaire),quality of life(12-item Short Form Health Survey),anxiety(7-item Generalized Anxiety Disorder Questionnaire),and depression(9-item Patient Health Questionnaire)were evaluated at the beginning and after treatment for 3 months.Results:Compared with baseline data,52 patients who participated in cardiac rehabilitation had longer 6-min walk distance(515.26±113.74 m vs 0.445.30±97.92 m,P<0.0002),higher proportions of“always exercise”(78.26% vs.28%,P<0.05),“always limit food with sugar”(65.22% vs 12%,P<0.05),“always eat fruits 200–400 g every day”(82.61% vs.4%,P<0.05).and“always eat vegetables 300–500 g every day”(21.74%vs.12%,P<0.06)after treatment for 3 months.The low-density lipoprotein cholesterol control rate(52.17% vs.28%,P<0.05)and the systolic blood pressure control rate(100%vs.68%,P<0.05)were also signifi cantly increased after treatment for 3 months in the cardiac rehabilitation group.No signifi cant increase was found in the control group after treatment for 3 months.No cardiac-event related to home exercise was reported in both groups.Conclusion:Home-based cardiac rehabilitation is a feasible and available cardiac rehabilitation mode in China.

Genome-wide identification and characterization of WUSCHEL-related homeobox(WOX) genes in Salix suchowensis

Members of the WUSCHEL-related homeobox(WOX)transcription factor family are essential for determining cell fate and regulating diverse developmental processes in plants.Many WOX genes have been systematically investigated in woody plants such as Populus trichocarpa,but not in Salix suchowensis.Whole-genome sequence data for S.suchowensis is now available for comprehensive study of WOX genes in S.suchowensis.We thus surveyed the genome of S.suchowensis and demonstrated active expression of 15 WOX genes.In a phylogenetic analysis of WOX genes,the 15 SsWOX genes clustered among the modern/WUS,intermediate and ancient clades similar to the WOX genes of Arabidopsis thaliana.Based on the conserved intron/exon structure,SsWOX genes in the same subgroup had similar conserved exon–intron structures and motif domains.Furthermore,among several SsWOX subgroups,WUS(Wuschel)-box and EAR(the ERF-associated amphiphilic repression)-like motifs were conserved.Expression profiles of WOX genes in roots,stems and leaves indicate that SsWOX genes have various conserved roles in the tissues.Comparative analysis of the expression patterns in Salix suchowensis with that of Arabidopsis suggests that different shoot regeneration abilities are controlled by different WOX genes in plants.The analysis provide an overview of differentially expressed SsWOX genes during shoot regeneration,but also contribute to understanding the evolution of WOX genes in Salicaceae and the interrelations of WOX genes and other transcription factors,providing targets for further study.

Review: Progress in the Preparation of Iron Based Magnetic Nanoparticles for Biomedical Applications

With unique physical properties, chemical properties, and biological effects, magnetic nanomaterials are important functional materials in many fields. In the past decades, iron based magnetic nanomaterials have attracted much attention in the biomedicine field due to their superior magnetic properties and great potential in biomedical applications. In particular, magnetic iron oxide nanoparticles(MIONPs) have been playing a crucial role in the biomedicine field because of their diagnostic and therapeutic functions. Meanwhile, MIONPs are benign, low toxic, biocompatible, and biodegradable, so they are the only inorganic magnetic nanomaterials approved by the U.S. Food and Drug Administration(FDA) for clinical use at present. In this review, we mainly introduce the progress in the preparation of iron based magnetic nanomaterials for biomedical applications, including pure iron nanoparticles, iron-based alloy nanoparticles, and MIONPs, with a focus on MIONPs. Also, we summarize the preparation methods of MIONPs and point out the importance of their developments.

Research Progress on the Development and Application of New Natural Tobacco Humectants

The research progress on the development and application of new natural tobacco humectants was reviewed in the paper.Plants,animals and microbes contain special moisturizing substances,showing distinctive advantages and outstanding effects in respect of the tobacco moisture content maintaining and cigarette suction comfort promoting.The development necessity,major types,functional mechanism and influence on cigarette quality of new natural tobacco humectants development were compared and elaborated.Additionally,the prospect of new natural tobacco humectants development and application was forecasted.

Organellar genome assembly methods and comparative analysis of horticultural plants

Although organellar genomes(including chloroplast and mitochondrial genomes)are smaller than nuclear genomes in size and gene number,organellar genomes are very important for the investigation of plant evolution and molecular ecology mechanisms.Few studies have focused on the organellar genomes of horticultural plants.Approximately 1193 chloroplast genomes and 199 mitochondrial genomes of land plants are available in the National Center for Biotechnology Information(NCBI),of which only 39 are from horticultural plants.In this paper,we report an innovative and efficient method for high-quality horticultural organellar genome assembly from next-generation sequencing(NGS)data.Sequencing reads were first assembled by Newbler,Amos,and Minimus software with default parameters.The remaining gaps were then filled through BLASTN search and PCR.The complete DNA sequence was corrected based on Illumina sequencing data using BWA(Burrows–Wheeler Alignment tool)software.The advantage of this approach is that there is no need to isolate organellar DNA from total DNA during sample preparation.Using this procedure,the complete mitochondrial and chloroplast genomes of an ornamental plant,Salix suchowensis,and a fruit tree,Ziziphus jujuba,were identified.This study shows that horticultural plants have similar mitochondrial and chloroplast sequence organization to other seed plants.Most horticultural plants demonstrate a slight bias toward A+T rich features in the mitochondrial genome.In addition,a phylogenetic analysis of 39 horticultural plants based on 15 protein-coding genes showed that some mitochondrial genes are horizontally transferred from chloroplast DNA.Our study will provide an important reference for organellar genome assembly in other horticultural plants.Furthermore,phylogenetic analysis of the organellar genomes of horticultural plants could accurately clarify the unanticipated relationships among these plants.

Epitaxial Growth and Characteristics of Nonpolar a-Plane InGaN Films with Blue-Green-Red Emission and Entire In Content Range

Nonpolar(1120)plane In_(x)Ga_(1-x)N epilayers comprising the entire In content(x)range were successfully grown on nanoscale Ga N islands by metal-organic chemical vapor deposition.The structural and optical properties were studied intensively.It was found that the surface morphology was gradually smoothed when x increased from 0.06 to 0.33,even though the crystalline quality was gradually declined,which was accompanied by the appearance of phase separation in the In_(x)Ga_(1-x)N layer.Photoluminescence wavelengths of 478 and 674 nm for blue and red light were achieved for x varied from 0.06 to 0.33.Furthermore,the corresponding average lifetime(τ_(1/e))of carriers for the nonpolar In Ga N film was decreased from 406 ps to 267 ps,indicating that a high-speed modulation bandwidth can be expected for nonpolar In Ga N-based light-emitting diodes.Moreover,the bowing coefficient(b)of the(1120)plane In Ga N was determined to be 1.91 e V for the bandgap energy as a function of x.

A Review of the Application of Additive Manufacturing in Prosthetic and Orthotic Clinics from a Biomechanical Perspective

Prostheses and orthoses are common assistive devices to meet the biomechanical needs of people with physical disabilities.The traditional fabrication approach for prostheses or orthoses is a materialwasting,time-consuming,and labor-intensive process.Additive manufacturing(AM)technology has advantages that can solve these problems.Many trials have been conducted in fabricating prostheses and orthoses.However,there is still a gap between the hype and the expected realities of AM in prosthetic and orthotic clinics.One of the key challenges is the lack of a systematic framework of integrated technologies with the AM procedure;another challenge is the need to design a prosthetic or orthotic product that can meet the requirements of both comfort and function.This study reviews the current state of application of AM technologies in prosthesis and orthosis fabrication,and discusses optimal design using computational methods and biomechanical evaluations of product performance.A systematic framework of the AM procedure is proposed,which covers the scanning of affected body parts through to the final designed adaptable product.A cycle of optimal design and biomechanical evaluation of products using finite-element analysis is included in the framework.A mature framework of the AM procedure and sufficient evidence that the resulting products show satisfactory biomechanical performance will promote the application of AM in prosthetic and orthotic clinics.