The Triterpenoids from Munronia pinnata and Their Anti-Proliferative Effects.

Six new tirucallane-type triterpenoids, named munropenes A-F (1-6), were extracted from the whole plants of Munronia pinnata using a water extraction method. Their chemical structures were determined based on detailed spectroscopic data. The relative configurations of the acyclic structures at C-17 of munropenes A-F (1-6) were established using carbon-proton spin-coupling constants (2,3JC,H) and inter-proton spin-coupling constants (3JH,H). Furthermore, the absolute configurations of munropenes A-F (1-6) were determined through high-performance liquid chromatography (HPLC), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. The antiproliferative effects of munropenes A-F were evaluated in five tumor cell lines: HCT116, A549, HepG2, MCF7, and MDAMB. Munropenes A, B, D, and F (1, 2, 4, and 6) inhibited proliferation in the HCT116 cell line with IC50 values of 40.90, 19.13, 17.66, and 32.62 µM, respectively.

Sequential gene expression analysis of cervical malignant transformation identifies RFC4 as a novel diagnostic and prognostic biomarker.

BACKGROUND: Cervical squamous cell carcinoma (SCC) is known to arise through increasingly higher-grade squamous intraepithelial lesions (SILs) or cervical intraepithelial neoplasias (CINs). This study aimed to describe sequential molecular changes and identify biomarkers in cervical malignant transformation. METHODS: Multidimensional data from five publicly available microarray and TCGA-CESC datasets were analyzed. Immunohistochemistry was carried out on 354 cervical tissues (42 normal, 62 CIN1, 26 CIN2, 47 CIN3, and 177 SCC) to determine the potential diagnostic and prognostic value of identified biomarkers. RESULTS: We demonstrated that normal epithelium and SILs presented higher molecular homogeneity than SCC. Genes in the region (e.g., 3q, 12q13) with copy number alteration or HPV integration were more likely to lose or gain expression. The IL-17 signaling pathway was enriched throughout disease progression with downregulation of IL17C and decreased Th17 cells at late stage. Furthermore, we identified AURKA, TOP2A, RFC4, and CEP55 as potential causative genes gradually upregulated during the normal-SILs-SCC transition. For detecting high-grade SIL (HSIL), TOP2A and RFC4 showed balanced sensitivity (both 88.2%) and specificity (87.1 and 90.1%), with high AUC (0.88 and 0.89). They had equivalent diagnostic performance alone to the combination of p16INK4a and Ki-67. Meanwhile, increased expression of RFC4 significantly and independently predicted favorable outcomes in multi-institutional cohorts of SCC patients. CONCLUSIONS: Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes during cervical carcinogenesis. RFC4 is proposed as a novel surrogate biomarker for determining HSIL and HSIL+, and an independent prognostic biomarker for SCC.

Total Synthesis of (-)-Nodulisporic Acids D, C, and B: Evolution of a Unified Synthetic Strategy.

A unified synthetic strategy leading to the total synthesis of (-)-nodulisporic acids D, C, and B is described. Key synthetic transformations include a nickel-chromium-mediated cyclization, an aromatic ring functionalization employing a novel copper-promoted alkylation, a palladium-catalyzed cross-coupling cascade/indole ring construction, and a palladium-mediated regio- and diastereoselective allylic substitution/cyclization reaction, the latter to construct ring D.

Relationship Between Stressful Life Events and Online Deviant Behaviors Among College Students: A Moderated Mediation Model.

With the gradual penetration of the Internet into the study and life of college students, the Internet not only brings convenience to young adults but also becomes a new channel for them to engage in deviant behaviors. This study explores the relationship between stressful life events and college students' online deviant behaviors, as well as the mediating role of negative automatic thoughts and the moderating role of perceived social support. Data is drawn from 448 college students (Mage = 20.10, SDage = 1.74). Results showed that stressful life events were significantly positively correlated with online deviant behaviors, and negative automatic thoughts mediated the relationship between stressful life events and online deviant behaviors. The relationship between stressful life events and online deviant behaviors, as well as that between negative automatic thoughts and online deviant behaviors, were both moderated by perceived social support. This study provides a practical guiding value for effectively preventing and intervening in college students' online deviant behaviors and maintaining the regular order of the online society.

A multi-variable predictive warning model for cervical cancer using clinical and SNPs data.

Introduction: Cervical cancer is the fourth most common cancer among female worldwide. Early detection and intervention are essential. This study aims to construct an early predictive warning model for cervical cancer and precancerous lesions utilizing clinical data and simple nucleotide polymorphisms (SNPs). Methods: Clinical data and germline SNPs were collected from 472 participants. Univariate logistic regression, least absolute shrinkage selection operator (LASSO), and stepwise regression were performed to screen variables. Logistic regression (LR), support vector machine (SVM), random forest (RF), decision tree (DT), extreme gradient boosting(XGBoost) and neural network(NN) were applied to establish models. The receiver operating characteristic (ROC) curve was used to compare the models' efficiencies. The performance of models was validated using decision curve analysis (DCA). Results: The LR model, which included 6 SNPs and 2 clinical variables as independent risk factors for cervical carcinogenesis, was ultimately chosen as the most optimal model. The DCA showed that the LR model had a good clinical application. Discussion: The predictive model effectively foresees cervical cancer risk using clinical and SNP data, aiding in planning timely interventions. It provides a transparent tool for refining clinical decisions in cervical cancer management.

A virtual visualization method for improving the manufacturing accuracy based VPP 3D printers.

Compared to traditional vat photopolymerization 3D printing methods, pixel blending technique provides greater freedom in terms of user-defined lighting sources. Based on this technology, scientists have conducted research on 3D printing manufacturing for elastic materials, biologically inert materials, and materials with high transparency, making significant contributions to the fields of portable healthcare and specialty material processing. However, there has been a lack of a universal and simple algorithm to facilitate low-cost printing experiments for researchers not in the 3D printing industry. Here, we propose a mathematical approach based on morphology to simulate the light dose distribution and virtual visualization of parts produced using grayscale mask vat photopolymerization 3D printing technology. Based on this simulation, we develop an auto-correction method inspired by circle packing to modify the grayscale values of projection images, thereby improving the dimensional accuracy of printed devices. This method can significantly improve printing accuracy with just a single parameter adjustment. We conducted experimental validation of this method on a vat photopolymerization printer using common commercial resins, demonstrating its feasibility for printing high precision structures. The parameters utilized in this method are comparatively simpler to acquire compared to conventional techniques for obtaining optical parameters. For researchers in non-vat photopolymerization 3D printing industry, it is relatively user-friendly.

Correlation between genetic alterations and clinicopathological features of papillary thyroid carcinomas.

OBJECTIVE: To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. METHODS: In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. RESULTS: Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (<45 years). Among the 22 genes tested, the BRAF mutation rates showed a significant difference between the PTC and benign groups. In the subgroup analysis, younger age (odds ratio = 12.512, 95% confidence interval: 3.126-50.087) was an independent risk factor for LNM. In further analyses, BRAF mutation was significantly associated with LNM in the older subgroup (age ≥ 45 years), suggesting that the BRAF mutation test has greater value for determining PTC prognosis in the older age group. CONCLUSIONS: Our findings will provide a more comprehensive understanding of the relationship between gene mutations and PTC and may contribute to improved PTC management.

Electromagnetic field-mediated chitosan/gelatin/nano-hydroxyapatite and bone-derived scaffolds regulate the osteoblastic and chondrogenic phenotypes of adipose-derived stem cells to construct osteochondral tissue engineering niche in vitro.

It is critical to explore the effects of electromagnetic field (EMF) on the construction of functional osteochondral tissue, which has shown certain clinical significance for the treatment of osteochondral injury. At present, there are few studies on the effect of the direction of EMF on cells. This study aimed to investigate the effects of EMF coupling on different parameters to control adipose-derived stem cells (ADSCs) proliferation and specific chondrogenic and osteogenic differentiation at 2D level and 3D level. The proliferation and differentiation of EMF-induced ADSCs are jointly regulated by EMF and space structure. In this study, Cs7/Gel3/nHAP scaffolds were prepared with good degradation rate (86.75 ± 4.96 %) and absorb water (1100 %), and the pore size was 195.63 ± 54.72 µm. The bone-derived scaffold with a pore size of 267.17 ± 129.18 µm was obtained and its main component was hydroxyapatite. Cs7/Gel3/nHAP scaffolds and bone-derived scaffolds are suitable as 3D level materials. The optimal EMF intensity was 2 mT for chondrogenic differentiation and proliferation and 1 mT for osteogenic differentiation and proliferation. It is noteworthy that EMF has a negative correlation with ADSCs proliferation in the vertical direction at 2D level, while it has a positive correlation with ADSCs proliferation at 3D level. EMF mediated 3D osteochondral scaffold provide good strategy for osteochondral tissue engineering construction.

Differentiation of reprogrammed human adipose mesenchymal stem cells toward neural cells with defined transcription factors.

Somatic cell reprogramming may become a powerful approach to generate specific human cell types for cell-fate determination studies and potential transplantation therapies of neurological diseases. Here we report a reprogramming methodology with which human adipose stem cells (hADSCs) can be differentiated into neural cells. After being reprogrammed with polycistronic plasmid carrying defined factor OCT3/4, SOX2, KLF4 and c-MYC, and further treated with neural induce medium, the hADSCs switched to differentiate toward neural cell lineages. The generated cells had normal karyotypes and exogenous vector sequences were not inserted in the genomes. Therefore, this cell lineage conversion methodology bypasses the risk of mutation and gene instability, and provides a novel strategy to obtain patient-specific neural cells for basic research and therapeutic application.

Study of Finite Element Simulation on the Mechano-Bactericidal Mechanism of Hierarchical Nanostructure Arrays.

Biomimetic nanostructures with bactericidal performance have become the research focus in constructing sterilization surfaces, but the mechano-bactericidal mechanism is still not fully understood, especially for the hierarchical nanostructure arrays with different heights. Herein, the interaction between Escherichia coli cells and nanostructure arrays was simulated by finite element, and the initial rupture points, i.e., critical action sites, of bacterial cells and the effects of nanostructure geometries on the cell rupture speed were analyzed based on the mechano-response of Escherichia coli cells on flat (identical heights) and hierarchical nanostructure arrays. The critical action sites of bacterial cells on nanostructure arrays are all at the three-phase junction zone of cell-liquid-nanostructure, but they are slightly shifted by the height difference ΔH of nanostructures on hierarchical nanopillar (NP)/nanosheet (NS) arrays, where the NP is higher than the NS. When ΔH < 20 nm, the site nears the NS corners, and when ΔH ≥ 20 nm, the site is consistent with that of the NP/NP array, i.e., the site locates at the three-phase junction zone of cell-liquid-high NP. In addition, except for decreasing the NP diameter, the NS thickness/width, or properly increasing the nanostructure spacing, the cell rupture can be accelerated via increasing the ΔH of nanostructures. ΔH = 40 nm is distinguished as the boundary for the effect of nanostructure ΔH on the cell rupture speed. When ΔH < 40 nm, the cell rupture speed rapidly increases as the ΔH increases; when ΔH ≥ 40 nm, the cell rupture speed reaches the maximum value and remains stable. This study provides a new strategy on how to design high-efficiency bactericidal surfaces.

Preparation and Characterization of Polylactic Acid/Nano Hydroxyapatite/Nano Hydroxyapatite/Human Acellular Amniotic Membrane (PLA/nHAp/HAAM) Hybrid Scaffold for Bone Tissue Defect Repair.

Bone tissue engineering is a novel and efficient repair method for bone tissue defects, and the key step of the bone tissue engineering repair strategy is to prepare non-toxic, metabolizable, biocompatible, bone-induced tissue engineering scaffolds of suitable mechanical strength. Human acellular amniotic membrane (HAAM) is mainly composed of collagen and mucopolysaccharide; it has a natural three-dimensional structure and no immunogenicity. In this study, a polylactic acid (PLA)/Hydroxyapatite (nHAp)/Human acellular amniotic membrane (HAAM) composite scaffold was prepared and the porosity, water absorption and elastic modulus of the composite scaffold were characterized. After that, the cell-scaffold composite was constructed using newborn Sprague Dawley (SD) rat osteoblasts to characterize the biological properties of the composite. In conclusion, the scaffolds have a composite structure of large and small holes with a large pore diameter of 200 µm and a small pore diameter of 30 µm. After adding HAAM, the contact angle of the composite decreases to 38.7°, and the water absorption reaches 249.7%. The addition of nHAp can improve the scaffold's mechanical strength. The degradation rate of the PLA+nHAp+HAAM group was the highest, reaching 39.48% after 12 weeks. Fluorescence staining showed that the cells were evenly distributed and had good activity on the composite scaffold; the PLA+nHAp+HAAM scaffold has the highest cell viability. The adhesion rate to HAAM was the highest, and the addition of nHAp and HAAM could promote the rapid adhesion of cells to scaffolds. The addition of HAAM and nHAp can significantly promote the secretion of ALP. Therefore, the PLA/nHAp/HAAM composite scaffold can support the adhesion, proliferation and differentiation of osteoblasts in vitro which provide sufficient space for cell proliferation, and is suitable for the formation and development of solid bone tissue.

Gelatin/sodium alginate hydrogel-coated decellularized porcine coronary artery to construct bilayer tissue engineered blood vessels.

Cardiovascular diseases and vascular trauma can be commonly found in the population. Scholars worldwide hope to develop small-diameter vascular grafts that can replace autologous vessels for clinical use. Decellularized blood vessels can retain the original morphology, structure, and physical properties of blood vessels, which is conducive to cell growth, proliferation, and differentiation. In this study, porcine coronary arteries (PCAs) were decellularized to prepare decellularized porcine coronary artery (DPCA), and bilayer hybrid scaffolds were prepared by coating gelatin and sodium alginate mixed hydrogel of seven different proportions and combined with mouse fibroblasts (L929 cells) to study the construction of tissue engineering vessels in vitro. The obtained bilayer hybrid scaffolds were 3-7 cm in length, 5 mm in external diameter, and 1 mm in average wall thickness. All seven bilayer hybrid scaffolds showed good biocompatibility after cell inoculation. Compared with 2D culture, cells on 3D scaffolds grew relatively slowly in the first 4 days, and the number of cells proliferated rapidly at 7 days. In the same culture days, different concentrations of hydrogel also had an impact on cell proliferation. With the increase of hydrogel content, cells on the 3D scaffold formed cell colonies faster. The results showed that the scaffold had good biocompatibility and could meet the needs of artificial blood vessel construction.

Low-Temperature Hydrothermal Synthesis of Novel 3D Hybrid Nanostructures on Titanium Surface with Mechano-bactericidal Performance.

Titanium is extensively employed in modern medicines as orthopedic and dental implants, but implant failures frequently occur because of bacterial infections. Herein, three types of 3D nanostructured titanium surfaces with nanowire clusters (NWC), nanowire/sheet clusters (NW/SC) and nanosheet clusters (NSC), were fabricated using the low-temperature hydrothermal synthesis under normal pressure, and assessed for the sterilization against two common human pathogens. The results show that the NWC and NSC surfaces merely display good bactericidal activity against Escherichia coli, whereas the NW/SC surface represents optimal bactericidal efficiency against both Escherichia coli (98.6 ± 1.23%) and Staphylococcus aureus (69.82 ± 2.79%). That is attributed to the hybrid geometric nanostructure of NW/SC, i.e., the pyramidal structures of ∼23 nm in tip diameter formed with tall clustered wires, and the sharper sheets of ∼8 nm in thickness in-between these nanopyramids. This nanostructure displays a unique mechano-bactericidal performance via the synergistic effect of capturing the bacteria cells and penetrating the cell membrane. This study proves that the low-temperature hydrothermal synthesized hybrid mechano-bactericidal titanium surfaces provide a promising solution for the construction of bactericidal biomedical implants.

Validation of the mechano-bactericidal mechanism of nanostructured surfaces with finite element simulation.

The mechano-bactericidal property of nanostructured surfaces has become the focus of intensive research toward the development of a new generation of antibacterial surfaces, especially in the current era of spreading antibiotic resistance. However, the mechanisms underlying nanostructured surfaces mechanically damaging bacteria remain unclear, which ultimately limits translational potential toward real-world applications. Using finite element simulation technique, we developed the three-dimensional thin wall with turgor pressure finite element model (3D-TWTP-FEM) of bacterial cell and verified the reliability of this model by the AFM indentation experiment simulation of the cell, and the cell model is able to simulate suspended bacterial cell and the process of cell adhering to the flat and nanopillar surfaces. Since bacterial cells suffer greater stress and deformation on the nanopillar surfaces, a two-stage model of the elastic and creep deformation stage of the cells on the nanostructured surfaces was developed. The calculations show that the location of the maximum stress/strain on the cells adhered to the nanopillar surfaces is at the liquid-cell-nanopillar three phase contact line. The computational results confirmed the ability of nanostructured surfaces to mechanically lyse bacteria and gave the effect of nanopillar geometry on the efficiency and speed of bacterial cell rupture. This study provides fundamental physical insights into how nanopillar surfaces can serve as effective and fast mechanical antimicrobial materials.

Mechanism Study of Bacteria Killed on Nanostructures.

It is important to study the bactericidal mechanism with nanostructures for the design and preparation of high-efficiency sterilization materials. In this paper, the interfacial energy gradient between cells and nanopillars is proposed to be the driving force to promote cells to migrate into nanostructures and get killed. The expressions of interfacial energy and its gradient were first established, then the deformation of cells pressured by nanostructures was calculated. The results show that the interfacial energy gradient or the pressure on cells is influenced by nanopillar parameters substantially. The smaller the nanopillar diameter and the larger the pitch, the greater the pressure on cells. Only high enough nanocolumns can ensure sufficient cell creep deformation and become punctured. Furthermore, a cell volume and its adhesion morphology also influence the interaction between cells and nanostructures. The smaller the cell volume, the greater the pressure on it. And the larger the contact angle of adhered cells, the greater the pressure on the cells by nanopillars. Besides, the wettability of substrate material also influences the interaction between cells and nanopillars. It can be concluded that the model is reasonable and reliable since its calculation results are in good accordance with the experimental measurements.

Development of an Effective Scalable Enantioselective Synthesis of the HIV-1 Entry Inhibitor BNM-III-170 as the Bis-Trifluoroacetate Salt.

We report here the development and optimization of a process synthesis for the HIV-1 entry inhibitor BNM-III-170 bis-TFA salt (1). The synthesis features a dynamic-kinetic resolution (DKR) to establish the initial stereogenicity. By taking advantage of significant sequence modifications of our first generation synthesis, inconjunction with the low solubility of late-stage intermediates, the overall efficiency of the synthesis has been significantly improved, now to proceed in an overall yield of 9.64% for the 16-steps, requiring only a single chromatographic separation.

Effect of neural stem cells on apoptosis of PC12 cells induced by serum deprivation.

Neural stem cells (NSCs) have a bright application prospect to be used to treat neurodegenerative diseases due to their capacity to give rise to the appropriate cell types when they are grafted. At present, however, the function of NSCs after transplantation is not quite ensured, whether to replace the degenerative cells or to secrete nutrient factors. On the other hand, pheochromocytoma cell line 12 (PC12) cells have been widely used for investigating Parkinson's disease (PD) since their apoptosis is similar to that of dopaminergic neuron cells. Therefore, the possible cytoprotective effects of NSCs on the apoptosis of PC12 cells induced by serum deprivation were investigated in this paper. PC12 cells were cocultured with NSCs in DMEM/F12 medium free of serum, and their morphologies, viabilities, and survival were observed with an inverted microscope and assessed with a CCK-8 assay. In addition, the concentrations of glial derived neurotrophic factor (GDNF) in different medium were detected with a GDNF Elisa kit, and the mechanism of NSC's protective effect on PC12 cell apoptosis induced by serum deprivation was analyzed. The results showed that (1) PC12 cell apoptosis induced by serum deprivation increased with time, and only about 44.25% PC12 cells survived after 72 h; (2) NSCs culture medium protected against PC12 cell apoptosis insignificantly; (3) NSCs' supernatant and NSCs mildly prevented PC12 cells from apoptosis; (4) the amount of GDNF secreted by NSCs increased after the coculture with the apoptotic PC12 cells induced by serum deprivation. It can be concluded that there exists clear interaction between NSCs and apoptotic PC12 cells, and that GDNF secretion from NSCs is one of the important mechanisms to prevent the apoptosis of PC12 cells.

Three-dimensional expansion: in suspension culture of SD rat's osteoblasts in a rotating wall vessel bioreactor.

OBJECTIVE: To study large-scale expansion of SD (Sprague-Dawley) rat's osteoblasts in suspension culture in a rotating wall vessel bioreactor (RWVB). METHODS: The bioreactor rotation speeds were adjusted in the range of 0 to 20 rpm, which could provide low shear on the microcarriers around 1 dyn/cm2. The cells were isolated via sequential digestions of neonatal (less than 3 days old) SD rat calvaria. After the primary culture and several passages, the cells were seeded onto the microcarriers and cultivated in T-flask, spinner flask and RWVB respectively. During the culture period, the cells were counted and observed under the inverted microscope for morphology every 12 h. After 7 days, the cells were evaluated with scanning electron microscope (SEM) for histological examination of the aggregates. Also, the hematoxylin-eosin (HE) staining and alkaline phosphatase (ALP) staining were performed. Moreover, von-Kossa staining and Alizarin Red S staining were carried out for mineralized nodule formation. RESULTS: The results showed that in RWVB, the cells could be expanded by more than ten times and they presented better morphology and vitality and stronger ability to form bones. CONCLUSIONS: The developed RWVB can provide the culture environment with a relatively low shear force and necessary three-dimensional (3D) interactions among cells and is suitable for osteopath expansion in vitro.

Culture of neural stem cells in calcium alginate beads.

Neural stem cells (NSCs) with the capacity of extensive self-renewal and multilineage differentiation have attracted more and more attention in research as NSCs will play an important role in the nerve disease treatment and nerve injury repair. The shortage of NSCs, both their sources and their numbers, however, is the biggest challenge for their clinic application, and hence, in vitro culture and expansion of NSCs is vitally important to realize their potentials. In this work, mouse-derived NSCs were cultured in three-dimensional calcium alginate beads (Ca-Alg-Bs). Gelling conditions, cell density, and cell harvest were determined by the exploration of formation and dissociation parameters for Ca-Alg-Bs. Additionally, the recovered and the subsequent induced cells were identified by immunofluorescence staining of Nestin, beta-tubulin, and GFAP. The results show that the 2-mm diameter Ca-Alg-Bs, prepared with 1.5% sodium alginate solution and 3.5% CaCl2 solution and with gelling for 10 min, is suitable for the NSCs culture. The seeding density of 0.8 x 10(5) cells x mL-1 for the encapsulation of NSCs resulted in the most expansion, and the NSCs almost doubled during the experiment. The average cell recovery rate is over 88.5%, with the Ca-Alg-Bs dissolving in 55 mM sodium citrate solution for 10 min. The recovered cells cultured in the Ca-Alg-Bs still expressed Nestin and had the capacity of multilineage differentiation into neurons and glial cells and, thus, remained to be NSCs. These results demonstrate that NSC expansion within Ca-Alg-Bs is feasible and provides further possibilities for NSC expansion in bioreactors of the scale of clinical relevance.

[Simulation of the growth of neurosphere cultured in bioreactors].

When the size of a neurosphere cultured in vitro reaches a certain critical value, a necrotic core will appear inside the neurosphere because of the limitation of oxygen or other nutrients transport from medium to the cells in the neurasphere. Large necrotic core will greatly reduce the expansion of NSCs. The cellular automaton (CA) model is applied in this article to model the growth of NSCs in sphere state. The appearance and enlargement of the necrotic core in a neurosphere is calculated by coupling the CA model with the nutrient diffusion analysis in bioreactors. The calculation results indicate that the culture conditions, such as seeding density, the concentration of nutrients in medium and the mass transfer coefficient between a neurosphere and medium, have some effects on the appearance of the necrotic core. However, the necrotic core mainly depends on the inner diffusion. It will certainly appear if the size of the neurosphere is large enough even the outside mass transfer is in a good condition in bioreactors. Additionally, the appearance of the necrotic core resulting from the shortage of oxygen is earlier than that caused by the limitation of glucose. And the growth of the necrotic core is very fast after its appearance, and the whole neurosphere may become necrotic. The model developed with cellular automaton and mass transfer is a good qualitative representation of NSCs growth in bioreactors.