Search

The flame front area is an important parameter to quantify the heat release rate. However, the limitations imposed by the measuring instruments and the measurement methodologies make it difficult to determine the flame front position in an image. This work introduces a method to detect and optimize the flame front boundary. A high‐speed camera was employed to continuously capture the flame images. By setting appropriate intensity thresholds, the impact noise can be eliminated from the image and the flame front boundary can be determined. The binary diagram of the image was morphologically processed to obtain the normalized area fluctuations of the flame front in a temporally resolved manner. Two flame types and combustion regimes were studied. A LABVIEW‐based program was used for the synchronous triggering of the camera, the photomultiplier, and the microphones. The normalized area and photomultiplier output signals of a multiple flame burner obtained within the same period were compared and combined with the spectrum information from the microphone in the cavity. The trend charts were investigated in terms of the Pearson correlation coefficient. The results showed a strong correlation, thereby verifying the feasibility of this method.

Abandoning the traditional deposition of as-prepared Cu2ZnSnS4 (CZTS) thin films in a glove box, a modified thiol-based solution system suitable for deposition in air is described to further reduce device production costs. In this modified approach, metal salts and thiourea are used as the starting materials and are dissolved in a mixed solution of thioglycolic acid and 2-methoxyethanol, forming a homogeneous precursor solution. The as-deposited CZTS thin films are obtained by spin-coating the precursor solution in air, followed by the selenization process to form large-grained Cu2ZnSn(S,Se)4 thin films. Combining the microstructural results with compositional analyses, the optimal selenization conditions for the Cu2ZnSn(S,Se)4 absorber layer were found to be 540°C and 10 min.

Background This study aimed to comprehensively investigate the effect of spread through air spaces (STAS) on clinicopathologic features, molecular characteristics, immunohistochemical expression, and prognosis in lung adenocarcinomas (ADC) and squamous cell carcinomas (SQCC) based on the 8th edition AJCC/UICC staging system. Methods In total, 303 ADC and 121 SQCC cases were assessed retrospectively. Immunohistochemical staining was performed for E-cadherin, vimentin, Ki67, survivin, Bcl-2, and Bim. Correlations between STAS and other parameters were analyzed statistically. Results STAS was observed in 183 (60.4%) ADC and 39 (32.2%) SQCC cases. In ADC, the presence of STAS was associated with wild-type EGFR, ALK and ROS1 rearrangements, low E-cadherin expression, and high vimentin and Ki67 expression. In SQCC, STAS was associated with low E-cadherin expression and high vimentin and survivin expression. Based on univariate analysis, STAS was associated with significantly shorter disease-free survival (DFS) and overall survival (OS) in ADC. In SQCC, STAS tended to be associated with shorter OS. By multivariate analysis, STAS was an independent poor prognostic factor in ADC for DFS but not OS. Stratified analysis showed that STAS was correlated with shorter DFS for stage I, II, IA, IB, and IIA ADC based on univariate analysis and was an independent risk factor for DFS in stage I ADC cases based on multivariate analysis. Conclusions Our findings revealed that STAS is an independent negative prognostic factor for stage I ADC using the new 8th edition AJCC/UICC staging system. Stage I patients with STAS should be followed up more closely and might need different treatment strategies.

To improve the isolation efficiency of parthenogenetic embryonic stem cells (pESCs) in mice, it is necessary to optimize the method to increase in vitro developmental competence of mice parthenogenetic blastocysts. Therefore, this study aims to investigate an optimal method for the production of mouse parthenogenetic blastocysts and isolation of pESC colonies by comparing the effects of two methods: (1) the treatment of histone deacetylase inhibitor PXD101 before, during, or after parthenogenetic activation; (2) parthenogenetic embryo aggregation; and (3) their combination treatment. The results suggest that application of PXD101 treatment and embryo aggregation could both improve the development of mouse parthenogenetic blastocysts (50 nM PXD101 treated 4 hours during activation and further 4 hours after activation: 40.0% vs. 20.0%; p

Reprogramming mediated with proteins provides a novel, simpler, and safer strategy for generating induced pluripotent stem cells (iPSCs); in order to efficiently produce the recombination proteins and optimize the gene delivery system, different agents were screened to efficiently transfect plasmid DNA (pDNA) encoding “Yamanaka factor” (Oct 4, Sox 2, Klf 4, or c-Myc) into human embryonic kidney (HEK)-293T cells. The results indicated that 10 μg/mL Poly-MAG (polyethyleneimine (PEI)-MIONP) combined with exogenous magnetic field, 5 μg/mL Lipofectamine® 2000, and 40 μg/mL PEI were, respectively, more suitable to deliver the pDNA encoding Oct 4 into HEK-293T cells in the same transfection reagent groups, but the cell survival rate in 10 μg/mL Poly-MAG treatment group was significantly higher than that in the latter two groups (P

A simple, rapid, efficient, and specialized culture system was successfully developed in this study to induce human embryonic stem cells into dopaminergic neurons in vitro. It only took 5 days to generate quickly and directly a large number of homogeneous neural stem cell (NSC) spheres by the introduction of small molecules LDN (inhibitor of BMP [bone morphogenetic protein] pathway that inhibits BMP type I receptors ALK2 and ALK3), SB431542 (inhibitor of TGF-β/Activin/Dodal pathway that inhibits ALK4, ALK5, and ALK7), CHIR99021 (inhibitors of GSK-3 [glycogen synthase kinase 3]), and basic fibroblast growth factor (bFGF). The dopaminergic neurons were successfully induced at day 25 (tyrosine hydroxylase [TH] expressed) and at day 32 (TH highly expressed) with high purity (TH/Tuj1: 84.14% and 93.15%, respectively) by the addition of FGF8 (fibroblast growth factor 8), sonic hedgehog (SHH), and Purmorphamine after the generation of NSC at day 5. And, the dopaminergic neurons induced by this system successfully survived and integrated into the striatum of cynomolgus monkey brain after transplantation, which verified the efficiency of the induction system developed in this study, suggesting the potential clinical application in cell therapy for neurological diseases.

Background: Instant monitoring of the therapeutic effect of systematic therapy in late-stage lung cancer is crucial for response assessment and strategy adjustment. Previous study found that specific plasma methylation markers may be applied to therapeutic effect assessment. In order to investigate the performance of plasma mSHOX2 in assessing the therapeutic effect and predicting the prognosis of stage IV lung cancer, we performed the study focusing on patients underwent chemotherapy or tyrosine kinase inhibitor (TKI)-based targeted therapy. Methods: Blood samples from 163 subjects, including 30 stage I, 29 stage II, 26 stage III and 68 stage IV lung cancer patients, were recruited in this study. Quantitative relationship between primary tumor size and the plasma mSHOX2 level was established. Blood samples before therapy and two cycles after therapy were obtained from 68 stage IV patients, and the mSHOX2 level was quantified as ΔΔCt. Results: Sharp decrease of plasma mSHOX2 level was seen in patients with partial response (PR) while not in those with stable disease (SD). The plasma mSHOX2 level change reflected the degree of response and correlated with the maximal diameter of primary tumors in linear relationship. The mSHOX2 levels before and two cycles after therapy were predictors of the overall survival, while the mSHOX2 level change or the tumor size change were not predictors of the overall survival. Furthermore, univariable and multivariable Cox regression revealed that mSHOX2 level before therapy was the only independent predictor of the overall survival with a hazard ratio of 1.414. Conclusions: mSHOX2 is effective for therapeutic effect assessment and prognosis prediction of stage IV lung cancer patients underwent systematic therapy.

Magnetic iron oxide nanoparticles (MIONPs) are particularly attractive in biosensor, antibacterial activity, targeted drug delivery, cell separation, magnetic resonance imaging tumor magnetic hyperthermia, and so on because of their particular properties including superparamagnetic behavior, low toxicity, biocompatibility, etc. Although many methods had been developed to produce MIONPs, some challenges such as severe agglomeration, serious oxidation, and irregular size are still faced in the synthesis of MIONPs. Thus, various strategies had been developed for the surface modification of MIONPs to improve the characteristics of them and obtain multifunctional MIONPs, which will widen the applicational scopes of them. Therefore, the processes, mechanisms, advances, advantages, and disadvantages of six main approaches for the synthesis of MIONPs; surface modification of MIONPs with inorganic materials, organic molecules, and polymer molecules; applications of MIONPs or modified MIONPs; the technical challenges of synthesizing MIONPs; and their limitations in biomedical applications were described in this review to provide the theoretical and technological guidance for their future applications.

Lineage reprogramming has become a potential strategy for therapy of cardiac diseases. Somatic cells can be directly converted into the induced cardiomyocytes (iCMs) without passing through an induced pluripotent stem cell stage; this strategy has some advantages such as directional differentiation and preferable security. However, there are still many challenges which need to be further studied, such as identification of safer induced factors, exploration of molecular mechanisms, improvement of the mature level of iCMs and so on. Therefore, the structures of key factors, including transcription factors, microRNAs (miRNAs), epigenetic regulators and small molecules and their functions in the cardiac development and lineage reprogramming, molecular mechanisms underlying lineage conversion, strategies for generating matured iCMs, and major challenges were reviewed to lay the foundation for further applications of iCMs.

Aim: To investigate the quantitative relationship between the positive detection rate (PDR) in colorectal tumor detection and the mSEPT9 level. Materials & methods: The level of blood mSEPT9 in various colorectal diseases was quantified by the Epi proColon 2.0 assay. ΔΔCt values were calculated representing the mSEPT9 level. A total of 1347 subjects were recruited in this quantitative study. Results: PDR or sensitivity was positively correlated with the progression of colorectal tumors and the mSEPT9 level in an exponential relationship. The mSEPT9 level of CRC exhibited a distinct pattern of distribution. Strong correlation was found between mSEPT9 level and PDR or sensitivity in various tumor differentiation, pathological types or metastasis. Conclusion: The quantitative profiling of blood mSEPT9 determines the detection performance on colorectal tumors.

Background: Central and peripheral location as well as thyroid transcription factor-I (TTF-1) expression was reported to be associated with different characteristics and prognosis of small-cell lung cancer (SCLC). This study aimed to investigate differential expression of PD-L1 in different SCLC subtypes, and in biopsy and resection specimens.Methods: We retrospectively analyzed 142 SCLC tumor samples using immunohistochemistry to correlate PD-L1 (22C3) expression with clinicopathologic features and survival data.Results: PD-L1 expression was found in 19.7% SCLCs (28/142) and was more frequent in females than in males (32%, 16/50 vs. 13%, 12/92, p = 0.009), in central type than in peripheral type SCLCs (26%, 26/100 vs. 4.8%, 2/42, p = 0.003), and in TTF-1 positive than in negative SCLCs (23.8%, 25/105 vs. 8.1%, 3/37, p = 0.039). PD-L1 expression was associated with vascular (p = 0.001) and lymphatic invasion (p = 0.001). There was no significant difference in PD-L1 expression between biopsy and resection specimens. On univariate analysis, patients with PD-L1 expression had significantly shorter progression-free survival (PFS; p = 0.026) and overall survival (OS; p = 0.012). Multivariate analysis revealed that PD-L1 expression was an independent prognostic factor for OS (HR, 2.317; 95% CI 1.199–4.478; p = 0.012) and PFS (HR, 1.636; 95% CI 0.990–2.703; p = 0.051) in SCLC.Conclusions: PD-L1 expression was more frequent in central type, TTF-1 positive SCLCs, and predicted a poor clinical outcome in these patients. Therefore, tumor location and TTF-1 expression could predict expression status of PD-L1, and could potentially serve as clinical response to immunotherapy.

Background: Breast ductal carcinoma hardly metastasizes to colorectum and the effect of surgery is controversial. We treated one case of patients with breast ductal carcinoma metastasizes to colorectum with surgery and discussed current management experience of breast cancer metastasizing to colorectum by reviewing the literature. Case Presentation: A 37-year-old woman underwent a modified radical mastectomy three years ago for right breast cancer and developed left breast cancer with right breast cancer suspiciously metastasizing to colorectum, left ovary along with oviduct, pancreas, and left acetabulum according to positron emission tomography-computed tomography. Then she had chosen to give up further therapy but was admitted to our department complaining of shapeless feces and mucus pus and blood in stool for 2 years with the process of aggravating symptoms for recent 2 months. Colonoscopy revealed the existence of colorectal carcinoma. She received laparoscopic combined abdominal perineal resection and bilateral ovarian salpingectomy. Postoperative pathology as well as immunohistochemistry supported the origin of primary breast infiltrating ductal cancer. She remained tamoxifen therapy and was alive until she was lost to follow-up.Conclusions: Clinicians must pay attention to any gastro-intestinal symptoms of patients with a medical history of breast cancer since the incipient symptoms of breast cancer metastasis to colorectum are insidious. Definite diagnosis may be difficult even by endoscopy. Surgery should be considered as a therapeutic option and definite diagnostic means combined with immunohistochemistry.

Background: The early detection of digestive cancers and precancerous diseases remains a significant challenge. This study aimed to investigate the performance of the blood methylated SEPT9 ( mSEPT9) assay, and the combination of this assay with serum protein markers, in hospital-based opportunistic screening strategies for digestive cancers. Methods: Opportunistic screening was performed in the participating hospitals on outpatients and inpatients who met specific inclusion criteria. We recruited a total of 2030 subjects, including 764 cancer patients [291 colorectal cancer (CRC), 239 gastric cancer (GC), 106 esophageal cancer (EC), and 128 hepatocellular carcinoma (HCC)], 423 subjects with precancerous diseases, and 843 normal subjects. All samples were transported to an authenticated clinical laboratory where the mSEPT9 tests were performed. Results: When used separately, the mSEPT9 detected CRC, GC, EC, and HCC, with a sensitivity of 76.6% [area under the receiver operating characteristic curve (AUC) = 0.86)], 47.7% (AUC = 0.76), 42.6% (AUC = 0.69), and 76.7% (AUC = 0.85) and a specificity of 94.6%, 92.3%, 92.5%, and 87.7%, respectively. The mSEPT9 assay also had potent ability to discriminate cancer from non-cancer subjects. The combination of mSEPT9 with CEA, CA724, SNCG, or AFP significantly enhanced the sensitivity for CRC, GC, EC, and HCC to 86.4% (AUC = 0.99, specificity = 92.8%), 63.6% (AUC = 0.86, specificity = 91.1%), 71.3% (AUC = 0.81, specificity = 82.1%), and 83.3% (AUC = 0.93, specificity = 85.1%), respectively. The performance of the mSEPT9 assay was influenced by cancer stage, patient age, pathological types, and the location of cancer. We also identified that mSEPT9 was an independent risk factor and was a valuable predictor for the long-term survival of digestive cancer patients, with a hazard ratio of 2.84, 2.07, 1.88, and 2.45, for CRC, GC, EC, and HCC, respectively. Conclusion: The blood mSEPT9 assay, whether used alone or in combination with serum protein markers, is effective for the opportunistic screening of digestive cancers. Furthermore, mSEPT9 is an independent risk factor and a predictive marker for the long-term survival of digestive cancer patients.

Objective. To investigate whether exercise preconditioning (EP) improves the rat cardiac dysfunction induced by exhaustive exercise (EE) through regulating NOD-like receptor protein 3 (NLRP3) inflammatory pathways and to confirm which intensity of EP is better. Method. Ninety healthy male Sprague Dawley rats were randomly divided into five groups: a control group (CON), exhaustive exercise group (EE), low-, middle-, and high-intensity exercise precondition and exhaustive exercise group (LEP + EE, MEP + EE, HEP + EE group). We established the experimental model by referring to Bedford’s motion load standard to complete the experiment. Then, the pathological changes of the myocardium were observed under a light microscope. Biomarker of myocardial injury in serum and oxidative stress factor in myocardial tissue were evaluated by ELISAs. The cardiac function parameters were detected using a Millar pressure and volume catheter. The levels of thioredoxin-interacting protein (TXNIP), thioredoxin protein (TRX), nuclear transcription factor kappa Bp65 (NF-ĸBp65), NLRP3, and cysteinaspartate specific proteinase 1 (Caspase-1) protein in rats’ myocardium were detected by western blotting. Results. 1. The myocardial structures of three EP + EE groups were all improved compared with EE groups. 2. The levels of the creatine phosphating-enzyme MB (CK-MB), reactive oxygen species (ROS), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α) in three EP + EE groups were all increased compared with CON but decreased compared with the EE group (P<0.05). 3. Compared with the CON group, slope of end-systolic pressure volume relationship (ESPVR), ejection fraction (EF), and peak rate of the increase in pressure (dP/dtmax) all dropped to the lowest level in the EE group (P<0.05), while the values of cardiac output (CO), stroke volume (SV), end-systolic volume (Ves), end-diastolic volume (Ved), and relaxation time constant (Tau) increased in the EE group (P<0.05). 4. Compared with the CON group, the expression levels of TXNIP, NF-ĸBp65, NLRP3, and Caspase-1 all increased obviously in the other groups (P<0.05); meanwhile, they were all decreased in three EP + EE groups compared with the EE group (P<0.05). 5. NLRP3 was positively correlated with heart rate, IL-6, and ROS, but negatively correlated with EF (P<0.01). Conclusion. EP protects the heart from EE-induced injury through downregulating TXNIP/TRX/NF-ĸBp65/NLRP3 inflammatory signaling pathways. Moderate intensity EP has the best protective effect.

Background Germline variations may contribute to lung cancer susceptibility besides environmental factors. The influence of germline mutations on lung cancer susceptibility and their correlation with somatic mutations has not been systematically investigated. Methods In this study, germline mutations from 1,026 non-small cell lung cancer (NSCLC) patients were analyzed with a 58-gene next-generation sequencing (NGS) panel containing known hereditary cancer-related genes, and were categorized based on American College of Medical Genetics and Genomics (ACMG) guidelines in pathogenicity, and the corresponding somatic mutations were analyzed using a 605-gene NGS panel containing known cancer-related genes. Results Plausible genetic susceptibility was found in 4.7% of lung cancer patients, in which 14 patients with pathogenic mutations (P group) and 34 patients with likely-pathogenic mutations (LP group) were identified. The ratio of the first degree relatives with lung cancer history of the P groups was significantly higher than the Non-P group (P=0.009). The ratio of lung cancer patients with history of other cancers was higher in P (P=0.0007) or LP (P=0.017) group than the Non-P group. Pathogenic mutations fell most commonly in BRCA2, followed by CHEK2 and ATM. Likely-pathogenic mutations fell most commonly in NTRK1 and EXT2, followed by BRIP1 and PALB2. These genes are involved in DNA repair, cell cycle regulation and tumor suppression. By comparing the germline mutation frequency from this study with that from the whole population or East Asian population (gnomAD database), we found that the overall odds ratio (OR) for P or LP group was 17.93 and 15.86, respectively, when compared with the whole population, and was 2.88 and 3.80, respectively, when compared with the East Asian population, suggesting the germline mutations of the P and LP groups were risk factors for lung cancer. Somatic mutation analysis revealed no significant difference in tumor mutation burden (TMB) among the groups, although a trend of lower TMB in the pathogenic group was found. The SNV/INDEL mutation frequency of TP53 in the P group was significantly lower than the other two groups, and the copy number variation (CNV) mutation frequency of PIK3CA and MET was significantly higher than the Non-P group. Pathway enrichment analysis found no significant difference in aberrant pathways among the three groups. Conclusions A proportion of 4.7% of patients carrying germline variants may be potentially linked to increased susceptibility to lung cancer. Patients with pathogenic germline mutations exhibited stronger family history and higher lung cancer risk.

In order to improve the gene-delivering efficiency of polyethylenimine-modified superparamagnetic iron oxide nanoparticle (PEI-SPION) and elucidate the related mechanisms, the binding ratio and protection actions of PEI-SPION to plasmid DNA (pDNA), the physical characteristics of PEI-SPION/pDNA complex, and effects of exogenous factors (including magnetic field, inhibitors, and activator) on gene transfection in human embryonic kidney 293T cells (HEK-293T cells) were explored here. The results showed that the diameter of PEI-SPION was about 45 nm. When PEI-SPION and pDNA encoding Oct 4 (pDNA-Oct 4) were mixed at the mass ratio of 1: 1, the hydrodynamic diameter (299.10 ± 5.01 nm) of conjugate complex was significantly smaller than that of complex at the mass ratio of 1: 2 (469.23 ± 28.86 nm; P 0.05), and similar results were found for treatments of nystatin. Compared with control group, 2-deoxy-D-glucose (2-DG) and amiloride could significantly decrease the transfection efficiency (P

To improve the isolation efficiency of parthenogenetic embryonic stem cells (pESCs) in mice, it is necessary to optimize the method to increase

This study aims to examine the influence of algorithm and subject-related factors, including cancer stage, age, sex, and cancer location, on the performance of the SEPT9 gene methylation test, an assay approved by the US FDA for colorectal cancer (CRC) screening. A total of 1225 subjects were recruited in this opportunistic screening study, including 388 CRC patients, 139 subjects with adenoma, 108 subjects with hyperplastic polyps, and 590 subjects with no evidence of disease (NED). Epi proColon 2.0 CE assay was used to examine the blood level of SEPT9 gene methylation. It was found that tests using 1/3 algorithm exhibited higher detection rate than those using the 2/3 algorithm for CRC, adenoma, hyperplastic polyps, while the false positive rate in subjects with NED was also higher with 1/3 algorithm. The positive detection rate (PDR) of the assay for stage 0 and I CRC were lower than later stages (Stage II, III and IV). Interestingly, the normal subjects above 60 years old exhibited significantly higher PDR than subjects from younger groups, while no significant change in PDR was observed among age groups in CRC patients. Furthermore, no difference in the PDR for CRC was found between male and female, and the PDR for CRC at various colorectal locations were essentially identical. Algorithm, cancer stage and age are factors affecting the detection rate of the SEPT9 assay, while sex and cancer location appeared to have no influence on its performance.

POLE/POLD1 gene variants have been suggested as potential markers for immunotherapy due to their significant association with the tumor mutational burden (TMB), an effective indicator for response prediction in immunotherapy. However, the correlation of POLE/POLD1 variants with MSI, MMR, TMB, MMR-related and key driver gene mutations needs to be defined to support patient recruitment and therapeutic effect assessment in immunotherapy. 1,392 Chinese cancer patients were recruited, and the correlation of POLE/POLD1 variants with existing immunotherapeutic markers and cancer pathways was investigated. A next-generation sequencing panel including 605 cancer-related genes was used for variant sequencing. It was found that the frequency of POLE variants was not statistically different from that in COSMIC database, while the frequency of POLD1 variants was significantly higher in lung cancer. c.857 C > G and c.2091dupC were potential high frequency variants in Chinese cancer patients. Patients carrying POLE damaging variants were significantly younger than POLE/POLD1 WT patients. Patients carrying POLE/POLD1 damaging variants exhibited significantly higher TMB and frequency of MMR gene variants than POLE/POLD1 WT patients. Patients with POLE damaging variants also exhibited significantly higher frequency of driver gene variants than POLE/POLD1 WT patients. Further analysis showed that POLE damaging variants may affect the cancer development through MMR, TGFβ and RTK/RAS/RAF signaling pathways, and POLD1 through MMR pathways. In conclusion, this study identified key characteristics and regions of POLE/POLD1 genes that correlates with TMB, MMR gene mutations and key driver gene mutations, and provided theoretical and practical basis for patient selection based on POLE/POLD1 gene status in immunotherapy.

BACKGROUND: Instant monitoring of the therapeutic effect of systematic therapy in late-stage lung cancer is crucial for response assessment and strategy adjustment. Previous study found that specific plasma methylation markers may be applied to therapeutic effect assessment. In order to investigate the performance of plasma mSHOX2 in assessing the therapeutic effect and predicting the prognosis of stage IV lung cancer, we performed the study focusing on patients underwent chemotherapy or tyrosine kinase inhibitor (TKI)-based targeted therapy. METHODS: Blood samples from 163 subjects, including 30 stage I, 29 stage II, 26 stage III and 68 stage IV lung cancer patients, were recruited in this study. Quantitative relationship between primary tumor size and the plasma mSHOX2 level was established. Blood samples before therapy and two cycles after therapy were obtained from 68 stage IV patients, and the mSHOX2 level was quantified as ΔΔCt. RESULTS: Sharp decrease of plasma mSHOX2 level was seen in patients with partial response (PR) while not in those with stable disease (SD). The plasma mSHOX2 level change reflected the degree of response and correlated with the maximal diameter of primary tumors in linear relationship. The mSHOX2 levels before and two cycles after therapy were predictors of the overall survival, while the mSHOX2 level change or the tumor size change were not predictors of the overall survival. Furthermore, univariable and multivariable Cox regression revealed that mSHOX2 level before therapy was the only independent predictor of the overall survival with a hazard ratio of 1.414. CONCLUSIONS: mSHOX2 is effective for therapeutic effect assessment and prognosis prediction of stage IV lung cancer patients underwent systematic therapy.

Summary Developing a model of primate neural tube (NT) development is important to promote many NT disorder studies in model organisms. Here, we report a robust and stable system to allow for clonal expansion of single monkey neuroepithelial stem cells (NESCs) to develop into miniature NT-like structures. Single NESCs can produce functional neurons in vitro, survive, and extensively regenerate neuron axons in monkey brain. NT formation and NESC maintenance depend on high metabolism activity and Wnt signaling. NESCs are regionally restricted to a telencephalic fate. Moreover, single NESCs can turn into radial glial progenitors (RGPCs). The transition is accurately regulated by Wnt signaling through regulation of Notch signaling and adhesion molecules. Finally, using the “NESC-TO-NTs” system, we model the functions of folic acid (FA) on NT closure and demonstrate that FA can regulate multiple mechanisms to prevent NT defects. Our system is ideal for studying NT development and diseases., Graphical Abstract, Highlights • Long-term cultured neuroepithelial stem cells (NESCs) can be induced from monkey ESCs • Single NESCs can self-organize into miniature neural tube (NT) structures • NESCs have high metabolism activity and are restricted to a telencephalic fate • The “NESC-TO-NTs” system can model and study RPGC transition and NT defect disease, Li, Ji, and colleagues develop a robust and stable system to allow for clonal expansion of single monkey neuroepithelial stem cells (NESCs) to develop into miniature NT-like structures, providing a tractable in vitro platform with which to model and study radial glial progenitor transition, neural tube development, and neural tube defects.

Non-human primates provide optimal models for the development of stem cell therapies. Although somatic cells have been converted into neural stem/progenitor cells, it is unclear whether telencephalic neuroepithelial stem cells (NESCs) with stable properties can be generated from fibroblasts in primate. Here we report that a combination of transcription factors (Oct4, Sox2, Klf4) with a new culture medium induces rhesus monkey fibroblasts into NESCs, which can develop into miniature neural tube (NT)-like structures at a cell level. Furthermore, single induced NESCs (iNESCs) can generate later-stage 3D-NTs after grown on matrigel in suspension culture. iNESCs express NT cell markers, have a unique gene expression pattern biasing towards telencephalic patterning, and give rise to cortical neurons. Via transplantation, single iNESCs can extensively survive, regenerate myelinated neuron axons and synapse structures in adult monkey striatum and cortex, and differentiate into cortical neurons. Successful transplantation is closely associated with graft regions and grafted cell identities. The ability to generate defined and transplantable iNESCs from primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and cell therapy.

Based on rigid and twisted heterocyclic phthalazinone unit as the core skeleton, novel hierarchical porous carbazole-containing porous organic polymers (PCMOPs) were successfully constructed through Friedel-Crafts reaction (PCMOP-Hs) and oxidation coupling reaction (PCMOP-Os), respectively, with anhydrous FeCl3 as catalyst. The structures of resultant PCMOPs were characterized by FT-IR, 13C CP-MAS NMR and WXRD. PCMOP-Hs displayed higher BET surface area (660–675 m2 g−1), CO2 uptake capacity (11.8–12.1 wt%, 273 K, 1 bar) and CO2/N2 selectivity (up to 78.46, IAST) than those of PCMOP-Os, respectively. Even though, PCMOP-Os both displayed high sensitivity and selectivity with the fluorescent quenching rate value up to 83% for 2,4-dinitrotoluene (DNT) and 70% for nitrobenzene (NB) in low concentration (10−2 mol/L). The properties along with large-scale and low-cost preparation make these hierarchical POPs potential candidates for gas storage and separation as well as fluorescence detection of explosives application.