Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors.

Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bound CRF1R and CRF2R with the stimulatory G protein. In both structures, UCN1 adopts a single straight helix with its N terminus dipped into the receptor transmembrane bundle. Although the peptide-binding residues in CRF1R and CRF2R are different from other members of class B GPCRs, the residues involved in receptor activation and G protein coupling are conserved. In addition, both structures reveal bound cholesterol molecules to the receptor transmembrane helices. Our structures define the basis of ligand-binding specificity in the CRF receptor-hormone system, establish a common mechanism of class B GPCR activation and G protein coupling, and provide a paradigm for studying membrane protein-lipid interactions for class B GPCRs.

Macrophage polarization-related gene signature for risk stratification and prognosis of survival in gliomas.

Macrophage polarization plays an essential role in tumour immune cell infiltration and tumour growth. In this study, we selected a series of genes distinguishing between M1 and M2 macrophages and explored their prognostic value in gliomas. A total of 170 genes were included in our study. The CGGA database was used as the training cohort and the TCGA database as the validation cohort. The biological processes and functions were identified by GO and KEGG analysis. Kaplan-Meier analysis was used to compare survival differences between groups. Importantly, we built a risk score model using Cox regression analysis based on the CGGA and verified it in the TCGA database and our sequencing data. Patients with gliomas in the high-risk group were associated with high pathologic grade, IDH WT status, MGMT promoter unmethylation, 1p19q non-codeletion and prone to have a poor outcome. GEPIA results revealed that CD300C, CNRIP1 and MYO1F are the most related genes of immune infiltrations. The differential expression of these genes between low-grade gliomas and glioblastomas was confirmed by q-RT-PCR. Macrophage polarization-related gene signatures can predict the malignancy and outcome of patients with gliomas and might act as a promising target for glioma immunotherapy in the future.

TRIM13 Reduces Damage to Alveolar Epithelial Cells in COPD by Inhibiting Endoplasmic Reticulum Stress-Induced ER-Phagy.

PURPOSE: Tripartite motif-containing protein 13 (TRIM13) directly or indirectly participates in autophagy and apoptosis. However, it remains unclear whether TRIM13 participates in chronic obstructive pulmonary disease (COPD) progression. This study aimed to reveal the molecular mechanisms through which TRIM13 regulates alveolar epithelial cell injury in COPD to provide new molecular targets for COPD treatment. METHODS: The TRIM13 expression levels were determined in clinical COPD patients and a rat emphysema model. A cigarette smoke-induced model of endoplasmic reticulum stress (ERS) and endoplasmic reticulum autophagy (ER-phagy) was developed using A549 cells, and the effects of TRIM13 gene overexpression/knockdown on ERS, ER-phagy, and cell apoptosis were assessed in these cells. RESULTS: TRIM13 expression was significantly decreased in the lung tissues of COPD patients and rats with emphysema. Moreover, the apoptosis level was significantly increased in the lung tissues of rats with emphysema. TRIM13 gene overexpression reduced the expression levels of ERS-related molecules (GRP78, GRP94, XBP-1, and eIF2a) in the COPD model; it also lowered the ER-phagy level, as evidenced by decreased number of autolysosomes observed by transmission electron microscopy, improved endoplasmic reticulum structure, reduced LC3-II/LC3-I and Beclin1 expression levels, and increased expression level of the autophagy inhibitory molecule Bcl-2. TRIM13 gene knockdown, however, led to opposite results. CONCLUSION: TRIM13 expression attenuated alveolar epithelial cell injury in COPD by inhibiting ERS-induced ER-phagy.

Evaluation of the potential probiotic Bacillus subtilis isolated from darkbarbel catfish (Pelteobagrus fulvidraco) on growth performance, serum immunity, and disease resistance of Aeromonas hydrophila.

This study aimed to identify potential probiotic strains of Bacillus subtilis from healthy fish gut microbiota for application in aquaculture. The effects of dietary B. subtilis administration on growth performance, serum enzyme activity, immune gene expression, and disease resistance in darkbarbel catfish (Pelteobagrus fulvidraco) were investigated. The isolate, identified through gene sequencing and biochemical tests, demonstrated resilience to pH 3.0% and 6.0% bile, and exhibited extracellular protease, cellulose, lipase, and amylase production. Darkbarbel catfish were fed diets with varying B. subtilis concentrations (0 CFU/kg [T0], 107 CFU/kg [T1], 108 CFU/kg [T2], and 109 CFU/kg [T3]). After 8 weeks, significant increases (p < 0.05) were observed in final body weight, weight gain rate, specific growth rate, serum lysozyme, serum superoxide dismutase, alkaline phosphatase, and total antioxidant capacity, whereas malondialdehyde levels significantly decreased. Feeding darkbarbel catfish with B. subtilis diets increased immunoglobulin M (IgM) and C3 gene expression (p < 0.05), indicating a positive impact on the fish's immune system. The strain upregulated interleukin 10 (IL-10) and transforming growth factor-ß (TGF-ß) expression and downregulated TNF-α and IL-1ß, suggesting potential anti-inflammatory effects. Following a 7-day challenge with Aeromonas hydrophila, fish fed with B. subtilis exhibited lower mortality, with higher survival rates in the T2 and T3 groups. In conclusion, supplementing darkbarbel catfish diets with B. subtilis effectively enhances growth performance, immune response, and disease resistance.

Ultra-high Q lithium niobate microring monolithically fabricated by photolithography assisted chemo-mechanical etching.

As one of the element photonic structures, the state-of-the-art thin-film lithium niobate (TFLN) microrings reach an intrinsic quality (Q) factor higher than 107. However, it is difficult to maintain such high-Q factors when monolithically integrated with bus waveguides. Here, a relatively narrow gap of an ultra-high Q monolithically integrated microring is achieved with 3.8 µm, and a high temperature annealing is carried out to improve the loaded (intrinsic) Q factor with 4.29 × 106 (4.04 × 107), leading to an ultra-low propagation loss of less than 1 dB/m, which is approximately 3 times better than the best values previously reported in ion-slicing TFLN platform.

Polygonatum sibiricum Polysaccharide Inhibited Liver Cancer in a Simulated Tumor Microenvironment by Eliminating TLR4/STAT3 Pathway.

Liver cancer is one of the most aggressive tumors and one of the most common malignant tumors which seriously threatens human health. Traditional Chinese medicine (TCM) was reported to resist the proliferation and metastasis of liver cancer cells. In this study, we aimed to explore the potential anti-cancer effect of Polygonatum sibiricum polysaccharide (PSP) on the tumor immune microenvironment in liver cancer cells. HepG2 and Hep3B cells were pretreated in the absence or the presence of PSP (20, 50, 100 µg/mL) for a period of 24 h. Subsequently, dendritic cells (DCs) were co-cultured with HepG2 and Hep3B cell supernatant to investigate the effect of PSP on the tumor microenvironment. The results showed that PSP dose-dependently inhibited proliferation and promoted apoptosis of HepG2 and Hep3B cells. Meanwhile, PSP dose-dependently inhibited migration, invasion, and epithelial-to-mesenchymal transition (EMT) of liver cancer cells. In addition, PSP dose-dependently induced inflammatory response of DCs, characterized by increases of interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α in DCs. Mechanically, PSP dose-dependently reduced the activation of the Toll-like receptor 4 (TLR4)/Signal transducer and activator of transcription 3 (STAT3) and noncanonical nuclear factor-kappa B (NF-κB) signaling pathways. TLR4 agonist lipopolysaccharide (LPS) reversed the anti-oncogenic effects of PSP in liver cancer cells. Taken together, PSP inhibited liver cancer in a simulated tumor microenvironment by eliminating TLR4/STAT3 pathway. PSP promises an important and useful alternative to liver cancer treatment.

Traditional Chinese herb formulas in diet enhance the non-specific immune responses of yellow catfish (Pelteobagrus fulvidraco) and resistance against Aeromonas hydrophila.

The effects of a traditional Chinese herbal mixture (TCHM) composed of Glycyrrhiza uralensis, Astragalus membranaceus, Rheum palmatum, Catsia tora and Lonicera japonica on immune response and disease resistance of yellow catfish (Pelteobagrus fulvidraco) were studied. Fish were fed diets containing 0% (control), 1.0%, 3.0% or 5.0% TCHM (w/w) for 28 d. Immune parameters including cytokine genes interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and Immunoglobulin M (IgM), acid phosphatase (ACP), alkaline phosphatase (AKP), lysozyme (LZM), catalase (CAT), superoxide dismutase (SOD) and immunoglobulin M (IgM) were measured during the test period. After 28 d of feeding, fish were infected with Aeromonas hydrophila, and mortality was recorded. The TCHM-supplementation diet stimulated ACP, AKP, LZM, CAT, SOD, and IgM activity in serum and induced IL-1ß, TNF-α, and IgM mRNA expression in the spleen. All TCHM groups showed reduced mortality after A. hydrophila infection compared to the control group. These results suggest that the TCHM-supplemented diet can improve fish immunity and disease resistance against A. hydrophila.

Antiparasitic Efficacy of Crude Plant Extracts and Compounds Purified from Plants against the Fish Monogenean Neobenedenia girellae.

Neobenedenia girellae is a pathogenic ectoparasite of many marine fishes, and it causes major epidemics in marine aquaculture. In this study, the efficacy of ethanol extracts of huangqi Astragalus membranaceus (known as milkvetch in North America), guanzhong Dryopteris setosa (known as beaded wood fern in North America), gancao Glycyrrhiza uralensis (known as Chinese licorice in North America), danshen Salvia miltiorrhiza (known as red sage in North America), and pomegranate Punica granatum, as well as seven phytochemicals (10-gingerol, curcumin, cynatratoside-C, emodin, kuwanon-G, kuwanon-O, and sophoraflavanone-G), against adult N. girellae was investigated. In vitro results indicated that pomegranate extract killed all adult N. girellae at a 62.5-mg/L concentration with an 8-h exposure, but gancao extract did not cause 100% mortality until a 1,000-mg/L concentration was used. Additionally, all adult N. girellae died after an 8-h exposure to cynatratoside-C, kuwanon-G, kuwanon-O, or sophoraflavanone-G at a concentration of 125 mg/L. Curcumin, emodin, and 10-gingerol at a concentration of 1,000 mg/L did not kill all parasites after an 8-h exposure. These findings demonstrate that plant extracts and active phytochemicals are potential sources of botanical drugs for controlling N. girellae infection in aquaculture.

[Single-particle cryo-electron microscopy opens new avenues in structural biology of G protein-coupled receptor].

G protein-coupled receptors(GPCRs)represent the largest class of cell surface receptors,mediating wide range of cellular and physiological processes through their transducers,G proteins and the-arrestins participate in almost all pathological processes. Recent technological advances are revolutionizing the utility of cryo-electron microscopy(cryo-EM),leading to a tremendous progress in the structural studies of biological macromolecules and cryo-EM has played a leading role in the structural biology of GPCR signaling complex. New discoveries of high-resolution threedimensional structures of GPCR signaling complexes based on cryo-EM have emerged vigorously,which depict the common structural characteristics of intermolecular interaction between GPCR and G protein complex-the conformational changes of the transmembrane helix 6 of receptors,and also demonstrate the structural basis of G protein subtype selectivity. Single-particle cryo-EM becomes an efficient tool for identifying the molecular mechanism of receptor-ligand interaction,providing important information for understanding GPCR signaling and the structure-based drug design.

[Neuronavigator-assisted microsurgical resection of glioma located in cerebral functional areas].

OBJECTIVE: To evaluate value of neuronavigator-assisted microsurgery of glioma located in cerebral functional areas.
 Methods: Patients with glioma located in cerebral functional areas were underwent operation in Xiangya Hospital. Of 64 patients, 34 patients were performed neuronavigator-assisted microsurgery, and 30 were underwent routine surgical operation.
 Results: The neuronavigator-assisted microsurgery group showed high complete resection rate with low neurological deficit and cerebral edema compared with the routine surgical group (P<0.05).
 Conclusion: Neuronavigator-assisted microsurgery is effective and characterized by accurate location, personalized operative incision design, and higher rate of tumor resection.

Can non-invasive positive pressure ventilation prevent endotracheal intubation in acute lung injury/acute respiratory distress syndrome? A meta-analysis.

The role of non-invasive positive pressure ventilation (NIPPV) in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is controversial. The aim of this study was to investigate whether NIPPV could prevent endotracheal intubation and decrease mortality rate in patients with ALI/ARDS. Randomized controlled trials (RCT) which reported endotracheal intubation and mortality rate in patients with ALI/ARDS treated by NIPPV were identified in Pubmed, Medline, Embase, Central Cochrane Controlled Trials Register, Chinese National Knowledge Infrastructure, reference lists and by manual searches. Fixed- and random-effects models were used to calculate pooled relative risks. This meta-analysis included six RCT involving 227 patients. The results showed that endotracheal intubation rate was lower in NIPPV (95% confidence interval (CI): 0.44-0.80, z = 3.44, P = 0.0006), but no significant difference was found either in intensive care unit (ICU) mortality (95% CI: 0.45-1.07, z = 1.65, P = 0.10) or in hospital mortality (95% CI: 0.17-1.58, z = 1.16, P = 0.25). Only two studies discussed the aetiology of ALI/ARDS as pulmonary or extra-pulmonary, and neither showed statistical heterogeneity (I(2) = 0%, χ(2) = 0.31, P = 0.58), nor a significant difference in endotracheal intubation rate (95% CI: 0.35-9.08, z = 0.69, P = 0.49). In conclusion, the early use of NIPPV can decrease the endotracheal intubation rate in patients with ALI/ARDS, but does not change the mortality of these patients.

Financial inclusion, environmental degradation, and the moderating role of ICT: a global perspective.

This study aims to investigate the global perspective on the relationship between financial inclusion and environmental degradation, taking into account the potential moderating role of information and communication technology (ICT). The research utilizes panel data from 131 countries, covering the period of 1995 to 2019. The findings show that financial inclusion has significant and positive impact on carbon emissions, implying that as financial inclusion increases, so do carbon emissions. Moreover, our findings reveal a significant negative moderating effect of the ICT on the relationship between financial inclusion and carbon emissions. This implies that the impact of financial inclusion on carbon emissions is contingent upon the level of ICT development. The robustness of these findings is confirmed through the use of alternative proxies for the explanatory and moderating variables, as well as alternative estimation methods. The outcomes of this study carry significant implications for both policy and practice.

Pretreatment of artesunate promoted hepatocyte proliferation by activating the PI3K/Akt/mTOR signaling pathway in mice.

PURPOSE: Artesunate (ART) has been implicated in regulating the many processes of liver injury, but its roles in liver regeneration still need to be illustrated. METHODS: In the present study, ART was used to pretreat hepatocyte cell line NCTC1469 to study the effect of ART on hepatocyte proliferation in vitro. Furthermore, the potency of ART as a regimen to promote liver regeneration and restore liver function was evaluated following partial hepatectomy (PH) on C57BL/6 mice. RESULTS: ART concentration-dependently promoted hepatocyte proliferation and reduced apoptosis. Cell cycle and Ki-67 immunohistochemical analyses demonstrated that ART supplementation promoted the proliferation of hepatocytes and accelerated liver regeneration. Our results provided evidence that ART improved liver function in a dose-dependent manner, as indicated by decreased serum alanine aminotransferase, aspartate aminotransferase, and increased albumin, and hepatocyte growth factor levels in PH mice. Meanwhile, ART promoted the PI3K/Akt/mTOR signaling in NCTC1469 cells and liver tissue of PH mice. In addition, PI3K inhibitor LY294002 blocked the promotion effect of ART on hepatocyte proliferation and cell cycle progression. CONCLUSION: ART promoted hepatocyte proliferation via activation of the PI3K/Akt/mTOR pathway, which was beneficial to liver regeneration of PH-induced liver injury.

Immunotoxicity of microplastics and polychlorinated biphenyls alone or in combination to Crassostrea gigas.

Microplastics (MPs) and polychlorinated biphenyls (PCBs) are pervasive pollutants in the marine environment, exerting adverse effects on marine organisms. While it is suggested that their exposure may compromise the immune responses of marine organisms, the cumulative immunotoxic effects remain uncertain. Additionally, the intricate mechanisms underlying the immunotoxicity of PCBs and MPs in marine organisms are not yet fully comprehended. To illuminate their combined biological impacts, Crassostrea gigas were exposed to 50 µg/L MPs (30-µm porous) alone, as well as 10 or 100 ng/L PCBs individually or in combination with 50 µg/L of MPs for 28 days. Our data demonstrated that oysters treated with the pollutants examined led to decreased total haemocyte count, inhibited phagocytosis of haemocytes, enhanced the intracellular contents of reactive oxygen species, lipid peroxidation and DNA damage, reduced lysozyme concentration and activity, gave rise to superoxide dismutase. Catalaseand glutathione S-transferaseactivity. The expression of three immune-related genes (NF-κB, TNF-α, TLR-6) was drastically suppressed by the PCBs and MPs treatment, while the apoptosis pathway-related genes (BAX and Caspase-3) showed a significant increase. In addition, compared to oysters treated with a single type of pollutant, coexposure to MPs and PCBs exerted more severe adverse impacts on all the parameters investigated, indicating a significant synergistic effect. Therefore, the risk of MPs and PCBs chemicals on marine organisms should be paid more attention.

AURKA inhibition shows promise as a therapeutic strategy for ARID1A-mutant colorectal cancer.

PURPOSE: Mutations in ARID1A frequently occur in colorectal cancer (CRC) cells. However, there are currently no clinical treatment options specifically addressing this aberration. The preliminary in vitro experiments revealed a synthetic lethal interaction between ARID1A and Aurora kinase A (AURKA) in colorectal cancer (CRC) cells. METHODS: We collected samples from 80 CRC patients and evaluated the efficacy of AURKA inhibitor (AURKAi) using the ATP-tumor chemosensitivity assay (ATP-TCA) on untreated ARID1A-proficient (ARID1A +) and ARID1A-deficient (ARID1A-) CRC patient samples. In addition, we validated this result by a clonogenic assay. Additionally, we examined the effects of AURKA inhibitors on cell cycle progression and apoptosis in ARID1A + and ARID1A- CRC patient samples using flow cytometry. RESULTS: The results showed that AURKAi selectively inhibited the growth of ARID1A- CRC cells. Furthermore, AURKA inhibitors significantly increased G2/M arrest and induced apoptosis in ARID1A- cells. CONCLUSION: We believe that AURKAi hold promise as potential therapeutics for ARID1A mutation colorectal cancer patients.

Recent Progresses on Hybrid Lithium Niobate External Cavity Semiconductor Lasers.

Thin film lithium niobate (TFLN) has become a promising material platform for large scale photonic integrated circuits (PICs). As an indispensable component in PICs, on-chip electrically tunable narrow-linewidth lasers have attracted widespread attention in recent years due to their significant applications in high-speed optical communication, coherent detection, precision metrology, laser cooling, coherent transmission systems, light detection and ranging (LiDAR). However, research on electrically driven, high-power, and narrow-linewidth laser sources on TFLN platforms is still in its infancy. This review summarizes the recent progress on the narrow-linewidth compact laser sources boosted by hybrid TFLN/III-V semiconductor integration techniques, which will offer an alternative solution for on-chip high performance lasers for the future TFLN PIC industry and cutting-edge sciences. The review begins with a brief introduction of the current status of compact external cavity semiconductor lasers (ECSLs) and recently developed TFLN photonics. The following section presents various ECSLs based on TFLN photonic chips with different photonic structures to construct external cavity for on-chip optical feedback. Some conclusions and future perspectives are provided.

Artificial intelligence-driven microbiome data analysis for estimation of postmortem interval and crime location.

Microbial communities, demonstrating dynamic changes in cadavers and the surroundings, provide invaluable insights for forensic investigations. Conventional methodologies for microbiome sequencing data analysis face obstacles due to subjectivity and inefficiency. Artificial Intelligence (AI) presents an efficient and accurate tool, with the ability to autonomously process and analyze high-throughput data, and assimilate multi-omics data, encompassing metagenomics, transcriptomics, and proteomics. This facilitates accurate and efficient estimation of the postmortem interval (PMI), detection of crime location, and elucidation of microbial functionalities. This review presents an overview of microorganisms from cadavers and crime scenes, emphasizes the importance of microbiome, and summarizes the application of AI in high-throughput microbiome data processing in forensic microbiology.

Low-Threshold Anti-Stokes Raman Microlaser on Thin-Film Lithium Niobate Chip.

Raman microlasers form on-chip versatile light sources by optical pumping, enabling numerical applications ranging from telecommunications to biological detection. Stimulated Raman scattering (SRS) lasing has been demonstrated in optical microresonators, leveraging high Q factors and small mode volume to generate downconverted photons based on the interaction of light with the Stokes vibrational mode. Unlike redshifted SRS, stimulated anti-Stokes Raman scattering (SARS) further involves the interplay between the pump photon and the SRS photon to generate an upconverted photon, depending on a highly efficient SRS signal as an essential prerequisite. Therefore, achieving SARS in microresonators is challenging due to the low lasing efficiencies of integrated Raman lasers caused by intrinsically low Raman gain. In this work, high-Q whispering gallery microresonators were fabricated by femtosecond laser photolithography assisted chemo-mechanical etching on thin-film lithium niobate (TFLN), which is a strong Raman-gain photonic platform. The high Q factor reached 4.42 × 106, which dramatically increased the circulating light intensity within a small volume. And a strong Stokes vibrational frequency of 264 cm-1 of lithium niobate was selectively excited, leading to a highly efficient SRS lasing signal with a conversion efficiency of 40.6%. And the threshold for SRS was only 0.33 mW, which is about half the best record previously reported on a TFLN platform. The combination of high Q factors, a small cavity size of 120 µm, and the excitation of a strong Raman mode allowed the formation of SARS lasing with only a 0.46 mW pump threshold.

Clinical sequencing reveals diagnostic, therapeutic, and prognostic biomarkers for adult-type diffuse gliomas.

Diffuse gliomas in adults are highly infiltrative and largely incurable. Whole exome sequencing (WES) has been demonstrated very useful in genetic analysis. Here WES was performed to characterize genomic landscape of adult-type diffuse gliomas to discover the diagnostic, therapeutic and prognostic biomarkers. Somatic and germline variants of 66 patients with adult-type diffuse gliomas were detected by WES based on the next-generation sequencing. TCGA and CGGA datasets were included to analyze the integrated diagnosis and prognosis. Among 66 patients, the diagnosis of 9 cases was changed, in which 8 cases of astrocytoma were corrected into IDH-wildtype glioblastoma (GBM), and 1 oligodendroglioma without 1p/19q co-deletion into astrocytoma. The distribution of mutations including ATRX/TP53 differed in three cohorts. The genetic mutations in GBM mainly concentrated on the cell cycle, PI3K and RTK pathways. The mutational landscape of astrocytoma was more similar to that of GBM, with the highest frequency in germline variants. Patients with IDH-mutant astrocytoma harboring SNVs of PIK3CA and PIK3R1 showed a significantly worse overall survival (OS) than wild-type patients. AEBP1 amplification was associated with shorter OS in GBM. Our study suggests that clinical sequencing can recapitulate previous findings, which may provide a powerful approach to discover diagnostic, therapeutic and prognostic markers for precision medicine in adult-type diffuse gliomas.

Electrophysiological characterisation of human umbilical cord blood-derived mesenchymal stem cells induced by olfactory ensheathing cell-conditioned medium.

Umbilical cord blood-derived marrow stromal cells (UCB-MSCs) with high proliferation capacity and immunomodulatory properties are considered to be a good candidate for cell-based therapies. But until now, little work has been focused on the differentiation of UCB-MSCs. In this work, UCB-MSCs were demonstrated to be negative for CD34 and CD45 expression but positive for CD90 and CD105 expression. The gate values of UCB-MSCs for CD90 and CD105 were 99.3 and 98.6 %, respectively. Two weeks after treatment, the percentage of neuron-like cells differentiated from UCB-MSCs was increased to 84 ± 12 % in the experimental group [treated with olfactory ensheathing cells (OECs)-conditioned medium] and they were neuron-specific enolase positive; few neuron-like cells were found in the control group (without OECs-conditioned medium). Using whole-cell recording, sodium and potassium currents were recorded in UCB-MSCs after differentiation by OECs. Thus, human UCB-MSCs could be differentiated to neural cells by secreted secretion from OECs and exhibited electrophysiological properties similar to mature neurons after 2 weeks post-induction. These results imply that OECs can be used as a new strategy for stem cell differentiation and provide an alternative neurogenesis pathway for generating sufficient numbers of neural cells for cell therapy.