Identification of potential key ferroptosis- and autophagy-related genes in myelomeningocele through bioinformatics analysis.

Myelomeningocele is a common congenital anomaly associated with polygenic disorders worldwide. However, the intricate molecular mechanisms underlying myelomeningocele remain elusive. To investigate whether ferroptosis and ferritinophagy contribute to the pathomechanism of myelomeningocele, differentially expressed genes (DEGs) were identified as novel biomarker and potential treatment agents. The GSE101141 dataset from Gene Expression Omnibus (GEO) was analyzed using GEO2R web tool to obtain DEGs based on |log2 fold change (FC)|≥1.5 and p < 0.05. Two datasets from the Ferroptosis Database (481 genes) and Autophagy Database (551 genes) were intersected with the DEGs from the GSE101141 dataset to identify ferroptosis- and autophagy-related DEGs using Venn diagrams. Functional and pathway enrichment, protein-protein interaction (PPI) network analyses were performed, and candidate genes were selected. Transcription factors (TFs), microRNAs (miRNAs), diseases and chemicals interacting with the candidate genes were identified. Receiver operating characteristic (ROC) curve analysis was performed to validate the diagnostic value of the candidate genes. Sixty ferroptosis-related and 74 autophagy-related DEGs were identified. These DEGs are involved in FoxO signaling pathway. Six candidate genes (EGFR, KRAS, IL1B, SIRT1, ATM, and MAPK8) were selected. miRNAs such as hsa-miR-27a-3p, hsa-miR-877-5p, and hsa-miR-892b, and TFs including P53, POU3F2, TATA are involved in regulation of candidate genes. Diseases such as schizophrenia, fibrosis, and neoplasms are the most relevant to the candidate genes. Chemicals, such as resveratrol, curcumin, and quercetin may have significant implications in the treatment of myelomeningocele. The candidate genes, especially MAPK8, also showed a high diagnostic value for myelomeningocele. These results help to shed light on the molecular mechanism of myelomeningocele and may provide new insights into diagnostic biomarker in the amniotic fluid and potential therapeutic agents of myelomeningocele.

Seismic sedimentology response characteristics of nearshore terminal fan in the suning area of Raoyang Sag, Bohai Bay Basin, NE China.

A nearshore terminal fan is a special water system formed in arid environments. The characterisation of its thin-channel sand bodies has long been a challenge restricting oil and gas exploration. This study takes the Suning area of the Raoyang Sag as an example and uses the principles of seismic sedimentology to conduct seismic sedimentary research on the nearshore terminal fan of the first member of the Palaeogene Shahejie Formation (Es1) based on three-dimensional seismic, logging, and core analysis. Seven fourth-order sequences (SQV7) were identified within Es1, deposited by a fluvial river system terminating at the contracting bank of a lake. Prograding terminal fan sedimentary facies on a gentle slope zone were observed in the root mean square seismic attributes after spectral decomposition. We have successfully resolved the sandstone within the studied terminal fan system using a 90° phase conversion of the seismic data and red-green-blue (RGB) fusion of the various seismic attributes. The upper subsegment of the Shahejie Formation developed extensive nearshore terminal fan sedimentation, and the seismic sedimentological response characteristics were mainly channel-like and strip-shaped geomorphic systems deposited on gentle slope zones, indicating distributary channels and distal basin sedimentation. This study enriches our understanding of nearshore fans and provides ideas for predicting favourable sand bodies in this type of sedimentary facies.

Inpp5e Regulated the Cilium-Related Genes Contributing to the Neural Tube Defects Under 5-Fluorouracil Exposure.

Primary cilia are crucial for neurogenesis, and cilium-related genes are involved in the closure of neural tubes. Inositol polyphosphate-5-phosphatase (Inpp5e) was enriched in primary cilia and closely related to the occurrence of neural tube defects (NTDs). However, the role of Inpp5e in the development of NTDs is not well-known. To investigate whether Inpp5e gene is associated with the neural tube closure, we established a mouse model of NTDs by 5-fluorouracil (5-FU) exposure at gestational day 7.5 (GD7.5). The Inpp5e knockdown (Inpp5e-/-) mouse embryonic stem cells (mESCs) were produced by CRISPR/Cas9 system. The expressions of Inpp5e and other cilium-related genes including intraflagellar transport 80 (Ift80), McKusick-Kaufman syndrome (Mkks), and Kirsten rat sarcoma viral oncogene homolog (Kras) were determined, utilizing quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, PCR array, and immunofluorescence staining. The result showed that the incidence of NTDs was 37.10% (23 NTDs/62 total embryos) and significantly higher than that in the control group (P < 0.001). The neuroepithelial cells of neural tubes were obviously disarranged in NTD embryos. The mRNA and protein levels of Inpp5e, Ift80, Mkks, and Kras were significantly decreased in NTD embryonic brain tissues, compared to the control (P < 0.05). Knockdown of the Inpp5e (Inpp5e-/-) reduced the expressions of Ift80, Mkks, and Kras in mESCs. Furthermore, the levels of α-tubulin were significantly reduced in NTD embryonic neural tissue and Inpp5e-/- mESCs. These results suggested that maternal 5-FU exposure inhibited the expression of Inpp5e, which resulted in the downregulation of cilium-related genes (Ift80, Mkks, and Kras), leading to the impairment of primary cilium development, and ultimately disrupted the neural tube closure.

Cytosine arabinoside exposure induced cytotoxic effects and neural tube defects in mice and embryo stem cells.

Cytosine arabinoside (Ara-C) is one of the most widely used chemotherapeutic agents for hematological malignancies. The residues of Ara-C have been detected in wastewater and river water with increased usage and discharge. As the ability to cross the placenta and the teratogenicity at low ng/L levels, the toxic effects on pregnant women and infants have been concerned. The toxicity of Ara-C exposure on early embryonic neurodevelopment has not been fully elucidated. In this study, pregnant C57BL/6 mice were injected with different doses of Ara-C on Gestation day (GD) 7.5 and assessed on GD11.5 and GD13.5 to explore the neural developmental effects of Ara-C. HE staining, immunofluorescence, western blot, EdU assay, and flow cytometry were utilized to determine the toxic effects of Ara-C in vivo and in vitro. Our results showed that Ara-C (15-22.5 mg/kg body weight) induced the occurrence of neural tube defects (NTDs). The expression of PH3 was markedly reduced in embryos with Ara-C-induced NTDs, compared to the control group (P < 0.05). In contrast, cell apoptosis was markedly increased. Increased expression levels of GFAP and decreased Nestin were observed in the embryonic brain tissues in Ara-C induced NTDs. The level of ß-catenin was also decreased on both GD11.5 and GD13.5. These results were confirmed in vitro using mouse Sv129 embryonic stem cells (mESC). Ara-C at a dose comparable to the environment level (0.05 nM) had cytotoxicity. Impaired Wnt/ß-catenin signaling pathway is involved in Ara-C exposure induced imbalance between cell proliferation, apoptosis, and differentiation, which might contribute to Ara-C-induced occurrence of NTDs. Our data indicated the environmental concentration of Ara-C had cytotoxicity and that maternal exposure to Ara-C induced NTDs. These results might provide more information to understand the environmental toxic impact of Ara-C on neurodevelopment.

Research progress on aging mechanism and drugs and the role of stem cells in anti-aging process.

There have been many discussions on longevity from ancient times to the present day. In the Laozi, it is said, "Heaven and earth are long and enduring because they do not arise from themselves, so they can live forever." In Zhuangzi - Zai You, it is also said, "Keep your mental peace, and your body will be healthy. Don't strain your body and don't consume your spirit to live a long life." It is clear that people attach importance to anti-aging and the desire for longevity. Throughout human history, we have treated aging as an inevitable process, but with the development of medical science, we have become more aware of the various molecular changes in the human body. In an aging society, more people are suffering from age-related diseases such as osteoporosis, Alzheimer's disease, and cardiovascular disease, which has led to a search for anti-aging. However, by 'living longer' we mean not only living but also living longer in good health. The mechanisms of aging are still unclear and there is a great deal of interest and curiosity in how to combat aging effectively. Some potential criteria exist for the determination of anti-aging drugs: the first criterion is the ability to exert life-extending effects in model organisms, preferably in mammals; the second criterion is the ability to prevent or delay several age-related diseases in mammals; and the third criterion is the ability to inhibit the transition of cells from a quiescent to a senescent state. Based on these criteria, the current anti-aging drugs often involved are rapamycin, metformin, curcumin and other polyphenols, polysaccharides, resveratrol, etc. The most studied and relatively well-understood pathways and factors of aging are currently known to include seven enzymes, six biological factors, and one chemical, which mainly involve more than ten pathways such as Nrf2/SKN-1; NFκB; AMPK; P13K/AKT; IGF; and NAD.

Clinical efficacy and safety of two different hematoporphyrin monomethyl ether-mediated photodynamic therapy regimen in Chinese children with port-wine stain.

Hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has achieved encouraging clinical outcomes in adult port-wine stain (PWS). Optimal treatment option for children with PWS was minimal. To compare whether the clinical effectiveness of HMME-PDT with the 5-min (fast) administration treatment regimen (FATR) was better than the 20-min (slow) administration treatment regimen (SATR) for PWS of children in vivo and in vitro. Thirty-four children with PWS were divided into two groups including FATR and SATR. The two groups received three times HMME-PDT, respectively. Treatment efficacy and safety were evaluated in vivo and in vitro. Erythema index (EI) was used to evaluate the clinical outcomes. Both FATR and SATR were effective and safe in children with PWS after HMME-PDT. There were significance differences between the two groups in reductions of EI after the second treatment (p < 0.001) and the third treatment (p < 0.001) with HMME-PDT. The serum HMME concentration reach the peak level at short time compare with SATR group. A significance increased superoxide levels were observed in FATR group compare to SATR groups in vitro (p < 0.05). Our study suggested that HMME-PDT was effective and safe for children with PWS, the therapy regimen with FATR was better in clinical efficacy than that of the SATR.

Neural Tube Defects and Folate Deficiency: Is DNA Repair Defective?

Neural tube defects (NTDs) are complex congenital malformations resulting from failure of neural tube closure during embryogenesis, which is affected by the interaction of genetic and environmental factors. It is well known that folate deficiency increases the incidence of NTDs; however, the underlying mechanism remains unclear. Folate deficiency not only causes DNA hypomethylation, but also blocks the synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP) and increases uracil misincorporation, resulting in genomic instabilities such as base mismatch, DNA breakage, and even chromosome aberration. DNA repair pathways are essential for ensuring normal DNA synthesis, genomic stability and integrity during embryonic neural development. Genomic instability or lack of DNA repair has been implicated in risk of development of NTDs. Here, we reviewed the relationship between folate deficiency, DNA repair pathways and NTDs so as to reveal the role and significance of DNA repair system in the pathogenesis of NTDs and better understand the pathogenesis of NTDs.

Genetic Effects of ITPK1 Polymorphisms on the Risk of Neural Tube Defects: a Population-Based Study.

Inositol is closely related to the occurrence of neural tube defects (NTDs). Inositol 1, 3, 4-trisphosphate 5/6-kinase (ITPK1) gene encoded an essential regulatory enzyme ITPK1, which is involved in inositol metabolism and has a critical role in the development of neural tube and axial mesoderm. It had been reported that some polymorphisms of critical genes in inositol pathways, including ITPK1, were associated with NTDs in Chinese pregnant women; however, the association between fetus ITPK1 polymorphisms and NTDs had not been reported. In a high incidence of NTDs region of China, a case-control study was performed to evaluate the association between fetal ITPK1 polymorphisms and NTDs. The ITPK1 polymorphisms were genotyped by iPLEX® Gold assay. Inositol levels in fetus brain tissues were analyzed. Three genetic polymorphisms of fetus ITPK1's, including rs3818175, rs2295394, and rs4586354, were statistically associated with spina bifida (NTD subtypes). A higher risk of spina bifida was associated with genotype GG of rs3818175, genotype CC of rs4586354, and genotype TT of rs2295394 (OR = 2.66, 95% CI [1.17-6.05], P = 0.017; OR = 2.22, 95% CI [1.02-4.80], P = 0.041; and OR = 2.33, 95% CI [1.00-5.48], P = 0.047), when compared with the other wild-type genotypes CC, TT, and CC, respectively. Decreased brain inositol level was found in NTDs fetuses, compared to normal controls. Inositol levels were found to significantly decrease with rs2295394 (CC genotype), rs4586354 (TT genotype), and rs3818175 (GC genotype) (P < 0.05). The polymorphisms of fetus ITPK1 were associated with the incidence of NTDs and might be a genetic risk factor for spina bifida.

Activation of the hedgehog signaling pathway is associated with the promotion of cell proliferation and epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps.

PURPOSE: To investigate the pathogenesis of the hedgehog (Hh) signaling pathway activated by inflammation in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: The 82 people including CRSwNP patients (case group) and nasal septal deviation patients (control group) were recruited. The samples in the case group were collected and classified into two groups: mucosal tissue of nasal polyps (NP group) and mucosal tissue adjacent to nasal polyps (NM group), the samples were collected from the control group as CM group. Clinical characteristics were assessed. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed to detect eosinophils (EOS), the expression of the key genes of the pathway and epithelial-mesenchymal transition (EMT) markers in the samples. RESULTS: There were significant differences in the nasal obstruction visual analog scale (VAS) score, rhinorrhea VAS score, percentage of blood EOS, blood EOS absolute counts and tissue EOS counts in the case group compared with the control group (P < 0.05). The EOS level and expression levels of PTCH1, SMO, Gli1, Gli2, Ki67 and vimentin were higher in NP group than in the other two groups (P < 0.05). E-cadherin expression was decreased in NP group (P < 0.05). A positive correlation between PTCH1 expression and CRSwNP Lund-Mackay score in NP group. CONCLUSIONS: Our results indicated that the activation of Hh signaling pathway might promote cell proliferation and EMT occurrence, ultimately leading to the development of CRSwNP, which might provide a new target for treatment.

BMP/Smad Pathway Is Involved in Lithium Carbonate-Induced Neural-Tube Defects in Mice and Neural Stem Cells.

Neural-tube defects (NTDs) are one type of the most serious birth defects. Studies have shown that inositol deficiency is closely related to the occurrence of NTDs. Bone morphogenetic protein (BMP)-mediated Smad signaling pathways have been implicated in neurogenesis and neural-tube closure. However, the role of the BMP/Smad pathway in inositol-deficiency-induced NTDs remains unclear. Inositol-deficiency models in C57 mice and mouse neural stem cells (mNSCs) were induced with Li2CO3 treatment or inositol withdrawal. The role of the BMP/Smad pathway in the regulation of cell proliferation and the development of NTDs was determined utilizing qRT-PCR, HE staining, Western blot, immunostaining, MTT assay, EdU staining, and flow cytometry. The intraperitoneal injection of Li2CO3 at Embryonic Day 7.5 induced the occurrence of NTDs. The mRNA levels of Bmp2, Bmp4, Smad1, Smad5, Smad8 and Runx2, the phosphorylation of Smad1/5/8, and the nuclear translocation of Runx2 were significantly increased in NTD embryonic brain tissues and mNSCs exposed to Li2CO3 or an inositol-free medium, which were suppressed by BMP receptor selective inhibitor LDN-193189. The Li2CO3-induced phosphorylation of Smad1/5/8 was inhibited by inositol supplementation. Cell proliferation was significantly promoted by Li2CO3 exposure or the absence of inositol in mNSCs, which was reversed by LDN-193189. These results suggest that the activation of the BMP/Smad signaling pathway might play an important role in the development of NTDs induced by maternal Li2CO3 exposure via inositol deficiency.

Unraveling the Mechanisms of Clinical Drugs-Induced Neural Tube Defects Based on Network Pharmacology and Molecular Docking Analysis.

Chemotherapeutic agents such as methotrexate (MTX), raltitrexed (RTX), 5-fluorouracil (5-FU), hydroxyurea (HU), and retinoic acid (RA), and valproic acid (VPA), an antiepileptic drug, all can cause malformations in the developing central nervous system (CNS), such as neural tube defects (NTDs). However, the common pathogenic mechanisms remain unclear. This study aimed to explore the mechanisms of NTDs caused by MTX, RTX, 5-FU, HU, RA, and VPA (MRFHRV), based on network pharmacology and molecular biology experiments. The MRFHRV targets were integrated with disease targets, to find the potential molecules related to MRFHRV-induced NTDs. Protein-protein interaction analysis and molecular docking were performed to analyze these common targets. Utilizing the kyoto encyclopedia of genes and genomes (KEGG) signaling pathways, we analyzed and searched the possible causative pathogenic mechanisms by crucial targets and the signaling pathway. Results showed that MRFHRV induced NTDs through several key targets (including TP53, MAPK1, HSP90AA1, ESR1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN) and multiple signaling pathways such as PI3K/Akt pathway, suggesting that abnormal proliferation and differentiation could be critical pathogenic contributors in NTDs induced by MRFHRV. These results were further validated by CCK8 assay in mouse embryonic stem cells and GFAP staining in embryonic brain tissue. This study indicated that chemotherapeutic and antiepileptic agents induced NTDs might through predicted targets TP53, MAPK1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN and multiple signaling pathways. More caution was required for the clinical administration for women with childbearing potential and pregnant.

Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/ß-catenin signaling pathway.

Neural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Our previous study has found that ethionine inhibits cell viability by disrupting the balance between proliferation and apoptosis, and preventing neural stem cells from differentiating into neurons and astrocytes. However, how ethionine participates in the pathogenesis of neural tube development through N6-methyladenosine (m6A) modification remains unknown. This study aims to investigate METTL3- and ALKBH5-mediated m6A modification function and mechanism in NTDs. Herein, our results demonstrate that SAM play not only a compensatory role, it also leads to changes of m6A modification in neural tube development and regulation. Additionally, these data implicate that METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/ß-catenin signaling pathway. Significantly, overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis. This research reveals an important role of SAM in development of NTDs, providing a good theoretical basis for further research on NTDs. This finding represents a novel epigenetic mechanism underlying that the m6A modification has profound and lasting implications for neural tube development.

Down-Regulation of Inpp5e Associated With Abnormal Ciliogenesis During Embryonic Neurodevelopment Under Inositol Deficiency.

The inositol polyphosphate-5-phosphatase E (Inpp5e) gene is located on chromosome 9q34.3. The enzyme it encodes mainly hydrolyzes the 5-phosphate groups of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5) P3) and phosphatidylinositol (4,5)-bisphosphate (PtdIns (4,5)P2), which are closely related to ciliogenesis and embryonic neurodevelopment, through mechanisms that are largely unknown. Here we studied the role of Inpp5e gene in ciliogenesis during embryonic neurodevelopment using inositol-deficiency neural tube defects (NTDs) mouse and cell models. Confocal microscopy and scanning electron microscope were used to examine the number and the length of primary cilia. The dynamic changes of Inpp5e expression in embryonic murine brain tissues were observed during Embryonic Day 10.5-13.5 (E 10.5-13.5). Immunohistochemistry, western blot, polymerase chain reaction (PCR) arrays were applied to detect the expression of Inpp5e and cilia-related genes of the embryonic brain tissues in inositol deficiency NTDs mouse. Real-time quantitative PCR (RT-qPCR) was used to validate the candidate genes in cell models. The levels of inositol and PtdIns(3,4) P2 were measured using gas chromatography-mass spectrometry (GC-MS) and enzyme linked immunosorbent assay (ELISA), respectively. Our results showed that the expression levels of Inpp5e gradually decreased in the forebrain tissues of the control embryos, but no stable trend was observed in the inositol deficiency NTDs embryos. Inpp5e expression in inositol deficiency NTDs embryos was significantly decreased compared with the control tissues. The expression levels of Inpp5e gene and the PtdIns (3,4) P2 levels were also significantly decreased in the inositol deficient cell model. A reduced number and length of primary cilia were observed in NIH3T3 cells when inositol deficient. Three important cilia-related genes (Ift80, Mkks, Smo) were down-regulated significantly in the inositol-deficient NTDs mouse and cell models, and Smo was highly involved in NTDs. In summary, these findings suggested that down-regulation of Inpp5e might be associated with abnormal ciliogenesis during embryonic neurodevelopment, under conditions of inositol deficiency.

Genetic Polymorphisms in DNA Repair Gene APE1/Ref-1 and the Risk of Neural Tube Defects in a High-Risk Area of China.

Apurinic/apyrimidinic endonuclease 1/redox-factor 1 (APE1/Ref-1) gene encodes a multifunctional protein involved in the DNA base excision repair (BER) pathway, which initiates repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone. APE1/Ref-1 polymorphisms are related to the occurrence of neural tube defects (NTDs), but the association between APE1/Ref-1 polymorphisms and NTDs is not reported in Chinese Han population. The aim of the present study was to evaluate the association of APE1/Ref-1 polymorphism and the risk of NTD occurrence for Han population in a high-risk area of China. APE1/Ref-1 genotypes were determined by iPLEX Gold SNP genotyping. AP sites and folate level of brain tissues were measured. The results showed that three polymorphisms (rs3136817, rs77794916, and rs1760944) of APE1/Ref-1 were statistically associated with NTD subtypes. Allele C of rs3136817, allele T of rs77794916, and allele G of rs1760944 were associated with an increased risk for encephalocele (OR = 2.52, 95% CI [1.25-5.07], P < 0.01; OR = 1.80, 95% CI [1.04-3.12], P = 0.04; and OR = 1.96, 95% CI [1.12-3.45], P = 0.02), compared with those harboring the alleles T, C, and T, respectively. The folate level in NTDs was lower than that in controls. DNA AP sites in the encephalocele were significantly higher than the control (P < 0.01). The three polymorphisms of APE1/Ref-1 were significantly related to NTD occurrence, which indicated that APE1/Ref-1 might be a potential genetic risk factor for encephalocele in a high-risk area of NTDs in China.

Neural tube defects: role of lithium carbonate exposure in embryonic neural development in a murine model.

BACKGROUND: Lithium carbonate (Li2CO3) is widely used in the treatment of clinical-affective psychosis. Exposure to Li2CO3 during pregnancy increases the risk of neural tube defects (NTDs) in offspring, which are severe birth defects of the central nervous system. The mechanism of Li2CO3-induced NTDs remains unclear. METHODS: C57BL/6 mice were injected with different doses of Li2CO3 intraperitoneally on gestational day 7.5 (GD7.5), and embryos collected at GD11.5 and GD13.5. The mechanisms of Li2CO3 exposure-induced NTDs were determined utilizing immunohistochemistry, western blotting, EdU imaging, enzymatic method, gas chromatography-mass spectrometry (GC-MS), ELISA and HE staining. RESULTS: The NTDs incidence was 33.7% following Li2CO3 exposure. Neuroepithelial cell proliferation and phosphohistone H3 level were significantly increased in NTDs embryos, compared with control group (P < 0.01), while the expressing levels of p53 and caspase-3 were significantly decreased. IMPase and GSK-3ß activity was inhibited in Li2CO3-treated maternal and embryonic neural tissues (P < 0.01 and P < 0.05, respectively), along with decreased levels of inositol and metabolites, compared with control groups (P < 0.01). CONCLUSIONS: Lithium-induced NTDs model in C57BL/6 mice was established. Enhanced cell proliferation and decreased apoptosis following lithium exposure were closely associated with the impairment of inositol biosynthesis, which may contribute to lithium-induced NTDs. IMPACT: Impairment of inositol biosynthesis has an important role in lithium exposure-induced NTDs in mice model. Lithium-induced NTDs model on C57BL/6 mice was established. Based on this NTDs model, lithium-induced impairment of inositol biosynthesis resulted in the imbalance between cell proliferation and apoptosis, which may contribute to lithium-induced NTDs. Providing evidence to further understand the molecular mechanisms of lithium-induced NTDs and enhancing its primary prevention.

Exosomes from human umbilical cord Mesenchymal stem cells attenuates stress-induced hippocampal dysfunctions.

Human Mesenchymal Stem Cells (MSCs) especially human umbilical cord MSCs is the novel regenerative cell resource for regenerative therapy. However, the biological underpinning of MSCs in neuroprotections requires deep understanding. Exosomes is an important biological factor due to its multiple types of contents with various biological function. In current study, we collected the exosome from umbilical cord mesenchymal stem cells (hUC-MSCs) and tested the neuroprotective effects to brain stress. Proteomic analysis indicates significant enriched protein components display the functions in metabolic regulation. We then injected the exosome (MSC-Ex) to adult mice by i.v injection. On physiological level, treatment of MSC-Ex increased the adiponectin level in peripheral central nervous system (CNS). Moreover, MSC-Ex significantly accelerated the differentiation of adult neural stem cells but did not benefit the related cognitive behavior. We then created acute brain disorder model with STZ intra-hippocampal injection. Compared with STZ group, treatment of MSC-Ex improved cognitive function. Moreover, MSC-Ex promotes hippocampal neurogenesis that was suppressed by STZ injection. In conclusion, hUC-MSCs derived exosome would exert the neural regenerative effects associating with its metabolism regulatory capacity.

Economic risk criteria for dams considering the relative level of economy and industrial economic contribution.

When a dam breaks, huge floods will be generated that may inundate urban areas, enterprises, farmlands, and infrastructure and cause giant economic losses. Economic risk criteria are a kind of basis for determining dam risk levels and to decide whether risk control measures should be taken or not. However, compared to loss-of-life risk criteria, much fewer economic risk criteria for dams have been proposed and implemented for two main reasons: (a) The ability of most areas to endure economic losses caused by dam breach changes over time because of the constant development of their economic levels; and (b) Economic development levels in an area are distinct from the levels in other areas, resulting in significant differences in the ability of different areas to endure economic losses caused by a dam breach. Therefore, an equivalent economic scale (EES) that indicates the relative economic level of an area to the whole country in a given period of time is a preferred measure. It was shown in this paper that EES has much more stable values than do ordinary economic measures; therefore, it was taken as the basic index for establishing economic risk criteria. Furthermore, due to the distinct economic loss rates of different industries, the index of industrial economic contribution (IEC) was introduced to determine the correction coefficient to modify the ESS to reflect the potential economic loss of the area to be evaluated. This is the first research that pays careful attention to the change of ability to endure economic losses, in which the established economic risk criteria are applicable over a relatively long time and for different areas based on the consideration of the relative level of the economy and the industrial economic contribution.

The Effects of Inositol Metabolism in Pregnant Women on Offspring in the North and South of China.

BACKGROUND Inositol is an essential nutrient for cell growth, survival and embryonic development. Myo-inositol is the predominant form in natural. To investigate the correlation between inositol metabolism and embryonic development, we assessed the metabolic characteristics of myo-inositol, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) of pregnant women in the North China (Yangquan and Weihai) and South China (Nanchang and Haikou) China. MATERIAL AND METHODS All data were collected by face-to-face interview during pregnant women health visits using a questionnaire. Plasma levels of myo-inositol, PI(4,5)P2 and PI(3,4,5)P3 from 89 randomly collected pregnant women were detected by gas chromatography-mass spectrometry and enzyme linked immunosorbent assay. RESULTS A total of 400 pregnant women were included in this survey. The plasma levels of myo-inositol and PI(4,5)P2 in the North China group of pregnant women were significantly higher than that in the South China group (P<0.01). The birth weight of fetuses in the North China group was heavier than that in the South China group (P<0.01). The birth length of fetuses in Yangquan was the longest among the 4 cities (P<0.01). The incidence rate of birth defects was 3.05% in the North China group, and 0.0% in the South China group. In bivariate linear correlation analysis, the body weight correlated with myo-inositol (r=0.5044, P<0.0001), PI(4,5)P2 (r=0.5950, P<0.0001) and PI(3,4,5)P3 (r=0.4710, P<0.0001), the body length was correlated with PI(4,5)P2 (r=0.3114, P=0.0035) and PI(3,4,5)P3 (r=0.2638, P<0.0130). CONCLUSIONS The plasma levels of myo-inositol and PI(4,5)P2 in pregnant women had significant difference between the North and the South of China, which might be correlated with fetal development and birth defects.

Automatic segmentation and measurement methods of living stomata of plants based on the CV model.

BACKGROUND: The stomata of plants mainly regulate gas exchange and water dispersion between the interior and external environments of plants and play a major role in the plants' health. The existing methods of stomata segmentation and measurement are mostly for specialized plants. The purpose of this research is to develop a generic method for the fully automated segmentation and measurement of the living stomata of different plants. The proposed method utilizes level set theory and image processing technology and can outperform the existing stomata segmentation and measurement methods based on threshold and skeleton in terms of its versatility. RESULTS: The single stomata images of different plants were the input of the method and a level set based on the Chan-Vese model was used for stomatal segmentation. This allowed the morphological features of the stomata to be measured. Contrary to existing methods, the proposed segmentation method does not need any prior information about the stomata and is independent of the plant types. The segmentation results of 692 living stomata of black poplars show that the average measurement accuracies of the major and minor axes, area, eccentricity and opening degree are 95.68%, 95.53%, 93.04%, 99.46% and 94.32%, respectively. A segmentation test on dayflower (Commelina benghalensis) stomata data available in the literature was completed. The results show that the proposed method can effectively segment the stomata images (181 stomata) of dayflowers using bright-field microscopy. The fitted slope of the manually and automatically measured aperture is 0.993, and the R2 value is 0.9828, which slightly outperforms the segmentation results that are given in the literature. CONCLUSIONS: The proposed automated segmentation and measurement method for living stomata is superior to the existing methods based on the threshold and skeletonization in terms of versatility. The method does not need any prior information about the stomata. It is an unconstrained segmentation method, which can accurately segment and measure the stomata for different types of plants (woody or herbs). The method can automatically discriminate whether the pore region is independent or not and perform pore region extraction. In addition, the segmentation accuracy of the method is positively correlated with the stomata's opening degree.