Electroacupuncture for hot flashes in early postmenopause: A study protocol for a randomized sham-controlled trial.

Introduction: Many early postmenopausal women experience hot flashes (HFs). Electroacupuncture (EA) is a safe and effective therapy for menopause-related symptoms. However, there are few rigorous clinical trials on this topic. This randomized controlled trial is designed to explore the feasibility and efficacy of EA in the treatment of early postmenopausal HF. Methods: This study is a randomized, controlled trial involving 72 early postmenopausal patients. Patients will be randomized 1:1 to the EA or sham acupuncture (SA) group. The acupuncture points that will be used are Hegu (LI4), Fuliu (KI7), Taixi (KI3), Shenshu (BL23), Guanyuan (CV4), and Sanyinjiao (SP6). Participants in each group will receive 18 acupuncture sessions over 6 weeks (three times per week). The primary outcome is the hot-flash score at the end of the 6 week of intervention. Secondary outcome measures are the Pittsburgh Sleep Quality Index, Menopause-Specific Quality of Life, Menopause Rating Scale, Traditional Chinese Medicine Syndrome Score Scale, and estradiol, follicle-stimulating hormone, luteinizing hormone, and anti-Mullerian hormone levels. Safety will be assessed at every visit. Conclusion: This prospective trial will evaluate the efficacy of EA in the treatment of HFs among early postmenopausal women. Our results will provide additional knowledge for clinicians in the treatment of HFs.

Establishing a novel and sensitive assay for bioactivity determination of anti-CD25 antibodies.

Anti-CD25 antibodies have been approved for renal transplantation and has been used prior to and during transplantation by the Food and Drug Administration (FDA). However, no reported bioassays have been reflected the mechanism of action (MOA) of anti-CD25 antibodies. Here, we describe the development and validation of a reporter gene assay (RGA) based on the engineered C8166-STAT5RE-Luc cells expressing endogenous IL-2 receptors and a STAT5-inducible element-driven firefly luciferase in C8166 cell lines. The RGA was fully validated according to the International Conference on the Harmonization of Technical Requirements for the Registration of Pharmaceuticals for the Human Use-Q2 (ICH-Q2). After optimization, the assay showed excellent specificity, linearity, accuracy, precision, and robustness. Due to the MOA relatedness and the excellent assay performance, the RGA is suitable for exploring the critical quality attributes (CQAs), release inspection, comparability and stability of anti-CD25 mAbs.

Functional reconstruction of the basal ganglia neural circuit by human striatal neurons in hypoxic-ischaemic injured brain.

Perinatal hypoxic-ischaemic encephalopathy is the leading cause of neonatal death and permanent neurological deficits, while the basal ganglia is one of the major nuclei that is selectively and greatly affected in the brains of hypoxic-ischaemic encephalopathy patients, especially in severe cases. Human embryonic stem cell-derived neurons have shown great potential in different types of brain disorders in adults. However, it remains unknown whether and how grafted human embryonic stem cell-derived neurons can repair immature brains with hypoxic-ischaemic encephalopathy. Here, by administrating genetically labelled human embryonic stem cell-derived striatal neural progenitors into the ipsilateral striatum of hypoxic-ischaemic encephalopathy-injured mice, we found that the grafted cells gradually matured into GABA spiny projection neurons morphologically and electrophysiologically, and significantly rescued the area loss of hypoxic-ischaemic encephalopathy-injured brains. Intriguingly, using immunohistochemical staining combined with enhanced ascorbate peroxidase-based immunoelectron microscopy and rabies virus-mediated trans-synaptic tracing, we show that the grafts start to extend axonal projections to the endogenous target areas (globus pallidus externa, globus pallidus internus, substantia nigra), form synapses with host striatal, globus pallidus and nigra neurons, and receive extensive and stable synaptic inputs as early as 2 months post-transplantation. Importantly, we further demonstrated functional neural circuits re-established between the grafted neurons and host cortical, striatal and substantial nigra neurons at 3-6 months post-transplantation in the hypoxic-ischaemic encephalopathy-injured brain by optogenetics combined with electrophysiological recording. Finally, the transplanted striatal spiny projection neurons but not spinal GABA neurons restored the motor defects of hypoxic-ischaemic encephalopathy, which were reversed by clozapine-N-oxide-based inhibition of graft function. These findings demonstrate anatomical and functional reconstruction of the basal ganglia neural circuit including multiple loops by striatal spiny projection neurons in hypoxic-ischaemic encephalopathy-injured immature brains, which raises the possibility of such a cell replacement therapeutic strategy for hypoxic-ischaemic encephalopathy in neonates.

Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors.

Oligodendrocyte spheroids (OL-spheroids) containing oligodendrocytes and neurons provide an accessible system to dissect demyelinating diseases and test therapeutic treatment. However, generation of human OL-spheroids is still technically challenging and time-consuming until now. Here, we presented evidence that overexpression of SOX10 and OLIG2 (SO) in human embryonic stem cells (hESCs)-derived ventral forebrain neural progenitors is sufficient to produce forebrain pre-oligodendrocytes (pre-OLs) and mature oligodendrocytes (OLs) within 20-40 days. More importantly, optimizing this procedure by overexpression of SO in ventral forebrain spheroids, we successfully generated OL-spheroids with pre-OLs, mature OLs, and neurons 40 days after OL-induction. We further demonstrated oligodendrocyte-neuron interactions and obvious axon myelination in OL-spheroids. Finally, over 30% cells developed into mature oligodendrocytes with forebrain identity and myelinate axons in mouse brain 3 months after transplantation. This study provides a strategy to generate forebrain OL-spheroids rapidly and efficiently which would facilitate development of new therapeutics for demyelinating disorders.

Generation of an induced pluripotent stem cell line from a patient with global development delay carrying DYRK1A mutation (c.1730T>A) and a gene correction isogenic iPSC line.

Mental retardation autosomal dominant 7 (MRD7), or DYRK1A Related Intellectual Disability Syndrome (OMIM 614104) is a developmental syndrome with microcephaly, intellectual disability, language delay and epileptic seizures. Haploinsufficiency of DYRK1A is the cause of MRD7. Here, we generated an induced pluripotent stem cell (iPSC) line with the mutation (DYRK1Ac.1730T>A) from the Peripheral blood mononuclear cell (PBMC) of a MRD7 patient along with an isogenic gene-corrected control iPSC line by CRISPR/Cas9 genome editing. Both iPSC lines showed full pluripotency, normal karyotype and differentiation capacity without integrating vectors. These DYRK1A mutant and isogenic gene-corrected iPSC control line provides a useful model to study the underlying molecular mechanisms of MRD7.

Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment.

Human brain development is a complex process involving neural proliferation, differentiation, and migration that are directed by many essential cellular factors and drivers. Here, using the NetBID2 algorithm and developing human brain RNA sequencing dataset, we identify synaptotagmin-like 3 (SYTL3) as one of the top drivers of early human brain development. Interestingly, SYTL3 exhibits high activity but low expression in both early developmental human cortex and human embryonic stem cell (hESC)-derived neurons. Knockout of SYTL3 (SYTL3-KO) in human neurons or knockdown of Sytl3 in embryonic mouse cortex markedly promotes neuronal migration. SYTL3-KO causes an abnormal distribution of deep-layer neurons in brain organoids and reduces presynaptic neurotransmitter release in hESC-derived neurons. We further demonstrate that SYTL3-KO-accelerated neuronal migration is modulated by high expression of matrix metalloproteinases. Together, based on bioinformatics and biological experiments, we identify SYTL3 as a regulator of cortical neuronal migration in human and mouse developing brains.

Assessment of Ecosystem Service Quality and Its Correlation with Landscape Patterns in Haidian District, Beijing.

Landscape architecture with urban green space as the main research object is an evidence-based science. It is an important issue to optimize green space systems from the point of view of ecosystem services. In this paper, high-resolution (1.5 m resolution) remote sensing images are combined with data-processing software, such as ENVI, ArcGIS, and Fragstats, to evaluate ecosystem service quality and compute the landscape pattern in the Haidian District (Beijing, China), so that the relationship between the ecosystem service quality and landscape pattern can be quantitatively studied and a strategy can be provided for green space optimization in cities. The following conclusions are drawn: (1) for the evaluated quality of 14 ecosystem services in Haidian District (refer to Section Analysis of the Association of the Percentage of Patches (PLAND) Index of Forest Land and Quality of Ecosystem Service in Haidian District). Forest land is the main provider of the ecosystem service in Haidian District, while construction land only provides cultural services; (2) on the whole, the spatial distribution of the ecosystem services in Haidian District gradually decreases from the west to the east, which basically matches with the spatial distribution of the forest land. The regulating service and supporting service are matched with the distribution of the urban green space. The cultural service is closely associated with history resource points; and (3) the analysis results of the association between landscape pattern and ecosystem service quality show that the percentage of patches (PLAND) index for forest land has a significant logarithmic relationship with the regulating service and supporting service. The critical value of the PLAND index is 30. Besides the Xishan area with the most coverage of forest land, the landscape shape index (LSI) of the brushwood has a logarithmic relationship with the ecosystem service quality. The critical value of the LSI value is 50. Finally, this paper proposes an area optimization strategy of green space in Haidian District from the view of the ecosystem system service. The Xishan area is classified into the ecosystem red line to control city expansion. The regulating and supporting services can be enhanced in the north flat area by improving the patch shape index. The ecosystem service capabilities can be improved by adding the forest land in the existing green space for the southeast urban areas.

Effect of transglutaminase on rennet-induced gelation of skim milk and soymilk mixtures.

BACKGROUND: Protein gels made from cow milk and soymilk can yield products of exceptional value. Transglutaminase (TG) affect rennet-induced gelation of proteins, and improves the functionality of the final products. In this paper, TG and rennet were added to skim milk and soymilk mixtures simultaneously, and the rennet-induced coagulation was studied. Diffusing wave spectroscopy and rheology measurements were used to access the structural changes of the mixtures during renneting. Syneresis analysis and microscopy can give more information for understanding the system. RESULTS: Soymilk and TG have synergetic effects and inhibit rennet-induced gelation to a certain degree. With increasing soymilk and TG, elastic index and storage modulus decreased, gelation time was delayed, and curd yield and moisture content increased. At excess soymilk and TG, no curds can be formed. There were significant effects of soymilk and TG on curd microstructure. Soymilk inhibited the aggregation of casein micelles and contributed to more coarse and heterogeneous networks. TG limited reorganization of the proteins, leading to more homogenous networks with small pores. CONCLUSION: The use of soymilk and TG simultaneously impair rennet-induced gelation and curd syneresis, and consequently lead to a higher yield of high-moisture curd. © 2018 Society of Chemical Industry.

Spatiotemporal Patterns of the Use of Urban Green Spaces and External Factors Contributing to Their Use in Central Beijing.

Urban green spaces encourage outdoor activity and social communication that contribute to the health of local residents. Examining the relationship between the use of urban green spaces and factors influencing their utilization can provide essential references for green space site selection in urban planning. In contrast to previous studies that focused on internal factors, this study highlights the external factors (traffic convenience, population density and commercial facilities) contributing to the use of urban green spaces. We conducted a spatiotemporal analysis of the distribution of visitors in 208 selected green spaces in central Beijing. We examined the relationship between the spatial pattern of visitor distribution within urban green spaces and external factors, using the Gini coefficient, kernel density estimation, and geographical detectors. The results of the study were as follows. The spatial distribution of visitors within central Beijing's green spaces was concentrated, forming different agglomerations. The three examined external factors are all associated with the use of green spaces. Among them, commercial facilities are the important external factor associated with the use of green spaces. For the selection of sites for urban green spaces, we recommend consideration of external factors in order to balance urban green space utilization.