Study on stability of formation for gravity field exploration subjected to disturbance based on prescribed performance control.

Double satellite formation for gravity field exploration is a complex space virtual instrument system with high-precision, whose normal manner is threatened by the space debris environment. The normal manner of the formation based on control with prescribed performance is studied. Based on the random impact of space debris, nonlinear dynamical equations with 20 variables are established considering the relative attitude of the double satellite. The interferential characteristics and expected stability under certain disturbance conditions by the space debris in low Earth orbit are analyzed. To simplify the relative motion of the formation and the motion of the test mass (TM) relative to the cage, a prescribed performance function is introduced to constrain the relative attitude errors of transient and steady states. An adaptive attitude control design method based on a prescribed performance function is proposed. Finally, the analysis is carried out. The results show that the probability of normal manner of the formation is about 78.45% in the first year and about 45.59% in the first three years. The normal manner of the double satellite formation for gravity field exploration can be effectively simulated and analyzed based on the prescribed performance control methods.

Biotechnological formation of dairy flavor inducing δ-lactones from vegetable oil.

Agroscope Culture Collection was screened to identify bacterial strains effective in production of dairy flavor inducing lactones using grapeseed oil as a substrate. Lentilactobacillus parafarraginis FAM-1079, Lactococcus lactis subsp. lactis FAM-17918, and L. lactis subsp. lactis biovar diacetylactis FAM-22003 showed the most efficient formation of targeted δ-lactones. The application of sublethal heat stress significantly increased target lactone production. The most profound improvement was for L. lactis subsp. lactis biovar diacetylactis where δ-octadecalactone generation was improved by factor of 9. The pre-fermentation step as well as growth phase in which bacteria are harvested did not have a significant impact on lactones yield. The lactone production process from vegetable oil developed in this study offers a new way of developing a natural flavor ingredient for incorporation into plant-based products.

[Data standard and data sharing in clinical cohort studies].

Data standard plays an important role in the process of data collection, Integration and sharing in clinical cohort studies, and more attention have been paid to it. This paper summarizes the 5 international proven data standard model, analyze their characteristics and development status, and match their data modules with the general data set of the clinical cohorts to evaluate the international data standard models' applicability and provide reference for the development and improvement of the data standard model for clinical cohort studies in China.

[Extraskeletal mesenchymal chondrosarcoma in central nerve system: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system (CNS). Methods: The clinicopathological findings, immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up. Results: The ages of patients ranged from 20-35 years. Three patients had intracranial lesions and one had intradural tumor. The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage. There was hemangiopericytoma-like pattern with calcification and ossification. The tumor cells were positive for VIM and SOX9; and the small cells were positive for CD99, NSE and NKX3.1. The cells in chondroid matrix were positive for S-100. All tumor cells were negative for markers including CKpan, EMA and desmin. At molecular analysis, HEY1-NCOA2 fusion transcripts were identified in three patients. The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2. Follow-up information was obtained in two patients, and both were free from recurrence or metastasis at 8 and 20 months. Conclusions: Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis. In addition to SOX9, NKX3.1 can be another useful antibody for the differential diagnosis. The combination of pathological characteristics, immunophenotype and genetic profile of tumor is essential for diagnosis.

[Quality assessment of global lung cancer screening guidelines and consensus].

Objective: To understand the research progress and quality of lung cancer screening guidelines and consensus in China and abroad, and to provide reference for the formulation of high-quality lung cancer screening guidelines in China. Methods: Databases including PubMed, Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, VIP and Wanfang Data were searched, websites and important references were also searched by hand retrieval. The Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) were used to assess the quality of newly published or updated guidelines and consensus. Results: A total of 9 guidelines and consensus published between 2015 and 2020 were included in this study, with countries including the United States, China, Canada, Saudi Arabia and South Africa. The field of scope and purpose and clarity of presentation scored relatively high but the rigor of development and applicability scored low. Five guidelines were judged to be A-level, all of which were published abroad, and the remaining four were B-level, including three guidelines and consensus issued by China and 1 guideline issued by South Africa. The report rate of RIGHT were higher in basic information and background, lower in review and quality assurance, funding and declaration and management of interests. There were 5 guidelines with a good level and 4 guidelines and consensus with a moderate level. The best overall quality guidelines were those published by the American College of Chest Physicians in 2018 and by the Canadian Task Force on Preventive Health Care in 2016. Conclusions: The number of countries and institutions that issue lung cancer screening guidelines and consensus had been increasing gradually, but the quality in China remained low. It is necessary to develop high-quality lung cancer screening guidelines suitable for China's national conditions in combination with evidence-based methods to guide practice.

[Feasibility on the development of maternal and child cohorts, based on the maternal and child care network].

Under the limitation of cross-sectional studies, more researchers are turning their attention to maternal and child cohort studies. However, some problems do exist in the traditional maternal and child cohort studies, if data is only gathered from the hospitals. The limitation would include the contents of research and the high rate of loss to follow-up. With the integration of different medical traits and the progress in big data, the development of maternal and child related cohorts, with characteristics of dynamic follow-up and data sharing, through combining the information and health service systems of different institutions, seem in urgent need. This paper aims to provide some basic achievements in conducting maternal and child cohorts that can serve the related health problems through full-life cycle, and provide new references on conducting cohort studies, aiming at special population or diseases.

CD4+Foxp3+ regulatory T cell differentiation mediated by endometrial stromal cell-derived TECK promotes the growth and invasion of endometriotic lesions.

Endometriosis is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissue. The proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) is significantly increased in the peritoneal fluid of women with endometriosis. The thymus-expressed chemokine TECK/CCL25 directly promotes the invasiveness of endometrial stromal cells (ESCs). The aim of this study was to investigate the effects of ESC-derived TECK on the crosstalk between Tregs and ESCs in the progress of endometriosis. We determined that the percentage of Tregs and the concentration of TECK increased in the peritoneal fluid with the progression of endometriosis. The supernatant from co-cultured human ESCs and macrophages not only induced Treg differentiation and increased Treg expression of interleukin-10 (IL-10), transforming growth factor-ß (TGF-ß) and CD73 by activating the AKT/STAT3 signaling pathway but also repressed Treg apoptosis by downregulating Fas and FasL expression and enhanced the Treg-mediated suppression of CD4(+)CD25(-) T cells. In addition, in vitro and in vivo trials confirmed that these effects could be inhibited by anti-TECK neutralizing Abs. The secretion of IL-10 and TGF-ß by Tregs increased MMP2 expression and decreased TIMP1 expression and further stimulated the proliferation and invasion of ESCs and the growth of ectopic lesions. These results indicate that TECK derived from ESCs and macrophages upregulates the number and function of Tregs in the ectopic milieu, which contributes to endometriotic immunotolerance and high levels of ESC proliferation and invasion, thereby facilitating the progression of endometriosis.

Elevated expression of connective tissue growth factor, osteopontin and increased collagen content in human ascending thoracic aortic aneurysms.

Little is known about the molecular mechanisms of ascending thoracic aortic aneurysms (ATAAs). Abnormal extracellular matrix changes and variations of vascular smooth muscle cells (VSMCs) have been implicated in abdominal aortic aneurysm formation. Our objective was to investigate the alterations of collagen, stimulators of collagen synthesis and synthetic VSMCs in patients with ATAA. Surgical samples from ATAA were taken from 20 patients, and 18 control aortas were obtained during coronary artery bypass surgery. All aortic wall specimens were fixed for histology and immunohistochemistry for collagen, connective tissue growth factor (CTGF) and osteopontin. Realtime polymerase chain reaction was used to determine their mRNA expression. Histology and semi- quantitative analysis demonstrated that protein levels of collagen, CTGF and osteopontin significantly increased by 1.9-, 1.4- and 2.2-fold, respectively (P< 0.01 for all) in the ATAA group than in the control group. Similar results were shown in mRNA levels of type laland Illal collagen, CTGF and osteopontin. The protein levels of CTGF and osteopontin were positively correlated with aortic diameter (r= 0.67, r= 0.73; P< 0.01 for both). In conclusion, overexpression of aortic CTGF and synthetic VSMCs marker (osteopontin), which is likely to be responsible for elevated aortic collagen content, may provide a potential mechanism for aneurysmal enlargement.

RANKL promotes the growth of decidual stromal cells in an autocrine manner via CCL2/CCR2 interaction in human early pregnancy.

OBJECTIVE: Receptor-activator of NF-κB ligand (TNFSF11, also known as RANKL) and its receptor RANK are essential regulators on bone remodeling, mammary gland development and hormone-associated breast cancer development. However, the expression pattern and role of RANKL/RANK axis in decidual stromal cells (DSCs) are unclear in human early pregnancy. STUDY DESIGN: We analyzed RANKL/RANK expression in DSCs by real-time PCR, immunhistochemistry, enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Then BrdU cell proliferation assay, flow cytometry assay and ELISA were performed to investigate the effect of recombinant human RANKL and DSCs-derived RANKL on the proliferation, apoptosis, chemokine (C-C motif) ligand 2 (CCL2) secretion, C-C chemokine receptor type 2 (CCR2) and other target proteins expression in DSCs in vitro, respectively. RESULTS: Here we show that DSCs co-express RANKL/RANK. Not only recombinant human (rh) RANKL but also the DSC-secreted RANKL stimulate proliferation and anti-apoptosis, and elevate CCL2 secretion and CCR2 expression of DSCs. Furthermore, the stimulatory effects on the proliferation, anti-apoptosis and the expression of Bcl-2 and Ki67 and inhibitory signaling on Fas ligand (FasL) in DSCs induced by RANKL can be partly reversed by the way of blocking CCL2 and or CCR2. CONCLUSIONS: Our results have revealed that RANKL/RANK signal promotes Bcl-2 and Ki67 and decreases FasL expression, and further as a positive regulator for stimulating the proliferation and growth of DSCs through up-regulating CCL2/CCR2 signal, which finally contributes to the establishment and maintenance of physiological pregnancy.

Focal adhesion kinase signaling is necessary for the Cyclosporin A-enhanced migration and invasion of human trophoblast cells.

OBJECTIVES: Our previous studies have shown that Cyclosporin A (CsA) promotes human trophoblast invasion via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. E-cadherin and matrix metalloproteinases (MMPs) are important mediators in trophoblast migration and invasion. Here, we further investigate the role of focal adhesion kinase (FAK) signaling in the CsA-induced trophoblast migration and invasion and ERK activation. STUDY DESIGN: The migration and invasion of human primary trophoblasts and JEG-3 cells were measured by transwell migration and matrigel invasion assays. The activation of FAK, Src and ERK induced by CsA were examined by western blot. The colocalization of FAK and Src was detected by dual immunofluorescence assay. The regulation of E-cadherin expression and matrix metalloproteinases (MMPs) activity was evaluated by western blot and gelatin zymography, respectively. RESULTS: CsA increased the phosphorylation of FAK and Src in human primary trophoblasts and JEG-3 cells. Meanwhile, the activated FAK and Src colocalized in the cytoplasm of JEG-3 cells. The FAK inhibitor Y15 or Src inhibitor PP2 could abrogate the phosphorylation of ERK, the enhanced migration and invasion and the activity of MMP2, 9 induced by CsA. In addition, these inhibitors also restored the expression of E-cadherin which is down-regulated by CsA. However, U0126, an inhibitor of ERK, had no significant effect on the CsA-induced activation of FAK and Src. CONCLUSIONS: FAK-Src signaling, the upstream signaling cascade of ERK activation, plays an important role in the CsA-induced migration and invasion via down-regulating expression of E-cadherin and up-regulating activity of MMP2, 9 in trophoblast cells. These results may help provide a rationale to develop a novel therapeutic strategy for pregnancy disorders from insufficient trophoblast invasion.

Detection of hepatitis B virus markers using a biosensor based on imaging ellipsometry.

A biosensor based on imaging ellipsometry (BIE) has been developed and validated in 169 patients for detecting five markers of hepatitis B virus (HBV) infection. The methodology has been established to pave the way for clinical diagnosis, including ligand screening, determination of the sensitivity, set-up of cut-off values (CoVs) and comparison with other clinical methods. A matrix assay method was established for ligand screening. The CoVs of HBV markers were derived with the help of receiver operating characteristic curves. Enzyme-linked immunosorbent assay (ELISA) was the reference method. Ligands with high bioactivity were selected and sensitivities of 1 ng/mL and 1 IU/mL for hepatitis B surface antigen (HBsAg) and surface antibody (anti-HBs) were obtained respectively. The CoVs of HBsAg, anti-HBs, hepatitis B e antigen, hepatitis B e antibody and core antibody were as follows: 15%, 18%, 15%, 20% and 15%, respectively, which were the percentages over the values of corresponding ligand controls. BIE can simultaneously detect up to five markers within 1 h with results in acceptable agreement with ELISA, and thus shows a potential for diagnosing hepatitis B with high throughput.

Fabrication and characterization of needle-like nano-HA and HA/MWNT composites.

Hydroxyapatite (HA) ceramic has been used in tissue engineering and orthopedics for its good biocompatibility and osteoconductivity. However, its clinical applications are usually limited by the low strength and brittleness. The objective of this research was to develop a new kind of HA composites in which multi-wall carbon nanotubes (MWNTs) were introduced to the HA ceramic matrix to improve the mechanical properties of the resulting composites. A simple chemical wet method was applied to synthesize the HA ceramic particles with the aid of surfactant and ultrasonication technique at normal atmospheric pressure. The morphology and microstructure of the synthesized HA were characterized by XRD and TEM as a function of treatment time. The results showed that the synthesized HA particles are needle-like with a length of 80-160 nm along the (211) direction and an aspect ratio of 5-15. MWNTs were treated with a mixture of nitric acid and sulfuric acid. The HA/MWNT composites were prepared by solution blending. The composites were sintered using a hot-press method. The mechanical properties of the HA/MWNT composites with different volume percentages of MWNTs were examined. The fracture toughness and flexural strength were improved by 50% and 28% separately when the volume percentage of MWNTs reached 7%.

The development of biosensor with imaging ellipsometry.

The concept of biosensor with imaging ellipsometry was proposed about ten years ago. It has become an automatic analysis technique for protein detection with merits of label-free, multi-protein analysis, and real-time analysis for protein interaction process, etc. Its principle, and related technique units, such as micro-array, micro-fluidic and bio-molecule interaction cell, sampling unit and calibration for quantitative detection as well as its applications in biomedicine field are presented here.

An essential role for mitogen-activated protein kinases, ERKs, in preventing heat-induced cell death.

Stimulation of mitogen-activated protein kinases (MAPKs) or extracellular signal regulated protein kinases (ERKs) after exposure of mammalian cells to ultraviolet (UV) and X-irradiation occurs through activation of receptor tyrosine kinases via Ras/Raf/Mek/ERKs cascade. This activation of MAPKs is proposed to play a role in the replacement of damaged proteins during these stresses. Heat shock also activates MAPKs; however, the signaling cascade and the biochemical and physiological links between activation by heat and downstream effects are unknown. In this report we demonstrate that, unlike irradiation, heat induces MAPKs through ceramide metabolism to sphingosine with stimulation of Raf-1 protein kinase. The activation of MAPKs by heat does not occur in all cell types, because the step(s) downstream of ceramide to activation of Raf-1 protein kinase is missing in myeloid leukemic cells such as HL-60, U937, and K562, while it is present in NIH3T3 fibroblasts. Heat-induced MAPK activation may enhance the ability of cells to survive a severe heat shock. Blocking 60-70% of the activity of MAPK (ERK1) by stable overexpression of the dominant negative allele ERK1-KR renders NIH3T3 and K562 cells up to 100-fold more sensitive to cytotoxic effects of heat. Conversely, NIH3T3 and K562 cells stably overexpressing the wild-type ERK1 develop resistance to killing by heat. These results suggest that increased thermal sensitivity of leukemic cells to thermal stress or other cancer therapy regimens could be attributable to lack of pertinent activation of the MAPK pathway by such stresses.

Glycogen synthase kinase 3beta and extracellular signal-regulated kinase inactivate heat shock transcription factor 1 by facilitating the disappearance of transcriptionally active granules after heat shock.

Heat shock transcription factor 1 (HSF-1) activates the transcription of heat shock genes in eukaryotes. Under normal physiological growth conditions, HSF-1 is a monomer. Its transcriptional activity is repressed by constitutive phosphorylation. Upon activation, HSF-1 forms trimers, acquires DNA binding activity, increases transcriptional activity, and appears as punctate granules in the nucleus. In this study, using bromouridine incorporation and confocal laser microscopy, we demonstrated that newly synthesized pre-mRNAs colocalize to the HSF-1 punctate granules after heat shock, suggesting that these granules are sites of transcription. We further present evidence that glycogen synthase kinase 3beta (GSK-3beta) and extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) participate in the down regulation of HSF-1 transcriptional activity. Transient increases in the expression of GSK-3beta facilitate the disappearance of HSF-1 punctate granules and reduce hsp-70 transcription after heat shock. We have also shown that ERK is the priming kinase for GSK-3beta. Taken together, these results indicate that GSK-3beta and ERK MAPK facilitate the inactivation of activated HSF-1 after heat shock by dispersing HSF-1 from the sites of transcription.

Analysis of the phosphorylation of human heat shock transcription factor-1 by MAP kinase family members.

The activation of heat shock transcription factor-1 (HSF-1) after treatment of mammalian cells with stresses such as heat shock, heavy metals, or ethanol induces the synthesis of heat shock proteins. HSF-1 is phosphorylated at normal growth temperature and is hyperphosphorylated upon stress. We recently presented evidence that HSF-1 can be phosphorylated by the mitogen activated protein kinase, ERK1, and that such phosphorylation appears to negatively regulate the activity of HSF-1. In this report, we have tested the ability of ERK1 to phosphorylate various HSF-1 deletion mutants. Our results show that ERK1 phosphorylation is dependent on a region of HSF-1 extending from amino acids 280 to 308. This region contains three serine residues that are potential ERK1 phosphorylation sites. The region falls within a previously defined regulatory domain of HSF-1. The possibility of protein kinases other than ERK1 phosphorylating HSF-1 was also examined using in-gel kinase assays. The results show that HSF-1 can be phosphorylated in a ras-dependent manner by other members of the MAP kinase family such as JNK and p38 protein kinases and possibly others.