ALBERT

Description: The ligands 2-pyrazol-1-yl-1H-indole (HL1) and 2- 1 , 2 , 4 -triazol-1-yl-1H-indole (HL2) individually reacted with Ti(NMe 2 ) 4 in tetrahydrofuran to form the corresponding complexes Ti(L1) 2 (NMe 2 ) 2 ( 1 ) and Ti(L2) 2 (NMe 2 ) 2 ( 2 ), respectively. The titanium complexes were fully characterized by NMR measurement and elemental analysis as well as the single-crystal X-ray diffraction of 1 and 2 . Both 1 and 2 exhibit high activities towards intermolecular hydroamination of terminal alkynes with high selectivity, and they also efficiently promote the ring-opening polymerization of ϵ-caprolactone.

Description: In the mammalian ovaries, the primordial follicle pool determines the reproductive capability over the lifetime of a female. The primordial follicle is composed of two cell members, namely the oocyte and the pre-granulosa cells that encircle the oocyte. However, it is unclear what factors are involved in the reorganization of the two distinct cells into one functional unit. This study was performed to address this issue. Firstly, in an in vitro reconstruction system, dispersed ovarian cells from murine fetal ovaries at 19.0 days post coitum (dpc) reassembled into follicle-like structures, independent of the physical distance between the cells, implying that either oocytes or ovarian somatic cells (OSCs) were motile. We then carried out a series of transwell assay experiments, and determined that it was in fact 19.0 dpc OSCs (as opposed to oocytes), which exhibited a significant chemotactic response to both fetal bovine serum and oocytes themselves. We observed that S100A8, a multi-functional chemokine, may participate in the process as it is mainly expressed in oocytes within the cysts/plasmodia. S100A8 significantly promoted the number of migrating OSCs by 2.5 times in vitro , of which 66.9% were FOXL2 protein-positive cells, implying that the majority of motile OSCs were pre-granulosa cells. In addition, an S100A8-specific antibody inhibited the formation of follicle-like reconstruction cell mass in vitro . And, the primordial follicle formation was reduced when S100a8 -specific siRNA was applied onto in vitro cultured 17.5 dpc ovary. Therefore, S100A8 could be a chemokine of oocyte origin, which attracts OSCs to form the primordial follicles. This article is protected by copyright. All rights reserved

Description: Lead-free single crystal ( Na 1/2 Bi 1/2 ) TiO 3 –1.5 at.% Bi ( Zn 1/2 Ti 1/2 ) O 3 (NBT–1.5BZT) with dimension of Φ35 mm × 12 mm was successfully grown by a top-seeded solution growth technique. The average and local structure were studied by a combination of X-ray diffraction and Raman spectroscopy. The electric and optical properties of 〈001〉-oriented single crystals were investigated systematically. Compared with pure NBT, the piezoelectric constant and transmission coefficient were both enhanced, that is, from 62 pC/N and ~60% to 121 pC/N and ~70%, respectively. Furthermore, domain structure observation suggested that the 〈110〉-oriented tetragonal ferroelastic domains in NBT were suppressed at room temperature with addition of BZT, which was responsible for the improved piezoelectric and optical properties of NBT–1.5BZT single crystal.

Description: ABSTRACT Titanium dioxide nanoparticles (TiO 2 NPs) have been used in environmental management, food, medicine, and industry. But TiO 2 NPs have been demonstrated to cross the blood–brain barrier and store up in the brain organization, leading to glutamate-mediated neurotoxicity. However, the neurotoxicity in the brain is not well understood. In this study, mice were exposed to 1.25, 2.5, or 5 mg/kg body weight TiO 2 NPs for 9 months, and the glutamate–glutamine cyclic pathway and expressions of glutamate receptors associated with the hippocampal neurotoxicity were investigated. Our findings showed elevations of glutamate release and phosphate-activated glutaminase activity, and reductions in glutamine and glutamine synthetase in the hippocampus following exposure to TiO 2 NPs. Furthermore, TiO 2 NPs significantly inhibited the expression of N -methyl- d -aspartate receptor subunits (including NR1, NR2A, and NR2B) and metabotropic glutamate receptor 2 in mouse hippocampus. These findings suggest that the imbalance of glutamate metabolism triggered inhibitions of glutamate receptor expression in the TiO 2 NP-exposed hippocampus. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014.

Description: Abstract A series of low‐temperature firing ceramics with scheelite structure, [Ca0.55(Sm1‐xBix)0.3]MoO4 (x = 0.2–0.95), were prepared via solid‐state reaction. The sintering temperature ranges from 660 to 760°C. A standard tetragonal scheelite phase was formed without secondary phase. When the x value was 0.95, the temperature coefficient of resonant frequency (τf) moved to a near zero value (−2.1 ppm/°C) with a dielectric constant 13.7 and the quality factor (Qf) of 33 200 GHz. The Raman spectra shows that the more vibration modes appeared with x value, which is due to the increasing of Bi concentration and results in increase in permittivities and decrease in Qf values. The classical harmonic oscillator model is used in the infrared spectra and extrapolate to the microwave range. The [Ca0.55(Sm1‐xBix)0.3]MoO4 ceramics show high‐performance microwave dielectric properties at low‐sintering temperature.

Description: Understanding the dynamics of double-thickening and uplifting of the Tibetan crust requires constraints on the magnitude and timing of crustal shortening. New elongation/inclination (E/I) corrected paleomagnetic data from ~26-22 Ma sediments indicate that the latitude of southern Tibet in the Early Miocene was 31.1 /-6.8/+5.2 °N, not significantly different from today. This implies that the southern margin of Asia, which was at 21-24°N latitude from the Late Cretaceous to the Early Eocene, advanced 8-10° northward between the Early Eocene and the latest Oligocene. Our results therefore suggest that at least 900-1100 km of continental shortening and significant regional uplift of the plateau occurred between the Early Eocene and Late Oligocene. Our results suggest that N-S intra-Asian convergence was considerably reduced around 26 Ma, corresponding to a transition from compression to extension within the Tibetan plateau.

Description: The evolution of the microphysical structures of a subtropical squall line observed during the Observation, Prediction and Analysis of Severe Convection of China (OPACC) field campaign in Eastern China is documented in this paper. The data collected from a C-band, polarimetric Doppler radar (reflectivity Z , differential reflectivity Z DR , and specific differential phase K DP ) and a disdrometer are used to investigate the variations of microphysical characteristics within the convective region during the formative, intensifying, and mature stages of the squall line. The microphysical characteristics of the squall line are noticeably different among these three stages. When the squall line develops from the formative stage to the mature stage, its radar-derived drop-size distribution (DSD) in the convective region evolves from continental-like convection to more maritime-like convection. Contrary to previous studies, the DSD characteristics of a convective line may not be simply locked to a geographical location but varied extensively throughout its life cycle. The polarimetric radar derived liquid water content below the freezing level in the convective region is three times higher than the ice water content above the freezing level. This, in conjunction with a low cloud base (~0.68 km) and a high freezing level (~5 km), indicates a deep warm cloud layer and the dominance of the warm rain process within this squall line.

Description: OBJECTIVE: POEMS syndrome is a rare plasma cell dyscrasia. Most patients had shrinking buccal pad fat and weight loss at disease onset, indicating abnormal lipid metabolism. Manifestations of POEMS syndrome, such as the elevated serum level of vascular endothelial growth factor, may also be mediated by lipids. However, the characteristics of serum lipidome of patients with POEMS syndrome have not been described. Therefore, this study aims to describe serum lipidome characteristics in patients with POEMS syndrome. METHODS: Serum samples of 24 POEMS syndrome patients newly-diagnosed at Peking Union Medical College from September, 2017 to July, 2018 were collected at baseline and after at least one cycle of treatment. Serum was also collected from a group of 24 healthy participants who were age-, gender-, BMI-matched with patients. UPLC-ESI-QTOF/MS profiling was used to analyze the molecular profile of lipid-containing organic extract of serum samples in the 320-1000 Da range. Multivariate data analysis (PCA and PLS-DA) was used to identify altered lipids between matched serum samples. For altered lipids between patients and healthy controls, lipid related genes were identified with the human metabolome database. Lipid related genes overlapped with genes in transcription files specific to POEMS syndrome compared with normal plasma cells, MGUS and MM reported in a Japanese series were identified. RESULTS : POEMS syndrome patients had serum lipidome distinct from normal people, which is characterized by a decrease in most altered fatty acyls (82.6%, 43/52) and glycerolipids (81.8%, 18/22). (Figure A) The baseline serum 17-oxo-20Z-hexacosenoic acid level was independently associated with disease(OR 1.07, 95% CI 1.01-1.13, p = 0.021). A two-fatty-acyl lipid model could be constructed by leave-one-out cross validation based on peak intensity of 17-oxo-20Z-hexacosenoic acid andΩ-3 arachidonic acid to identify patients and healthy control with an accuracy of 100%. (Figure B) Comparing serum lipids pre- and post-treatment, 100% (14/14) altered fatty acyls and glycerolipids (3/3) increased after treatment, of which 50% fatty acyls and all glycerolipids overlapped with baseline decreased lipids compared with healthy control. (Figure C) In patients with complete or partial VEGF remission after treatment, sphingolipids AS 1-1, Cer(d18:1/17:0) and glycerophospholipid lysoPE(0:0/18:2(9Z,12Z)) was lower than in patient with poor VEGF remission. (Figure D) Of all 358 genes related with altered lipids between patients and healthy control, 6 genes were reported to be upregulated in CD138+ cells in the bone marrow of POEMS syndrome than in MGUS and 8 genes than in MM. MGLL, a gene with function of converting monoacylglycerides to free fatty acids and glycerol, was expressed higher in POEMS syndrome than in both MGUS and MM and may be related with decreased serum glycerolipids. PLA2G2D, a gene encodes a secreted member of the phospholipase A2 family, was expressed higher in POEMS syndrome than in MGUS and may be responsible for decreased lysolipids after treatment. CONCLUSION: POEMS syndrome patients had a distinct serum lipidome characteristic from healthy control. A two-lipids model could distinguish patients and healthy people with high accuracy. Altered lipids and lipids related genes indicate POEMS syndrome specific alteration in glycerolipids and lysolipids metabolism compared with MGUS and MM, providing a potential insight for further study of molecular mechanism of POEMS syndrome. Figure Disclosures No relevant conflicts of interest to declare.

Description: OBJECTIVE: POEMS syndrome is a rare plasma cell dyscrasia and there is currently no standard treatment. Current treatments include melphalan, autologous stem cell transplantation (ASCT) and novel regimens. However, the efficacy of these treatments has not previously been retrospectively compared in large cohorts. Therefore, this study aims to compare the efficacy and survival of three treatment regimens in patients with POEMS syndrome in our 18-year cohort. METHODS: We retrospectively analyzed the clinical records of 347 patients with newly diagnosed POEMS syndrome who were diagnosed and treated in our hospital from January 2000 to December 2017 with complete treatment and follow-up data. Patients were divided into three groups according to the initial first-line treatment regimen: melphalan + dexamethasone (MDex, N = 79) for 9 months, autologous stem cell transplantation (ASCT, N = 165), or lenalidomide + dexamethasone for 1 year (LDex, N= 103). Hematologic complete remission rates (CRH), vascular endothelial growth factor (VEGF) complete remission rates (CRV), and neurological remission rates (RN) were compared for three regimens, as well as progression-free survival (PFS) and overall survival (OS). Hematologic complete remission was negative IFE and no FLC in serum or urine. The VEGF complete remission was normalized VEGF (

Description: Background: POEMS syndrome is a rare plasma cell dyscrasia. Despite the presence of monoclonal protein, POEMS syndrome patients commonly have less than 5% monoclonal plasma cells in the bone marrow. Only one study has reported the genetic and transcriptional features of bone marrow plasma cells, and the underlying role of aberrant plasma cells is not well understood. Herein, in the current study, we aimed to characterize the genetic profile of bone marrow CD138-positive cells from Chinese patients with newly diagnosed POEMS syndrome. Methods: Forty-two patients with newly diagnosed POEMS syndrome based on the International Myeloma Working Group criteria at our institute were included in our study. Twenty milliliters of bone marrow aspirates was obtained and sorted by magnetic microbeads conjugated to monoclonal human anti-CD138 antibodies. The mutational features of these bone marrow plasma cells were analyzed using a two-step strategy. DNA of the bone marrow plasma cells from ten patients was first sequenced by whole exome sequencing to find significantly mutated genes and mutated driver genes, with paired peripheral blood mononuclear cells as a control. Bone marrow plasma cells of an additional thirty-two patients were then analyzed by target region sequencing to validate the mutations. Results: Whole exome sequencing of 10 newly diagnosed patients showed a total of 170 somatic mutations in exonic regions and splicing sites. Three significantly mutated genes-LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)-and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, CUX1) were identified in five patients. The mutation spectrum of WES revealed C 〉 T/G 〉 A as the most common mutation type, while the mutation signature was not the same as known signatures reported in various cancer types. For significant pathway and gene ontology analysis, 69 genes with possibly pathogenic nonsynonymous mutations were selected. Mutated genes were enriched in pathways including "chromatin organization", "chromatin modifying enzymes", and "apoptosis", and terms such as "cellular anatomical entity", "regulatory region nucleic acid binding" and "centrosome" that are used to describe cellular structure construction. To evaluate the mutation prevalence of genes identified in WES, we performed target region sequencing of 77 candidate genes in 32 other patients. The candidate gene list consisted of significantly mutated genes and known driver genes identified in WES, recurrently mutated genes previously detected in POEMS syndrome, the VEGF gene, and genes of light-chain amyloidosis, multiple myeloma, hematopoietic disease or lymphoid neoplasm in the public databases. As a result, a total of 32 mutated genes were identified in 28 of 32 patients. Genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Conclusions: Heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome were revealed in our study. The mutational landscape of POEMS syndrome might share some similarity to that of other plasma cell diseases. Disclosures No relevant conflicts of interest to declare.