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Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages, and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. In contrast, later stages featured more diverse lipids alterations, including fatty acids and their derivatives, triglycerides, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, and phosphatidylinositols. These alterations underscored unique perturbations in cell membrane stability, proliferation, and survival during cancer development and progression, offering potential targets for early detection and prognosis of human ovarian cancer.TeaserTime-resolved lipidome remodeling in an ovarian cancer model is studied through lipidomics and machine learning.

Lake-source thermal district networks can efficiently supply heating and cooling to buildings and thus save energy and CO2 emissions. However, it remains unclear to which degree they are a sustainable alternative at a larger geographical scale. An evaluation of the potential of developing technically and economically feasible lake-source district systems in Europe was performed in this study, with an integrated spatial explicit techno-economic assessment that accounts for different boundary conditions, such as electricity price, CO2 price and climate change. The feasibility of covering building energy demand near lakes was found to be particularly sensitive to the relationship between capital costs from network design and operational costs from heat pumps, associated electricity consumption and CO2 emissions. Results suggest a European techno-economic potential of 1.9 TWh/y considering only direct cooling and 11.3 TWh/y if thermal networks supply both direct heating and cooling by heat pumps. Respective electricity savings are 0.36 TWh/y and 0.78 TWh/y. An estimated 17% of the cooling demand near European lakes can thus be covered by viable cooling-only lake-source systems. For combined systems, the viable potential is estimated to be 7% of the total combined heating and cooling demand. Lake-source district systems are found to be particularly promising for Italy, Germany, Turkey and Switzerland. The integration of lake-source thermal networks should rarely lead to severe lake water temperature alteration and therefore not limit the techno-economic potential. The introduced methodology allows for a combined evaluation of technological, ecological and economic boundary conditions for using lakes as a source for district heating and cooling. Thereby, a more realistic estimation of their potential implementation becomes possible, enabling informed energy planning for central or decentral system configurations., Energy Conversion and Management, 283, ISSN:0196-8904, ISSN:1879-2227

Supplementary Materials - PDF files 113K, Materials and Methods

Purpose: The growth and survival of neurofibromatosis type 2 (NF2)–deficient cells are enhanced by the activation of multiple signaling pathways including ErbBs/IGF-1R/Met, PI3K/Akt, and Ras/Raf/Mek/Erk1/2. The chaperone protein HSP90 is essential for the stabilization of these signaling molecules. The aim of the study was to characterize the effect of HSP90 inhibition in various NF2-deficient models.Experimental Design: We tested efficacy of the small-molecule NXD30001, which has been shown to be a potent HSP90 inhibitor. The antiproliferative activity of NXD30001 was tested in NF2-deficient cell lines and in human primary schwannoma and meningioma cultures in vitro. The antitumor efficacy of HSP90 inhibition in vivo was verified in two allograft models and in one NF2 transgenic model. The underlying molecular alteration was further characterized by a global transcriptome approach.Results: NXD30001 induced degradation of client proteins in and suppressed proliferation of NF2-deficient cells. Differential expression analysis identified subsets of genes implicated in cell proliferation, cell survival, vascularization, and Schwann cell differentiation whose expression was altered by NXD30001 treatment. The results showed that NXD30001 in NF2-deficient schwannoma suppressed multiple pathways necessary for tumorigenesis.Conclusions: HSP90 inhibition showing significant antitumor activity against NF2-related tumor cells in vitro and in vivo represents a promising option for novel NF2 therapies. Clin Cancer Res; 19(14); 3856–70. ©2013 AACR.

Supplementary Figure Legends - PDF files 65K, Figure Legends

Supplementary Figure 1 - PDF files 5795K, Induction of apoptosis by NXD30001 in NF2-deficient cells

Supplementary Table 2 - XLS file 40K, qPCR validation of transcriptome

Supplementary Figure 2 - PDF files 4552K, Global transcriptome profiling of NXD30001 efficacy

Supplementary Table 1 - XLS file 28K, PCR primers for NF2 mutation screening

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional “down” conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD “up”. Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern. Supplementary Information The online version contains supplementary material available at 10.1007/s13238-021-00871-6.

Ageing is an unavoidable process in humans and a major factor for the increasing risk of various diseases. In the United States, more than 50% of rheumatoid arthritis patients are middle-aged or elderly, but the risk factors and mechanisms by which ageing increases the incidence of rheumatoid arthritis are not known. It has been suggested that the accumulation of DNA fragments increases the risk of autoimmune diseases, such as systemic lupus erythematosus. DNA fragments are a common nucleic acid metabolite in ageing organisms as well as in the serum of humans and animals with rheumatoid arthritis; therefore, we hypothesize that DNA fragments are one of the factors contributing to the development of rheumatoid arthritis due to ageing. First, we analysed two in vitro DNA damage response models by using a gene silencing approach and determined that the DNA fragment clearance gene TREX1 can regulate inflammatory factor release in normal cells. Second, after TREX1 expression was knocked down locally or systemically in rats via the Cre-LoxP system and compared with that in AIA(adjuvant-induced arthritis) model rats treated with AAV-TREX1, it was determined that DNA fragments can result in manifestations of arthritis and abnormal activation of the immune system in rats. These results, including the low expression of the TREX1 gene in clinical patient and AIA model samples and the results of immunohistochemical, Western blot, and transcriptome analyses, revealed that the TREX1 gene can regulate cellular senescence-associated secretory phenotype (SASP)-related manifestations and showed that dysregulation of c-Jun and c-Fos, components of the TREX1 transcription factor AP-1, is associated with SASP induction. Finally, it was confirmed in vitro that different causes of decreased c-Fos expression can inhibit TREX1 expression. These DNA fragments are potent producers of inflammation-releasing mediators, and TREX1 is an effective degrader of DNA fragments; it is also a key gene that regulates cellular immunity and ageing. Therefore, effectively clearing excess DNA fragments from the body and ensuring the health of senescent cells may be a potential prevention strategy for RA.

Halogenated carbazoles are a new class of persistent organic pollutants with dioxin-like toxicity, and this study focused on the microbial degradation of 1,3,6,8-tetrabromocarbazole. In this study, a novel 1,3,6,8-tetrabromocarbazole (1,3,6,8-TBCZ) degrading strain TB-1 was isolated from contaminated soil and identified as

Coxsackie virus B5 (CVB5), a main serotype in human Enterovirus B (EVB), can cause severe viral encephalitis and aseptic meningitis among infants and children. Currently, there is no approved vaccine or antiviral therapy available against CVB5 infection. Here, we determined the atomic structures of CVB5 in three forms: mature full (F) particle (2.73 Å), intermediate altered (A) particle (2.81 Å), and procapsid empty (E) particle (2.95 Å). Structural analysis of F particle of CVB5 unveiled similar structures of "canyon," "puff," and "knob" as those other EV-Bs. We observed structural rearrangements that are alike during the transition from F to A particle, indicative of similar antigenicity, cell entry, and uncoating mechanisms shared by all EV-Bs. Further comparison of structures and sequences among all structure-known EV-Bs revealed that while the residues targeted by neutralizing MAbs are diversified and drive the evolution of EV-Bs, the relative conserved residues recognized by uncoating receptors could serve as the basis for the development of antiviral vaccines and therapeutics.

Background Colonoscopy is the reference standard for the detection of colorectal cancer but it is an invasive technique and has the risk of bowel perforation and bleeding. Unlike colonoscopy, sedation is not required in computed tomography colonography and requires additional reassurance endoscopy. The objectives of the study were to compare the diagnostic performance of computed tomography colonography against colonoscopy for a diagnosis of colorectal cancer. Methods Data regarding any polyp ≥10 mm diameter (ø) and n = 318), colonoscopy (n = 318), and surgical pathology (n = 77) for symptomatic colorectal cancer patients were collected and analyzed. Lesion ulceration, extramural invasion, and/ or lesion shouldering was considered as a suspicious polyp. Beneficial scores for decision making of curative surgeries were evaluated for each modality. The cost of diagnosis of colorectal cancer was also evaluated. Results Either of diagnosis showed polyps ≥10 mm ø in 27 patients and polyps of 50 patients were p Conclusion Computed tomographic colonography would be a non-inferior alternative than colonoscopy for a diagnosis of colorectal cancer. Level of evidence III.

SummaryThe SARS-CoV-2 Omicron with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the Spike (S) from Omicron reveals amino acid substitutions forging new interactions that stably maintain an “active” conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of viral fusion step. Alterations in local conformation, charge and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Apart from already existing mutations, we have identified three new immune escape sites: 1) Q493R, 2) G446S and 3) S371L/S373P/S375F that confers greater resistance to five of the six classes of RBD-antibodies. Structure of the Omicron S bound with human ACE2, together with analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the spike (S) from Omicron reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of the viral fusion step. Alterations in local conformation, charge, and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Structure of the Omicron S bound with human ACE2, together with the analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members, as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies, sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics., Graphical abstract, Mutations in the SARS-CoV-2 Omicron variant improve spike trimer stability that supports viral attachment but appears to compromise viral fusion. They also perturb the confirmation of antigenic sites for antibody recognition, which may contribute to immune evasion.

Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-resistant and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between “hot” immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines.One sentence summaryA third booster dose of inactivated vaccine produces a highly sifted humoral immune response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.

The molecular mechanisms underlying the antineoplastic properties of metformin combined with nelfinavir remain elusive. To explore this question, transmission electron microscopy (TEM) was used to observe the combinatorial effect of inducing autophagosome formation in human cervical cancer cells. Western blotting respectively assayed protein expression of LC3I, LC3II, Beclin-1, Autophagy-related protein 7 (Atg7), Autophagy-related protein 3 (Atg3), NAD-dependent deacetylase sirtuin-3 (SIRT3) and major histocompatibility complex class I chain-related gene A (MICA). Lactate dehydrogenase (LDH) cytotoxicity assay evaluated natural killer (NK) cell cytotoxicity in the presence of metformin and nelfinavir in combination or each drug alone. Using tumor xenografts in a nude mouse model, antitumor efficacy of the drug combination was assessed. We found that the drug combination could induce autophagosome formation in human cervical cancer cells. The biomarker proteins of autophagy, including Beclin-1, Atg7 and Atg3, decreased, but the ratios of LC3I/II increased. We also found that this drug combination sensitizes human cervical cancer cells to NK cell-mediated lysis by increasing the protein of SIRT3 and MICA. Moreover, this drug combination markedly induced autophagy of SiHa xenografts in nude mice. Therefore, it can be concluded that metformin, in combination with nelfinavir, can induce SIRT3/mROS-dependent autophagy and sensitize NK cell-mediated lysis in human cervical cancer cells and cervical cancer cell xenografts in nude mice. Thus, our findings have revealed the detailed molecular mechanisms underlying the antitumor effects of metformin in combination with nelfinavir in cervical cancer.

The molecular mechanisms underlying the anti-neoplastic properties of metformin, a first-line drug for type 2 diabetes, remain elusive. To explore the novel anti-neoplastic mechanisms of metformin, the transwell chamber and wound-healing assays were used to evaluate its effects on the migration and invasion of human cervical cancer cells. Real-time PCR and Western blotting were used to measure the gene and protein expression, respectively, of microRNA (miRNA) miR-142-3p, long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript-1 (MALAT1), and high-mobility group AT-hook 2 (HMGA2). The dual-luciferase reporter assay system was used to examine the direct interaction between miR-142-3p and lncRNA MALAT1 and HMGA2. Immunofluorescence was used to detect the protein expression of HMGA2. In addition, tumor xenografts in a nude mouse model were developed to evaluate the anti-tumor efficacy of metformin. We found that metformin could suppress cervical cancer migration and invasion. During the process of tumor metastasis, miR-142-3p was significantly upregulated, whereas lncRNA MATAL1 and HMGA2 were suppressed by metformin. The binding site that allow the direct interaction between miR-142-3p and MALAT1 were located in the 3' untranslated region (3' UTR) of lncRNA MATAL1 and HMGA2 at base pairs (bp) 4452-5255, while that between miR-142-3p and HMGA2 was located at bp 1562-2521 of HMGA2. Metformin markedly inhibited the growth and angiogenesis of SiHa xenografts in nude mice. In conclusion, this study provides evidence that metformin can prevent the MALAT1/miR-142-3p sponge from developing anti-neoplastic properties in human cervical cancer cells and cervical cancer cell xenografts in nude mice. Thus, our findings demonstrate the novel anti-tumor effects of metformin in cervical cancer.

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enter the host cells through the interaction between its receptor binding domain (RBD) of spike glycoprotein with angiotensin-converting enzyme 2 (ACE2) receptor on the plasma membrane of host cell. Neutralizing antibodies and peptide binders of RBD can block viral infection, however, the concern of accessibility and affordability of viral infection inhibitors has been raised. Here, we report the identification of natural compounds as potential SARS-CoV-2 entry inhibitors using the molecular docking-based virtual screening coupled with bilayer interferometry (BLI). From a library of 1871 natural compounds, epigallocatechin gallate (EGCG), 20(R)-ginsenoside Rg3 (RRg3), 20(S)-ginsenoside Rg3 (SRg3), isobavachalcone (Ibvc), isochlorogenic A (IscA) and bakuchiol (Bkc) effectively inhibited pseudovirus entry at concentrations up to 100 μM. Among these compounds, four compounds, EGCG, Ibvc, salvianolic acid A (SalA), and isoliensinine (Isl), were effective in inhibiting SARS-CoV-2-induced cytopathic effect and plaque formation in Vero E6 cells. The EGCG was further validated with no observable animal toxicity and certain antiviral effect against SARS-CoV-2 pseudovirus mutants (D614G, N501Y, N439K & Y453F). Interestingly, EGCG, Bkc and Ibvc bind to ACE2 receptor in BLI assay, suggesting a dual binding to RBD and ACE2. Current findings shed some insight into identifications and validations of SARS-CoV-2 entry inhibitors from natural compounds., Graphical Abstract ga1

Glaucoma is the leading cause of irreversible blindness in the world and trabeculectomy remains still the most commonly performed filtration surgery. Failure of trabeculectomy is due to the formation of scarring, which is associated with the increased fibroblast proliferation, activation, and collagen deposition at the site of the drainage channel with subconjunctival fibrosis. Our previous study has revealed that zinc oxide (ZnO) nanoparticles could efficiently decrease the expressions of TGF-β1 and inhibit fibroblast-mediated collagen lattice contraction. However, the mechanism underlying ZnO nanoparticle-induced fibroblast apoptosis is still unclear. In the present study, we investigated the effect of ZnO nanoparticles on the reactive oxygen species (ROS) and mitochondrial membrane potential (Δψm) in human Tenon fibroblasts (HTFs). Moreover, we also explored the influence of ZnO nanoparticles on the expression of Caspase-3, Caspase-9, apoptotic protease-activating factor-1 (Apaf-1), fibroblast-specific protein-1 (FSP-1), collagen III, and E-cadherin. The results indicated that ZnO nanoparticles markedly inhibit HTFs viability and decrease the Δψm in a concentration-dependent pattern. Exposure of HTFs to ZnO nanoparticles could also induce the elevated Caspase-3, Caspase-9, and Apaf-1 expression, decrease the levels of FSP-1, collagen III, and E-cadherin expression, leading to HTFs apoptosis. Our results suggested that elevated ROS and activated Caspase signaling play a fundamental role in ZnO nanoparticle-induced HTFs apoptosis.

Chinese jujube (Ziziphus jujuba Mill.) is an economically important fruit crop in China and mainly cultivated on land with high salinity and drought conditions in northern China. WRKY transcription factors (TFs) are involved in plant development and in responses to multiple abiotic stresses. In this study, we identified 61 and 52 putative ZjWRKY TFs in &lsquo, Junzao&rsquo, and &lsquo, Dongzao&rsquo, at the genome-wide level. Tissue expression profiling showed that 7 genes were constitutively expressed at high level in all tissues of &lsquo, Transcriptome analysis revealed that 39 ZjWRKY genes were expressed during &lsquo, jujube fruit ripening. Among these genes, the transcript abundance of 19 genes were differentially expressed between &lsquo, Qingjiansuanzao&rsquo, fruit. In addition, RT-qPCR analyses revealed that 30, 14, and 18 ZjWRKY genes responded to drought, NaCl, and ABA treatments, respectively. Taken together, ZjWRKY genes expression dynamics during jujube fruit development, ripening, and their differences between jujube and wild jujube would provide insights into their possible roles regulating fruit ripening. In addition, those ZjWRKY genes responded strongly to drought and salt stress, which provide candidate ZjWRKY genes for facilitating tolerance breeding.

Effects of short-chain inulin on apparent characteristics, textural and aging properties of Chinese steamed bread (CSB) were investigated. Specific volume, ratio of height to diameter and sensory assessment scores increased initially with increasing inulin substitution and then started decreasing as inulin substitution increased further, and reached the highest value with 5.0% inulin substitution. CSB with inulin (2.5%, 5.0%, 7.5%, 10.0% w/w) were all much whiter based on L*a*b* assessment. The substitution of inulin improved textural properties of fresh CSB but accelerated the aging rate. It was found that moisture migration was an important factor affecting the aging rate of CSB. It indicated that appropriate amount of short-chain inulin could improve the quality of CSB. The results could provide a theoretical basis for the practical application of inulin to CSB. Practical Applications Inulin has a potential for developing a novel Chinese steamed bread (CSB) with better functionality and more nutritional benefit. The optimal substitution proportion is 5.0% with the consideration of improving the quality of CSB, such as the volume, color, and texture. The research provides a theoretical basis for the practical application of inulin to CSB and possesses a board market prospect.

The flower is a plant reproductive organ that forms part of the fruit produced as the flowering season ends. While the number and identity of proteins expressed in a jujube (Ziziphus jujuba Mill.) flower is currently unknown, integrative proteomic and transcriptomic analyses provide a systematic strategy of characterizing the floral biology of plants. We conducted a shotgun proteomic analysis on jujube flowers by using a filter-aided sample preparation tryptic digestion, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, transcriptomics analyses were performed on HiSeq2000 sequencers. In total, 7,853 proteins were identified accounting for nearly 30% of the ‘Junzao’ gene models (27,443). Genes identified in proteome generally showed higher RPKM (reads per kilobase per million mapped reads) values than undetected genes. Gene ontology categories showed that ribosomes and intracellular organelles were the most dominant classes and accounted for 17.0% and 14.0% of the proteome mass, respectively. The top-ranking proteins with iBAQ >1010 included non-specific lipid transfer proteins, histones, actin-related proteins, fructose-bisphosphate aldolase, Bet v I type allergens, etc. In addition, we identified one pollen-specificity S-locus F-box-like gene located on the same chromosome as the S-RNase gene. Both of these may activate the behaviour of gametophyte self-incompatibility in jujube. These results reflected the protein profile features of jujube flowers and contributes new information important to the jujube breeding system.

Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer.

Probing into the Quality Control Circle (QCC) activities in improving the delayed cord clamp rate (DCC) of newborns undergoing vaginal delivery. By setting up QCC team, to investigate and diagnose the problems of DCC rate of newborns undergoing vaginal delivery in our hospital in 2017, therefore, to draw up our new target and the responding measurement. After that, we analyze and discuss the data, and finally filter the valid data. Finally, we compare the two sets of situations and data. According to the investigation of DCC rate undergoing vaginal delivery and the relative Maternal-and-Infant outcome in August to November in 2017, after setting up QCC activities, it shows the DCC rate of newborns undergoing vaginal delivery has an significant increased, from 35.1% to 82.3%, duration of the Third Stage of Labor, hospitalization rate of Neonatal intensive Care Nursing (NICU), Apgar score, incidence of postpartum hemorrhage, asphyxia neonatorum and hyperbilirubinemia has no statistical sence (P>0.05). The Quality Control Circle (QCC) activities can effectively improve the delayed cord clamp rate (DCC) of newborns undergoing vaginal delivery, without affecting the incidence of undesirable Maternal-and-Infant outcome. And the quality control circle activities can be fed back and improved through the PDCA cycle to make it more scientific and practical.

Solvothermal reactions of Ln2O3, As and S in diethylenetriamine (dien) at 170 °C for 6 days afforded two structural types of lanthanide thioarsenates with the general formulae [Ln(dien)2(μ-1κ,2κ2-AsS4)]n [Ln=Sm(1), Eu(2), Gd(3)] and [Ln(dien)2(1κ2-AsS4)] [Ln=Tb(4), Dy(5), Ho(6)]. The Ln2O3 oxides were converted to [Ln(dien)2]3+ complex units in the solvothermal reactions. The As atom binds four S atoms, forming a tetrahedral AsS4 unit. In 1−3, the AsS4 units interconnect the [Ln(dien)2]3+ cations via Ln−S bonds as tridentate μ-1κ,2κ2-AsS4 bridging ligands, resulting in the neutral coordination polymers [Ln(dien)2(μ-1κ,2κ2-AsS4)]n (Ln1). In 4−6, the AsS4 units coordinate with the Ln3+ ion of [Ln(dien)2]3+ as 1κ2-AsS4 chelating ligands to form neutral coordination compounds [Ln(dien)2(1κ2-AsS4)] (Ln2). The Ln3+ ions are in nine- and eight-coordinated environments in Ln1 and Ln2, respectively. The formation of Ln1 and Ln2 is related with ionic size of the Ln3+ ions. Optical absorption spectra showed that 1−6 have potential use as semiconductors with the band gaps in the range 2.18−3.21 eV.

Lanthanide selenidostannates (H3O)n[Ce(tepa)(μ-1κ2:2κ2-Sn2Se6)]n (1), [{Yb(tepa)(μ-OH)}2(μ-1κ:2κ-Sn2Se6)]n·nH2O (2), [Htrien]2[{Ln(trien)(tren)}2(μ-1κ:2κ-Sn2Se6)][Sn2Se6] (Ln=Ce(3), Nd(4)) and [{Yb(dien)2}2(μ-OH)2]Sn2Se6 (5) were solvothermally prepared in different ethylene polyamines. The Sn2Se6 unit connects [Ce(tepa)]3+ and [{Yb(tepa)(μ-OH)}2]4+ fragments with tetradentate μ-1κ2Se1,Se2:2κ2Se5,Se6 and bidentate μ-1κSe1:2κSe5 bridging coordination modes in tepa, to form polymers 1 and 2, respectively. It joins two [Ln(trien)(tren)]3+ fragments as a μ-1κSe1:2κSe5 ligand to form binuclear complexes 3 and 4 in trien. Unlike the Sn2Se6 units in 1–4 that bind with Ln(III) centers as Se-donor ligands, the Sn2Se6 unit in 5 exists as a discrete ion. The syntheses of 1–5 show that the ethylene polyamines play an important role in the complexation of Sn2Se6 ligand with Ln(III) centers. Compounds 1–5 exhibit optical band gaps in the range of 2.09–2.42 eV, which are influenced by the complexation of Sn2Se6 with Ln(III) centers.

Purpose: The growth and survival of neurofibromatosis type 2 (NF2)–deficient cells are enhanced by the activation of multiple signaling pathways including ErbBs/IGF-1R/Met, PI3K/Akt, and Ras/Raf/Mek/Erk1/2. The chaperone protein HSP90 is essential for the stabilization of these signaling molecules. The aim of the study was to characterize the effect of HSP90 inhibition in various NF2-deficient models. Experimental Design: We tested efficacy of the small-molecule NXD30001, which has been shown to be a potent HSP90 inhibitor. The antiproliferative activity of NXD30001 was tested in NF2-deficient cell lines and in human primary schwannoma and meningioma cultures in vitro. The antitumor efficacy of HSP90 inhibition in vivo was verified in two allograft models and in one NF2 transgenic model. The underlying molecular alteration was further characterized by a global transcriptome approach. Results: NXD30001 induced degradation of client proteins in and suppressed proliferation of NF2-deficient cells. Differential expression analysis identified subsets of genes implicated in cell proliferation, cell survival, vascularization, and Schwann cell differentiation whose expression was altered by NXD30001 treatment. The results showed that NXD30001 in NF2-deficient schwannoma suppressed multiple pathways necessary for tumorigenesis. Conclusions: HSP90 inhibition showing significant antitumor activity against NF2-related tumor cells in vitro and in vivo represents a promising option for novel NF2 therapies. Clin Cancer Res; 19(14); 3856–70. ©2013 AACR.

Organic hybrid europium hexachalcogenidodistannates [{Eu(en)3}2(μ-OH)2]Sn2S6 (1), [{Eu(en)3}2(μ-OH)2]Sn2Se6 (2), and [Eu(dien)3]2[(Sn2S6)(SH)2] (3) (en = ethylenediamine, dien = diethylenetriamine) were solvothermally synthesized by the reactions of Sn, S (or Se) and Eu2O3 in en and dien solvents, respectively. Compounds 1–3 crystallize in monoclinic space group P21/n. Crystallographic data for 1: a = 10.1158(13), b = 11.3793(14), c = 14.9487(15) A, β = 98.209(4)°, V = 1703.1(3) A3, Z = 2. For 2: a = 10.1359(19), b = 11.771(2), c = 15.423(3) A, β = 99.322(5)°, V = 1815.8(6) A3, Z = 2. For 3: a = 11.6559(10), b = 15.1677(13), c = 14.1732(13) A, β = 95.682(2)°, V = 2493.4(4) A3, Z = 2. The Eu3+ ion forms binuclear tetravalent [{Eu(en)3}2(μ-OH)2]4+ complex cation to act as counter ion to the [Sn2S6]4− and [Sn2Se6]4− anions in 1 and 2. But it is coordinated with three dien ligands to form the mononuclear trivalent [Eu(dien)3]3+ complex cation in 3. The cations and anions are connected into 3-dimensional networks via O–H···S, N–H···S, or N–H···Se hydrogen bonds, respectively. New europium hexachalcogenidodistannate [{Eu(en)3}2(μ-OH)2]Sn2S6, [{Eu(en)3}2(μ-OH)2]Sn2Se6, and [Eu(dien)3]2[(Sn2S6)(SH)2] with 3-dimensional H-bonding network structures were respectively prepared in ethylenetediamine (en) and diethylenetetriamine (dien) under mild solvothermal conditions.

Two types of 4f–3d thiostannates with general formula [Hen]2[Ln(en)4(CuSn3S9)]⋅0.5 en (Ln1; Ln=La, 1; Ce, 2) and [Hen]4[Ln(en)4]2[Cu6Sn6S20]⋅3 en (Ln2; Ln=Nd, 3; Gd, 4; Er, 5) were prepared by reactions of Ln2O3, Cu, Sn, and S in ethylenediamine (en) under solvothermal conditions between 160 and 190 °C. However, reactions performed in the range from 120 to 140 °C resulted in crystallization of [Sn2S6]4− compounds and CuS powder. In 1 and 2, three SnS4 tetrahedra and one CuS3 triangle are joined by sharing sulfur atoms to form a novel [CuSn3S9]5− cluster that coordinates to the Ln3+ ion of [Ln(en)4]3+ (Ln=La, Ce) as a monodentate ligand. The [CuSn3S9]5− unit is the first thio-based heterometallic adamantane-like cluster coordinating to a lanthanide center. In 3–5, six SnS4 tetrahedra and six CuS3 triangles are connected by sharing common sulfur atoms to form the ternary [Cu6Sn6S20]10− cluster, in which a Cu6 core is enclosed by two Sn3S10 fragments. The topological structure of the novel Cu6 core can be regarded as two Cu4 tetrahedra joined by a common edge. The Ln3+ ions in Ln1 and Ln2 are in nine- and eightfold coordination, respectively, which leads to the formation of the [CuSn3S9]5− and [Cu6Sn6S20]10− clusters under identical synthetic conditions. The syntheses of Ln1 and Ln2 show the influence of the lanthanide contraction on the quaternary Ln/Cu/Sn/S system in ethylenediamine. Compounds 1–5 exhibit bandgaps in the range of 2.09–2.48 eV depending on the two different types of clusters in the compounds. Compounds 1, 3, and 4 lost their organic components in the temperature range of 110–350 °C by multistep processes.

New heterometallic thioantimonates(III) [Co(dien)2]HgSb2S5 (1), [Ni(dien)2]HgSb2S5 (2) and [H2dien]HgSb8S14 (3), and a mixed-valent thioantimonate(III,V) [Co(dien)2]2Sb4S9 (4) were solvothermally prepared in diethylenetriamine (dien) solvent from Co(Ni)–Hg–Sb–S, Hg–Sb–S and Co–Sb–S systems, respectively. In 1 and 2, the bimeric subunit Sb2S5 condenses with HgS4 tetrahedron via sharing common S atoms to form an one-dimensional [HgSb2S5]n2n− chain, in which a new μ3-1κ2S1,S5:2κS2:3κS4 bridging mode of the Sb2S5 subunit is obtained. In 3, four SbS3 trigonal pyramids and a linear HgS2 unit condense via sharing S atoms to generate an one-dimensional double-lined [HgSb8S14] n2n− chain. In 4, three SbIIIS3 pyramids and a SbVS4 tetrahedron share common corners to form an one-dimensional mixed-valent [Sb4S9]n4n− anion. The syntheses of 1–4 demonstrated that the Hg2+ ion is easily incorporated into thioantimonate networks, and has a higher affinity to S than that of transition metals. 1–4 exhibit semiconducting properties with optical band gaps in 2.0–2.4 eV.