M2 macrophage-derived paracrine factor TNFSF13 affects the fibrogenic alterations in endothelial cells and cardiac fibroblasts by mediating the NF-κB and Akt pathway.

Heart failure remains a global threaten to public health, cardiac fibrosis being a crucial event during the development and progression of heart failure. Reportedly, M2 macrophages might affect endothelial cell (ECs) and fibroblast proliferation and functions through paracrine signaling, participating in myocardial fibrosis. In this study, differentially expressed paracrine factors between M0/1 and M2 macrophages were analyzed and the expression of TNFSF13 was most significant in M2 macrophages. Culture medium (CM) of M2 (M2 CM) coculture to ECs and cardiac fibroblasts (CFbs) significantly promoted the cell proliferation of ECs and CFbs, respectively, and elevated α-smooth muscle actin (α-SMA), collagen I, and vimentin levels within both cell lines; moreover, M2 CM-induced changes in ECs and CFbs were partially abolished by TNFSF13 knockdown in M2 macrophages. Lastly, the NF-κB and Akt signaling pathways were proved to participate in TNFSF13-mediated M2 CM effects on ECs and CFbs. In conclusion, TNFSF13, a paracrine factor upregulated in M2 macrophages, could mediate the promotive effects of M2 CM on EC and CFb proliferation and fibrogenic alterations.

Effect of Chemical Composition of Metal-Organic Crosslinker on the Properties of Fracturing Fluid in High-Temperature Reservoir.

To investigate the effect of the chemical composition of a metal-organic crosslinker on the performances of fracturing fluid in high-temperature conditions, four zirconium (Zr) crosslinkers and one aluminum-zirconium (Al-Zr) crosslinker with a polyacrylamide were used. The crosslinkers possessed the same Zr concentration, but they differed in component amounts and the order of the addition of the crosslinker components, leading to different chemical compositions in the crosslinkers. The fracturing fluids prepared by different tested crosslinkers were compared in terms of properties of rheological behavior, sand-carrying ability, microstructure, and gel breaking characteristics. The results showed that the fracturing fluids prepared by zirconium lactic acid, ethanediamine, and sorbitol crosslinkers offered the slowest viscosity development and highest final viscosity compared to the zirconium lactic acid crosslinker and the zirconium lactic acid and ethanediamine crosslinker. The zirconium sorbitol, lactic acid, and ethanediamine crosslinker exhibited a faster crosslinking rate and a higher final viscosity than the zirconium lactic acid, ethanediamine, and sorbitol crosslinker; the crosslinker showed crosslinking density and crosslinking reactivity, resulting in more crosslinking sites and a higher strength in the fracturing fluid. The Al-Zr-based crosslinker possessed better properties in temperature and shear resistance, viscoelasticity, shear recovery, and sand-carrying ability than the Zr-based crosslinker due to the synergistic crosslinking effect of aluminum and zirconium ions. The tertiary release gelation mechanism of the Al-Zr-based fracturing fluid achieved a temperature resistance performance in the form of continuous crosslinking, avoiding the excessive crosslinking dehydration and reducing viscosity loss caused by early shear damage. These results indicated that the chemical compositions of metal-organic crosslinkers were important factors in determining the properties of fracturing fluids. Therefore, the appropriate type of crosslinker could save costs without adding the additional components required for high-temperature reservoirs.

Fracturing Fluid Polymer Thickener with Superior Temperature, Salt and Shear Resistance Properties from the Synergistic Effect of Double-Tail Hydrophobic Monomer and Nonionic Polymerizable Surfactant.

To develop high-salinity, high-temperature reservoirs, two hydrophobically associating polymers as fracturing fluid thickener were respectively synthesized through aqueous solution polymerization with acrylamide (AM), acrylic acid (AA), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), nonionic polymerizable surfactant (NPS) and double-tail hydrophobic monomer (DHM). The thickener ASDM (AM/AA/AMPS/NPS/DHM) and thickener ASD (AM/AA/AMPS/DHM) were compared in terms of properties of water dissolution, thickening ability, rheological behavior and sand-carrying. The results showed that ASDM could be quickly diluted in water within 6 min, 66.7% less than that of ASD. ASDM exhibited salt-thickening performance, and the apparent viscosity of 0.5 wt% ASDM reached 175.9 mPa·s in 100,000 mg/L brine, 100.6% higher than that of ASD. The viscosity of 0.5 wt% ASDM was 85.9 mPa·s after shearing for 120 min at 120 °C and at 170 s-1, 46.6% higher than that of ASD. ASDM exhibited better performance in thickening ability, viscoelasticity, shear recovery, thixotropy and sand-carrying than ASD. The synergistic effect of hydrophobic association and linear entanglement greatly enhancing the performance of ASDM and the compactness of the spatial network structure of the ASDM was enhanced. In general, ASDM exhibited great potential for application in extreme environmental conditions with high salt and high temperatures.

α-Synuclein activates innate immunity but suppresses interferon-γ expression in murine astrocytes.

Glial activation and neuroinflammation contribute to pathogenesis of neurodegenerative diseases, linked to neuron loss and dysfunction. α-Synuclein (α-syn), as a metabolite of neuron, can induce microglia activation to trigger innate immune response. However, whether α-syn, as well as its mutants (A53T, A30P, and E46K), induces astrocyte activation and inflammatory response is not fully elucidated. In this study, we used A53T mutant and wild-type α-syns to stimulate primary astrocytes in dose- and time-dependent manners (0.5, 2, 8, and 20 µg/ml for 24 hr or 3, 12, 24, and 48 hr at 2 µg/ml), and evaluated activation of several canonical inflammatory pathway components. The results showed that A53T mutant or wild-type α-syn significantly upregulated mRNA expression of toll-like receptor (TLR)2, TLR3, nuclear factor-κB and interleukin (IL)-1ß, displaying a pattern of positive dose-effect correlation or negative time-effect correlation. Such upregulation was confirmed at protein levels of TLR2 (at 20 µg/ml), TLR3 (at most doses), and IL-1ß (at 3 hr) by western blotting. Blockage of TLR2 other than TLR4 inhibited TLR3 and IL-1ß mRNA expressions. By contrast, interferon (IFN)-γ was significantly downregulated at mRNA, protein, and protein release levels, especially at high concentrations of α-syns or early time-points. These findings indicate that α-syn was a TLRs-mediated immunogenic agent (A53T mutant stronger than wild-type α-syn). The stimulation patterns suggest that persistent release and accumulation of α-syn is required for the maintenance of innate immunity activation, and IFN-γ expression inhibition by α-syn suggests a novel immune molecule interaction mechanism underlying pathogenesis of neurodegenerative diseases.

Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis.

Osteoporosis is a major public health problem. It is mainly characterized by low bone mineral density (BMD) and/or low-trauma osteoporotic fractures (OF), both of which have strong genetic determination. The specific genes influencing these phenotypic traits, however, are largely unknown. Using the Affymetrix 500K array set, we performed a case-control genome-wide association study (GWAS) in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls). A follow-up replication study was conducted to validate our major GWAS findings in an independent Chinese sample containing 390 cases with hip OF and 516 controls. We found that a SNP, rs13182402 within the ALDH7A1 gene on chromosome 5q31, was strongly associated with OF with evidence combined GWAS and replication studies (P = 2.08x10(-9), odds ratio = 2.25). In order to explore the target risk factors and potential mechanism underlying hip OF risk, we further examined this candidate SNP's relevance to hip BMD both in Chinese and Caucasian populations involving 9,962 additional subjects. This SNP was confirmed as consistently associated with hip BMD even across ethnic boundaries, in both Chinese and Caucasians (combined P = 6.39x10(-6)), further attesting to its potential effect on osteoporosis. ALDH7A1 degrades and detoxifies acetaldehyde, which inhibits osteoblast proliferation and results in decreased bone formation. Our findings may provide new insights into the pathogenesis of osteoporosis.

Study on the Low-Temperature Rheology of Polar Drilling Fluid and Its Regulation Method.

Drilling fluid is the blood of drilling engineering. In the polar drilling process, the ultra-low temperature environment puts high demands on the rheological performance of drilling fluids. In this paper, the effects of temperature, ice debris concentration and weighting agent on the rheological properties of drilling fluids were studied. It was found that the lower the temperature and the higher the ice debris concentration, the higher the drilling fluid viscosity, but when the ice debris concentration was below 2%, the drilling fluid rheology hardly changed. Secondly, the low temperature rheological properties of drilling fluid were adjusted by three different methods: base fluid ratio, organoclay, and polymers (dimer acid, polymethacrylate, ethylene propylene copolymer, and vinyl resin). The results showed that the base fluid rheological performance was optimal when the base fluid ratio was 7:3. Compared with polymers, organoclay has the most significant improvement on the low temperature rheological performance of drilling fluid. The main reason is that organoclay can transform the drilling fluid from Newtonian to non-Newtonian fluid, which exhibits excellent shear dilution of drilling fluid. The organoclay is also more uniformly dispersed in the oil, forming a denser weak gel mesh structure, so it is more effective in improving the cuttings carrying and suspension properties of drilling fluids. However, the drilling fluid containing polymer additives is still a Newtonian fluid, which cannot form a strong mesh structure at ultra-low temperatures, and thus cannot effectively improve the low-temperature rheological performance of drilling fluid. In addition, when the amount of organoclay is 2%, the improvement rate of the yield point reaches 250% at -55 °C, which can effectively improve the cuttings carrying and suspension performance of drilling fluid at ultra-low temperature.

Review of the Perspectives and Study of Thermo-Responsive Polymer Gels and Applications in Oil-Based Drilling Fluids.

Thermoresponsive polymer gels are a type of intelligent material that can react to changes in temperature. These materials possess excellent innovative properties and find use in various fields. This paper systematically analyzes the methods for testing and regulating phase transition temperatures of thermo-responsive polymer gels based on their response mechanism. The report thoroughly introduces the latest research on thermo-responsive polymer gels in oil and gas extraction, discussing their advantages and challenges across various environments. Additionally, it elucidates how the application limitations of high-temperature and high-salt conditions can be resolved through process optimization and material innovation, ultimately broadening the scope of application of thermo-responsive polymer gels in oil and gas extraction. The article discusses the technological development and potential applications of thermo-responsive polymer gels in oil-based drilling fluids. This analysis aims to offer researchers in the oil and gas industry detailed insights into future possibilities for thermo-responsive polymer gels and to provide helpful guidance for their practical use in oil-based drilling fluids.

The mechanical properties and sustainability of phosphogypsum-slag binder activated by nano-ettringite.

The cementitious material based on phosphogypsum (PG) and ground granulated blast furnace slag (GBFS) demonstrates good economy and sustainability, whereas its drawback of ultra-slow strength development seems unacceptable. In this study, an attempt to drive the hydration of PG-GBFS and further facilitate the strength development by introducing nano-ettringite (NE) was carried out. The impact of 1- 5 % NE on the compressive strength, hydration process, dissolution behavior, and microstructure evolution of PG-GBFS were investigated. The results showed that the incorporation of NE significantly increased the compressive strength of PG-GBFS. At 7 d, the strength grew from 0 MPa to a range of 7.6- 20.2 MPa, and at 28 d, it was enhanced from 22.9 MPa to a range of 45.6- 79.0 MPa. The reason was that the introduction of NE induced the formation of AFt, thereby accelerating the hydration process and promoting the development of the skeletal network, resulting in higher early strength. Besides, NE facilitated the formation of C-S(A)-H gel, which further refined the pore structure and led to continuous growth in later strength. Additionally, PG-GFBS with 5 % NE exhibited significantly lower total costs (35.0 % of NaOH-activated slag and 51.7 % of water glass-activated slag) and lower carbon emissions (30.8 % of NaOH-activated slag and 49.8 % of water glass-activated slag) at the same 28 d compressive strength, indicating its strong competitiveness in both sustainability and economy.

Fabrication and property evaluation of calcium-oxide-loaded microcapsules during supplemental heat-based exploitation of natural gas hydrates.

The exploitation of natural gas hydrates (NGHs) by traditional methods is far lower than the commercial target. Calcium oxide (CaO)-based in situ supplemental heat combined with depressurization is a novel method for effectively exploiting NGHs. In this study, we propose an in situ supplemental heat method with the sustained-release CaO-loaded microcapsules coated with polysaccharide film. The modified CaO-loaded microcapsules were coated with polysaccharide films using covalent layer-by-layer self-assembly and wet modification process, with (3-aminopropyl) trimethoxysilane as the coupling agent and modified cellulose and chitosan as the shell materials. Microstructural characterization and elemental analysis of the microcapsules verified the change in the surface composition during the fabrication process. We found that the overall particle size distribution was within the range of 1-100 µm, corresponding to the particle size distribution in the reservoir. Furthermore, the sustained-release microcapsules exhibit controllable exothermic behavior. The decomposition rates of the NGHs under the effect of CaO and CaO-loaded microcapsules coated with one and three layers of polysaccharide films were 36.2, 17.7, and 11.1 mmol h-1, respectively, while the exothermic time values were 0.16, 1.18, and 6.68 h, respectively. Finally, we propose an application method based on sustained-release CaO-loaded microcapsules used for the supplemental heat-based exploitation of NGHs.

Molecular Simulation of Interactions between High-Molecular-Polymer Flocculation Gel for Oil-Based Drilling Fluid and Clay Minerals.

China has abundant shale gas resources with great potential, which may serve as a significant support for the development of a "low-carbon economy". Domestic shale gas resources are buried deeply and difficult to exploit due to some prevalent issues, such as long horizontal sections, severe development of reservoir fractures, strong sensitivity to water, borehole instability, etc. Compared to water-based drilling fluids, oil-based drilling fluid exhibits better inhibition and good lubricity and is thus broadly used in shale gas drilling, but it is confronted with the challenge of removing the harmful solid phase. Selective chemical flocculation is one of the most effective methods of removing the harmful solid phase in oil-based drilling fluid. In this study, interactions between the flocculation gel for oil-based drilling fluid and clay minerals were investigated by molecular simulation, which revealed the molecular-scale selectivity of the flocculation gel for rock cuttings with negative charges. Calculations showed that the flocculation gel is highly effective for the flocculation of negatively charged cuttings, but it is ineffective for flocculating neutral cuttings. The flocculation gel is not very effective for cuttings with high hydrophilicity, and it is totally ineffective for flocculating cuttings with poor hydrophilicity. Within a limited concentration range, the flocculation effect can be enhanced by increasing the flocculation gel concentration. The performance of the flocculation gel declined at elevated temperatures.

A Temperature-Sensitive Polymeric Rheology Modifier Used in Water-Based Drilling Fluid for Deepwater Drilling.

Rheology modifiers are essential for the flat rheology of water-based drilling fluids in deepwater. The low temperature thickening of deepwater water-based drilling fluids results in dramatic rheological changes in the 20-30 °C range. To address such problems, NIPAM with a self-polymerized product LCST of 32-35 °C was selected as the main body for synthesis. While introducing the hydrophilic monomer AM to enhance the thickening properties, the hydrophobic monomer BA was selected to reduce the LCST of the product. In this paper, a temperature-sensitive polymeric rheology modifier (PNBAM) was synthesized by emulsion polymerization using N-isopropyl acrylamide, acrylamide, and butyl acrylate as monomers. The PNBAM was characterized using infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and nuclear magnetic resonance hydrogen spectroscopy (NMR). The rheological properties, temperature resistance, and salt resistance of PNBAM in the base fluid (BF) were tested. The performance of PNBAM in the drilling fluid system was also evaluated, and a water-based drilling fluid system of flat rheology for deepwater was formulated. The rheological modification mechanism of PNBAM was analyzed by turbidity analysis, particle size analysis, and zeta analysis. Experimental results show that PNBAM has good rheological properties. PNBAM is temperature resistant to 150 °C, salt-resistant to 30 wt%, and calcium resistant to 1.0 wt%. PNBAM also has good flat rheology characteristics in drilling fluid systems: AV4°C:AV25°C = 1.27, PV4°C:PV25°C = 1.19. Mechanistic analysis showed that the LCST (Lower Critical Solution Temperature) of 0.2 wt% PNBAM in an aqueous solution was 31 °C. Through changes in hydrogen bonding forces with water, PNBAM can regulate its hydrophilic and hydrophobic properties before and after LCST, which thus assists BF to achieve a flat rheological effect. In summary, the temperature-sensitive effect of PNBAM has the property of enhancing with increasing temperature. While the tackifying effect of conventional rheology modifiers diminishes with increasing temperature, the temperature-sensitive effect of PNBAM gives it an enhanced thickening effect with increasing temperature, making it a more novel rheology modifier compared to conventional treatment additives. After LCST, compared to conventional rheology modifiers (XC), PNBAM has a more pronounced thermo-thickening effect, improving the main rheological parameters of BF by more than 100% or even up to 200% (XC less than 50%). This contributes to the flat rheology of drilling fluids. PNBAM has good application prospects and serves as a good reference for the development of other rheology modifiers.

Temperature- and Salt-Resistant Micro-Crosslinked Polyampholyte Gel as Fluid-Loss Additive for Water-Based Drilling Fluids.

With increasing global energy consumption, oil/gas drilling has gradually expanded from conventional shallow reservoirs to deep and ultra-deep reservoirs. However, the harsh geological features including high temperature and high salinity in ultra-deep reservoirs have become a critical challenge faced by water-based drilling fluids (WDFs), which seriously deteriorate the rheology and fluid loss properties, causing drilling accidents, such as wellbore instability and formation collapse. In this study, a novel temperature- and salt-resistant micro-crosslinked polyampholyte gel was synthesized using N,N-dimethylacrylamide, diallyldimethyl ammonium chloride, 2-acrylamido-2-methylpropanesulfonic acid, maleic anhydride and chemical crosslinking agent triallylamine through free radical copolymerization. Due to the synergistic effect of covalent micro-crosslinking and the reverse polyelectrolyte effect of amphoteric polymers, the copolymer-based drilling fluids exhibit outstanding rheological and filtration properties even after aging at high temperatures (up to 200 °C) and high salinity (saturated salt) environments. In addition, the zeta potential and particle size distribution of copolymer-based drilling fluids further confirmed that the copolymer can greatly improve the stability of the base fluid suspension, which is important for reducing the fluid-loss volume of WDFs. Therefore, this work will point out a new direction for the development of temperature- and salt-resistant drilling fluid treatment agents.

Comparative Studies on Thickeners as Hydraulic Fracturing Fluids: Suspension versus Powder.

To overcome the problems of long dissolution time and high investment in surface facilities of powder thickeners in hydraulic fracturing, a novel suspension of a thickener as a fracturing fluid was prepared using powder polyacrylamide, nano-silica, and polyethylene glycol by high-speed mixing. The suspension and powder were compared in terms of properties of solubility, rheological behavior, sand carrying, drag reduction, and gel breaking. The results showed that the suspension could be quickly diluted in brine within 5 min, whereas the dissolution time of powder was 120 min. The suspension exhibited better performance in salt resistance, temperature resistance, shear resistance, viscoelasticity, sand carrying, and drag reduction than powder. The powder solution was broken more easily and had a lower viscosity than suspension diluent. These improvements in properties of the suspension were due to the dispersion of nano-silica in the polymer matrix; the mobility of thickener chains was inhibited by the steric hindrance of the nano-silica. Nano-silica particles acted as crosslinkers by attaching thickener chains, which strengthened the network structure of the thickener solution. The presence of hydrogen bonds between the thickener matrix and the nano-silica restricted the local movement of thickener chains, leading to a stronger spatial network. Therefore, this novel suspension showed good potential for fracturing applications.

Kinetic Hydrate Inhibition of Natural Gels in Complex Sediment Environments.

Natural gels are emerging as a hotspot of global research for their greenness, environmental-friendliness, and good hydrate inhibition performance. However, previous studies mostly performed experiments for simple pure water systems and the inhibition mechanism in the sediment environment remains unclear. Given this, the inhibition performance of xanthan gum and pectin on hydrate nucleation and growth in sediment environments was evaluated via hydrate formation inhibition tests, and the inhibition internal mechanisms were revealed via a comprehensive analysis integrating various methods. Furthermore, the influences of natural gels on sediment dispersion stability and low-temperature fluid rheology were investigated. Research showed that the sediments of gas hydrate reservoirs in the South China Sea are mainly composed of micro-nano quartz and clay minerals. Xanthan gum and pectin can effectively inhibit the hydrate formation via the joint effects of the binding, disturbing, and interlayer mass transfer suppression processes. Sediments promote hydrate nucleation and yet inhibit hydrate growth. The interaction of sediments with active groups of natural gels weakens the abilities of gels to inhibit hydrate nucleation and reduce hydrate formation. Nonetheless, sediments help gels to slow down hydrate formation. Our comprehensive analysis pointed out that pectin with a concentration of 0.5 wt% can effectively inhibit the hydrate nucleation and growth while improving the dispersion stability and low-temperature rheology of sediment-containing fluids.

Oxygen vacancy BiO2-x/Bi2WO6 synchronous coupling with Bi metal for phenol removal via visible and near-infrared light irradiation.

The introduction of oxygen-defects has been a versatile strategy to enhance photocatalysis efficiency. In this work, a 2D/3D Bi/BiO2-x/Bi2WO6 heterojunction photocatalyst with rich oxygen-defective was in sequence prepared through a facile solvothermal method, which displays favorable photocatalytic activity towards organic contaminants under visible-NIR light irradiation. The enhancement in photocatalytic performance can be attributed to the synergistic effect between oxygen-vacancy-rich heterojunction and the localized surface plasmon resonance induced by metallic Bi. The functional group interaction, surface morphology, crystal structure, element composition, and tuned bandgap were investigated by FT-IR, SEM, Raman shift, ICP-MS, and XPS technique. The spectrum response performance of the photocatalyst was verified by UV-visible DRS analysis. Results of photodegradation experiments toward organic contaminants showed that the prepared photocatalyst can degrade 90% of phenol in 20 mins under visible-NIR light irradiation, both Z-scheme heterojunction and the introduction of Bi metal contribute to the enhancement in the photocatalytic activity. The results of the DFT calculation suggest that the valence band-edge hybridization within BiO2-x and Bi2WO6 can effectively enhance the photocatalytic performance by increasing the migration efficiencies of electron-hole pairs. Moreover, a possible mechanism was proposed on the results of EIS, ESR and GC-MS tests. This work offers a novel insight for synthesizing efficient visible-NIR light photocatalysis by activating the semiconductors with Bi metal.

Potent immunosuppressive and anti-inflammatory bisindole alkaloids from Melodinus fusiformis.

Phytochemical investigation of Melodinus fusiformis led to a new aspidosperma-aspidosperma bisindole alkaloid (BIA), bis-19ß-hydroxyvenalstonidine (1), together with three known BIAs (2-4). The structures were established by extensive analysis of their HRESIMS, NMR data, and comparing with the reported data. BIA 1 is an almost symmetrical structure, linked by C3-C14' bond, while BIAs 2-4 are reported for the first time from the plant. The cytotoxic, immunosuppressive and anti-inflammatory activities of BIAs 1-4 were evaluated in vitro. BIAs 1, 3 and 4 showed good toxicity against MOLT-4 cell lines with IC50 values in the range of 1.5-17.5 -M. BIA 2 exhibited the strongest inhibitory effect against MCF-7 cell lines with an IC50 value of 7.1 µM. BIA 1 significantly inhibited Con A-stimulated mice splenocytes proliferation equal to that of the positive control (DXM) in a concentration-dependent manner. BIAs 1 and 2 were able to decrease the NO production in LPS-induced RAW 264.7 cells at 30 µM concentration. BIA 2 showed similar inhibition of nitric oxide release, compared to that of DXM. Furthermore, BIA 2 remarkably inhibited the levels of IL-6 and TNF-α compared to the LPS induced group. Interestingly, BIA 2 displayed an inhibitory effect on TNF-α production similar to that of dexamethasone at a concentration of 20 µM.

Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis.

Osteoporosis, a highly heritable disease, is characterized mainly by low bone-mineral density (BMD), poor bone geometry, and/or osteoporotic fractures (OF). Copy-number variation (CNV) has been shown to be associated with complex human diseases. The contribution of CNV to osteoporosis has not been determined yet. We conducted case-control genome-wide CNV analyses, using the Affymetrix 500K Array Set, in 700 elderly Chinese individuals comprising 350 cases with homogeneous hip OF and 350 matched controls. We constructed a genomic map containing 727 CNV regions in Chinese individuals. We found that CNV 4q13.2 was strongly associated with OF (p = 2.0 x 10(-4), Bonferroni-corrected p = 0.02, odds ratio = 1.73). Validation experiments using PCR and electrophoresis, as well as real-time PCR, further identified a deletion variant of UGT2B17 in CNV 4q13.2. Importantly, the association between CNV of UGT2B17 and OF was successfully replicated in an independent Chinese sample containing 399 cases with hip OF and 400 controls. We further examined this CNV's relevance to major risk factors for OF (i.e., hip BMD and femoral-neck bone geometry) in both Chinese (689 subjects) and white (1000 subjects) samples and found consistently significant results (p = 5.0 x 10(-4) -0.021). Because UGT2B17 encodes an enzyme catabolizing steroid hormones, we measured the concentrations of serum testosterone and estradiol for 236 young Chinese males and assessed their UGT2B17 copy number. Subjects without UGT2B17 had significantly higher concentrations of testosterone and estradiol. Our findings suggest the important contribution of CNV of UGT2B17 to the pathogenesis of osteoporosis.

HRESIMS-guided isolation of aspidosperma-scandine type bisindole alkaloids from Melodinus cochinchinensis and their anti-inflammatory and cytotoxic activities.

The Melodinus species have been proved to be good resources of bisindole alkaloids. Six bisindole alkaloids were isolated from the leaves and stems of Melodinus cochinchinensis (Lour.) Merr. guided by HRESIMS data analysis. Among them, melokhanines K-M, epi-scandomelonine, and epi-scandomeline possessed aspidosperma-scandine skeleton linked by a C-C bond while meloyine II had a scandine-scandine skeleton. The structures were established by extensive spectroscopic analysis of their HRESIMS and NMR data. Melokhanines K-M were undescribed compounds, while epi-scandomelonine, epi-scandomeline and meloyine II were known compounds, which were reported from Melodinus species for the first time. The anti-inflammatory and cytotoxic activities of the isolates were also evaluated in vitro. Melokhanine K and meloyine II showed potent inhibitory activity on the production of nitric oxide, interleukin-6, and tumor necrosis factor-α in LPS-induced RAW 264.7 macrophages, whereas epi-scandomelonine and epi-scandomeline exhibited certain cytotoxic activity against MOLT-4 cells with IC50 values 5.2 and 1.5 µM, respectively.

4,5-Diaza-9H-fluoren-9-imine.

In the title compound, C(11)H(7)N(3), the diaza-fluorene rings are almost coplanar with an r.m.s. deviation of 0.0160 Å. In the crystal structure, C-H⋯N hydrogen bonds link mol-ecules into sheets parallel to the ab plane. Mol-ecules are also stacked regularly along the c axis by a variety of π-π inter-actions with centroid-centroid distances in the range 3.527 (2)-3.908 (2) Å.

N-(4,5-Diaza-9H-fluoren-9-yl-idene)-4-meth-oxy-aniline.

In the title compound, C(18)H(13)N(3)O, the diaza-fluorene ring system is almost coplanar (r.m.s. deviation = 0.0640 Å) and subtends an angle of 61.5 (4)° with the plane of the meth-oxy-substituted benzene ring. In the crystal structure, pairs of C-H⋯O hydrogen bonds link mol-ecules into centrosymmetric dimers parallel to the ab plane. Mol-ecules are also stacked in an obverse fashion along the c axis by a variety of π-π inter-actions with centroid-centroid distances in the range 3.557 (2)-3.921 (2) Å.