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1.
Ovarian hyperstimulation syndrome (OHSS) is one of the most life-threatening and potentially fatal complications associated with controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) treatment. Although the pathogenesis of OHSS remains unclear, elevated serum estradiol (E2) levels before human chorionic gonadotropin (hCG) administration are associated with the risk of OHSS. The pineal hormone melatonin and its receptors are expressed in human granulosa cells and have been shown to stimulate E2 production. However, the effect of melatonin on the expression of aromatase, an enzyme responsible for a key step in the biosynthesis of E2, in human granulosa cells remains to be determined. Here, we demonstrate that melatonin upregulates aromatase expression in primary cultured human granulosa-lutein (hGL) cells through the melatonin receptor-mediated PKA-CREB pathway. Using a mouse model of OHSS, we demonstrate that administration of the melatonin receptor inhibitor luzindole inhibits the development of OHSS. In addition, the expression of ovarian aromatase and serum E2 levels are upregulated in OHSS mice compared to control mice, but this upregulation is attenuated by inhibition of the function of melatonin. Moreover, clinical results reveal that aromatase expression levels are upregulated in hGL cells from OHSS patients. Melatonin and E2 levels in the follicular fluid are significantly higher in OHSS patients than in non-OHSS patients. Furthermore, melatonin levels are positively correlated with E2 levels in follicular fluid. This study helps to elucidate the mechanisms mediating the expression of aromatase in hGL cells and provides a potential mechanism explaining the high E2 levels in patients with OHSS.Subject terms: Endocrine reproductive disorders, Endocrine reproductive disorders  相似文献   
2.
Metabolic glycan engineering (MGE) coupled with nitroxide spin-labeling (SL) was utilized to investigate the heterogeneous environment of cell surface glycans in select cancer and normal cells. This approach exploited the incorporation of azides into cell surface glycans followed by a click reaction with a new nitroxide spin label. Both sialic acid and N-acetylglucosamine (GlcNAc) were targeted for spin labelling. Although each of these moieties experiences a diverse and heterogeneous glycan environment, their EPR spectra and hence mobility are both characterized as a linear combination of two distinct spectra where one component reflects a highly mobile or uncrowded micro-environment with the second component reflecting more restricted motion, reflective of increased crowding and packing within the glycocalyx. What differs among the spectra of the targeted glycans is the relative percentage of each component, with sialic acid moieties experiencing on average an ∼80% less crowded environment, where conversely GlcNAc/GalNAz labeled sites reported on average a ∼50% more crowded environment. These distinct environments are consistent with the organization of sugar moieties within cellular glycans where some residues occur close to the cell membrane/protein backbone (i.e. more restricted) and others are more terminal in the glycan (i.e. more mobile). Strikingly, different cell lines displayed varied relative populations of these two components, suggesting distinctive glycan packing, organization, and composition of different cells. This work demonstrates the capability of SDSL EPR to be a broadly useful tool for studying glycans on cells, and interpretation of the results provides insights for distinguishing the differences and changes in the local organization and heterogeneity of the cellular glycocalyx.

Metabolic glycan engineering (MGE) coupled with nitroxide spin-labeling (SL) was utilized to investigate the heterogeneous environment of cell surface glycans in select cancer and normal cells.  相似文献   
3.
We describe the synergistic utilization of titanocene/photoredox dual catalysis driven by visible light for the radical opening/spirocyclization of easily accessible epoxyalkynes. This environmentally benign process uses the organic donor–acceptor fluorophore 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN) as a photocatalyst and Hantzsch ester (HE) as an electron donor instead of stoichiometric metallic reductants. The photocatalytic conditions showed exceptionally high reactivity for the synthesis of privileged and synthetically challenging spirocycles featuring a spiro all-carbon quaternary stereocenter. Cyclic voltammetry (CV) studies suggest that Cp2TiIIICl is the catalytically active species.

We describe the synergistic utilization of titanocene/photoredox dual catalysis driven by visible light for radical opening/spirocyclization of easily accessible epoxyalkynes.

Over the last few decades, radical-based transformations have been increasingly used in organic synthesis due to their salient features, such as ease of generation, mild reaction conditions, and broad functional group compatibility.1,2 As a mild single-electron-transfer (SET) reagent, titanocene monochloride (Cp2TiIIICl) is considered a formidable tool in contemporary radical chemistry due to its ability to promote various fundamental radical-based transformations.3–7 Cp2TiIIICl was first introduced by Nugent and RajanBabu as a very mild stoichiometric reagent for the reductive opening of epoxides.8–11 Later, the catalytic conditions developed by Gansäuer et al. (Scheme 1a)12 employing stoichiometric amounts of active metals in combination with 2,4,6-collidine·HCl further expanded its applications and led to the discovery of a number of novel transformations.13–16 The key to success was the formation of a stable complex A in reactions while decreasing the concentration of active Cp2TiIIICl.17,18 We were interested in the radical opening/cyclization reaction of epoxides which has attracted considerable attention from the synthetic community and has been used numerous times in the synthesis of natural products.19,20 Nevertheless, this reaction required stoichiometric metallic reductants and proceeded slowly particularly with sterically hindered substrates even with high catalyst loading.21 Therefore, the development of an eco-friendly and efficient catalytic system with an expanded substrate scope is highly desirable.Open in a separate windowScheme 1Cp2TiIIICl mediated radical opening/spirocyclization of epoxides; (a) generation of TiIIIvia a metal reduction approach; (b) dual titanocene/photoredox catalysis; (c) examples of drugs and natural products containing heterospirocycles.In recent years metallaphotoredox catalysis has been a new and rapidly growing research subject.22–29 Photoredox processes can directly modulate the oxidation state of metals by electron transfer (ET).30–33 Given that the generation of TiIII is a SET process, we envisioned that the reduction could be facilitated by a photoredox-controlled process while overcoming the aforementioned limitations. On the other hand, spirocycles bearing a chiral spiro all-carbon quaternary carbon are particularly attractive synthetic targets in pharmaceutical development (Scheme 1c).34–36 Such privileged rigid 3D structures offer the concomitant ability to project functionalities in all three-dimensional orientations and led to enhanced pharmacological activities of molecules. Thus significant attention has been paid to their synthesis.37,38 Against this backdrop, here we describe our efforts on the synthesis of various heterospirocycles with the aid of photoredox catalysis.We chose epoxyalkyne 2a as a model substrate for optimization of reaction conditions. After a systematic variation of different reaction parameters, we were pleased to identify the optimal reaction conditions in which a mixture of Cp2TiCl2 (5.0 mol%), [Ir(dtbbpy)(ppy)2]PF6 (1a, 1.0 mol%, EIII/II1/2 = −1.51 V vs. SCE in MeCN), HE (1.2 equiv.) and 2a (1.0 equiv.) in THF at room temperature under the irradiation of a 10 W 450 nm light emitting diode (LED) lamp for 12 hours afforded the desired product 3a in an excellent yield of 96% (13 : 1 d.r.) upon isolation (entry 1). Using a commercial 23 W compact fluorescent lamp (CFL) instead of the 10 W 450 nm LED did not compromise the overall yield of the reaction (entry 2). Notably, when the loading of Cp2TiCl2 was decreased to as low as only 2.0 mol%, the reaction still led to full conversion and produced 3a in 95% yield (entry 3). Further screening of other photosensitizers revealed that the cheap and readily obtained organic dye 4CzIPN 1b is a competent alternative, which led to full conversion with 94% isolated yield (entry 4). Importantly, the reaction did not proceed in the absence of Cp2TiCl2, HE, the photocatalyst, or visible light (entries 5–8). Various solvents, including DMF, MeOH, DMSO, and MeCN, were screened, and they all resulted in poor conversion. The use of other organic electron donors, such as triethylamine, triethanolamine, and ascorbic acid, afforded the product in poor yield.With satisfactory reaction conditions established, we then explored the scope of the cyclization reaction using 4CzIPN as the photosensitizer. Positively, the cyclization reaction worked well and afforded the desired variably heterospirocyclic products in good to excellent yield (Tables 2 and and3).3). The reaction allows the rapid construction of various 5/5, 5/6, 5/7 and 5/8 spiro-ring fused systems (3a–3k) bearing tetrahydrofuran or pyrrolidine motifs via the 5-exo cyclization pathway. Interesting, the diastereoselectivity of the cyclization reaction is highly correlated with the ring size in the substrates. Heterospirocycles containing a 5/5 spiro-ring fused system (3a–3f) were obtained with surprisingly high diastereoselectivity. In some cases (3b, 3c, and 3e) only a single isomer was obtained. The product 3d with a sterically hindered t-butyloxy carbonyl (Boc) protecting group on the N atom was obtained with reduced diastereoselectivity (5 : 1 d.r.). The diastereoselectivities dropped in 5/6, 5/7 and 5/8 spiro-ring fused systems. Given that enantioenriched epoxides could be easily obtained (e.g. via sharpless asymmetric epoxidation), this strategy provides access to optically active spirocycles featuring an all-carbon quaternary stereocenter with the transfer of stereochemical information from epoxides (3c, 3e and 3f). Bis-heterospirocyclic scaffolds were frequently employed in pharmaceutical chemistry. For example, bis-heterospirocyclic 3d is the core structure of DLK inhibitors39 and XEN402 (ref. 40) (scheme 1c), which are used for treating neurodegeneration and congenital erythromelalgia respectively. Furthermore, 6-exo cyclization was also investigated under the standard conditions and smoothly produced a serious of drug-like 6-(trifluoromethyl)-3-pyridinesulfonyl piperidine derivatives including 6/5, 6/6 and 6/7 spiro-ring fused systems (5a–5k) in generally excellent yields. Moreover, cyclization reactions with epoxy-alkynes afforded products containing exocyclic-alkenes and free alcohols which were suitable for further functionalization. This approach provides access to a broad range of novel spirocyclic piperidine and pyrrolidine spirocycles which could be of interest to synthetic and medicinal chemists.Scope of 5-exo and 6-exo cyclizationa,b,c,d
Open in a separate windowaReaction conditions: 2 and 4 (100 mg, 0.1 M in THF).bIsolated yield.c 3c, 3e and 3f were synthesized from enantiomer pure epoxides.dYields within parentheses are based on catalytic conditions using metal as a reductant: CpTi2Cl2 (5 mol%), Zn (2.0 eq.), coll·HCl (2.5 eq.), THF, 20 hours.Additive effect on Ti-catalyzed cyclizationa,b
Open in a separate windowaIn all cases, 2l was used as the substrate and the yield of 3l was determined with 1H NMR.bValues within parentheses are recovery yields of the additives determined with 1H NMR.To examine the scalability of the reaction, gram-scale synthesis of 3a and 3c was performed under the standard conditions with 23 W CFL irradiation. Pleasingly, 92% (3a) and 89% (3c) isolated yields were obtained respectively without any deterioration. Furthermore, an additive-based investigation41 was performed and the results are summarized (Table 3). From this screening, we found that 11 out of 12 additives have no adverse impact on the yield of the reaction. The additives were recovered after the reaction, including benzoxazole 6a, quinazolinone 6b, collidine 6c, tetrahydroquinoline 6d, benzothiazole 6e, indole 6f, and benzofuran 6h. However, quinoxaline 6l strongly inhibited Ti catalysis and 3l was produced in only 23% yield. Notably, the reaction is compatible with various functional groups including phenols 6g, free alcohols and alkene 6j, iodobenzene 6i, ester 3m, ether 3n, dioxolane 5i, lactone 5k, and alkyne 3e. The generality of the dual Ti/4CzIPN catalysis system was further demonstrated by a highly related hydrogen transfer reaction of epoxides which could exclusively provide anti-Markovnikov alcohols (see the ESI S8). The low-cost of 4CzIPN, broad compatibility with sensitive functional groups, and simple operation conditions are appealing for laboratory and industrial applications.Importantly, the reactions were re-subjected to metal reduction catalytic conditions for comparison with the photocatalytic conditions and the yields are shown within parentheses (Table 2d). It clearly showed that the yields were generally lower. Particularly, we found that the yields dropped dramatically as the steric encumbrance of the substrates increased. For example, substrates containing dioxolane (2g, 4i) or a 7/8-membered-ring (2j, 2k, 4j) afforded the products (3g, 5i, 3j, 3k, 5j) in less than 10% yield with the recovery of the starting materials.  相似文献   
4.
The chelating ligands of boric acid and amino trimethyl phosphonate prepared a novel flame retardant (BAP) for the cotton fabric. A stable chemical and coordination bond was formed on the surface of the cotton fibers by a simple three-curing finishing process to make the fabric exhibits excellent durable flame retardancy. Cotton fabrics' tensile strength and whiteness got substantially retained after BAP treatment. 90 g/L BAP-treated samples (3 curing times, 50 laundry cycles) showed good flame retardancy and durability, holding the largest limit oxygen index, 29.7%, and the shortest damage length, 61 mm. A condensed phase and gas phase synergistic flame retardant mechanism was concluded by thermogravimetric, cone calorimeter tests, and thermogravimetric infrared analysis.  相似文献   
5.
Crystallization-driven self-assembly (CDSA) was employed for the preparation of monodisperse cationic cylindrical nanoparticles with controllable sizes, which were subsequently explored for their effect on antibacterial activity and the mechanical properties of nanocomposite hydrogels. Poly(ɛ-caprolactone)-block-poly(methyl methacrylate)-block-poly[2-(tert-butylamino) ethyl methacrylate] (PCL-b-PMMA-b-PTA) triblock copolymers were synthesized using combined ring-opening and RAFT polymerizations, and then self-assembled into polycationic cylindrical micelles with controllable lengths by epitaxial growth. The polycationic cylinders exhibited intrinsic cell-type-dependent antibacterial capabilities against gram-positive and gram-negative bacteria under physiological conditions, without quaternization or loading of any additional antibiotics. Furthermore, when the cylinders were combined into anionic alginate hydrogel networks, the mechanical response of the hydrogel composite was tunable and enhanced up to 51%, suggesting that cationic polymer fibers with controlled lengths are promising mimics of the fibrous structures in natural extracellular matrix to support scaffolds. Overall, this polymer fiber/hydrogel nanocomposite shows potential as an injectable antibacterial biomaterial, with possible application in implant materials as bacteriostatic agents or bactericides against various infections.  相似文献   
6.
A sensitive electrochemiluminescence (ECL) biosensor for the specific DNA sequence of hepatitis C virus (HCV) was developed based on the efficient quenching effect of the ferrocene cluster functionalized gold nanoparticles (Fc@AuNPs) on the ECL of electrodeposited silica@Ru(bpy)32+-chitosan-graphene oxide nanocomposite (SiO2@Ru−CS−GO). Graphene oxide (GO) can accelerate electron transfer rate, thus improving the ECL of Ru(bpy)32+ on electrode surface. The molecular beacons (MB) was fixed to SiO2@Ru−CS−GO by glutaraldehyde (GA) using the Schiff reaction between amino groups of chitosan (CS) and MB. The ECL of SiO2@Ru−CS−GO was depressed greatly by the Fc@AuNPs labelled at the end of MB, then, a stronger ECL was observed when the distance between Fc@AuNPs and SiO2@Ru−CS−GO increased after the hybridization of target DNA with MB. Under optimum conditions, the restored ECL intensity increased linearly with the target DNA concentration in the range of 1.0×10−16∼1.0×10−10 mol ⋅ L−1, and the limit of detection (LOD) is 1.4×10−17 mol ⋅ L−1. The proposed method exhibits acceptable stability and reproducibility. In general, the constructed HCV biosensor can be used for the sensitive detection of HCV in human serum, suggesting potential application prospects in bioanalysis.  相似文献   
7.
Dopamine (DA) plays an essential role in the central nervous, renal, hormonal and cardiovascular systems. Various modified carbon nanotubes (CNT)-based dopamine sensors have been reported, but inexpensive, highly sensitive plain CNT-based ones are seldom studied. In this work, a facile and inexpensive CNT-based DA sensor is made by rich-defect multi-walled carbon nanotubes (RD-CNT) via an ultrasound method. The defect and elemental states of the RD-CNT are systematically studied by transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), Raman spectroscopy, X-ray powder diffraction (XRD) and X-ray-photoelectron spectroscopy (XPS). Results show that massive holes and cracks exist in RD-CNT. The level of defects increases from the additional exposed edges. The electrochemical characterizations indicate that the electrochemical sensor has the highest sensitivity of 438.4 μA/(μM ⋅ cm2) among all carbon materials-based DA sensors while well meeting the clinically required detection range and selectivity. The DA sensor was further used to detect live healthy human serum and live PC12 cells with satisfactory results, thus holding great promise for an inexpensive but sensitive DA sensor in practical applications of clinical diagnosis and biological research.  相似文献   
8.
Journal of Solid State Electrochemistry - Ni-rich layered cathode materials LiNixCoyMn(1-x–y)O2 (x ≥ 0.8) suffer from capacity decay due to structural deterioration during...  相似文献   
9.
Fu  Yajing  Li  Ji  Wang  Hairui  Zhang  Jiahao  Ma  Zhijun  Yi  Qiong  Liu  Jianwen  Wang  Shiquan 《Journal of Solid State Electrochemistry》2023,27(9):2523-2531
Journal of Solid State Electrochemistry - FeS2/CoS and FeS2/CoS/C composites were synthesized by solvothermal method and following vapor phase vulcanization at mild temperature with binary oxide...  相似文献   
10.
The full reaction photosynthesis of H2O2 that can combine water-oxidation and oxygen-reduction without sacrificial agents is highly demanded to maximize the light-utilization and overcome the complex reaction-process of anthraquinone-oxidation. Here, a kind of oxidation-reduction molecular junction covalent-organic-framework (TTF-BT-COF) has been synthesized through the covalent-coupling of tetrathiafulvalene (photo-oxidation site) and benzothiazole (photo-reduction site), which presents visible-light-adsorption region, effective electron-hole separation-efficiency and photo-redox sites that enables full reaction generation of H2O2. Specifically, a record-high yield (TTF-BT-COF, ≈276 000 μM h−1 g−1) for H2O2 photosynthesis without sacrificial agents has been achieved among porous crystalline photocatalysts. This is the first work that can design oxidation-reduction molecular junction COFs for full reaction photosynthesis of H2O2, which might extend the scope of COFs in H2O2 production.  相似文献   
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