SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation.

Germ cell division and differentiation require intimate contact and interaction with the surrounding somatic cells. Luteinizing hormone (LH) triggers epidermal growth factor (EGF)-like growth factors to promote oocyte maturation and developmental competence by activating EGF receptor (EGFR) in somatic cells. Here, we showed that LH-EGFR signaling-activated sphingosine kinases (SphK) in somatic cells. The activation of EGFR by EGF increased S1P and calcium levels in cumulus-oocyte complexes (COCs), and decreased the binding affinity of natriuretic peptide receptor 2 (NPR2) for natriuretic peptide type C (NPPC) to release the cGMP-mediated meiotic arrest. These functions of EGF were blocked by the SphK inhibitor SKI-II, which could be reversed by the addition of S1P. S1P also activated the Akt/mTOR cascade reaction in oocytes and promoted targeting protein for Xklp2 (TPX2) accumulation and oocyte developmental competence. Specifically depleting Sphk1/2 in somatic cells reduced S1P levels and impaired oocyte meiotic maturation and developmental competence, resulting in complete female infertility. Collectively, SphK-produced S1P in somatic cells serves as a functional transmitter of LH-EGFR signaling from somatic cells to oocytes: acting on somatic cells to induce oocyte meiotic maturation, and acting on oocytes to improve oocyte developmental competence.

Oocyte-secreted factor TGFB2 enables mouse cumulus cell expansion in vitro.

Cumulus expansion is necessary for the release of a fertilizable oocyte from the ovary, which is critical for the normal fertilization of mammals. Cumulus expansion requires cooperation between epidermal growth factor (EGF)-like growth factors and oocyte paracrine factors. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are well-known paracrine factors secreted by oocytes. In addition, transforming growth factor-ß2 (TGFB2) was primarily expressed in oocytes and its membrane receptors type 1 receptor (TGFBR1) and type 2 receptor (TGFBR2) were located in cumulus cells. In our present study, TGFB2 induced expansion of oocytectomized (OOX) complexes and increased the expression of expansion-related genes in the presence of EGF, suggesting that TGFB2 enables cumulus expansion. Inhibition of TGF-ß signaling with SD208 blocked TGFB2-promoted cumulus expansion. Furthermore, in the culture of OOX complexes from mice of Tgfbr2-specific depletion in granulosa cells, TGFB2-promoted cumulus expansion and the expression of expansion-related genes were impaired. These results suggest that TGFB2 could induce cumulus expansion through TGFBR-SMAD2/3 signaling. Tgfb2-specific depletion in oocytes using Zp3-Cre mice had no effect on cumulus expansion in vivo, possibly due to the compensatory effect of other cumulus expansion-enabling factors. Taken together, TGFB2 is involved in expansion-related gene expression and consequent cumulus expansion.

Flexible nano-cloth-like Ag cluster@rGO with ultrahigh SERS sensitivity for capture-optimization-detection due to effective molecule-substrate interactions.

Surface-enhanced Raman scattering (SERS) is a rapid and promising detection technique for trace molecules. A central goal of research in this area is to achieve the highly sensitive detection of molecules built on a systematic understanding of enhancement mechanisms. Herein, we develop a Ag cluster@rGO composite nanostructure, which utilizes strong molecular adsorption to achieve ultrahigh SERS sensitivity. Ag clusters are prepared without additional reducing agents, leaving a low carbon footprint in the fabrication process. Finite-difference time-domain (FDTD) simulations show strong electromagnetic field enhancements generated at the edges and interstices of Ag clusters due to the specificity of their structure. Density Functional Theory (DFT) calculations show that the HOMO-LUMO energy gap value is significantly reduced when Ag cluster@rGO forms a composite system with the target molecule, which enables efficient charge transfer between the substrate and molecules, resulting in charge transfer enhancement. A detection limit of 10-14 M using our substrate can be achieved for the environmental pollutant dye rhodamine 6G (Rh6G). The detection limits of bisphenol A (BPA) and its derivatives reach nanomolar levels with good signal stability. More importantly, we demonstrate the ability to rapidly screen BPA migration in Chinese Baijiu. Our SERS platform can be further developed for environmental pollution control and food safety.

Empirical Expression of AC Susceptibility of Magnetic Nanoparticles and Potential Application in Biosensing.

Magnetic nanoparticles (MNPs) have been widely studied for use in biomedical and industrial applications. The frequency dependence of the magnetization of magnetic nanoparticles is analyzed for different AC excitation fields. We employ a Fokker-Planck equation, which accurately describes AC magnetization dynamics and analyze the difference in AC susceptibility between Fokker-Planck equation and Debye model. Based on these results we proposed a simple, empirical AC susceptibility model. Simulation and experimental results showed that the proposed empirical model accurately describes AC susceptibility, and the AC susceptibility constructed with the proposed empirical equation based on Debye model agrees well with the measured results. Therefore, we can utilize the proposed empirical model in biomedical applications, such as the estimation of the hydrodynamic size and temperature, which is expected to apply to biologicals assays and hyperthermia.

Desulfonylation via Radical Process: Recent Developments in Organic Synthesis.

As the "chemical chameleon", sulfonyl-containing compounds and their variants have been merged with various types of reactions for the efficient construction of diverse molecular architectures by taking advantage of their incredible reactive flexibility. Currently, their involvement in radical transformations, in which the sulfonyl group typically acts as a leaving group via selective C-S, N-S, O-S, S-S, and Se-S bond cleavage/functionalization, has facilitated new bond formation strategies which are complementary to classical two-electron cross-couplings via organometallic or ionic intermediates. Considering the great influence and synthetic potential of these novel avenues, we summarize recent advances in this rapidly expanding area by discussing the reaction designs, substrate scopes, mechanistic studies, and their limitations, outlining the state-of-the-art processes involved in radical-mediated desulfonylation and related transformations. With a specific emphasis on their synthetic applications, we believe this review will be useful for medicinal and synthetic organic chemists who are interested in radical chemistry and radical-mediated desulfonylation in particular.

Sgpl1 deletion elevates S1P levels, contributing to NPR2 inactivity and p21 expression that block germ cell development.

Sphingosine phosphate lyase 1 (SGPL1) is a highly conserved enzyme that irreversibly degrades sphingosine-1-phosphate (S1P). Sgpl1-knockout mice fail to develop germ cells, resulting in infertility. However, the molecular mechanism remains unclear. The results of the present study showed that SGPL1 was expressed mainly in granulosa cells, Leydig cells, spermatocytes, and round spermatids. Sgpl1 deletion led to S1P accumulation in the gonads. In the ovary, S1P decreased natriuretic peptide receptor 2 (NPR2) activity in granulosa cells and inhibited early follicle growth. In the testis, S1P increased the levels of cyclin-dependent kinase inhibitor 1A (p21) and apoptosis in Leydig cells, thus resulting in spermatogenesis arrest. These results indicate that Sgpl1 deletion increases intracellular S1P levels, resulting in the arrest of female and male germ cell development via different signaling pathways.

Three-Component Bisannulation for the Synthesis of Trifluoromethylated Tetracyclic Aza-Aromatics through Six C(sp3)-F Bond Cleavage and Four C-N Bond Formation.

An unprecedented and expeditious tandem bisannulation of polyfluoroalkylated tetralones with benzamidines to access various fluoroalkyl tetracyclic [1,3]-diazepines through multiple C-N bond formation and C(sp3)-F bond cleavage is reported. The process features high regio-/chemoselectivities, broad substrate scope, good functional group tolerance, procedural simplicity, mild reaction conditions, and scale-up synthesis. Mechanistic studies showed that the distinctive fluorine effect of polyfluoroalkyl tetralone plays a vital role for the aza-tetracycle construction.

Active Basal Plane Catalytic Activity via Interfacial Engineering for a Finely Tunable Conducting Polymer/MoS2 Hydrogen Evolution Reaction Multilayer Structure.

The fixation of the catalyst interface is an important consideration for the design of practical applications. However, the electronic structure of MoS2 is sensitive to its embedding environment, and the catalytic performance of MoS2 catalysts may be altered significantly by the type of binding agents and interfacial structure. Interfacial engineering is an effective method for designing efficient catalysts, arising from the close contact between different components, which facilitates charge transfer and strong electronic interactions. Here, we have developed a layer-by-layer (LbL) strategy for the preparation of interfacial MoS2-based catalyst structures with two types of conducting polymers on various substrates. We demonstrate how the assembled partners in the LbL structure can significantly impact the electronic structures in MoS2. As the number of bilayers grows, using polypyrrole as a binder remarkably increases the catalytic efficacy as compared to using polyaniline. On the one hand, the ratio of S22- (or S2-), which is related to the remaining active hydrogen evolution reaction (HER) species, is further increased. On the other hand, density functional theory calculations indicate that the interfacial charge transport from the conducting polymers to MoS2 may boost the HER activity of the interfacial structure of the conducting polymer/MoS2 by decreasing the adsorption free energy of the intermediate H* at the S sites in the basal plane of MoS2. The optimized catalytic efficacy of the (conducting polymer/MoS2)n assembly peaks is obtained with 16 assembly cycles. In preparing interfacial catalytic structures, the LbL-based strategy exhibits several key advantages, including the flexibility of choosing assembly partners, the ability to fine-tune the structures with precision at the nanometer scale, and planar homogeneity at the centimeter scale. We expect that this LbL-based catalyst immobilization strategy will contribute to the fundamental understanding of the scalability and control of highly efficient electrocatalysts at the interface for practical applications.

Copper(II)-Mediated Ring Opening/Alkynylation of Tertiary Cyclopropanols by Using Nonmodified Terminal Alkynes.

The copper(II)-mediated ring opening/alkynylation of cyclopropanol by employing inexpensive and commercially available terminal alkyne is developed. The reactions proceeded efficiently to afford synthetically useful alk-4-yn-1-ones in moderate to good yields with good functional group tolerance. Control experiments showed that the reaction presumably proceeds via the formation of intermediates of copper homoenolate and/or alkynylcopper species.

Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys.

AIM: Clonidine is an alpha2 adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus monkeys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse. METHODS: Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic) dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine. RESULTS: Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized responses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previously treated with clonidine. CONCLUSION: Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may reduce subsequent effects of drugs of abuse after prolonged abstinence.