Poly(vinylpyridine-co-vinylpyridine N-oxide) Excipients Mediate Rapid Dissolution and Sustained Supersaturation of Posaconazole Amorphous Solid Dispersions.

The chemical structure of excipients molecularly mixed in an amorphous solid dispersion (ASD) has a significant impact on properties of the ASD including dissolution behavior, physical stability, and bioavailability. Polymers used in ASDs require a balance between hydrophobic and hydrophilic functionalities to ensure rapid dissolution of the amorphous dispersion as well as sustained supersaturation of the drug in solution. This work demonstrates the use of postpolymerization functionalization of poly(vinylpyridine) excipients to elucidate the impact of polymer properties on the dissolution behavior of amorphous dispersions containing posaconazole. It was found that N-oxidation of pyridine functionalities increased the solubility of poly(vinylpyridine) derivatives in neutral aqueous conditions and allowed for nanoparticle formation which supplied posaconazole into solution at concentrations exceeding those achieved by more conventional excipients such as hydroxypropyl methylcellulose acetate succinate (HPMCAS) or Eudragit E PO. By leveraging these functional modifications of the parent poly(vinylpyridine) excipient to increase polymer hydrophilicity and minimize the effect of polymer on pH, a new polymeric excipient was optimized for rapid dissolution and supersaturation maintenance for a model compound.

Linear Block Copolymer Synthesis.

Block copolymers form the basis of the most ubiquitous materials such as thermoplastic elastomers, bridge interphases in polymer blends, and are fundamental for the development of high-performance materials. The driving force to further advance these materials is the accessibility of block copolymers, which have a wide variety in composition, functional group content, and precision of their structure. To advance and broaden the application of block copolymers will depend on the nature of combined segmented blocks, guided through the combination of polymerization techniques to reach a high versatility in block copolymer architecture and function. This review provides the most comprehensive overview of techniques to prepare linear block copolymers and is intended to serve as a guideline on how polymerization techniques can work together to result in desired block combinations. As the review will give an account of the relevant procedures and access areas, the sections will include orthogonal approaches or sequentially combined polymerization techniques, which increases the synthetic options for these materials.

Distorted Sandwich α-Diimine PdII Catalyst: Linear Polyethylene and Synthesis of Ethylene/Acrylate Elastomers.

The introduction of m-xylyl substituents to α-diimine PdII catalyst promotes living ethylene polymerization at room temperature and low pressure to yield high molecular weight polyethylene (PE) with low branching (<17/1000 C). m-Xylyl groups provide a highly effective blockage to the axial sites of the catalytic center and form a distorted sandwich geometry. The shielding prevents chain-transfer and easy accessibility of polar monomers, leading to a living polymerization. Conducting a light irradiation as part of the one-step metal-organic insertion light initiated radical (MILRad) process leads to diblock copolymers of ethylene and acrylates. Incorporation of different acrylate block sequences can significantly modify the mechanical and chemical properties of block copolymers which can be modulated to be a hard plastic, elastomer, or semi-amorphous polymer.

Lattice QCD Calculations of Transverse-Momentum-Dependent Soft Function through Large-Momentum Effective Theory.

The transverse-momentum-dependent (TMD) soft function is a key ingredient in QCD factorization of Drell-Yan and other processes with relatively small transverse momentum. We present a lattice QCD study of this function at moderately large rapidity on a 2+1 flavor CLS dynamic ensemble with a=0.098 fm. We extract the rapidity-independent (or intrinsic) part of the soft function through a large-momentum-transfer pseudoscalar meson form factor and its quasi-TMD wave function using leading-order factorization in large-momentum effective theory. We also investigate the rapidity-dependent part of the soft function-the Collins-Soper evolution kernel-based on the large-momentum evolution of the quasi-TMD wave function.

Olefins and Vinyl Polar Monomers: Bridging the Gap for Next Generation Materials.

The inherent differences in reactivity between activated and non-activated alkenes prevents copolymerization using established polymer synthesis techniques. Research over the past 20 years has greatly advanced the copolymerization of polar vinyl monomers and olefins. This Review highlights the challenges associated with conventional polymerization systems and evaluates the most relevant methods which have been developed to "bridge the gap" between polar vinyl monomers and olefins. We discuss advancements in heteroatom tolerant coordination-insertion polymerizations, methods of controlling radical polymerizations to incorporate olefinic monomers, as well as combined approaches employing sequential polymerizations. Finally, we discuss state-of-the-art stimuli-responsive systems capable of facile switching between catalytic pathways and provide an outlook towards applications in which tailored copolymers are ideally suited.

Proton Isovector Helicity Distribution on the Lattice at Physical Pion Mass.

We present a state-of-the-art calculation of the isovector quark-helicity Bjorken-x distribution in the proton using lattice-QCD ensembles at the physical pion mass. We compute quasidistributions at proton momenta P_{z}∈{2.2,2.6,3.0} GeV on the lattice and match them systematically to the physical parton distribution using the large-momentum effective theory. We reach an unprecedented precision through high statistics in simulations, large-momentum proton matrix elements, and control of excited-state contamination. The resulting distribution with combined statistical and systematic errors is in agreement with the latest phenomenological analysis of the spin-dependent experimental data, in particular, Δu[over ¯](x)>Δd[over ¯](x).

Electrophobic Scalar Boson and Muonic Puzzles.

A new scalar boson which couples to the muon and proton can simultaneously solve the proton radius puzzle and the muon anomalous magnetic moment discrepancy. Using a variety of measurements, we constrain the mass of this scalar and its couplings to the electron, muon, neutron, and proton. Making no assumptions about the underlying model, these constraints and the requirement that it solve both problems limit the mass of the scalar to between about 100 keV and 100 MeV. We identify two unexplored regions in the coupling constant-mass plane. Potential future experiments and their implications for theories with mass-weighted lepton couplings are discussed.

Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats.

OBJECTIVE: Sitagliptin, a dipeptidyl peptidase IV (DPP-Ⅳ) inhibitor, has a biological role in improving the serum levels of glucagon-like peptide 1 (GLP-1). Hence, we sought to determine the effect of sitagliptin on myocardial inflammation, collagen metabolism, lipid content and myocardial apoptosis in diabetic rats. MATERIALS AND METHODS: The type 2 diabetic rat model was induced by low-dose streptozotocin and a high-fat diet. Characteristics of diabetic rats were evaluated by electrocardiography, echocardiography and blood analysis. Cardiac inflammation, fibrosis, cardiomyocyte density, lipid accumulation, and receptor-interacting protein kinase 3 (RIP3) level, related to apoptosis, were detected by histopathologic analysis, RT-PCR and western blot analysis to evaluate the effects of sitagliptin on myocardial remodeling of the left ventricle. RESULTS: Diabetic rats showed myocardial hypertrophy or apoptosis, inflammation, lipid accumulation, myocardial fibrosis, elevated collagen content, RIP3 overexpression, and left-ventricular dysfunction. Sitagliptin could reverse the overexpression of RIP3 and alleviate cellular apoptosis in myocardial tissues. It could significantly improve left-ventricular systolic pressure and +dp/dt max, reduce the E/E' ratio, left ventricular end diastolic pressure, -dp/dt max and Tau in diabetic rats. CONCLUSIONS: Sitagliptin might have a myocardial protective effect by inhibiting apoptosis, inflammation, lipid accumulation and myocardial fibrosis in diabetic rats, for a potential role in improving left-ventricular function in diabetes.

Therapeutic effects of the soluble epoxide hydrolase (sEH) inhibitor AUDA on atherosclerotic diseases.

In this study, we aimed to detect the effects of the soluble epoxide hydrolase (sEH) inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) on atherosclerotic diseases and to explore its mechanism. The atherosclerosis animal model was constructed by ApoE-/- mice. To determine the optimal therapeutic concentration of AUDA, different concentrations of AUDA were infused into ApoE-/- mice, with controls receiving infusions of normal saline alone. Mouse body weight and serum total cholesterol, triglyceride, LDL and HDL levels were measured. The western blotting (WB) method was used to detect the expression of TLR4 and NFKB in the aortic wall of the AUDA-treated and control mice. After the animals were sacrificed, we performed Oil Red O staining of the aortic sinus atherosclerotic plaque area followed by quantitative analysis of the aortic atherosclerotic plaque size and the percentage of lumen area in the two groups of mice. The expression levels of inflammatory cytokines, adhesion molecules and chemokines in the AUDA group were significantly decreased compared to the saline-treatment group (P < 0.05). The optimal AUDA concentration was found to be 0.35 ml/mg. AUDA significantly inhibited the expression of TLR4 and NFκB in ApoE-/- mouse aortas and reduced the aortic sinus plaque area of the ApoE-/- mouse group (P < 0.05). In conclusion, AUDA can regulate blood lipid balance, which may be one of the mechanisms for its protective effects on the cardiovascular system.

Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy.

BACKGROUND: Several types of T cells have been associated with the pathogenesis of unexplained recurrent spontaneous abortion (URSA), including Th1/Th2/Th17/Tregs cell. It has been appreciated that immunotherapy with paternal or third party lymphocytes is an effective method of treatment for URSA patients. The balance of Th1/Th2 cells could be maintained and an increase of Treg cells would be beneficial after immunotherapy; however, the mechanism by which the Th17/Treg balance affects URSA has not yet been fully elucidated. METHODS: Here, we used flow cytometry, liquid chip technology and quantitative real-time PCR (qPCR) methods to characterize Th17/Treg cell populations after immunotherapy. We found that after immunotherapy in URSA patients, the percentage of Th17 cells decreased and the percentage of Treg cells in peripheral blood mononuclear cells (PBMC) increased, as detected by flow cytometry. RESULTS: Immunotherapy may induce a decrease in the Th17/Treg ratio and the Treg bias, which may be beneficial for the maintenance of pregnancy. The expression level of ROR gamma t, a transcription factor found in Th17 cells, decreased and the expression of the Treg-specific transcription factor Foxp3 increased in peripheral blood as detected by qPCR. Immunotherapy may induce a decrease in the ratio of ROR gamma t to Foxp3 and a Treg cell bias, which would be beneficial for pregnancy maintenance. The secretion of the Treg-associated cytokine TGF-beta, as well as Th2 cytokines, was increased in serum, while the secretion of Th17-associated cytokine IL-17A and Th1 cytokine production was decreased. The Th1/Th2 cytokine ratio significantly decreased. Similarly, the Th17/Treg ratio significantly decreased in the total patient after immunotherapy. CONCLUSIONS: These results indicate that in patients with URSA, immunotherapy with mononuclear cells derived from the baby's father could affect both Th1/Th2 and Th17/Treg balance, and we found that the Th2 and Treg bias would be beneficial for pregnancy, which may lead to a balancing of the Th17/Treg ratio in URSA patients after immunotherapy.

Preparation of chondroitin sulfate-g-poly(ε-caprolactone) copolymers as a CD44-targeted vehicle for enhanced intracellular uptake.

Chondroitin sulfate-g-poly(ε-caprolactone) (CP) copolymers were synthesized via atom transfer radical addition (ATRA). The CP copolymers self-assembled into micelles in water, and the micelles could be used to encapsulate a hydrophobic anticancer drug, camptothecin (CPT), in the core for tumor targeting delivery. The physicochemical properties of the micelles and CPT-loaded micelles were thoroughly characterized. For the in vitro test, the CPT release, the protection of the lactone ring of CPT from hydrolysis and the cellular uptake of CPT were studied. The cell-killing and apoptosis-inducing effects using the CPT-loaded micelles were significantly better than using free CPT against CRL-5802 cells. The micellar internalization into CRL-5802 cells was primarily via CD44 and clathrin dual-mediated endocytosis. For the in vivo test, the therapeutic efficacy of the CPT-loaded micelles was studied in a non-small-cell lung cancer xenograft animal model. The CPT-loaded micelles showed good inhibition in tumor growth as compared with a commercial product, CPT-11, in CRL-5802 tumor-bearing mice. The in vitro and in vivo data suggested the CP-based micelles are promising anticancer drug vehicles for lung cancer targeting.

Human oocyte vitrification with corona radiata, in autologous follicular fluid supplemented with ethylene glycol, preserves conventional IVF potential: birth of four healthy babies.

The aim of this study was to examine the effects of vitrification with autologous follicular fluid (AFF) supplemented with ethylene glycol (EG) and sucrose on human oocytes with corona radiata. A total of 182 human oocytes with corona radiata from fifteen infertile patients were vitrified using either equilibration solutions (ES) and vitrification solution (VS) consisting of AFF, EG and sucrose (AFF group, n=67) or commercial ES and VS (control group, n=115). All oocytes were thawed in the next cycle, with surviving oocytes being inseminated by conventional IVF. The clinical outcome of vitrified-warmed oocytes by both vitrification methods was analysed retrospectively. In the AFF group, six patients received embryo transfer, with three couples taking four healthy babies home. In the control group, nine patients received embryo transfer, with four couples taking five healthy babies home. There was no significant difference in the survival rate (91.0 vs 92.2%), two pronuclei (2PN) fertilisation rate (73.8 vs 73.6%), cleavage rate (100 vs 100%), top-quality embryo rate (62.2 vs 59.2%), clinical pregnancy rate (50.0 vs 44.4%), implantation rate (33.3 vs 25%) or take-home baby rate (50.0 vs 44.4%) between the AFF group and the control group, respectively. These results show that AFF supplemented with EG and sucrose is an efficient, cost-effective cryoprotectant for human oocyte cryopreservation. A corona radiata on vitrified-warmed oocytes retains the oocytes' fertilisation capability in conventional IVF.

A retrospective study on IVF/ICSI outcome in patients with anti-nuclear antibodies: the effects of prednisone plus low-dose aspirin adjuvant treatment.

BACKGROUND: Anti-nuclear antibodies (ANA) are suspected of having relevance to adverse reproductive events. METHODS: This study aims to investigate the potential effect of ANA on IVF/ICSI outcome and the therapeutic role of prednisone plus low-dose aspirin (P + A) adjuvant treatment in ANA + patients. The first IVF/ICSI cycles without P + A of sixty-six ANA + women were enrolled as the ANA + group, and the 233 first IVF/ICSI cycles of matched ANA- women served as the ANA- group. The ANA + group was divided into the Titre < =1:320 subgroup and the Titre > 1:320 subgroup. Twenty-one ANA + women with adverse outcomes in their first cycles (ANA + cycles without P + A) received P + A adjuvant treatment for three months before the second IVF/ICSI cycle (ANA + cycles with P + A). The clinical characteristics and the IVF/ICSI outcomes were compared, respectively, between 1) the ANA + group and the ANA- group, 2) the Titre < =1:320 subgroup and the Titre > 1:320 subgroup, and 3) the ANA + cycles without P + A and the ANA + cycles with P + A. RESULTS: No significant differences were observed between each of the two-group pairs in the clinical characteristics. The ANA + group exhibited significantly lower MII oocytes rate, normal fertilisation, pregnancy and implantation rates, as well as remarkably higher abnormal fertilisation and early miscarriage rates. The Titre < =1:320 subgroup's IVF/ICSI outcomes were as poor as those of the Titre > 1:320 subgroup. After the P + A adjuvant treatment, the number of two pro-nuclei, perfect embryos and available embryos, and the implantation rate increased significantly. CONCLUSIONS: These observations suggest that ANA could exert a detrimental effect on IVF/ICSI outcome that might not be titre-dependent, and P + A adjuvant treatment could be useful for ANA + patients. This hypothesis should be verified in further prospective randomised studies.

Circulating levels of ß2-microglobulin and cystatin C are associated with left atrial size: additional link between the kidney and the heart.

OBJECTIVE: More attention is being paid to the relationship between kidney dysfunction and cardiovascular events Characteristic features include renal dysfunction, left ventricular (LV) and left atrial (LA) enlargement. The aim of this study is to evaluate the relationships between circulating levels of ß2-microglobulin (ß2-m) and cystatin C and left atrial size in patients with coronary artery disease. MATERIALS AND METHODS: We recruited 300 patients who presented with chest tightness or chest pain and subsequently underwent coronary angiography. Of these, 202 patients were diagnosed with coronary artery disease (CAD) and 98 patients without CAD (non-CAD). Laboratory measurements included liver, kidney function (urea nitrogen, creatinine, ß2-m and cystatin C), fasting glucose, and lipid analysis. CrCl were calculated according to Cockroft-Gault formula. Echocardiology was used to evaluate the cardiac structure and function. RESULTS: Significant differences of ß2-m and cystatin C exist and no difference of creatinine and CrCl existed between the two groups. LA diameters were positively related to circulating levels of ß2-m in the CAD group (r = 0.452, p < 0.001) and non-CAD group (r = 0.360, p < 0.001), and the similar relationships between LAD and circulating levels of cystatin C in the CAD group (r = 0.302, p < 0.001) and non-CAD group (r = 0.243, p = 0.016). LA diameters were negatively related to CrCl in both groups. After multivariate logistic regression analysis, the data indicated that the independent cardiovascular risk factors of LA enlargement for the patients with CAD were age, BMI, systolic blood pressure, LV mass, LVEDD, E/A, Em/Am, CrCl, and circulating levels of ß2-m (OR = 1.630, 95% CI: 1.115 - 2.384, p = 0.012), cystatin C (OR = 4.504, 95% CI: 1.478 - 13.726, p = 0.008). CONCLUSIONS: A linear correlation exists between circulating levels of ß2-m or cystatin C and LA diameters. Higher circulating levels of ß2-m or cystatin C are independent cardiovascular risk factors of LA enlargement in patients with CAD, and could be a link between the kidney and the heart.

Inhibition of follicular development induced by chronic unpredictable stress is associated with growth and differentiation factor 9 and gonadotropin in mice.

Chronic psychosocial stress negatively affects ovarian function. Ovarian follicular development is regulated by both pituitary-derived gonadotropins and intraovarian regulatory factors. To date, the suppressive effects of chronic stress on the ovary have been observed to be manifested mainly as an inhibition of gonadotropin release. It is not clear whether there are any other intraovarian regulatory mechanisms involved in this process. Growth and differentiation factor 9 (GDF9) is an important, oocyte-specific paracrine regulator required for follicular development. In this study, the chronic unpredictable mild stress model was used to produce psychosocial stress in mice. The number of different developmental stages of follicles was counted on ovarian sections stained with hematoxylin and eosin. Real-time PCR and Western blotting were used to detect the mRNA and protein levels, respectively, of GDF9. The results show that chronic unpredictable stress inhibits follicular development, increases follicular atresia, and suppresses GDF9 expression. Exogenous gonadotropin treatment partly restores the repressed antral follicular development, but has no effect on the repressed secondary follicular development associated with chronic stress. Treatment with recombinant GDF9 restores secondary follicular development. Cotreatments with GDF9 and gonadotropins restore both secondary and antral follicular development in stressed mice. These findings demonstrate that inhibition of follicular development induced by chronic unpredictable stress is associated with GDF9 and gonadotropin.

Fertilization rates are improved after IVF if the corona radiata is left intact in vitrified-warmed human oocytes.

BACKGROUND: Before human MII oocytes are vitrified they are usually denuded from their cumulus cells. In this study we wanted to investigate the effects of an intact corona radiata on the vitrification and fertilization of human oocytes. METHODS: The study comprised two different parts. In Part 1, 36 MII stage oocytes, from 6 patients, were randomly assigned into a control group, a group of vitrified-warmed oocytes without a corona radiata and a group of vitrified-warmed oocytes with an intact corona radiata. In each group of 12, 6 oocytes were used for evaluation of the zona pellucida solubility (hardening) and another 6 oocytes were used for the analysis of their ultrastructure. In addition, six polyspermically fertilized oocytes were used as positive controls for zona pellucida hardening. In Part 2, 16 patients in total produced 107 fresh and 98 vitrified-warmed oocytes, with or without an intact corona radiata. All oocytes were fertilized via conventional IVF and embryos were transferred according to our standard ET routines. The oocyte survival and fertilization rates, embryo quality and pregnancy and implantation rates were evaluated. RESULTS: There were no differences in oocyte survival, zona pellucida solubility (hardening) or the number of cortical granules between the vitrified-warmed and fresh oocytes. There were also no differences in the zona pellucida solubility and the number of cortical granules between vitrified-warmed oocytes with or without an intact corona radiata. However, the oocytes with an intact corona radiata had a higher fertilization rate after conventional IVF insemination. No differences were seen in the survival and cleavage rates, the percentage of high-quality embryos or the clinical outcome. CONCLUSIONS: Zona hardening and ultrastructural damage do not seem to occur in vitrified human oocytes. An intact corona radiata in vitrified-warmed oocytes retains their fertilization capacity in conventional IVF, but does not improve the embryo quality. Poor fertilizing capacities of vitrified-warmed oocytes without an intact corona radiata seem to have been due to the complete removal of the cumulus cells.

[Ultra-rapid cryopreservation of human spermatozoa with different concentrations of sucrose].

OBJECTIVE: To explore the feasibility of ultra-rapid freezing of human spermatozoa in the cryogenic vial with different concentrations of sucrose solution. METHODS: We divided 40 normal semen samples prepared with the routine swim-up technique into 6 aliquots, 1 as the control and the other 5 cryopreserved with sucrose solution at the concentrations of 0.15, 0.20, 0.25 and 0.30 mol/L, respectively. After thawing, we determined and compared the motility, progressive motility and plasma membrane integrity of the sperm among the 6 groups. RESULTS: The motility, progressive motility and plasma membrane integrity of the sperm were significantly lower after thawing than before cryopreservation ([96.2 +/- 1.8]%, [93.8 +/- 2.8]% and [99.0 +/- 0.8 ]%) (P<0.05). Post-thawing sperm motility was (55.5 +/- 6.3)% in the 0.20 mol/L sucrose group, significantly higher than in the 0.15, 0.25 and 0.30 mol/L groups ([45.9 +/- 6.6]%, [50.4 +/- 9.4]% and [45.5 +/- 11.2]%) (P<0.05), and it was (53.6 +/- 5.0)% in the conventional freezing group, with no statistically significant difference from the 0.20 and 0.25 mol/L sucrose cryopreservation groups (P> 0.05), but remarkably higher than in the 0.15 and 0.30 mol/L groups (P<0.05). Post-thawing progressive sperm motility exhibited no statistically significant differences between the 0.20 mol/L sucrose and conventional freezing groups ([44.4 +/- 7.4]% vs [42.3 +/- 8.1]%, P>0.05), but markedly higher in both than in the 0.15, 0.25 and 0.30 mol/L sucrose groups ([37.1 +/- 8.3 ]%, [33.1 +/- 9.2]% and [22.0 +/- 9.1]%) (P<0.05). Post-thawing plasma membrane integrity was significantly higher in the 0.20 mol/L sucrose cryopreservation group ( [70.1 +/- 6.9]%) than in either the conventional freezing group ([63.1 +/- 6.8]%) or the 0.15, 0.25 and 0.30 mol/L sucrose groups ([57.7 +/- 8.3]%, [63.5 +/- 10.7]% and [57.8 +/- 12.9]%) (P<0.05). CONCLUSION: As a simple, safe and effective method, ultra-rapid freezing with sucrose solution at the final concentration of 0.20 mol/L can be used for the cryopreservation of human spermatozoa.

[Research on population dynamics of Lonicera macranthoides aphid and natural enemy in Xiushan and evolution of pesticides].

OBJECTIVE: To study the population dynamics of aphid on Lonicera macranthoides and their natural enemy in Xiushan and control method of pesticide so as to provide scientific basis for its integrated pests management (IPM). METHOD: The field investigation and the field controlling trial were carried out for the research. RESULT: Semiaphis heraclei was the dominant species among L. macranthoides aphids. The population dynamics of apterous aphids went through five consecutive stages: initial, fluctuating, rising, peak and declining. The population dynamics of alate aphids was 4-7 days later than that apterous aphid's. Significant positive correlations were found between the population size of spiders and ladybugs which were natural enemies and number of aphids. The result of pesticides against aphids in field trial showed that 25% thiamethoxam WG, 70% imidacloprid WG and 20% acetamiprid WP had well controlling effect. CONCLUSION: Aphids on L. macranthoides could be well controlled while 25% thiamethoxam WG, 70% imidacloprid WG and 20% acetamiprid WP are sprayed during the period of aphid population raising, the early April to the mid May.

Spironolactone alleviates myocardial fibrosis via inhibition of Ets-1 in mice with experimental autoimmune myocarditis.

Spironolactone improves cardiac structure, function and prognosis in patients with heart failure and delays the progression of cardiac fibrosis. However, the exact underlying mechanism of this process remains to be elucidated. The present study therefore aimed to explore the protective effect and underlying mechanism of the aldosterone receptor antagonist, spironolactone, on myocardial fibrosis in mice with experimental autoimmune myocarditis (EAM). The EAM model was induced in BALB/c mice via immunization with murine cardiac α-myosin heavy chain sequence polypeptides. The cardiac function of the mice was assessed using echocardiography and the levels of inflammatory cytokines were quantified using ELISA. E26 transformation-specific sequence-1 (Ets-1) expression was knocked down using lentivirus-mediated small interference RNA. Total collagen deposition was assessed using Masson's trichrome and Ets-1, TGF-ß1, Smad2/3, collagen I and III protein expression levels were detected using immunohistochemistry and western blotting. MMP-2 and MMP-9 mRNA expression levels and activity was determined using reverse transcription-quantitative PCR and gelatin zymography, respectively. The results of the present study demonstrated that spironolactone significantly improved myocardium hypertrophy, diastolic cardiac function and decreased myocardial inflammation and collagen deposition induced by EAM. Spironolactone treatment significantly inhibited Ets-1 and smad2/3 phosphorylation. In addition, inhibition of Ets-1 reduced the expression and activity of MMP-2 and MMP-9 and decreased cardiac fibrosis in EAM mice. The results indicated that the improvement of myocardial fibrosis by spironolactone may be associated with the TGF-ß1/Smad-2/3/Ets-1 signaling pathway in EAM mice.

A new species and a key to eleven species of the genus Conophyma Zubovsky, 1898 (Orthoptera, Acridoidea, Catantopidae, Conophyminae) from China.

A new species and a key to eleven species of of the genus Conophyma Zobovsky, 1898 from China is described in this paper. The new species Conophyma lini sp. nov. is similar to C. xiai Zhang et al, 2015, but differs from latter by: vertex longer, apex narrower; minimum width of interspace 1.6 times length in mesosternum; posterior margin of epiproct waved, with angular projection in the middle, furculae small and width of Epiphallus 2.5 times high. Type specimens are deposited in the Northwest Plateau Institute of Biology, Chinese Academy of Sciences, Xining, Qinghai 810001, China.