Design, Total Synthesis, and Evaluation of C(13)−C(14) Cyclopropane Analogues of (+)-Discodermolide

The design, total synthesis, and biological evaluation of two C(13)−C(14)-cyclopropyl analogues [(+)-1 and (+)-2] of (+)-discodermolide have been achieved. Key features of the syntheses include highly stereoselective, hydroxyl-directed cyclopropanations of vinyl iodides and higher order cuprate-mediated cross-coupling reactions between cyclopropyl iodides and alkyl iodides. Biological evaluation revealed that neither orientation of the cyclopropyl methylene completely substitutes for the C(14) methyl found in (+)-discodermolide (3)

Design, Total Synthesis, and Evaluation of C(13)−C(14) Cyclopropane Analogues of (+)-Discodermolide

The design, total synthesis, and biological evaluation of two C(13)−C(14)-cyclopropyl analogues [(+)-1 and (+)-2] of (+)-discodermolide have been achieved. Key features of the syntheses include highly stereoselective, hydroxyl-directed cyclopropanations of vinyl iodides and higher order cuprate-mediated cross-coupling reactions between cyclopropyl iodides and alkyl iodides. Biological evaluation revealed that neither orientation of the cyclopropyl methylene completely substitutes for the C(14) methyl found in (+)-discodermolide (3)

Table_2_Fixed Gonadotropin-Releasing Hormone Antagonist Protocol Versus Flexible Progestin-Primed Ovarian Stimulation Protocol in Patients With Asynchronous Follicular Development During Controlled Ovulation Stimulation: A Retrospective Study.doc

Protocols utilizing gonadotropin-releasing hormone (GnRH) antagonists have emerged as mainstream procedures for ovarian stimulation; however, GnRH increases the risk for periodic cancellation of embryos. Therefore, this study aimed to compare the pregnancy outcomes of a fixed GnRH antagonist protocol and a flexible progestin-primed ovarian stimulation (fPPOS) protocol in patients with asynchronous follicular development during controlled ovulation stimulation and to explore the feasibility of converting patients undergoing a fixed GnRH antagonist protocol to an fPPOS protocol. This was the first retrospective study exploring the fPPOS protocol in patients with asynchronous follicular development, and it was conducted in a public reproductive medicine center from January to December 2020. We included infertile women. All participants were scheduled to undergo administration of a GnRH antagonist on the fifth day of controlled ovulation stimulation. The study group included 129 women who were converted from the fixed GnRH antagonist protocol to the fPPOS protocol for their asynchronous follicular development, while the antagonist group consisted of 258 women (ratio 1:2) who proceeded with a fixed GnRH antagonist protocol. On the second or third day of the menstrual period, 100–300 IU/day gonadotropin injections were administered. For patients who were converted to the fPPOS protocol, medroxyprogesterone acetate tablets at 10 mg/day were started on the fifth day of stimulation or when only one leading follicle reached 14 mm and the other follicles were ≤10 mm in diameter, whichever came first. The rates of embryo implantation, clinical pregnancy, and early pregnancy loss were obtained. The number of oocytes retrieved and the number of high-quality embryos in the antagonist group were significantly higher than those in the fPPOS group (P = 0.039 and P = 0.025, respectively). No significant differences in the rates of embryo implantation, clinical pregnancy, and early pregnancy loss were observed between the two groups. Our study found that in patients who were scheduled for administration of GnRH antagonists but presented with asynchronous follicular development on the fifth stimulation day, it was feasible to switch to the fPPOS protocol.</p

Table_1_Fixed Gonadotropin-Releasing Hormone Antagonist Protocol Versus Flexible Progestin-Primed Ovarian Stimulation Protocol in Patients With Asynchronous Follicular Development During Controlled Ovulation Stimulation: A Retrospective Study.doc

Protocols utilizing gonadotropin-releasing hormone (GnRH) antagonists have emerged as mainstream procedures for ovarian stimulation; however, GnRH increases the risk for periodic cancellation of embryos. Therefore, this study aimed to compare the pregnancy outcomes of a fixed GnRH antagonist protocol and a flexible progestin-primed ovarian stimulation (fPPOS) protocol in patients with asynchronous follicular development during controlled ovulation stimulation and to explore the feasibility of converting patients undergoing a fixed GnRH antagonist protocol to an fPPOS protocol. This was the first retrospective study exploring the fPPOS protocol in patients with asynchronous follicular development, and it was conducted in a public reproductive medicine center from January to December 2020. We included infertile women. All participants were scheduled to undergo administration of a GnRH antagonist on the fifth day of controlled ovulation stimulation. The study group included 129 women who were converted from the fixed GnRH antagonist protocol to the fPPOS protocol for their asynchronous follicular development, while the antagonist group consisted of 258 women (ratio 1:2) who proceeded with a fixed GnRH antagonist protocol. On the second or third day of the menstrual period, 100–300 IU/day gonadotropin injections were administered. For patients who were converted to the fPPOS protocol, medroxyprogesterone acetate tablets at 10 mg/day were started on the fifth day of stimulation or when only one leading follicle reached 14 mm and the other follicles were ≤10 mm in diameter, whichever came first. The rates of embryo implantation, clinical pregnancy, and early pregnancy loss were obtained. The number of oocytes retrieved and the number of high-quality embryos in the antagonist group were significantly higher than those in the fPPOS group (P = 0.039 and P = 0.025, respectively). No significant differences in the rates of embryo implantation, clinical pregnancy, and early pregnancy loss were observed between the two groups. Our study found that in patients who were scheduled for administration of GnRH antagonists but presented with asynchronous follicular development on the fifth stimulation day, it was feasible to switch to the fPPOS protocol.</p

Facile Approach to Large-Scale Synthesis of 1D Calcium and Titanium Precipitate (CTP) with High Electrorheological Activity

Nanorods of calcium and titanium precipitate (CTP) were prepared via a simple precipitation route in an ethanol/water mixed solution system under mild conditions. The obtained rodlike particles were highly uniform in width (23 ± 3 nm), and its length could be tuned by adjusting the concentration of oxalic acid reactant. The nanorods materials show a promising electrorheological activity, of which ER efficiency was about 4 times higher that of granular CTP suspensions. The facile synthesis route may be regarded as a green chemistry method, and its novelty relies on the large-scale production of 1D CTP giant ER materials

1286391_Table 1_Associations between urinary phthalate concentrations and antral follicle count among women undergoing in vitro fertilization.docx

BackgroundPhthalates are ubiquitously used in a variety of products and have an adverse effect on folliculogenesis. However, previous epidemiological studies on the associations between phthalate exposure and antral follicle count (AFC) produced conflicting results. The present study aimed to evaluate the associations between urinary phthalate metabolite concentrations and AFC among women undergoing in vitro fertilization (IVF).MethodsWe collected 525 urine samples and measured 8 phthalate metabolites from IVF patients. Poisson regression models were conducted to evaluate the associations between phthalate metabolite concentrations and AFC. In addition, participants were stratified into a younger group (ResultsSignificant positive associations were observed among urinary MBP, MEOHP and ∑PAEs concentrations and AFC after adjusting for age, BMI, year of study and infertility diagnosis. Compared with women in the first tertile, women in the third tertile of MBP and MEOHP had 7.02% (95% CI: 1.18%, 12.9%) and 8.84% (95% CI: 2.83%, 14.9%) higher AFC, respectively, and women in the second and third tertiles of ∑PAEs had 6.19% (95% CI: 0.37%, 12.0%) and 9.09% (95% CI: 3.22%, 15.0%) higher AFC, respectively. In addition, MBP, MEOHP and ∑PAEs also had significant positive associations with AFC in trend tests for dose-response. In the age-stratified analysis, we found a stronger relationship between phthalate metabolite concentrations and AFC among older women and an inverse association among younger women. We observed similar results in the sensitivity analyses.ConclusionWe found positive associations between phthalate exposure and AFC, which support the idea that phthalate exposure may accelerate primordial follicle recruitment and lead to higher AFC in women undergoing IVF. More studies are needed to better understand their relationships.</p

Enzyme activities analysis of C4H and TAT in transgenic lines and controls of <i>S. miltiorrhiza</i>.

<p>Data presented here are the mean of three replicates with error bars indicating ± SD. The asterisks indicate statistically significant differences (<i>P</i><<i>0.05</i>) compared to the empty vector control. control: untransformed plant; ox-VC, RNAi-VC: empty vector controls of <i>SmMYB39</i>-overexpressing lines and <i>SmMYB39</i>-RNAi lines; ox-3, ox-17, ox-28: <i>SmMYB39</i>-overexpressing lines; RNAi-11, RNAi-19, RNAi-25: <i>SmMYB39</i>-RNAi lines; C4H: cinnamic acid 4-hydroxylase; TAT: tyrosine aminotransferase.</p

Primers used for the quantitative real-time PCR analysis.

<p>Primers used for the quantitative real-time PCR analysis.</p

Relative expression levels of <i>SmMYB39</i> (A) and total phenolics content (B) in different tissues of <i>S. miltiorrhiza</i>.

<p>The results were analyzed using the comparative Ct method and presented as fold-changes compared with the root. The <i>S. miltiorrhiza actin</i> gene was used as an internal control to normalize expression levels. Data presented here are the mean of three replicates with error bars indicating ± SD.</p

Analysis of related phenolic compounds contents in transgenic lines and controls of <i>S. miltiorrhiza</i>.

<p>Data presented here are the mean of three replicates with error bars indicating ± SD. The asterisks indicate statistically significant differences (<i>P</i><<i>0.05</i>) compared to the empty vector control. control: untransformed plant; ox-VC, RNAi-VC: empty vector controls of <i>SmMYB39</i>-overexpressing lines and <i>SmMYB39</i>-RNAi lines; ox-3, ox-17, ox-28: <i>SmMYB39</i>-overexpressing lines; RNAi-11, RNAi-19, RNAi-25: <i>SmMYB39</i>-RNAi lines.</p