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Si-Wu-Tang (SWT) has become a common basic prescription for supplementing blood and regulating menstruation, and enjoys the reputation of "the first prescription in gynecology". It is often reported in the treatment of premature ovarian failure (POF). However, knowledge of its specific mechanism is still limited.This study aimed to identify the potential effects and underlying mechanisms of SWT on POF.After confirming the therapeutic effect of SWT on POF mice induced by cyclophosphamide, we further clarified the promoting effect of SWT on ovarian follicle development by detecting the expression of key factors related to follicle development in the ovary in different ways.Then, network pharmacology and gene expression profiling of POF from the GEO database were used to clarify the underlying mechanisms. Molecular biology and molecular docking analysis were applied for final mechanism verification.Our results showed that SWT increased body weight, ovarian index, reversed disordered serum hormone levels, and menstrual cycle in POF mice. After SWT treatment, the number of follicles at all levels in mice with POF also recovered. Using molecular biology techniques, it was proven that SWT can improve follicle development and angiogenesis in the microenvironment. The network pharmacology and gene expression profiling from the GEO database indicated that the PI3K/Akt signaling pathway may be the reason why SWT improves ovarian function in mice with POF. Subsequently, further Western blot and immunoprecipitation indicated that SWT indeed inhibited the PI3K/Akt signaling pathway in mice with POF. In addition, this conclusion was further confirmed by molecular docking experiments.SWT can improve ovarian function in POF mice induced by cyclophosphamide, and its mechanism is related to the inhibition of the PI3K/Akt signaling pathway.

Let $$[a_1(x),a_2(x), a_3(x),\ldots ]$$ denote the continued fraction expansion of a real number $$x \in [0,1)$$ . This paper is concerned with certain exceptional sets of the Borel–Bernstein Theorem on the growth rate of $$\{a_n(x)\}_{n\geqslant 1}$$ . As a main result, the Hausdorff dimension of the set $$\begin{aligned} E_{\sup }(\psi )=\left\{ x\in [0,1):\ \limsup \limits _{n\rightarrow \infty }\frac{\log a_n(x)}{\psi (n)}=1\right\} \end{aligned}$$ is determined, where $$\psi :{\mathbb {N}}\rightarrow {\mathbb {R}}^+$$ tends to infinity as $$n\rightarrow \infty $$ .

Let $[a_1(x),a_2(x),a_3(x),\cdots]$ be the continued fraction expansion of $x\in (0,1)$. This paper is concerned with certain sets of continued fractions with non-decreasing partial quotients. As a main result, we obtain the Hausdorff dimension of the set \[\left\{x\in(0,1): a_1(x)\leq a_2(x)\leq \cdots,\ \limsup\limits_{n\to\infty}\frac{\log a_n(x)}{\psi(n)}=1\right\}\] for any $\psi:\mathbb{N}\rightarrow\mathbb{R}^+$ satisfying $\psi(n)\to\infty$ as $n\to\infty$., Comment: 14 pages

Ethnopharmacological relevance Premature ovarian failure (POF) is a severe illness, characterized by premature menopause with a markedly decrease in ovarian function, which leads to infertility. Si-Wu-Tang (SWT), also called “the first prescription of gynecology” by medical experts in China, is widely used as the basic formula in regulating the menstrual cycle and treating infertility. However, the potential effect and underlying mechanisms of action of SWT on the treatment of POF have not yet been elucidated. Purpose This study aimed to explore the therapeutic effect and underlying molecular mechanism of action of SWT on the treatment of POF in C57BL/6 mice. Materials and methods The main compounds of SWT were identified by high-performance liquid chromatography (HPLC). POF model groups were established by a single intraperitoneal injection of cyclophosphamide (Cy, 100 mg/kg). SWT or dehydroepiandrosterone (DHEA) were administered via oral gavage for 28 consecutive days. Ovarian function and pathological changes were evaluated by hormone levels, follicular development, and changes in angiogenesis. Furthermore, statistical analyses of fertility were also performed. Results Treatment with SWT significantly improved estrogen levels, the number of follicles, antioxidant defense, and microvascular formation in POF mice. Moreover, SWT significantly activated the Nrf2/HO-1 and STAT3/HIF-1α/VEGF signaling pathways to promote angiogenesis, resulting in a better fertility outcome when compared to the model group. Conclusions Our findings indicated that SWT protected ovarian function of Cy-induced POF mice by improving the antioxidant ability and promoting ovarian angiogenesis, thereby providing scientific evidence for the treatment of POF using SWT.

Let k n ( x ) be the n -th partial quotient of the generalized continued fraction (GCF) expansion of x . This paper is concerned with the growth rate of k n ( x ) . When the parameter function satisfies − 1 ϵ ( k ) ≤ 1 , we obtain the Hausdorff dimension of the sets E ϕ = { x ∈ ( 0 , 1 ) : lim n → ∞ ⁡ log ⁡ k n ( x ) ϕ ( n ) = 1 } for any nondecreasing ϕ with lim n → ∞ ⁡ ( ϕ ( n + 1 ) − ϕ ( n ) ) = ∞ and lim n → ∞ ⁡ ϕ ( n + 1 ) / ϕ ( n ) = 1 . Applications are given to several kinds of exceptional sets related to the GCF expansion.

Let [Formula: see text] be the Lüroth expansion of [Formula: see text]. This paper is concerned with the growth rate of the partial maximum [Formula: see text]. We completely determined the Hausdorff dimension of the set [Formula: see text] when [Formula: see text] tends to infinity with polynomial or exponential rates.

Controlled ovarian hyperstimulation (COH) is widely used for the treatment of infertility, while the long-term effects of COH on the reproductive function in female offspring are currently unknown. Based on the fact that COH could cause high E2 levels in women throughout pregnancy and excess estrogenic exposure during fetal development is harmful to subsequent adult ovarian function, we assumed the hypothesis that COH disrupts reproductive function in female offspring. To test this hypothesis, COH was induced in mice to obtain female offspring by pregnant mare serum gonadotropin (PMSG) and HCG, and then we evaluated pubertal transition, serum levels of E2, anti-Mullerian hormone (AMH), FSH and LH, mRNA expressions ofEsr1,Amhr2,FshrandLhcgrin ovaries, number of follicles and ovarian histology. We also investigated the apoptosis of follicles by TUNEL; the mRNA expressions ofFas,FasL,Bax,Bcl2, and caspase 3, 8 and 9 by quantitative real-time PCR; and the protein expressions of cleaved-caspase (CASP) 3, 8 and 9 by Western blot. Moreover, we further observed estrous cyclicity in young adult offspring, performed follicle counting and measured the level of AMH in both serum and ovary. COH could induce detrimental pregnancy outcomes, as well as delayed pubertal transition and irregular estrous cycle due to the aberrant growth and maturation of follicles in female offspring. Our novel findings add new evidence to better understand the potential risks of COH on the reproductive function in female offspring, raising the awareness that COH could exert adverse effects on female offspring, rather than just obtain more oocytes for fertilization.

The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation (COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare's serum gonadotrophin (PMSG), followed by 7.5 IU human chorionic gonadotrophin (HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group (NC), COH implantation dysfunction model group (COH), low dosage of Bu-Shen-An-Tai recipe group (LOW), middle dosage of Bu-Shen-An-Tai recipe group (MID) and high dosage of Bu-Shen-An-Tai recipe group (HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17β-estradiol (E2) and progesterone (P4) were determined by radioimmunoassay (RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope (TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis- related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of E2 and P4, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It's helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.

BACKGROUND Vasa (a DEAD-box helicase, also known as Ddx4) is an ATP-dependent RNA helicase highly conserved among all animals. Research on the presence and function of DDX4 in female mammals is limited. To gain greater insight into its distribution and role in female mice, we detected the expression of DDX4 protein in the ovaries and analyzed its expression pattern. MATERIAL AND METHODS MVH was detected in the cytoplasm of oocytes in all non-apoptotic follicles. RESULTS In the present study, we found that higher expression levels of ~55-60 kDa MVH isoform in the ovaries were followed by the accumulations of preovulatory follicles. CONCLUSIONS Higher levels of MVH protein in the ovaries might prepare oocytes for the competence to resume meiosis.

We describe lightweight three-dimensional (3D) graphene hybrid SiO2 aerogels (GSAs) with hierarchically robust interconnected networks fabricated via an in situ deposition procedure after a hydrothermal assembling strategy with graphene oxide sheets. The nano-/micron-thick SiO2 coating conformably grew over porous graphene templates with two constituents (e.g., graphene and SiO2) and formed chemically bonded interfaces. In addition, it significantly refined the primary graphene pores by hundreds of microns into smaller porous patterns. Studies of its mechanical properties verified that the graphene interframework made the ceramic composites elastic, while SiO2 deposition enhanced the strength required it to resist deformation. The higher SiO2 contents resulted in lower elasticity but larger strength because of the apparent nanosize effect of SiO2 ceramic thickness, GSAs with a density of 82.3&ndash, 250.3 mg/cm3 (corresponding to SiO2 sol with concentration ranging from 5 to 20 wt %) could reach a good balance of strength and elasticity. Benefiting from hierarchical micronetworks consisting of semiclosed or closed pores, GSAs offer excellent thermal-insulation performance, with thermal conductivity as low as 0.026 W/(m&middot, K). GSAs offer improved fire-resistant capacity rather than that of pure carbon-based aerogels via the synergic protection of SiO2 ceramic accretion. This highlights the promising applications of GSAs as lightweight thermal-shielding candidates for industrial equipment, civil architectures, and defense transportation vehicles.

Three-dimensional (3D) graphene/nano-copper scaffolds (rGCSs) was fabricated using a one-step chemical deposition on 3D reduced graphene oxide architecture (rGOA). The nano-copper was conformably grown on the rGOA substrate with a uniform morphology. Due to combined effects between the graphene skeleton and the nano-copper, the rGCSs demonstrated excellent antibacterial properties in the colony counting experiments. In addition, an rGCSs device was designed to further investigate the antibacterial performance for sewage management. The antibacterial killing rate was up to 100% for Escherichia coli and Staphylococcus aureus, and the nano-copper deposits were immobilized on the reduced graphene oxide sheets during the circulation process. This suggests that rGCSs is a highly-efficient antibacterial candidate for practical applications in sewage systems.

We give explicit estimates of the Fourier decay rate of some coin-tossing type measures, which generalizes a classical result of Hartman and Kershner. Using an elementary method originated from Cassels and Schmidt, we also prove that almost every point is absolutely normal with respect to such measures. As an application, we present some new examples of measures whose Fourier decay rate could be as slow as possible, yet almost all points are absolutely normal, which complements a result of R. Lyons on the set of non-normal numbers.

Bushen Huoxue recipe (BSHXR) is a classic Chinese herbal prescription for nourishing the kidney and activating blood circulation. It consists of six herbs: Astragali radix, Angelicae sinensis radix, Ligustici Chuanxiong Rhizoma, Cuscutae semen, Taxilli Herba, and Dipsaci Radix, and the main active constituents of BSHXR are ferulic acid, calycosin-7-glucopyranoside, hyperoside, quercitrin, and asperosaponin VI. In clinical practice, BSHXR is traditionally used to treat failed pregnancy and its complications. However, little is known about the underlying mechanism of BSHXR for the treatment of implantation loss during early pregnancy. In the current study, controlled ovarian hyperstimulation was induced in mice as our implantation loss model, and we evaluated the effects of BSHXR on implantation, decidualization, decidual angiogenesis, and reproductive outcome. We showed that BSHXR could regulate the supraphysiological levels of serum estrogen and progesterone observed in these mice, and also act on estrogen and progesterone receptors in the stroma and epithelium. BSHXR also enhanced FGF2 expression in the vascular sinus folding area of the decidua, thus potentially reducing implantation loss during early pregnancy and contributing to placentation and survival of the fetuses. Taken together, our findings provide scientific evidence for the application of BSHXR in the clinic as a treatment for implantation loss during early pregnancy, and warrant further investigation of BSHXR as an effective treatment for failed pregnancy and its complications.

Ethnopharmacological relevance Bushen Huoxue recipe (BHR) is a Chinese herbal prescription composed of ten herbs and it is widely used for the treatment of diminished ovarian reserve (DOR). This study investigates the potentially beneficial effects and underlying mechanism of BHR on a cyclophosphamide (CTX) induced model of DOR in mice. Materials and methods Granules of BHR were first subjected to high performance liquid chromatography (HPLC) to determine the exact ingredients within the mixture. We then induced DOR in mice by injecting them with 90 mg/kg of CTX. Following the single intraperitoneal injection, mice then received either saline or BHR for 21 days. To assess the effects of BHR on DOR, we examined splenic and ovarian morphology, estrous cycle duration, ovarian index, follicle number, body weight, and concentration of serum E2 and FSH. To explore the immunological mechanism behind the effects, mouse splenocytes were isolated in order to analyze the proportion of CD4+, CD8+ T cells and Th1, Th17 and Treg subsets by flow cytometry. The serum levels of IFN-γ, TNF-α, IL-4, IL-17A, IL-6 and IL-10 were detected using Cytometric Bead Array (CBA). Additionally, the mRNA expression levels of T-bet, RORγt and Foxp3 were measured with quantitative real-time PCR. Results Our results show that following treatment with BHR in DOR mice, several measures showed significant improvement. The morphology of the ovary and spleen, estrous cycle duration, body weight, ovarian index, and serum levels of E2 and FSH recovered to approximately normal levels and the loss of follicles at all stages was significantly attenuated. Furthermore, the elevated proportions of CD4+ T cells, Th1, Th17, Treg subsets and the increased serum levels of IFN-γ, TNF-α, IL-17A, IL-6 and IL-10 as well as the mRNA expressions of T-bet, RORγt and Foxp3 in DOR mice were significantly decreased. Conclusions Our results show that BHR is a promising candidate to treat DOR mice and this beneficial effect may be mediated through the downregulation of augmented autoimmunity.

Let [Formula: see text] and [Formula: see text] be real numbers. The run-length function of [Formula: see text]-expansions denoted by [Formula: see text] is defined as the maximal length of consecutive zeros in the first [Formula: see text] digits of the [Formula: see text]-expansion of [Formula: see text]. It is known that for Lebesgue almost all [Formula: see text], [Formula: see text] increases to infinity with the logarithmic speed [Formula: see text] as [Formula: see text] goes to infinity. In this paper, we calculate the Hausdorff dimension of the subtle set for which [Formula: see text] grows to infinity with other speeds. More precisely, we prove that for any [Formula: see text], the set [Formula: see text] has full Hausdorff dimension, where [Formula: see text] is a strictly increasing function satisfying that [Formula: see text] is non-increasing, [Formula: see text] and [Formula: see text] as [Formula: see text]. This result significantly extends the existing results in this topic, such as the results in [J.-H. Ma, S.-Y. Wen and Z.-Y. Wen, Egoroff’s theorem and maximal run length, Monatsh. Math. 151(4) (2007) 287–292; R.-B. Zou, Hausdorff dimension of the maximal run-length in dyadic expansion, Czechoslovak Math. J. 61(4) (2011) 881–888; J.-J. Li and M. Wu, On exceptional sets in Erdős–Rényi limit theorem, J. Math. Anal. Appl. 436(1) (2016) 355–365; J.-J. Li and M. Wu, On exceptional sets in Erdős–Rényi limit theorem revisited, Monatsh. Math. 182(4) (2017) 865–875; Y. Sun and J. Xu, A remark on exceptional sets in Erdős–Rényi limit theorem, Monatsh. Math. 184(2) (2017) 291–296; X. Tong, Y.-L. Yu and Y.-F. Zhao, On the maximal length of consecutive zero digits of [Formula: see text]-expansions, Int. J. Number Theory 12(3) (2016) 625–633; J. Liu, and M.-Y. Lü, Hausdorff dimension of some sets arising by the run-length function of [Formula: see text]-expansions, J. Math. Anal. Appl. 455(1) (2017) 832–841; L.-X. Zheng, M. Wu and B. Li, The exceptional sets on the run-length function of [Formula: see text]-expansions, Fractals 25(6) (2017) 1750060; X. Gao, H. Hu and Z.-H. Li, A result on the maximal length of consecutive 0 digits in [Formula: see text]-expansions, Turkish J. Math. 42(2) (2018) 656–665, doi: 10.3906/mat-1704-119].