Search

Nearly one-fifth of patients with non-small cell Lung Cancer (NSCLC) will develop liver metastases (LMs), and the overall treatment strategy of LMs will directly affect the survival of patients. However, some retrospective studies have found that patients receiving chemotherapy or targeted therapy have a poorer prognosis once LMs develop. In recent years, multiple randomised controlled trials (RCTS) have shown significant improvements in outcomes for patients with advanced lung cancer following the introduction of immune checkpoint inhibitors (ICIs) compared to conventional chemotherapy. ICIs is safe and effective in patients with LMs, although patients with LMs are mostly underrepresented in randomised clinical trials. However, NSCLC patients with LMs have a significantly worse prognosis than those without LMs when treated with ICIs, and the mechanism by which LMs induce systemic anti-tumour immunity reduction is unknown, so the management of LMs in patients with NSCLC is a clinical challenge that requires more optimised therapies to achieve effective disease control. In this review, we summarised the mechanism of ICIs in the treatment of LMs, the clinical research and treatment progress of ICIs and their combination with other therapies in patients with LMs from NSCLC. [ABSTRACT FROM AUTHOR]

Given the difficulties in measuring the effective wind speed of wind turbine during the maximum power point tracking (MPPT) process and the unknown nature of the system, this paper proposes a neural network super-twisted sliding mode control (NNST-SMC) method with echo state network (ESN) wind speed estimation. The rotor speed and electromagnetic power are taken as ESN inputs, and the effective wind speed is estimated through the inverse model of wind turbine dynamics. The super-twisted algorithm (STA) can effectively improve the chattering problem of the traditional sliding mode control (SMC) system. The RBF neural network is introduced to compensate for disturbance and uncertainty characteristics of the wind turbine. Results show that compared with the neural network first-order sliding mode control (NNSMC) and super-twisted sliding mode control (ST-SMC), the proposed method can improve the efficiency of wind energy utilization. [ABSTRACT FROM AUTHOR]

Malignant peritoneal mesothelioma (MPeM) is a rare and highly invasive malignant tumor with a lack of specificity in clinical manifestations, which can easily lead to misdiagnosis and missed diagnosis. Due to the difficulty of early diagnosis, most patients are already in the advanced stage when diagnosed, and the prognosis is poor. At present, there is no standard treatment strategy, and the existing treatment methods are not effective, the duration of remission is short, which cannot meet the clinical needs. Here we describe a patient with advanced MPeM, initially misdiagnosed as ovarian cancer, who responded to treatment with bevacizumab in combination with albumin-bound paclitaxel and cisplatin. In preparation for cytoreductive surgery (CRS), MPeM was confirmed by laparoscopic peritoneal nodule biopsy combined with histological and immunohistochemical results. Subsequently, due to intolerable neurotoxicity after chemotherapy, she received oral anlotinib therapy on April 25, 2022, and remained stable disease (SD) with the medication, having achieved more than 14 months of progression-free survival (PFS) as of the date of our manuscript submission. The patient's total treatment time was over 19 months. These treatments delayed tumor progression, reduced drug side effects, maintained a good quality of life, and further extended overall survival (OS). Our experience is that on the one hand, it is necessary to increase the clinician's understanding of the disease, and make full use of tissue samples and immunohistochemical staining to reduce the occurrence of misdiagnosis. On the other hand, based on preliminary evidence, we found that oral anlotinib offers a viable maintenance treatment strategy for patients with advanced mesothelioma, which needs to be further explored in future studies. [ABSTRACT FROM AUTHOR]

The visualization of bone imaging in vivo is of great significance for the understanding of some bone-related diseases or physiological processes. Herein, a bone-targeted NIR-II small molecule (TTQF-SO3), which was modified with multiple sulfonate groups, was successfully fabricated for the second near-infrared (NIR-II) bone imaging. In vitro studies revealed that TTQF-SO3 showed high affinity for hydroxyapatite and excellent macrophage accumulation ability. In in vivo assays, TTQF-SO3 displayed high bone uptake ability and high NIR-II bone imaging quality, demonstrating the specific bone-targeting ability of the sulfonate-containing probe. In addition, the noninvasive NIR-II imaging detection in bone calcium loss was successfully verified in osteoporosis mice models. Moreover, the negative charge characteristic of TTQF-SO3 showed efficient lymphoid enrichment in living mice by intravenous injection. Overall, these warrant that our TTQF-SO3 is an optimal bone-targeted diagnostic agent for high-quality NIR-II imaging, highlighting its potential promise for clinical translation. [ABSTRACT FROM AUTHOR]

Increasing carbon dioxide (CO2) promotes photosynthesis and mitigates heat stress‐induced deleterious effects on plants, but the regulatory mechanisms remain largely unknown. Here, we found that tomato (Solanum lycopersicum L.) plants treated with high atmospheric CO2 concentrations (600, 800, and 1000 µmol mol−1) accumulated increased levels of melatonin (N‐acetyl‐5‐methoxy tryptamine) in their leaves and this response is conserved across many plant species, including Arabidopsis, rice, wheat, mustard, cucumber, watermelon, melon, and hot pepper. Elevated CO2 (eCO2; 800 µmol mol−1) caused a 6.8‐fold increase in leaf melatonin content, and eCO2‐induced melatonin biosynthesis preferentially occurred through chloroplast biosynthetic pathways in tomato plants. Crucially, manipulation of endogenous melatonin levels by genetic means affected the eCO2‐induced accumulation of sugar and starch in tomato leaves. Furthermore, net photosynthetic rate, maximum photochemical efficiency of photosystem II, and transcript levels of chloroplast‐ and nuclear‐encoded photosynthetic genes, such as rbcL, rbcS, rbcA, psaD, petB, and atpA, significantly increased in COMT1 overexpressing (COMT1‐OE) tomato plants, but not in melatonin‐deficient comt1 mutants at eCO2 conditions. While eCO2 enhanced plant tolerance to heat stress (42°C) in wild‐type and COMT1‐OE, melatonin deficiency compromised eCO2‐induced thermotolerance in comt1 plants. The expression of heat shock proteins genes increased in COMT1‐OE but not in comt1 plants in response to eCO2 under heat stress. Further analysis revealed that eCO2‐induced thermotolerance was closely linked to the melatonin‐dependent regulation of reactive oxygen species, redox homeostasis, cellular protein protection, and phytohormone metabolism. This study unveiled a crucial mechanism of elevated CO2‐induced thermotolerance in which melatonin acts as an essential endogenous signaling molecule in tomato plants. [ABSTRACT FROM AUTHOR]

Conjugated small‐molecule (CSM) phototheranostic agents that operate in the second near‐infrared (NIR‐II) region have garnered significant attention in the field of biomedicine. However, a lack of fluorescence‐emitting ability hinders their use in precise fluorescence imaging (FI)‐guided photothermal therapy (PTT). Herein, a two‐pronged fluorescence intensification strategy—molecular engineering for rational bandgap modulation and lipid‐intercalation to combat fluorescence quenching—is used to develop NIR‐II‐excited ultrabright donor–acceptor–donor‐based (D–A–D)‐based zwitterionic CSM nanoagent for tumor phototheranostics. The molecular engineering strategy produces the NIR‐II‐excited D–A–D‐based zwitterionic fluorophore (BTFQ) that exhibits a high NIR‐II fluorescence quantum yield (QY = 0.65%) in dichloromethane. More importantly, BTFQ complexed with liposome (DMPC) to form the zwitterion–liposome nanoagent (BTFQ/DMPC) shows a negligible loss of QY (0.63%) in aqueous media. Moreover, because BTFQ/DMPC possesses excellent photothermal conversion efficiency (PCE = 30.8%) performance, it can be used to realize efficient in vivo 1064 nm single‐photon high‐resolution NIR‐II FI guided NIR‐II PTT. This study introduces a new avenue for the development of NIR‐II‐excited NIR‐II FI/PTT agents for precise and effective tumor treatment. [ABSTRACT FROM AUTHOR]

To improve bone metastases treatment efficacy, current strategies are focused on the integration of chemotherapy with phototheranostic. However, the success of phototheranostic approaches is hampered by the limited tissue penetration depth of near‐infrared‐I (NIR‐I) light (700–900 nm). In this study, a NIR‐II (1000–1700 nm) excitation phototheranostic (BTZ/Fe2+@BTF/ALD) is presented for NIR‐II fluorescence imaging and NIR‐II photoacoustic imaging‐guided NIR‐II photothermal therapy (PTT), chemotherapy, and chemodynamic therapy (CDT) of breast cancer bone metastases. This phototheranostic is developed by integrating a dopamine‐modified NIR‐II absorbing donor–acceptor–donor small molecule (BBT‐FT‐DA), the boronate anticancer drug bortezomib (BTZ), and Fe2+ ions, as CDT catalysts, into an amphiphilic PEGylated phospholipid modified with the bone‐targeting ligand alendronate. In acidic and hydrogen peroxide (H2O2) over expression tumor microenvironment, the boronate–catechol linkage is cleaved and BTZ and Fe2+ ions are released to initiate the Fenton reaction, that is, chemotherapy and CDT, respectively, are initialized. It is confirmed using the murine 4T1 bone metastasis model that BTZ/Fe2+@BTF/ALD significantly suppresses the progression of tumor cells in the bone tissue via a synergistic NIR‐II PTT/chemotherapy/CDT effect. Overall, this work provides fresh insights to guide the development of NIR‐II phototheranostics for breast cancer bone metastases. [ABSTRACT FROM AUTHOR]

With the widespread application of lithium-ion battery packs, it calls for efficient balancing methods to improve the performance of these battery systems. The relevant research has focused on the design of equalization circuits and control strategies while neglecting quantitative analysis and comparison of battery active equalization structures from the systematic level. In this paper, we propose an improved system-theoretic modeling approach for active equalization structures that takes into account the battery's constraints, including equalization current rate and SOC operation range. Accordingly, the mathematical models of various active equalization structures are derived that can describe their equalization dynamic behavior. Then, the analytical algorithms are developed to estimate the balancing time of active equalization structures online. Finally, extensive numerical simulations are conducted to evaluate and compare the average performance of these equalization systems in term of equalization time. It then comes up with a comprehensive comparison among them. Consequently, the Multicell-to-Multicell (MC2MC) balancing structure benefits the fast balancing speed and the lowest sensitive to initial batteries’ SOCs. The global structure has the lowest implementation cost and the series structure benefits the simplest control. Moreover, the module-based structures have faster balancing speed when each module contains about 4–6 batteries. [ABSTRACT FROM AUTHOR]

To improve students' performance effectively, many Chinese universities are establishing systems to predict student's academic performance and sending student's academic early alerts. With student's population of over 600,000, Chinese-foreign cooperation in running schools (CFCRS) has become one of the booming higher education forms in China. Compared with students in the non-cooperatively running programs, CFCRS students' academic performances are weaker on average. To predict the academic-at-risk students and provide efficient supports to the students, a precise and prompt academic prediction is in great need. Therefore, this research aims at representing a more efficient and accurate model to predict academic performance of CFCRS students which will be based on graph convolutional network. In this research, student's similarity is measured on academic performance by Pearson correlation coefficient. An undirected graph in which similar students are connected is conducted. Feature matrix is composed of students' previous grades. In addition, graph convolutional network is trained based on the undirected graph and feature matrix. In the experiment, it shows that this model predicts certain student's performance on certain course from the final exam results in previous semesters, which might improve learning efficiency and teaching quality. With an average accuracy of 81.5%, graph convolutional network outperforms support vector machine and random forest models. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that exist as complex mixtures in vivo. When humans are simultaneously exposed to these compounds, the development of atherosclerosis is known to be enhanced. However, the roles of miRNA in TCDD- and PCB-induced atherosclerosis are largely unknown. Therefore, the present study is aimed at elucidating the possible dysregulation of miRNAs in atherogenesis induced by coexposure to TCDD and PCBs. Eight-week-old male ApoE-/- mice were coexposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) by intraperitoneal injection four times over a 6-week period. Microarray analysis of miRNAs and mRNAs in the liver of ApoE-/- mice with or without TCDD and Aroclor1254 coexposure was performed. We discovered that 68 miRNAs and 1312 mRNAs exhibited significant expression changes in response to TCDD and PCB coexposure and revealed that both changed miRNAs and mRNAs are involved in cardiovascular disease processes. An integrated miRNA-mRNA approach indicated that miRNA-26a-5p, miRNA-193a-3p, and miRNA-30c-5p participated in specific TCDD and Aroclor1254 coresponsive networks which are relevant to the cardiovascular system development and function network. Furthermore, our results also indicated that miRNA-130a-3p and miRNA-376a-3p were novel players in the regulation of TCDD- and Aroclor1254-induced atherosclerosis pathways. In summary, our finding provided new insights into the mechanism of atherosclerosis in response to TCDD and PCB coexposure. [ABSTRACT FROM AUTHOR]

Polytetrafluoroethylene (PTFE), which has an extremely low coefficient of friction and good thermal and chemical stability, is widely used as a self-lubricating material. In this study, the thermal oxidative-ageing mechanisms of PTFE were studied using infrared spectroscopy and molecular dynamics simulations, and the influence of the thermal oxidative-ageing time on its tribological properties was investigated under a high load (20 MPa). Results indicated that thermal oxidative-ageing resulted in oxidation fracture, generating CF 2 O products, followed by further oxidation to CFO 2 as ageing time increased. The dynamic friction coefficient of PTFE fluctuated significantly under heavy load, and its wear rate fluctuated over a small range but showed a decreasing trend with increased ageing. [Display omitted] • Thermal oxidative-aging mechanisms of PTFE are evaluated experimentally. • Molecular dynamics simulations predict thermal oxidative aging of PTFE with time. • Tribological properties under high load are affected by thermal oxidative aging. • The dynamic friction coefficient of PTFE fluctuates significantly under heavy load. • The wear rate tends to decrease with increasing aging time. [ABSTRACT FROM AUTHOR]

It is very important to improve the electrical conductivity of polymer nanocomposites (PNCs), which can be used under the external field. In this work, by employing a coarse-grained molecular dynamics simulation, the effect of the external fields (tensile field and shear field) on the conductive probability of PNCs has been investigated in details by tuning the nanofiller shape. By carefully analyzing the conductive network, compared with the rod filler and the sphere filler, the Y filler and the X filler can protect the conducive networks well from their breakage perpendicular to the external fields, which thus can significantly enhance the conductive probability under the external fields. In other words, compared with under the quiescent state, the decrease or the increase of the conductive probability under the external fields depends on the nanofiller shape. Meanwhile, it is interesting to find that both the directional conductive probabilities parallel to the shear field and perpendicular to the shear field increase with the shear rate for the Y fillers, which further reflects their high conductive probability under the shear field. The reason can be attributed to two aspects: (1) the gradual aggregation of Y fillers under the external field; (2) the multi-arm structures of Y fillers. In summary, this work presents some further understanding how to improve the electrical conductivity of PNCs under the external fields by tuning the nanofiller shape. Image 1 [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A series of novel 25-OCH 3 -PPD derivatives were synthesized. • Cytotoxic activities of the derivatives were evaluated on five human tumor cell lines. • Compounds 3a , 14a and 18a exhibited strong anti-tumor activities. • Having aromatic ester at the C3 position could enhance the antiproliferative activities. Abstract Previously we have reported that 25-OCH 3 -PPD could suppress the reproduction of cancer cells and cause apoptosis without obvious toxicity. Herein, we aimed to enhance its bioactivity by introducing aromatic groups to its dammarane-type skeleton. These synthesized derivatives were tested for their inhibitory activities against five cancer cell lines. Of them, compounds 3a , 14a and 18a had the strongest antiproliferative activities against tumor cells (IC 50 < 15 µM, 5-fold to 10-fold increases than 25-OCH 3 -PPD). Especially compound 14a displayed the most potent activity against DU145, MCF-7 and HepG2 cells (IC 50 = 6.7 ± 0.8, 4.3 ± 0.8 and 5.8 ± 0.6 µM, respectively). Structure-activity relationships demonstrated that having aromatic ester at the C3 position could improve the bioactivity. The data provided new insights into exploring novel antiproliferative lead compounds. [ABSTRACT FROM AUTHOR]

Aim: Resistance to platinum-based therapeutic agents is the major contributor to epithelial ovarian cancer (EOC) mortality. There is an urgent need to better understand the underlying mechanisms. Here we investigated the role of serpins in EOC chemoresistance and related mechanisms, and found that SERPINE1 played an important role in chemoresistance in A2780cp cells.Materials and Methods: A2780cp and A2780s cells were used in our study. Microarray screening was used to identify the gene expression change under carboplatin treatment. A cell-counting kit-8 was used to detect the sensitivity of ovarian cancer cells after treatment. The expression of SERPINE1 was silenced by siRNA. The levels of SERPINE1 and epithelial-mesenchymal transition (EMT)-related proteins were confirmed by Western blot. MassArray EpiTYPER quantitative DNA methylation analysis was introduced to evaluate the methylation of the promoter of SERPINE1.Results: Microarray data showed that SERPINE1 and SERPINE2 increased most dramatically under carboplatin treatment in A2780cp cells. Carboplatin treatment could significantly increase the expression of SERPINE1 and induce the EMT process, with decreased expression of E-cadherin and increased expression of Vimentin, Snail and Twist. Knockdown of SERPINE1, but not SERPINE2, in A2780cp cells could inhibit the EMT process. We also found that hypomethylation in the promoter of SERPINE1 might result in the increased expression of SERPINE1 and subsequent EMT process in A2780cp cells.Conclusion: Our study suggested that SERPINE1 may be a promising therapeutic target for chemoresistance. [ABSTRACT FROM AUTHOR]

The article reports the results of intracytoplasmic sperm injection (ICSI) or in vitro fertilisation (IVF), and the risk they could cause to the temperament of the child as well as the anxiety the mothers feel about the same. Particular focus is given to the multidimensional anxiety that the mother of the child goes through during the ICSI or IVF, the anxiety levels of the mother before the transvaginal oocyte retrieval (TVOR), and the maternal anxiety during gestation.

Among the notable complications of direct hemodynamic reconstruction for moyamoya disease (MMD) is cerebral hyperperfusion syndrome (CHS). In this study, we evaluated hemodynamic changes in small regional microvasculature (SRMV) around the anastomosis site by using indocyanine green (ICG)-FLOW800 video angiography and verified that it better predicted the onset of CHS. Intraoperative ICG-FLOW800 analysis was performed on 31 patients (36 cerebral hemispheres) with MMD who underwent superficial temporal artery-middle cerebral artery (MCA) bypass grafting at our institution. The regions of interest were established in the SRMV and thicker MCA around the anastomosis. Calculations were made for half-peak to time (TTP1/2), cerebral blood volume (CBV), and cerebral blood flow (CBF). According to the presence or absence of CHS after surgery, CHS and non-CHS groups of patients were separated. The results showed that ΔCBV and ΔCBF were substantially greater in SRMV than in MCA (p < 0.001). Compared with the non-CHS group, ΔCBF and ΔCBV of SRMV and MCA were considerably greater in the CHS group (p < 0.001). ΔCBF and ΔCBV on the ROC curve for both SRMV and MCA had high sensitivity and specificity (SRMV: ΔCBF, AUC = 0.8586; ΔCBV, AUC = 0.8158. MCA: ΔCBF, AUC = 0.7993; ΔCBV, AUC = 0.8684). ICG-FLOW800 video angiography verified the differential hemodynamic changes in the peri-anastomotic MCA and SRMV before and after bypass surgery in patients with MMD. [ABSTRACT FROM AUTHOR]

Aluminium-stabilized calcium-based materials are currently an excellent solution for capturing CO 2 directly from industrial flue gas. However, there is still no report on the technology of low-cost and large-scale assembly of Ca 3 Al 2 O 6 and CaO. In this study, we innovatively put forward a silicon-assisted strategy to facilely synthesize high-purity Ca 3 Al 2 O 6 and evaluate its cyclic performance for stabilizing uptake CO 2 after assembly. With regard to the Si/Al ratio of 0.2, Ca 3 Al 2 O 6 was prepared selectively among 850–900 °C, with only 5.2% CaO residually. The introduction of silicon inhibited the formation of Ca 5 Al 6 O 14 by-products and the mechanism of silicon at the calcium-aluminum interface was also explained by systematic characterization. The Ca 3 Al 2 O 6 modified sorbent with simple assembly showed extremely high cycle stability improvement compared with the pure precipitated calcium carbonate derived CaO. These works provide technical guidance for the industrial scale-up of the rational design of Al-stabilized calcium-based adsorption materials. [ABSTRACT FROM AUTHOR]

Solid amine adsorption is considered to be the most promising technology for post-combustion CO 2 capture, but it still has drawbacks due to the high cost of supports and the easy occurrence of CO 2 -induced chemical deactivation. Herein, we propose a novel eco-friendly method for realizing efficient and stable solid amine adsorbents. A calcium silicate hydrate (CSH) support with a pore volume of 3.0 cm3 g−1 is synthesized from coal fly ash (CFA) with the pore-expanded assistance of azeotropic distillation, and then the PEI@CSH adsorbents are prepared by impregnation. The adsorption capacity of the prepared 60%PEI@CSH-0.1 adsorbent reaches 198 mg g−1 and exhibits an excellent cyclic stability, with an attenuation of only 1.9% after 10 cycles under ideal regeneration conditions. Even under realistic regeneration conditions, the CO 2 uptake remains at 103 mg g−1 after 10 cycles, which shows obvious advantages over that of commercial SiO 2 supports. By using FT-IR, solid-state NMR and DFT calculations, we found that the CSH support promotes the conversion of primary amines to secondary amines in PEI molecules, and thus effectively inhibits the inactivation induced by the formation of urea compounds. Therefore, the PEI@CSH adsorbents provide a low-cost and high-efficiency approach for both in-situ CFA utilization and CO 2 mitigation inside coal-fired power plants. [Display omitted] • PEI@CSH adsorbents showed excellent adsorption capacity and cyclic stability. • The surface chemical property of CSH led to the anti-urea PEI@CSH adsorbents. • Solid-phase NMR and DFT calculation were applied for clarifying anti-urea mechanism. • PEI@CSH adsorbents realized both in-situ CFA utilization and CO 2 mitigation. [ABSTRACT FROM AUTHOR]

Objective To survey effective treatment strategies for cesarean scar pregnancy (CSP). Methods The clinical data of 78 patients diagnosed with CSP from January 2010 to December 2013 were reviewed. Results Among these patients, 17 patients were first treated at our hospital; of them, 2 were misdiagnosed. The other 61 patients were referred from other hospitals; of them, 21 were initially misdiagnosed. There were 9 patients who were treated with laparotomy, 50 patients with curettage after uterine artery embolization (UAE) with or without local methotrexate (MTX) infusion, 10 patients with dilatation and curettage, 6 patients with transvaginal sonographic guided local intragestational MTX injection, and 3 patients with systemic MTX injection. All patients finally recovered. Patients with excessive vaginal hemorrhage underwent either emergency UAE treatment or laparotomy. These two treatments had similar success rates (81.82% vs. 100%, χ 2 =0.289, P>0.05). Conclusions The accurate diagnosis of CSP is important. Curettage after UAE with or without local MTX infusion is a safe and effective method. [ABSTRACT FROM AUTHOR]

In the current work, 12 novel 25-hydroxyprotopanaxadiol (25-OH-PPD) derivatives were synthesized by reacting with chloroacetyl chloride. And their in vitro antitumor activities were evaluated on six human tumor cell lines by MTT assay. The results demonstrated that, as compared with 25-OH-PPD, compounds 4 , 6 and 7 exhibited higher cytotoxic activity on all tested cell lines. Of them, compound 4 showed strongly inhibition against MCF-7, HCT-116 and Lovo cells with IC 50 values of 1.7, 1.6 and 2.1 μM, respectively. The IC 50 values of compound 6 against HCT-116 and 7 against MCF-7 were the lowest (1.2 and 1.6 μM, respectively). It was also noted that compound 4 showed a 20- to 100-fold greater growth inhibition than ginsenoside-Rg 3 (an anti-cancer regular drug in China). In conclusion, the data revealed that compounds 4 , 6 and 7 were potential candidates for anti-tumor treatment and may be useful for the development of novel antiproliferative agents. [ABSTRACT FROM AUTHOR]

The association between polycystic ovary syndrome (PCOS) and metabolic syndrome (MetS) is not widely recognized or properly assessed in adolescents. The aim of this study was to conduct a systematic review and meta-analysis to provide reliable results concerning MetS development in adolescents with PCOS. We searched studies published in PubMed, Medline, and Web of Science from January 2010 to December 2020. The quality of studies was assessed by the Newcastle–Ottawa Scale (NOS), and the data analysis was performed with Stata 14.0. Twelve articles were finally included in the systematic review and meta-analysis. The results suggested that adolescents with PCOS have more than three times the odds of having MetS than controls (OR 3.32, 95% CI [2.14, 5.14]). Obese adolescents with PCOS also had a higher risk of MetS than those with obesity but without PCOS (OR 3.97, 95% CI [1.49, 10.53]). Compared to those without PCOS, systolic blood pressure was higher in adolescents with PCOS (weighted mean difference (WMD) 3.85, 95% CI [1.73, 5.97]), while diastolic blood pressure was higher only in girls with PCOS who had a normal weight (WMD 3.52, 95% CI [1.57, 5.48]). The levels of triglycerides were higher in obese adolescents with PCOS than in those with obesity but without PCOS (WMD 27.84, 95% CI [10.16, 45.51]). PCOS could increase the frequency of MetS by influencing blood pressure and lipid metabolism independent of obesity as early as the adolescent period. Thus, clinicians should perform early interventions in adolescents with PCOS and follow up the relevant indicators of MetS to decrease the risk of poor long-term prognosis. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore whether hyperandrogenism induces epigenetic alterations of peroxisome proliferator-activated receptor gamma 1 (PPARG1), nuclear corepressor 1 (NCOR1), and histone deacetylase 3 (HDAC3) genes in granulosa cells (GCs) of polycystic ovary syndrome (PCOS) women and whether these alterations are involved in the ovarian dysfunction induced by hyperandrogenism. Thirty-two infertile PCOS women and 147 infertile women with tubal blockage were recruited. PCOS women were divided into the hyperandrogenism (HA) PCOS group ( n = 13) and nonhyperandrogenism (N-HA) PCOS group ( n = 19). Sixty female Sprague-Dawley rats were used for PCOS model establishment. In GCs of HA PCOS women, PPARG1 mRNA expression was lower, whereas NCOR1 and HDAC3 mRNA expression were higher than N-HA PCOS women and controls ( P < 0.05). When all women were divided into successful and failed pregnancy subgroups according to the following clinical pregnancy outcome, we found lower PPARG1 mRNA levels and higher NCOR1 and HDAC3 mRNA levels in the failed subgroup of HA PCOS ( P < 0.05). Two hypermethylated CpG sites in the PPARG1 promoter and five hypomethylated CpG sites in the NCOR1 promoter were observed only in HA PCOS women ( P < 0.01 to P < 0.0005). The acetylation levels of histone H3 at lysine 9 and p21 mRNA expression were decreased in human GCs treated with dihydrotestosterone in vitro ( P < 0.05). PCOS rat models also showed alterations of PPARG1, NCOR1, and HDAC3 mRNA expression and methylation changes of PPARG1 and NCOR1, consistent with the results from humans. Hyperandrogenism induces the epigenetic alterations of PPARG1, NCOR1, and HDAC3 in GCs, which are involved in the ovarian dysfunction of HA PCOS. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this article was to conduct a systematic review with meta-analysis of the trials of acupuncture during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment on the outcomes of clinical pregnancy, biochemical pregnancy, ongoing pregnancy, implantation rate, live birth, and miscarriage. Search strategy: The search was conducted by using MEDLINE®, SCISEARCH, the Cochrane Menstrual Disorders and Subfertility Group trials register, AMED, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Wanfang Database, China Academic Journal Electronic full text Database in China National Knowledge Infrastructure, Index to Chinese Periodical Literature, ISI Proceedings for conference abstracts, and ISRCTN Register and Meta-register for randomized controlled trials. Data collection and analysis: Study selection, quality appraisal, and data extraction were performed independently and in duplicate. The measures of treatment effect were the pooled relative risks (RR) of achieving clinical pregnancy, biochemical pregnancy, ongoing pregnancy, implantation rate, live birth, or miscarriage for women in the acupuncture group compared with women in the control group. Results: Using the random-effects model, pooling of the effect estimates from all of the 17 trials showed no significant difference in the clinical pregnancy outcome between the acupuncture and the control groups (RR=1.09, 95% confidence interval (CI) 0.94-1.26, p=0.25). No significant differences in the biochemical pregnancy, ongoing pregnancy, implantation rate, live birth, or miscarriage outcomes were found between the acupuncture and the control groups (biochemical pregnancy: RR=1.01, 95% CI 0.84-1.20, p=0.95; ongoing pregnancy: RR=1.20, 95% CI 0.93-1.56, p=0.16; implantation rate: RR=1.22, 95% CI 0.93-1.62, p=0.16; live birth: RR=1.42, 95% CI 0.92-2.20, p=0.11; miscarriage outcomes: RR=0.94, 95% CI 0.67-1.33, p=0.74). Conclusions: No significant benefits of acupuncture are found to improve the outcomes of IVF or ICSI. [ABSTRACT FROM AUTHOR]

In this study, we tested the hypothesis that human neutrophil α-defensins (HNPs) inhibit hepatic glucose production through a signaling pathway distinct from insulin. The effect of HNP-1 on fasting blood glucose levels and the expression of hepatic gluconeogenic genes was first examined. Using hyperinsulinemic-euglycemic clamps, we determined the effect of HNP-1 on endogenous glucose production, hepatic expression of key gluconeogenic genes and glucose uptake in skeletal muscle in Zucker diabetic fatty rats. In isolated primary hepatocytes, we studied the effect of HNP-1 and -2 on glucose production, expression of gluconeogenic genes, and phosphorylation of Akt, c-Src, and FoxO1. Our results show that HNP-1 reduced blood glucose levels of both normal mice and Zucker diabetic fatty rats predominantly through suppression of hepatic glucose production. HNPs inhibited glycogenolysis and gluconeogenesis in isolated hepatocytes. HNPs also suppressed expression of key gluconeogenic genes including phosphoenoylpyruvate carboxyl kinase and glucose-6-phosphatase. To investigate the mechanism, we found that HNPs stimulated phosphorylation of Akt and FoxO1 without activating IRS1. Nevertheless, HNPs activated c-Src. Blockade of c-Src activity with either a chemical inhibitor PP2 or an alternative inhibitor CSK prevented the inhibitory effect of HNPs on gluconeogenesis. Together, our results support the hypothesis that HNPs can suppress hepatic glucose production through an intracellular mechanism distinct from the classical insulin signaling pathway. [ABSTRACT FROM AUTHOR]

Epigallocatechin-3-gallate (EGCG), a main catechin of green tea, has been suggested to inhibit hepatic gluconeogenesis. However, the exact role and related mechanism have not been established, In this study, we examined the role of EGCG in hepatic gluconeogenesis at concentrations that are reachable by ingestion of pure EGCG or green tea, and are not toxic to hepatocytes. Our results show in isolated hepatocytes that EGCG at relatively low concentrations (≤1 μM) inhibited glucose production via gluconeogenesis and expression of key gluconeogenic genes. EGCG was not toxic at these concentrations while demonstrating significant cytotoxicity at 10 μM and higher concentrations. EGCG at 1 μM or lower concentrations effective in suppressing hepatic gluconeogenesis did not activate the insulin signaling pathway, but activated 5′-AMP-activated protein kinase (AMPK). The EGCG suppression of hepatic gluconeogenesis was prevented by blockade of AMPK activity. In defining the mechanism by which EGCG activates AMPK, we found that the EGCG activation of AMPK was mediated by the Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Furthermore, our results show that the EGCG activation of AMPK and EGCG suppression of hepatic gluconeogenesis were both dependent on production of reactive oxygen species (ROS), which was a known activator of CaMKK. Together, our results demonstrate an inhibitory role for EGCG in hepatic gluconeogenesis and shed new light on the mechanism by which EGCG suppresses gluconeogenesis. [ABSTRACT FROM AUTHOR]

Free fatty acid (FFA) is believed to be a major environmental factor linking obesity to Type II diabetes. We have recently reported that FFA can induce gluconeogenesis in hepatocytes through p38 mitogen-activated protein kinase (p38). In this study, we have investigated the role of p38 in oleate-induced hepatic insulin resistance. Our results show that a prolonged treatment of primary hepatocytes with oleate blunted insulin suppression of hepatic gluconeogenesis, and decreased insulin-induced phosphorylation of Akt in a p38-dependent manner. Reduction of the insulin-induced Akt phosphorylation by oleate correlated with activation of p38. In the presence of p38 inhibition, prolonged exposure of hepatocytes to oleate failed to reduce insulin-stimulated phosphorylation of Akt. An siRNA against p38α prevented oleate suppression of the insulin-induced phosphorylation of Akt. Furthermore, a prolonged exposure of hepatocytes to oleate decreased insulin-induced tyrosine phosphorylation of IRS1/2, while slightly increasing serine phosphorylation of IRS. The decrease of insulin-stimulated tyrosine phosphorylation of IRS1/2 in hepatocytes by oleate was reversed by the inhibition of p38. We further show that a prolonged exposure of primary hepatocytes to oleate elevated the protein level of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in a p38-dependent manner, but had no effect on the mRNA level of PTEN. Knocking down the PTEN gene prevented oleate to inhibit insulin activation of Akt and insulin suppression of gluconeogenesis. Together, results from this study demonstrate a critical role for p38 in oleate-induced hepatic insulin resistance. [ABSTRACT FROM AUTHOR]

Hepatic lipogenesis is the principal route to convert excess carbohydrates into fatty acids and is mainly regulated by two opposing hormones, insulin and glucagon. Although insulin stimulates hepatic lipogenesis, glucagon inhibits it. However, the mechanism by which glucagon suppresses lipogenesis remains poorly understood. In this study, we have observed that p38 mitogen-activated protein kinase plays an inhibitory role in hepatic lipogenesis. Levels of plasma triglyceride and triglyceride accumulation in the liver were both elevated when p38 activation was blocked. Expression levels of central lipogenic genes, including sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase, hydroxy-3-methylglutaryl coenzyme A reductase, farnesyl pyrophosphate synthase, and cytochrome P-450-51, were decreased in liver by fasting and in primary hepatocytes by glucagon but increased by the inhibition of p38. In addition, we have shown that p38 can inhibit insulin-induced expression of key lipogenic genes in isolated hepatocytes. Our results in hepatoma cells demonstrate that p38 plays an inhibitory role in the activation of the SREBP-1c promoter. Finally, we have shown that transcription of the PGC-1β gene, a key coactivator of SREBP-1c, was reduced in liver by fasting and in isolated hepatocytes by glucagon. This reduction was significantly reversed by the blockade of p38. Insulin-induced expression of the PGC-1β gene was enhanced by the inhibition of p38 but suppressed by the activation of p38. Together, we have identified an inhibitory role for p38 in the transcription of central lipogenic genes, SREBPs, and PGC-1β and hepatic lipogenesis. [ABSTRACT FROM AUTHOR]

Free fatty acids (FFA) are considered as a causative link between obesity and diabetes. In various animal models and in humans FFA can stimulate hepatic gluconeogenesis. Although the in vivo role of FFA in hepatic gluconeogenesis has been clearly established, the intracellular role of FFA and related signaling pathway remain unclear in the regulation of hepatic gluconeogenic gene transcription. In this study, we have identified p38 mitogen-activated protein kinase (p38) as a critical signaling component in FFA-induced transcription of key gluconeogenic genes. We show in primary hepatocytes that both mid- and long-chain fatty acids (saturated or unsaturated) could activate p38 and increase levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, and peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) gene transcripts. The FFA-induced expression of PEPCK and PGC-1α genes and gluconeogenesis in isolated hepatocytes could be blocked by the inhibition of p38. Furthermore, PGC-1α phosphorylation by p38 was necessary for FFA-induced activation of the PEPCK promoter. Additionally, FFA stimulated phosphorylation of cAMP-response element-binding protein (CREB) through p38. The overexpression of the dominant-negative CREB prevented FFA-induced activation of the PEPCK promoter. Finally, we show that FFA activation of p38 requires protein kinase C5. Together, our results indicate that p38 plays a critical role in FFA-induced transcription of gluconeogenic genes, and the known gluconeogenic regulators, PGC-1α and CREB, are also integral parts of FFA-stimulated transcription of gluconeogenic genes. [ABSTRACT FROM AUTHOR]

Hepatic gluconeogenesis is essential for maintaining blood glucose levels during fasting and is the major contributor to postprandial and fasting hyperglycemia in diabetes. Gluconeogenesis is a classic cAMP/protein kinase A-dependent process initiated by glucagon, which is elevated in the blood during fasting and in diabetes. In this study, we have shown that p38 mitogen-activated protein kinase (p38) was activated in liver by fasting and in primary hepatocytes by glucagon or forskolin. Fasting plasma glucose levels were reduced upon blockade of p38 with either a chemical inhibitor or small interference RNA in mice. In examining the mechanism, inhibition of p38 suppressed glueoneoganesis in liver, along with expression of key gluconeogenic genes, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Peroxisome proliferator-activated receptor γ, coactivator 1α and cAMP-response element-binding protein have been shown to be important mediators of hepatic gluconeogenesis. We have shown that inhibition of p38 prevented transcription of the PPARγ coactivator 1α gene as well as phosphorylation of cAMP-response element-binding protein. Together, our results from in vitro and in vivo studies define a model in which cAMP-dependent activation of genes involved in gluconeogenesis is dependent upon the p38 pathway, thus adding a new player to our evolving understanding of this physiology. [ABSTRACT FROM AUTHOR]

We compared the social adjustment among Chinese children born after intracytoplasmic sperm injection (ICSI) vs those after in vitro fertilisation (IVF) and identify factors related to the adjustment. The social adaptation of 86 ICSI and 165 IVF conceived children of 4-6 years of age was assessed using the Infants-Junior Middle School Students' Social-Life Abilities Scale. There was no significant difference between the ICSI and IVF-conceived groups on the item of communication, self-dependence, locomotion, work skills, socialisation, self-management and total scores. Compared with routine IVF, ICSI does no harm to the social adaptation of children conceived through this technology. [ABSTRACT FROM AUTHOR]

Phthalates (PAEs), a group of environmental endocrine disruptors, are associated with oxidative stress and have adverse effects on female ovarian reserves. However, this association has been poorly investigated, particularly with respect to clinical evidence. In this study, we provided clinical evidence of a relationship between exposure levels of PAEs, oxidative stress and decreased ovarian reserve (DOR). Firstly, the urinary concentrations of metabolites of PAEs were measured by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), and the biomarkers of oxidative stress, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), were determined. Finally, statistical analyses were conducted to describe the relationship between the PAEs exposure, oxidative stress and DOR. We found that the levels of monomethyl phthalate (MMP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), and mono-(2-ethyl-5-hydroxypentyl) phthalate (MECPP) in the DOR group were significantly higher than those in the control group. There was a significant negative association between AMH and MMP, MiBP levels. and a significant positive association between FSH and MMP levels. PAEs exposure was also associated with a significant increase in MDA levels and decrease in SOD levels. In conclusion, the exposure of PAEs was closely associated with DOR, potentially mediated by oxidative stress pathways; however, small sample size was a limitation in this study. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder affecting women in their reproductive years. Emerging evidence suggests that the maternal-fetal immune system is crucial for proper pregnancy. However, whether immune function is altered at the end of pregnancy in PCOS women and the underlying molecular mechanisms is currently unexplored. Herein, the basic maternal immune system was investigated (n = 136 in the control group; n = 103 in the PCOS group), and whole-transcriptome sequencing was carried out to quantify the mRNAs, miRNAs, and lncRNAs expression levels in fetal side placental tissue of women with PCOS. GO, KEGG, and GSEA analysis were employed for functional enrichment analysis. The process of identifying hub genes was conducted utilizing the protein-protein interaction network. CIBERSORT and Connectivity Map were deployed to determine immune cell infiltration and predict potential drugs, respectively. A network of mRNA-miRNA-lncRNA was constructed and then validated by qRT-PCR. First, red blood cell count, neutrophil count, lymphocyte count, hypersensitive C-reactive protein, and procalcitonin were significantly elevated, while placental growth factor was hindered in PCOS women. We identified 308 DEmRNAs, 77 DEmiRNAs, and 332 DElncRNAs in PCOS samples. Functional enrichment analysis revealed that there were significant changes observed in terms of the immune system, especially the chemokine pathway. Eight genes, including FOS, JUN, EGR1, CXCL10, CXCR1, CXCR2, CXCL11, and CXCL8, were considered as hub genes. Furthermore, the degree of infiltration of neutrophils was dramatically decreased in PCOS tissues. In total, 57 ceRNA events were finally obtained, and immune-related ceRNA networks were validated. Some potential drug candidates, such as enalapril and RS-100329, could have a function in PCOS therapy. This study represents the inaugural attempt to evaluate the immune system at the end of pregnancy and placental ceRNA networks in PCOS, indicating alterations in the chemokine pathway, which may impact fetal and placental growth, and provides new therapy targets. [ABSTRACT FROM AUTHOR]

di-(2-Ethylhexyl) phthalate (DEHP) has potential reproductive toxicity. Bu-Shen-Tian-Jing formulations (BSTJFs) are beneficial for female reproductive capacity. However, BSTJF2 has much lower cytotoxicity than BSTJF1. To investigate the effects of BSTJFs on ovarian granulosa cells exposed to DEHP and determine the potential molecular mechanisms. Human granulosa-like tumor cell line (KGN) cells were divided into control, DEHP, BSTJF1 and BSTJF2 groups. The DEHP group were given 1 μM DEHP for 24 h. They were then given BSTJF1 at 200 μg/mL or BSTJF2 at 100 μg/mL for 24 h. The control group was treated with the same concentration of DMSO (0.1%). Oxidative stress and mitochondrial function were measured. The mRNA and protein expression levels of HDAC3 and HSP90AA were determined. Integrative network pharmacology analysis of BSTJF2 was also performed. DEHP (1 μM) significantly suppressed the proliferation of KGN cells by 17%, significantly increased ROS levels by 28% and MDA levels by 47%, significantly decreased MMP levels by 22% and mtDNA copy by 30%. DEHP significantly increased protein expression of HDAC3 by 21%and HSP90AA by 64%. All these changes were significantly reversed by BSTJFs. Integrative network pharmacology analysis revealed HSP90AA was a key target (degree = 8). Both RGFP966 and BSTJF2 significantly reversed the increased expression of HDAC3 and HSP90AA, attenuated oxidative stress, and mitochondrial damage which were induced by DEHP. BSTJFs might have therapeutic potential on oxidative stress and mitochondrial damage through the HDAC3/HSP90AA pathway which encourages further clinical trials. [ABSTRACT FROM AUTHOR]

Wet scrubber systems (WSSs) are commonly used for effective flue gas cleaning by removing acid gases and dust. To determine the influence of a WSS on polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and flue gas particles, a field study was carried out in a full-scale municipal solid waste (MSW) incinerator (850 t/d). Phase-separated samples at four flue gas sampling points and two scrubbing solution sampling points were collected for PCDD/F analysis. Two particle samples at the WSS inlet and outlet were simultaneously obtained for TEM-EDS analysis. The memory effect inside the WSS apparently elevated the PCDD/F I-TEQ concentration from 0.0056 to 0.0088 ng I-TEQ Nm−3 by increasing the mass concentrations of 17 congeners. A PCDD/F flux chart was established to interpret the adsorption/desorption mechanism of PCDD/Fs inside the WSS that showed apparent desorption from scrubbing solution. The potential interaction relationship between PCDD/F and flue gas particles were also observed, that was, the desorbed PCDD/Fs from scrubbing solution might be adsorbed by flue gas particles again and therefore enhanced the concentration of solid-phase PCDD/Fs from 0.0236 to 0.0411 ng Nm−3. Furthermore, TEM-EDS analysis indicated that the WSS could evidently remove some soluble particles and reduce the particle size. And the variation in morphology, elemental composition, and distribution of flue gas particles were observed during the scrubbing process. This study systematically analyzed the memory effect of PCDD/Fs and firstly investigated the specific impact of WSS on flue gas particles, thereby improving the comprehensive understanding of WSS applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: During pregnancy many women may experience negative emotions and sleep disturbances. This systematic review and meta‐analysis was conducted to assess the efficacy of cognitive behavioural therapy for insomnia (CBT‐I) or sleep disturbance in pregnant women. From the earliest available publications to 15 April 2022, seven electronic literature databases were searched: PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Database for Chinese Science and Technology Journal. Randomised controlled trials of CBT‐I in pregnant women with insomnia or sleep disorders were included. The methodological bias of the included studies was assessed using the Cochrane risk of bias tool. The meta‐analysis was performed using RevMan 5.4 software. Stata Statistical Software: Release 15 was used for sensitivity analysis and publication bias. We included eight randomised controlled trials involving 743 pregnant women. Meta‐analysis showed that, compared with the control group, CBT‐I significantly improved the Insomnia Severity Index (mean difference [MD] = −4.25, 95% confidence interval [CI, −6.32, −2.19], p < 0.001), The Pittsburgh Sleep Quality Index (MD = −3.30, 95% CI [−4.81, −1.79], p < 0.001), sleep onset latency (standardised mean difference [SMD] = −1.25, 95% CI [−2.01, −0.50], p = 0.001), anxiety (SMD = −0.99, 95% CI [−1.32, −0.67], p < 0.001), and depression (SMD = −0.40, 95% CI [−0.72, −0.07], p = 0.02). No significant differences were found in total sleep time (SMD = 0.31, 95% CI [−0.54, 1.17], p = 0.47) and sleep efficiency (SMD = 0.80, 95% CI [−0.53, 2.13], p = 0.24). CBT‐I significantly improved pregnant women's sleep quality, insomnia severity, depression, and anxiety. This meta‐analysis provides evidence that CBT‐I is valid for insomnia or sleep disturbances during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: As one of the most common endocrine disorders in women of reproductive age, polycystic ovary syndrome (PCOS) is highly heterogeneous with varied clinical features and diverse gestational complications among individuals. The patients with PCOS have 2-fold higher risk of preterm labor which is associated with substantial infant morbidity and mortality and great socioeconomic cost. The study was designated to identify molecular subtypes and the related hub genes to facilitate the susceptibility assessment of preterm labor in women with PCOS. Methods: Four mRNA datasets (GSE84958, GSE5090, GSE43264 and GSE98421) were obtained from Gene Expression Omnibus database. Twenty-eight candidate genes related to preterm labor or labor were yielded from the researches and our unpublished data. Then, we utilized unsupervised clustering to identify molecular subtypes in PCOS based on the expression of above candidate genes. Key modules were generated with weighted gene co-expression network analysis R package, and their hub genes were generated with CytoHubba. The probable biological function and mechanism were explored through Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. In addition, STRING and Cytoscape software were used to identify the protein-protein interaction (PPI) network, and the molecular complex detection (MCODE) was used to identify the hub genes. Then the overlapping hub genes were predicted. Results: Two molecular subtypes were found in women with PCOS based on the expression similarity of preterm labor or labor-related genes, in which two modules were highlighted. The key modules and PPI network have five overlapping five hub genes, two of which, GTF2F2 and MYO6 gene, were further confirmed by the comparison between clustering subgroups according to the expression of hub genes. Conclusions: Distinct PCOS molecular subtypes were identified with preterm labor or labor-related genes, which might uncover the potential mechanism underlying heterogeneity of clinical pregnancy complications in women with PCOS. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholestasis of pregnancy (ICP) is a common gestational complication characterized by pruritus and elevated bile acids, usually occurring in the third trimester when the serum estrogen and progesterone levels are highest. Hyperandrogenism during pregnancy is a pathological state that is mostly induced by polycystic ovary syndrome (PCOS) but rarely by concomitant androgen-secreting ovarian tumours. To date, no correlation has been drawn between ICP and hyperandrogenism.Case Presentation: Here, we present a rare case of early-onset severe ICP in a PCOS patient conceived via in vitro fertilization-embryo transfer, with worsening hirsutism and acne due to high levels of testosterone and dehydroepiandrosterone sulphate, both of which were produced by a fast-growing ovarian Sertoli-Leydig cell tumour. Her serum estradiol was also very high, which was speculated to be converted from the circulating androgens by the placenta. She had preterm premature rupture of membranes and delivered at 30 weeks, followed by a rapid remission of ICP as her serum estradiol dropped. However, the excessive androgens did not retreat until the large ovarian tumour was surgically removed.Conclusion: This unusual case highlights the concurrence of original hyperandrogenism and subsequent hyperestrogenism during pregnancy and the resultant confounding manifestations. Obstetricians should be aware of the potential association between androgen excess and ICP via placental aromatization. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the biological characterization of HIV type 1 (HIV-1) CRF07_BC infection among men who have sex with men (MSM). From November 2011 to November 2013, a total of 66 blood samples were collected from MSM with acute HIV-1 infection with CRF07_BC subgroup strains. Deletion in the gag p6 region was detected by sequence alignment and comparative analysis. Peripheral blood mononuclear cells (PBMCs) of HNXX1301–1307 samples were separated by density gradient centrifugation. Nested polymerase chain reaction (nPCR) was used to amplify the viral DNA. The near full-length HIV-1 DNA products were ligated to the long terminal repeat (LTR) vector plasmid (07BCLTR) to construct a full-length HIV clone. The molecular clone was transfected into HEK-293T cells, TZM-b1 cells and patients’ PBMCs. The pregenome of an infectious molecular clone of HIV-1 (pNL4-3) was amplified, and a subclone with CRF07_BC was developed to construct the full-length chimeric molecular clone pNL4-3/07BCLTR. Detection of p24 antigen and luciferase activity was used to measure the in vitro infectivity of pNL4-3/07BCLTR. Among the 66 MSM patients infected with CRF07_BC strains, deletion mutations of the Gag P6 proteins were found in 7 of 18CRF07_BC strains; deletion mutations of 2–13 amino acids in different regions were discovered in 6 strains; and the remaining 42 strains did not show deletions. Seven strains with amino acids deficiency in the P6 protein accounted for 27% of all strains and 75% of all deletion genotype strains. A total of 186 full-length molecular clones of CRF07_BC were constructed. There were 5, 9, 10 and 11 clones of HNXX1302, HNXX1304, HNXX1305 and HNXX1306 that resulted in p24-positive supernatant when transfected into HEK-293T cells. Full-length clones of HNXX1302, HNXX1304, HNXX1305 and HNXX1306 showed slight infection in the transfected TZM-b1 cells, as judged by the fluorescence values of TZM-b1 cells 48 h post-transfection. However, we were unable to transfect the patients’ PMBCs with the above four clones. The phylogenetic tree of the C2V3 segment of the Env gene showed that a significant gene cluster was formed by all of the chimeric full-length HNXX1306 clones, and the bootstrap value for this cluster was 97.5%. Patients’ PBMCs could be infected by 1306N6, 1306N13 and 1306N22 chimeric full-length clones. The CRF07_BC subtype (6889–7407 nucleotide residues of HXB2) is one of the most prevalent epidemic HIV-1 virus strains among the MSM population. The full-length chimeric molecular clone pNL4-3/07BCLTR may significantly improve the in vitro infectivity of the CRF07_BC strain. [ABSTRACT FROM AUTHOR]

Mitochondrial function and glucose metabolism play important roles in bidirectional signaling between granulosa cells (GCs) and oocytes. However, the factors associated with mitochondrial function and glucose metabolism of GCs in polycystic ovary syndrome (PCOS) are poorly understood, and their potential downstream effects on oocyte quality are still unknown. The aim of this study was to investigate whether there are alterations in mitochondrial-related functions and glucose metabolism in ovarian GCs of women with PCOS and the role of Sirtuin 3 (SIRT3) in this process. Here, we demonstrated that women with PCOS undergoing in vitro fertilization and embryo transfer had significantly lower rates of metaphase II oocytes, two-pronuclear fertilization, cleavage, and day 3 good-quality embryos. Germinal vesicle- and metaphase I-stage oocytes from women with PCOS exhibited increased mitochondrial reactive oxygen species (ROS), decreased mitochondrial membrane potential, and downregulation of glucose-6-phosphate dehydrogenase. GCs from women with PCOS presented significant alterations in mitochondrial morphology, amount, and localization, decreased membrane potential, reduced adenosine triphosphate (ATP) synthesis, increased mitochondrial ROS and oxidative stress, and insufficient oxidative phosphorylation (OXPHOS) together with decreased glycolysis. SIRT3 expression was significantly decreased in GCs of PCOS patients, and knockdown of SIRT3 in KGN cells could mimic the alterations in mitochondrial functions and glucose metabolism in PCOS GCs. SIRT3 knockdown changed the acetylation status of NDUFS1, which might induce altered mitochondrial OXPHOS, the generation of mitochondrial ROS, and eventually defects in the cellular insulin signaling pathway. These findings suggest that SIRT3 deficiency in GCs of PCOS patients may contribute to mitochondrial dysfunction, elevated oxidative stress, and defects in glucose metabolism, which potentially induce impaired oocytes in PCOS. [Display omitted] • Women with polycystic ovary syndrome have impaired oocyte quality. • Granulosa cells of polycystic ovary syndrome show altered mitochondrial functions. • Granulosa cells of polycystic ovary syndrome show defects in glycolysis. • Sirtuin 3 deficiency exists in granulosa cells of polycystic ovary syndrome. • Sirtuin 3 regulates acetylation status of NDUFS1 and insulin signaling pathway. [ABSTRACT FROM AUTHOR]

The genetic pathogenesis of selective intrauterine growth restriction (sIUGR) remains elusive, with evidence suggesting an important role of epigenetic factors such as microRNAs. In this study, we explored the relevance of miR-373-3p to the occurrence of sIUGR. Hypoxia enhanced the levels of miR-373-3p and hypoxia-inducible factor (HIF)-1α, while HIF-1α knockdown not only boosted the migration and proliferation of HTR8 cells but also suppressed the hypoxia-induced upregulation of miR-373-3p and SLC38A1. By contrast, HIF-1α overexpression induced miR-373-3p downregulation and SLC38A1 upregulation, reducing cell growth and migration, which could be reversed by a miR-373-3p inhibitor. Importantly, the miR-373-3p inhibitor and mimic reproduced phenomena similar to those induced by HIF-1α downregulation and overexpression, respectively (including altered SLC38A1 expression, mTOR activation, cell growth, and migration). Mechanistically, the miRNA regulated cell behaviors and related mTOR signaling by targeting SLC38A1 expression through an interaction with the 3 ′ -untranslated region of SLC38A1. The placental tissues of smaller sIUGR fetuses exhibited miR-373-3p and HIF-1α upregulation, SLC38A1 downregulation, and activated mTOR. Overall, miR-373-3p appears to restrict the growth and migration of HTR8 trophoblast cells by targeting SLC38A1, as observed in the placental tissues associated with smaller sIUGR fetuses, and it could have utility in the diagnosis and treatment of this disorder. [ABSTRACT FROM AUTHOR]

Objective: Endometriosis is a common benign disease in women of reproductive age. Qu's formula (QUF) is a patented Chinese herbal medicine for treating endometriosis that has been proven to be effective in treating and preventing the recurrence of endometriosis. This study is aimed to discover its molecular mechanism and to explore the potential drug targets. Methods: A QUF target and endometriosis-related gene set was identified by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases and five disease-gene databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, and a protein–protein interaction (PPI) network was established to discover the potential mechanism. MalaCards was searched for targets and signaling pathways related to endometriosis, and the search results were also used to identify the key factors in QUF. Molecular docking was performed to visualize the interactions between the effective molecules and proteins encoded by critical genes. Cell experiments and molecular dynamics (MD) simulations were used to further validate the therapeutic effects of the active compounds in QUF on endometriosis. Results: A compound-target network with 117 nodes (94 genes and 23 active compounds) and 224 edges was generated. The results of GO and KEGG analyses indicated that QUF could act by regulating the immune response, apoptosis and proliferation, oxidative stress, and angiogenesis. VEGFA, CXCL8, CCL2, IL1B and PTGS2 were selected for molecular docking analysis from two critical subnetworks with high correlation scores in MalaCards, and the active compounds of QUF had binding potential and high affinity for them. The mRNA expression levels of CCL2, IL1B and PTGS2 significantly decreased after treatment with quercetin. MD simulations showed that the combinations of quercetin and these proteins were relatively stable. Conclusion: The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism by which QUF protects against endometriosis. Our findings not only confirm the clinical effectiveness of QUF but also provide a foundation for further experimental study. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether maternal PCOS could impact growth and development in offspring at an early age through continuous observation from age 3 months to 6 years. Methods: This prospective study was conducted in 198 children born to mothers with PCOS and 227 children born to healthy mothers in Ningbo (Zhejiang Province, China) between October 2012 and July 2015. Measurements of offspring height, weight, head circumference, and teething were examined by trained professionals through age 6 years. Height, weight, and body mass index (BMI) were analysed using repeated measures analysis of variance between the PCOS and control groups. Results: Offspring born to women with PCOS showed significantly higher BMI at age 12, 18, and 30 months and 5 years (P = 0.040, P = 0.000, P = 0.000, and P = 0.023, respectively). Female offspring born to women with PCOS showed significantly increased body weight at 3, 8, 12, 18, and 30 months, and 3 and 6 years (P = 0.027, P = 0.008, P = 0.010, P = 0.034, P = 0.047, P = 0.040, and P = 0.035, respectively) and significantly higher BMI at 3, 8, 12, 18, and 30 months (P = 0.009, P = 0.016, P = 0.029, P = 0.000, and P = 0.000, respectively). After adjusting for maternal, paternal, and pregnancy confounders, PCOS status presented significant associations with weight at age 3, 8, and 12 months and 3 years (P = 0.005, P = 0.004, P = 0.021, P = 0.035 respectively), and with BMI at age 3 and 8 months (P = 0.011 and P = 0.014) in female offspring. Conclusions: Maternal PCOS is associated with an increased risk of developing obesity in female offspring. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS), as a common endocrine disease in reproductive-age women, which is characterized by both reproductive and metabolic disorders. Cang-Fu-Dao-Tan Formula (CFDTF) is an effective and relatively safe treatment for PCOS. However, the underlying mechanism is poorly understood. To explore the effective compounds and mechanisms of CFDTF in treating PCOS based on UPLC/Q-TOF-MS/MS, network pharmacology and molecular experiments. The UPLC/Q-TOF-MS/MS and TCMSP, SwissTargetPrediction databases were used to identify the active ingredients of CFDTF. Then GeneCards, Disgenet, Drugbank databases were used to obtain the PCOS related targets. Based above, the Drug-component-target (D-C-T) network and protein-protein-interaction (PPI) network were built to analysis the key targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed to find the potential mechanisms. Finally, molecular docking analysis, molecular dynamics (MD) simulations and molecular experiments were used to confirm the interactions among the active compounds, targets and explore the potential mechanisms. A total of 20 compounds were identified by UPLC/Q-TOF-MS/MS, and 136 active compounds by TCMSP from CFDTF. After removing the duplicate results, there were 370 targets related to both CFDTF and PCOS, among which, MAPK3, AKT1, RELA, EGF, TP53 and MYC were proved to have high interactions with the components. The mechanisms of CFDTF against PCOS were related to PI3K-Akt, mTOR, MAPK signaling pathways, and the in vitro experiments proved that the CFDTF positively regulated the cell proliferation and inhibited the apoptosis levels in PCOS cell model. The combination of UPLC/Q-TOF-MS/MS, systematic network pharmacology and molecular experiments identified that the quercetin, hesperidin, and glycyrrhizin disaccharide are the TOP 3 effective compounds of CFDTF in treating PCOS and the potential mechanisms may involve in regulating proliferation and apoptosis of granulosa cells. • Cang-Fu-Dao-Tan Formula (CFDTF) is an effective and relatively safe treatment for polycystic ovary syndrome (PCOS). • The quercetin, hesperidin, and glycyrrhizin disaccharide are the TOP 3 effective compounds of CFDTF in treating PCOS. • MAPK3, AKT1, RELA, EGF, TP53 and MYC were proved to have high interactions with the active components. • The potential mechanisms may involve in regulating proliferation and apoptosis of granulosa cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • An innovative manner was used in the co-pyrolysis for more CO 2 consumption. • CP CO2 evaluation was innovatively constructed and realized in the CO 2 -looping system. • More CO 2 entered into pyrolysis products by Ca-based additives for improving CP CO2. • CaO not only improved CP CO2 by 21.2% but also reduced the total HMs at 500 ℃. • Mechanism for CO 2 assisted Ca-based on CP CO2 with temperature was proposed. In this study, the CO 2 -looping system was firstly attempted to build for exploring the effect of calcium-based (Ca-based) additives on pyrolytic characteristics and products in co-pyrolysis of sewage sludge (SS) and biomass. Then, an innovation method for the consumption of CO 2 (CP CO2) evaluation was proposed and carried out in the CO 2 -looping system, in which it was evaluated based on the syngas volume and CO 2 proportion. The results revealed that the addition of CaO and Ca(OH) 2 could significantly improve CP CO2 by 21.2% in the co-pyrolysis of 500 ℃, while the CaCO 3 addition decreased the CP CO2 by 1.0%. Besides, the co-pyrolysis temperature more than 700 ℃ would play more significant role on the CP CO2 than the addition of Ca-based additives. Then the effect of Ca-based types on biochar characteristics was also identified accompanied by the bio-oil composition. Results showed that the CaO and Ca(OH) 2 additives not only increased biochar mass and pH, but also enhanced the dissolved organic carbon content and the variety of dissolved organic matter, and reduced the total HMs content. Meanwhile, it was 15 types of components that was identified in bio-oil by NIST mass spectral library, found that the intensity of heptadecanenitrile and estra-1,3,5(10)-trien-17 beta-ol was influenced by Ca-based additives. Moreover, the CaO and Ca(OH) 2 played important roles for improving the CP CO2 in the CO 2 -looping system, which was further verified by Fact Sage. Finally, the mechanism for the Ca-based additives on CP CO2 was proposed at different co-pyrolysis temperatures. These findings can widen paths for biochar application and development of CO 2 capture materials. [ABSTRACT FROM AUTHOR]

In the paper, an event triggering adaptive control method based on neural network (NN) is proposed for a class of uncertain nonlinear systems with external disturbances. In order to reduce the network resource utilization, a novel event-triggered condition by the Lyapunov approach is proposed. In addition, the NN controller and adaptive parameters determined by the Lyapunov stability method are updated only at triggered instants to reduce the amount of calculation. Only one NN is used as the controller in the entire system. The stability analysis results of the closed-loop system are obtained by the Lyapunov approach, which shows that all the signals in the systems with bounded disturbance are semi-globally bounded. Zeno behavior is avoided. Finally, the analytical design is confirmed by the simulation results on a two-link robotic manipulator. [ABSTRACT FROM AUTHOR]

Abstract: Twelve water channels (aquaporins) are expressed in mammalian reproductive systems, and play very important roles in maintaining water homeostasis in reproductive cells. Impairment of their functions can result in attenuated male and female fertility. Alteration of AQPs expression is also found in reproductive tissues of the patients with polycystic ovarian syndrome, endometriosis or endometrium carcinoma. A lot of data have increased understanding of the functions and mechanisms of regulation of aquaporins at both the molecular and the clinical level. Researches have also focused on aquaporins as therapeutic targets. This review discusses recent advances in uncovering the physiological and pathophysiological roles of aquaporins in the reproductive systems. [Copyright &y& Elsevier]

Background: Chinese herbal medicine (CHM) has significant effects that improve the reproductive functions of patients with polycystic ovary syndrome (PCOS). However, the intergenerational effects of CHM on offspring and the underlying mechanism of CHM remain unclear. This study aimed to explore the effects and the underlying mechanism of CHM, specifically the Bu-Shen-Tian-Jing formula (BSTJF), on model rats with polycystic ovary syndrome (PCOS) and the neurobehavioral alterations of female offspring born to PCOS rats administered BSTJF. Methods: High-performance liquid chromatography-mass spectrometry (HPLC–MS) and network pharmacology analysis were performed to identify the active ingredients and potential targets of BSTJF. Moreover, PCOS model rats were used to validate the role of BSTJF in reproduction and progeny neural development and to confirm the network pharmacological targets. Results: A total of 91 constituents were characterized from BSTJF. The 20 most significant KEGG pathways and the high-frequency genes of these pathways were predicted to be putative targets of these molecules. The rat experiment showed that the downregulation of FOS protein expression in the ovarian granulosa cells of the PCOS group was reversed by BSTJF. The target residence time of the 5-week-old female offspring of the BSTJF group was higher than that of the PCOS group in the water maze experiment. Compared to the PCOS group, the changes in dendritic spine density, ultrastructure of neurons and synapses, and Gabrb1 and Grin2b protein expression levels in the hippocampus of female offspring were partially reversed in the BSTJF group. Conclusions: BSTJF can effectively improve ovarian follicle development in PCOS rats and has positive effects on pubertal neurobehavioral alterations in the female offspring of these rats by reversing dendritic spine density, the ultrastructure of neurons and synapses, and the Gabrb1 and Grin2b protein expression levels in the hippocampus. [ABSTRACT FROM AUTHOR]

Background: Maternal polycystic ovary syndrome (PCOS) has potential detrimental effects on the neurodevelopment of offspring. This study aimed to evaluate the brain metrics in fetuses of women with PCOS based on fetal magnetic resonance imaging (MRI).Methods: This retrospective study included 60 pregnant women with PCOS (PCOS group) and 120 pregnant non-PCOS women (control group). Fetal MRI was performed followed an ultrasound and for numerous clinical indications including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member. Fetal brain biometry and apparent diffusion coefficient (ADC) value were analysed.Results: After adjusting for potential confounders, fetuses in the PCOS group showed the following characteristics compared to fetuses in the control group: (1) smaller cerebral fronto-occipital diameter (FOD), vermian height (VH) and anteroposterior diameter of the pons (APDP) (evident before 32 weeks; P = 0.042, P = 0.002 and P = 0.016, respectively); (2) larger left and right biparietal index (evident before 32 weeks; P = 0.048 and P = 0.025, respectively); (3) smaller left lateral ventricle (LV) (evident after 32 weeks; P = 0.005); (4) larger anteroposterior diameter of the vermis (APDV) and hippocampal infolding angle (HIA) (evident after 32 weeks; P = 0.003 and P < 0.001, respectively); (5) higher ADC value in frontal white matter (FWM) and in basal ganglia (BG) (evident before and after 32 weeks; all P < 0.05).Conclusions: There exist a different pattern of brain metrics in PCOS offspring in utero. [ABSTRACT FROM AUTHOR]

This paper describes the synthesis and ring-opening polymerization of a new functional dioxanone monomer 5-benzyloxymethyl-1,4-dioxan-2-one (BDON) in bulk using stannous octoate [Sn(Oct)2], aluminium isopropoxide [Al(OiPr)3] or aluminium isobutoxide [Al(OiBu)3] as an initiator. The influences of reaction conditions such as polymerization temperature, polymerization time, initiator and initiator concentration on the monomer conversion and molecular weight have been investigated. The protecting benzyl groups of poly(5-benzyloxymethyl-1,4-dioxan-2-one) (PBDON) were subsequently removed by catalytic hydrogenation to give poly(5-hydroxymethyl-1,4-dioxan-2-one) (PHDON) with pendant hydroxyl groups. The polymers obtained were characterized by FTIR, 1H NMR, 13C NMR, GPC and DSC. In vitro degradation rates of the three poly(dioxanone) PHDON, PBDON and PDON under different conditions were also investigated. On the other hand, several copolymers P(BDON-co-DON)s were also synthesized. Deprotection of the benzyl groups in the copolymers afforded the corresponding hydroxyl-containing P(HDON-co-DON)s. Bovine serum albumin (BSA), a model protein drug, was encapsulated with PDON, PBDON or P(HDON-co-DON) to form microparticles and release behavior of these microparticles were studied. [Copyright &y& Elsevier]

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine and metabolic disorder. Chinese herbal medicine has some advantages in the treatment of PCOS with its unique theoretical system and rich clinical practice experiences. The present study was to investigate the potential mechanisms of Bu-Shen-Jian-Pi Formula (BSJPF) on the treatment of PCOS. The combination of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS) rapid analysis, network pharmacology, molecular docking analysis and bio-experiments were firstly conducted to identify the main effective components of BSJPF, and to predict the potential mechanisms. The ovarian granulosa cell line (KGN) was treated with testosterone to construct the PCOS model in vitro, and the cells were further treated with the lyophilized powder of BSJPF. The levels of proliferation, autophagy and apoptosis were detected to explore the mechanisms of BSJPF on treating PCOS. Firstly, thirty-six active compounds were identified in BSJPF and thirty-one potential targets on PCOS were found. Then, PI3K and PDK1 were verified to have good binding activity with the active compounds through molecular docking analysis. In bio-experiments, BSJPF significantly alleviated the arrested proliferation of KGN cells in G0/G1 phase and reduced the active levels of autophagy and apoptosis of KGN cells induced by testosterone. Additionally, the inhibition of autophagy diminished apoptosis, while the repression apoptosis enhanced autophagy. Finally, BSJPF significantly decreased the FOXO1 expression levels induced by testosterone, especially for nuclear FOXO1, and significantly activated the PI3K/AKT pathway. BSJPF significantly alleviated the activated autophagy and apoptosis in KGN induced by testosterone through PI3K/AKT1/FOXO1pathway, which is an effective treatment for PCOS. [Display omitted] [ABSTRACT FROM AUTHOR]