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Research Question: What is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles?, Design: This retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used., Results: In the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17-2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03-3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles., Conclusions: A thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The widespread use of microplastics and their harmful effects on the environment have emerged as serious concerns. However, the effect of microplastics on the immune system of mammals, particularly their offspring, has received little attention. In this study, polystyrene microplastics (PS-MPs) were orally administered to male mice during lactation. Flow cytometry was used to assess the immune cells in the spleens of both adult male mice and their offspring. The results showed that mice exposed to PS-MPs exhibited an increase in spleen weight and an elevated number of B and regulatory T cells (Tregs), irrespective of dosage. Furthermore, the F 1 male offspring of the PS-MPs-exposed group had enlarged spleens; an increased number of B cells, T helper cells (Th cells), and Tregs; and an elevated ratio of T helper cells 17 (Th17 cells) to Tregs and T helper cells 1 (Th1 cells) to T helper cells 2 (Th2 cells). These results suggested a pro-inflammatory state in the spleen. In contrast, in the F 1 female offspring exposed to PS-MPs, the changes in splenic immune cells were less pronounced. In the F 2 generation of mice with exposed to PS-MPs, minimal alterations were observed in spleen immune cells and morphology. In conclusion, our study demonstrated that exposure to real human doses of PS-MPs during lactation in male mice altered the immune status, which can be passed on to F 1 offspring but is not inherited across generations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microplastics (MPs) pollution poses a global environmental challenge with significant concerns regarding its potential impact on human health. Toxicological investigations have revealed multi-system impairments caused by MPs in various organisms. However, the specific reproductive hazards in human contexts remain elusive, and understanding the transgenerational reproductive toxicity of MPs remains limited. This study delves into the reproductive toxicity resulting from lactational exposure to polystyrene MPs (PS-MPs) in female mice, extending the inquiry to assess the reproductive effects on their offspring bred by rigorous natural mating. The MPs dosage corresponds to the detected concentration in infant formula prepared using plastic bottles. By systematically evaluating the reproductive phenotypes of F0 female mice from birth to adulthood, we found that female mice exposed to PS-MPs exhibited delayed puberty, disturbed estrous cyclicity, diminished fertility, elevated testosterone, abnormal follicle development, disrupted ovarian steroidogenesis, and ovarian inflammation. Importantly, the observed inheritable reproductive toxicity manifested with gender specificity, showcasing more pronounced abnormalities in male offspring. Specifically, reproductive disorders did not manifest in female offspring; however, a significant decrease in sperm count and viability was observed in PS-MPs-exposed F1 males. Testicular transcriptomics analysis of F1 males significantly enriched pathways associated with reproductive system development and epigenetic modification, such as male germ cell proliferation, DNA methylation, and histone modification. In summary, real-life exposure to PS-MPs impaired the reproductive function of female mice and threateningly disrupted the spermatogenesis of their F1 male offspring, which raises serious concerns about inter- and trans-generational reproductive toxicities of MPs in mammals. These findings underscore the potential threats of MPs to human reproductive health, emphasizing the need for continued vigilance and research in this critical area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Four new drimane-type sesquiterpenoids and two new nucleoside derivatives (1-6), were isolated from the fungus Helicoma septoconstrictum. Their structures were determined based on the combination of the analysis of their HR-ESI-MS, NMR, ECD calculations data and acid hydrolysis. All the isolated compounds were detected for their bio-activities against MDA-MB-231, A549/DDP, A2780 and HepG2 cell lines. Helicoside C (4) exhibited superior cytotoxicity against the A2780 cell line with IC 50 7.5 ± 1.5 µM. The analysis of reactive oxygen species (ROS) revealed that Helicoside C induced an increase in intracellular ROS. Furthermore, the flow cytometry and mitochondrial membrane potential (MMP) analyses unveiled that Helicoside C mediated mitochondrial-dependent apoptosis in A2780 cells. The western blotting test showed that Helicoside C could suppress the STAT3's phosphorylation. These findings offered crucial support for development of H. septoconstrictum and highlighted the potential application of drimane-type sesquiterpenoids in pharmaceuticals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest None.

Research Question: What are the different characteristics of vaginal microbial composition between patients with endometrial polypoid lesions and controls?, Design: This cohort study compared the pre-operative microbial compositions of vaginal samples in a cohort of 703 women with endometrial polypoid lesions [293 and 410 women diagnosed and not diagnosed with polyps pathologically (polyps group and not-polyps group, respectively] and 703 women in the control group. Bacterial abundance, diversity, differential taxa and microbial network structure were assessed using 16S rRNA gene sequencing. Predictive algorithms were used to determine the functional pathways of vaginal microbiota within the cohort., Results: The control group exhibited higher relative abundance of Lactobacillus crispatus in comparison with the polypoid lesions group (P = 0.0427). Beta diversity of vaginal microbiota differed significantly between the groups (P < 0.05). Comparing the polyps group with the not-polyps group, Leptotrichia spp. and Cutibacterium spp. were more abundant in the polyps group, and Fannyhessea spp., Acinetobacter spp. and Achromobacter spp. were more abundant in the not-polyps group. The control group exhibited higher abundance of Bifidobacterium spp., Achromobacter spp. and Escherichia/Shigella spp. (false discovery rate < 0.05). Furthermore, the polyps group and not-polyps group displayed more complex co-occurrence networks compared with the control group., Conclusions: The results of this study provide compelling evidence supporting associations between vaginal microbiota and endometrial polypoid lesions, highlighting the potential relationship between a well-balanced vaginal microbial ecosystem and a healthy intrauterine environment., (Copyright © 2023. Published by Elsevier Ltd.)

Background: A possible role of PM 2.5 components on ovarian reserve has not been adequately unexplored., Objective: To evaluate the association between PM 2.5 components and women' ovarian reserve over critical exposure periods in northern China, where the level of air pollution is among the nation's highest., Methods: We included 15,102 women with serum anti-Müllerian hormone (AMH) measurements from the Center for Reproductive Medicine of Shandong University during 2015-2019. Concentrations of PM 2.5 and its five major components (0.1° × 0.1°), including sulfate, nitrate, ammonium, organic matter, and black carbon, were assigned to each residential address. Multivariable linear mixed effect models combined with constituent-residual models were performed to estimate the effect sizes of essential components over six short- to long-term exposure periods., Results: The strength of association was stronger during the process from primary to small antral follicle compared with other longer windows. For every interquartile range increase in PM 2.5 mass was associated with - 8.7% (95%CI: -12.3%, -4.9%) change in AMH and the effect size was greatest for sulfate. Women with the lower level of attained education and those living inland were more susceptible compared with other population subgroups., Conclusion: Exposure to specific components of air pollution during critical exposure windows is associated with a decline in ovarian reserve. These data add to the growing body of evidence that environmental factors have adverse effects on reproductive health, particularly for vulnerable population subgroups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Elucidating the effect of fertigation on soil hydraulic parameters and water-solute transportation is fundamental to the design of farmland irrigation systems and their sustainable utilization. Few studies have focused on soil hydraulic parameters or water infiltration characteristics or how they are influenced by urea solution concentration. In this study, the clay loam and sandy loam in Yangling District of Shaanxi Province, China, were used as test soil, and experiments involving seven urea solution concentrations (0.2, 0.4, 0.6, 0.8, 1, 3, and 5 g/L) and a control treatment (0 g/L) were conducted to explore the influence of the various urea solution concentrations on soil hydraulic parameters and water infiltration characteristics. The results indicated that the cumulative infiltration and wetting front migration depth increased with urea solution concentration, as accurately estimated using the Kostiakov model and a power function, respectively. In addition, the coefficients of the Kostiakov model and the power function increased with urea solution concentration. Treatment with multiple concentrations of urea solution resulted in an increase in the volume of macro pores in the soil but a reduction in the volume of mesopores and micro pores in the soil, leading to increases in the saturated water content, saturated hydraulic conductivity, soil water diffusivity, and infiltration capacity and a reduction in the water-holding capacity of the soil. The effect of urea solute potential on the inhibition of soil water movement is small, and this inhibitory effect is far weaker than the improvement effect of the urea solution on soil structure, and hence enhance the soil water infiltration capacity. Our results increase the understanding of soil hydrological mechanisms and may be usefully applied for improving the management of fertigation., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Research Question: Do infertile women with positive tuberculin skin test (TST) results have a higher risk of adverse pregnancy outcomes after IVF or intracytoplasmic sperm injection and embryo transfer (ICSI-ET) and does preventive anti-tuberculosis treatment applied to infertile women with positive TST results before IVF/ICSI-ET affect pregnancy and neonatal outcomes?, Design: This was a retrospective cohort analysis of 6283 infertile women who underwent IVF/ICSI-ET treatment for the first time at the Reproductive Hospital affiliated to Shandong University from November 2016 to September 2022. None of the participants had prior tuberculosis or active tuberculosis. According to their TST results, 5947 patients who had never received preventive anti-tuberculosis treatment were divided into a TST-positive group (1704 cases) and a TST-negative group (4243 cases). A total of 504 patients with TST (+++) results (using the 20 mm sclerosis threshold) were divided into a treated TST (+++) group (336 cases) and an untreated TST (+++) group (168 cases) according to whether they received preventive anti-tuberculosis treatment before IVF/ICSI-ET. The outcome measures were pregnancy outcomes and neonatal outcomes., Results: There were no significant differences in pregnancy or neonatal outcomes between the TST-positive group and the TST-negative group (P > 0.05). In the TST (+++) group, there were no significant differences in pregnancy or neonatal outcomes between the treated TST (+++) group and the untreated TST (+++) group (P > 0.05)., Conclusions: For infertile women undergoing IVF/ICSI-ET without prior tuberculosis or active tuberculosis, positive TST results and preventive anti-tuberculosis treatments prior to IVF/ICSI-ET do not affect pregnancy or neonatal outcomes., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Previously, studies of coastal eutrophication have usually focused on the nutrients input from adjacent land sectors, such as rivers, submarine-ground discharges, and atmospheric depositions. Here we report two examples of well-managed seasonal eutrophication phenomena in coastal marine environments, where nutrients come predominantly from offshore: one by humans and the other by nature (higher trophic animals). In the Sanggou Bay of North China, the total amount of incoming nutrients from the open Yellow Sea is taken up by seaweeds. Seaweed, in turn, supports bivalves culture activities and absorbs nutrients emitted by finfish. In the Academy Bay of Russian Far East, a relatively high plankton primary production sustains throughout the salmon-returning season when nutrients are released from the massive carcasses of dead fish after return from the ocean to their natal streams to spawn and die. This high plankton productivity, in turn, fuels higher trophic ecosystem constituents, including whale populations of global importance. In the future, dominance of nutrients from marine sources needs to be seriously considered in studies of coastal eutrophication., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of research interests in this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: To address the situation that the accuracy of concentration intervals (CI) corresponding to dipstick grades is not given by the manufacturers or literature, we developed a method that determined reasonable dipstick grades with concentration intervals (GCIs) based on the percent agreement (PA) and discussed the GCI application to comparability among currently dipstick tests., Methods: By comparing the results of 2 dipstick tests (iChem and KU-500) with the quantitative test (AU5800), the GCIs were verified and established based on the PAs, which were calculated and used as an indicator of GCI's accuracy. The overlap (percent) between the 2 GCIs with the same grade (2 dipstick devices), was calculated and used to evaluate the agreement between their test results., Results: After verification and adjustment, the GCI and PA combinations for iChem Velocity were as follows: - (<0.1 g/l, 85 %), ± (0.1-0.3 g/l, 66 %), 1+ (0.3-1 g/l, 78 %), 2+ (1-3 g/l, 74 %), 3+ (3-6 g/l, 77 %), and 4+ (≥6 g/l, 84 %). The determined GCI and PA combinations for KU-500 were: - (<0.1.2 g/l, 75 %), ± (0.12-0.5 g/l, 63 %), 1+ (0.5-1.2 g/l, 69 %), 2+ (1.2-3.2 g/l, 76 %), and 3+ (≥3.2 g/l, 82 %). The GCI overlaps between the 2 dipstick devices were - (83 %), ± (45 %), 1+ (56 %), 2+ (82 %), and 3+ or ≥3+ (94 %). The overall overlap was 72 %. Since the overlaps ± (45 %) and 1+ (56 %) were within the overlap reject limit for any grade (70 %), and the overall overlap (72 %) was within the overall overlap reject limit (80 %), the test results of the 2 devices were not comparable., Conclusions: GCIs can be verified and established correctly based on PAs, and industry standards for dipstick tests can be established based on GCIs and PAs. Comparability between dipstick devices, historical data, and literature data can be roughly determined based on the overlap., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This retrospective study aimed to evaluate the safety and efficacy of cutting balloon angioplasty and conventional balloon angioplasty in supra-aortic arterial lesions caused by Takayasu arteritis., Methods: A total of 46 patients with supra-aortic arterial lesions between January 2011 and December 2018 were included. Cutting balloon angioplasty was applied for 17 patients with 24 supra-aortic arterial lesions (group A), while 29 patients with 36 supra-aortic arterial lesions received conventional balloon angioplasty (group B). The preoperative clinical manifestation, operation result, and postoperative outcomes were recorded and compared in the 2 groups., Results: Dizziness, visual disturbance, and unequal/absent pulses were the most common manifestations. The technical success of revascularization was 93.5% (43/46) in patients and 93.3% (56/60) in lesions. The stent implantation rate in group A was significantly lower than that in group B (4.2% vs. 50% in lesions, P < 0.05). Restenosis was the most common complication in both groups. Although the early (≤30 days) and late (>30 days) complications in group A were less than those in group B, there was no significant difference between the 2 groups (P > 0.05). Moreover, the primary-assisted patency of cutting balloon angioplasty and conventional balloon angioplasty at 1, 2, and 5 years were 66.7%, 62.5%, and 62.5% and 61.1%, 58.2%, and 49.8%, there was no significant difference between the 2 groups (P > 0.05), respectively., Conclusions: Compared with conventional balloon angioplasty, cutting balloon angioplasty could be considered a safe and effective alternative for supra-aortic arterial lesions caused by Takayasu arteritis, demonstrating better patency and clinical benefit., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Immune dysregulation has long been proposed to be associated with adenomyosis, but the underlying mediators and mechanisms remain largely unexplored. Here, we used flow cytometry to investigate the alterations in immune cell subsets in adenomyotic uteri and analyze the phenotype and function of abnormal immune cells. We found that an increase in cluster of differentiation (CD)8 + T-cell number was the predominant alteration in ectopic lesions in patients with adenomyosis and was significantly associated with the severity of adenomyosis. Importantly, we identified an exhausted natural killer group protein 2A (NKG2A) + CD8 + T-cell subset that was associated with the severity of adenomyosis and found that the number of these cells was significantly increased in the eutopic endometrium and ectopic lesions. In addition, the increases in the expression of NKG2A ligand histocompatibility leucocyte antigen E and interleukin-15 in glandular epithelial cells in the adenomyotic microenvironment might contribute to CD8 + T-cell exhaustion by promoting NKG2A expression on CD8 + T cells or inhibiting the effector function of these cells. In conclusion, our data revealed a previously unrecognized role for NKG2A + CD8 + T-cell exhaustion in the pathogenesis of adenomyosis, indicating that therapeutic interventions designed to target and reinvigorate exhausted CD8 + T cells may be beneficial for patients with adenomyosis., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

A robust output feedback nonlinear control method is proposed for output tracking of an uncertain three-tank system by using only the level sensor of the target tank. By using a coordinate transformation, we first transform the system model into a canonical form with uncertainties. The canonical system's state variables are estimated by a higher-order sliding mode differentiator based on the measurement of the target tank's liquid level. Then based on the estimated state variables, a continuous full-order sliding mode controller is constructed which can eliminate the effects of both the additive and multiplicative uncertainties. Rigorous analysis is carried out to clarify the control performance. And the effectiveness of the proposed method is verified by experimental studies on the Inteco Multi-tank system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. Published by Elsevier Ltd. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail., Data Sources: The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using "minimally invasive" and "hepatocellular carcinoma" or "liver cancer" as the keywords., Results: Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC., Conclusions: A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis., (Copyright © 2022 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: Lack of evidence exists on whether air pollution exposure may affect ovarian reserve, especially for Chinese women., Objectives: To explore the association between exposure to various air pollutants and anti-Müllerian hormone (AMH), a predictor of ovarian reserve, over different exposure windows in Shandong Province, China., Methods: We enrolled 18,878 women who had AMH measurements in the Center for Reproductive Medicine, Shandong University during 2010-2019. Daily average concentrations of ambient particulate matter with diameters ≤1 μm/2.5 μm/10 μm (PM 1 , PM 2.5 , and PM 10 ), nitrogen dioxide (NO 2 ) and ozone (O 3 ) were developed at a spatial resolution of 0.01° × 0.01°, and assigned to the residential addresses. Three exposure windows were considered, i.e., the process from primary to small antral follicle stage (W1), from primary to secondary follicle stage (W2), and from secondary to small antral follicle stage (W3). The air pollution-AMH association was fitted using the multivariable linear mixed effect model with adjustment for potential confounders. Stratified analyses were performed by age group, overweight status, residential region, and educational level., Results: The level of AMH changed by -8.8% (95% confidence interval (CI): -12.1%, -5.3%), -2.1% (95% CI: -3.5%, -0.6%), -1.9% (95% CI: -3.3%, -0.5%), and -4.5% (95% CI: -7.1%, -1.9%) per 10 μg/m 3 increase in PM 1 , PM 2.5 , PM 10 , and NO 2 , respectively, during W1. The effect estimates were significant during W2 for PM 1 , PM 2.5 and NO 2 while minimal association was observed in W3. Greater vulnerability for certain air pollutants were observed for women who lived in inland areas and were less educated., Conclusions: We found that ovarian reserve was negatively associated with air pollution exposure for women, particularly from the primary to secondary follicle stage. The effect estimate increased by the reduction in the diameter of PMs, which also varied across population sub-groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Research Question: Adenomyosis is a common uterine disorder of uncertain causes. Can transcriptomic analyses of the endometrium and myometrium reveal potential mechanisms underlying adenomyosis pathogenesis?, Design: Transcriptomic profiles of eutopic endometrium and myometrium from women with and without diffuse adenomyosis and with symptomatic FIGO type 2-5 fibroids in the proliferative phase of the menstrual cycle were assessed using RNA sequencing and bioinformatic analysis. Differentially expressed genes (DEG) and potential pathways were validated by quantitative reverse transcription polymerase chain reaction, immunoblotting and Masson staining, using additional clinical samples., Results: Top biological processes in the endometrium of women with versus without adenomyosis, enriched from DEG, comprised inflammation, extracellular matrix (ECM) organization, collagen degradation and hyaluronan synthesis, which are key in cell migration and cell movement. Top biological processes enriched from DEG in the myometrium of women with versus without adenomyosis revealed ECM organization dysfunction, abnormal sensory pain perception and gamma aminobutyric acid (GABA) synaptic transmission. Dysregulation of prolactin signalling was also enriched in eutopic endometrium and in the myometrium of women with adenomyosis., Conclusions: Overall, our results support the invasive endometrium theory in the pathogenesis of adenomyosis, in which inflammation induces ECM remodelling resulting in a track for subsequent endometrial collective cell migration and onset of adenomyosis. Moreover, abnormal myometrial GABA synaptic transmission may contribute to dysmenorrhoea in women with adenomyosis and is a possible target for novel therapeutic development. Prolactin signalling abnormalities may serve as another opportunity for therapeutic intervention., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A series of dihydrotriazine derivatives bearing 5-aryloxypyrazole moieties were designed, and their anticancer activities against three human cancer cell lines (SGC-7901, HepG-2 and MCF-7) and one non-cancer cell line (LO2) were explored using the MTT assay in vitro. Most of the compounds exhibited potent antiproliferative activities against the three cancer cell lines, with compound 10e (IC 50  = 2.12 µM) exhibiting the most potent antiproliferative activity against HepG-2 cells. Interestingly, autophagy was observed in the 10e-treated HepG-2 cells. Compound 10e also increased reactive oxygen species (ROS) levels and resulted in marked HepG-2 cells apoptosis. Further studies revealed that compound 10e could enhance the expression of Cl-PARP, Cl-caspase-3, and Cl-caspase-9. In addition, 10e triggered the formation of autophagosomes by promoting LC3-II and Beclin-1 expression. These results might be useful for exploring and developing dihydrotriazine derivatives as novel anticancer agents., (Copyright © 2022. Published by Elsevier Inc.)

Lipids play vital roles in many physiological and pathological processes in living organisms. Due to the high structural diversity and the numerous isomers and isobars of lipids, high-coverage and high-accuracy lipidomic analysis of complex biological samples remain the bottleneck to investigate lipid metabolism. Here, we developed the trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) based four-dimensional untargeted lipidomics to support accurate lipid identification and quantification in biological samples. We first demonstrated that the TIMS based multi-dimensional separation improved the differentiations of isomeric and isobaric lipids, and increased the purity of precursor ion isolation and the quality of MS/MS spectra. Hyphenation of TIMS and PASEF technologies significantly improved the coverages of MS/MS spectra. These technological advantages jointly improved the coverage and accuracy of lipid identification in untargeted lipidomics. We further demonstrated that the CCS values of lipids acquired using TIMS were highly consistent with those from drift tube ion mobility spectrometry (DTIMS). Lipid identification and quantification results of NIST human plasma samples were also verified with inter-laboratory reports. Finally, we applied the TIMS-MS based untargeted lipidomics to characterize the spatial distributions of 1393 distinctive lipids in the mouse brain, and demonstrated that diverse lipid distributions and compositions among brain regions contributed to different functions of brain regions. Altogether, TIMS-MS based four-dimensional untargeted lipidomics significantly improved the coverage and accuracy of untargeted metabolomics, thereby facilitating a system-level understanding of lipid metabolism in biological organisms., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment., Methods: In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72., Results: A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P > 0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P < 0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/m 2 (Asian criteria) [odds ratio (OR): 0.414; 95% confidence interval (95% CI): 0.190-0.899; P = 0.012] and weight gain (OR: 0.187; 95% CI: 0.050-0.693; P = 0.026) were less likely to have NASH resolution. Among patients without NASH at baseline, 22 (3.7%) developed NASH. Baseline BMI ≥ 23 kg/m 2 (OR: 12.506; 95% CI: 2.813-55.606; P = 0.001) and weight gain (OR: 5.126; 95% CI: 1.674-15.694; P = 0.005) were predictors of incident NASH., Conclusions: Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021. Published by Elsevier B.V.)

Sterols are an important type of lipids, and play many important roles in physiological and pathological processes. However, comprehensive analysis of sterols especially identification of unknown sterols is challenging. In this work, LC-MS with all ion fragmentation (AIF) technology was developed for untargeted analysis of sterols in biological samples. AIF technology provided holistic and multi-dimensional characterization for both knowns and unknowns sterols, including accurate m/z, isotope pattern, retention time (RT), and co-eluted peak profiles between MS1 and MS2 ions in one analysis. We further developed an analysis strategy by integrating the multi-dimensional properties to support unambiguous identification of sterols, including distinguishing sterol isomers. The developed strategy enabled to identify a total of 23 sterols in mouse samples, and quantified 19 sterols in mouse liver tissues. More importantly, we demonstrated that AIF based multi-dimensional analysis provided a possibility to identify sterols without chemical standards and facilitated to discover novel compounds with sterol-like structures in biological samples. In summary, we employed the LC-MS based AIF technology to develop multi-dimensional characterization and identification of both known and unknown sterols in complex biological samples. The comprehensive analysis of sterols facilitates to provide molecular insights to many physiological and pathological activities in biology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Single component molecular dyad donor-acceptor junction is an important type of organic solar cells. Understanding the optoelectronic properties of molecular dyad plays the critical role to develop active layer materials for such kind of solar cells. Here, diathiafulvalene-functionalized diketopyrrolopyrrole-fullerene (DFDPP-Ful) was selected as the representative system, and the geometries, electronic structures and excitation properties of DFDPP-Ful monomer and dimer were systematically investigated based on extensive quantum chemistry calculations. The transition configurations and molecular orbitals show that the effective electron donor and acceptor are DFDPP and fullerene moieties, respectively. It also found the light harvesting is dominated by local excitation in DFDPP moiety. Meanwhile, the hybridization and quasi-degeneration between charge transfer (CT) and local excitation exist. The dimer data suggest that the increased excited states contribute to the expanding of absorption spectra, and the excitations exhibit both the intermolecular and intra-molecular CTs. Also, the remarkable CT energy differences among the different dimer models for the lowest CT excited states support the strong interface and energy disorder in such system. Therefore, the suggestions for developing molecular dyad of single component organic solar cells would be the combination of increasing light absorption, enhancing CT and local excitation hybridization, as well as suppressing energy and interface disorder by the aid of molecular design., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lipids are an important class of biomolecules, and play many essential functions in biology. Ion mobility-mass spectrometry (IM-MS) has emerged as a promising technology for lipidomics by providing a holistic and multi-dimensional characterization of lipid structures. However, the lipid identification using the multi-dimensional match (i.e., MS1, retention time, collision cross section, and MS/MS spectra) gives multiple lipid candidates, and often over-reports the structural information. Here, we developed a lipid identification strategy that integrated library-based match and rule-based refinement for accurate lipid structural elucidation in IM-MS based lipidomics. The new strategy took the advantage of multi-dimensional information for high-coverage identification, while it also utilized the fragmentation rules to determine the accurate structural information. We demonstrated that the combined strategy accurately determined the lipid structures as lipid species level, fatty acyl level, or fatty acyl position level for different lipid classes in the lipid standard mixture and various biological samples. The combined strategy efficiently reduced the redundancy and improved the accuracy for different lipid classes, and identified a total of 440-960 lipid species in various biological samples. Finally, we performed quantitative lipidomics analysis of NIST SRM 1950 human plasma using IM-MS technology. The measured concentrations of most quantified lipids (>80%) were highly consistent with values reported from other independent laboratories. In summary, the developed lipid identification strategy allowed for the accurate identification of lipid structures, and facilitated accurate lipid quantification in IM-MS based untargeted lipidomics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Research Question: Is there a difference in live birth rate between a freeze-only strategy and fresh embryo transfer, and what is the effect of varying progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration?, Design: A secondary analysis of data from three randomized trials comparing the live birth rate after elective frozen versus fresh embryo transfer, which respectively enrolled 1508 women with polycystic ovary syndrome, 2157 ovulatory women who underwent cleavage-stage embryo transfer and 1650 ovulatory women who underwent single blastocyst transfer. Women were randomly assigned to the frozen or fresh embryo transfer group in the original trials. The primary outcome was live birth rate after the initial embryo transfer., Results: The live birth rate after a freeze-only strategy was consistently higher than fresh embryo transfer at any progesterone concentration on the day of HCG administration. Nonetheless, the between-group difference in live birth rate after frozen versus fresh embryo transfer was greater in women with progesterone concentrations ≥1.14 ng/ml (52.7% versus 37.3%, odds ratio (OR) 1.88, 95% confidence interval (CI) 1.55-2.27, P = 7.89  ×  10 -11 ) than in women with progesterone concentrations <1.14 ng/ml (53.3% versus 48.1%, OR 1.23, 95% CI 1.08-1.41, P = 0.002). In women with progesterone concentration ≥1.14 ng/ml, frozen embryo transfer also resulted in higher rates of conception and clinical pregnancy than fresh embryo transfer., Conclusion: In women with normal or high ovarian response, a freeze-only strategy resulted in a higher live birth rate than fresh embryo transfer, irrespective of progesterone concentration. Moreover, women with progesterone concentration ≥1.14 ng/ml may benefit more from a freeze-only strategy., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Feed-water valves are widely used in nuclear power plants to regulate the flow rate of the water supplying to steam generators, and thus holding the water level in steam generators at desired values. The flow rate characteristics of feed-water valves have important effects on the management quality of the water level in steam generators and therefore influence the safety and the efficiency of nuclear power plants. In this paper, the effects of throttling window shapes on the flow rate characteristics through feed-water valves are investigated in two aspects, the overall performances and the fluid dynamics. First of all, a dimensionless parameter defining throttling window shapes is proposed for the quantitative assessment. Then, for the analysis of overall performances, the rated flow coefficient, the loss coefficient, and the inherent valve characteristics are investigated. A revised fitting function is obtained to predict the inherent valve characteristics with different throttling window shapes for engineering applications. Finally, for the observation of the fluid dynamics, the velocity characteristics and the pressure characteristics are both discussed. The wear conditions are predicted at different relative travels and throttling window shapes. This paper provides a reference for researchers dealing with the design work of feed-water valves and is beneficial for the improvement of the whole water level control system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 ISA. Published by Elsevier Ltd. All rights reserved.)

Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. The study aimed to investigate the effects and molecular mechanism of miR-139-5p/SLC7A11 on the proliferation and metastasis of PANC., Methods: Bioinformatics was used to analyze the differentially expressed genes in the TCGA database. PANC cell lines with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and have been used to detect cell proliferation, invasion and metastasis of PANC Subsequently, bioinformatic analysis and dual luciferase reporter assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mice model was used to explore the functions of miR-139-5p in PANC tumorigenicity., Results: MiR-139-5p could regulate and affect the protein expression of P13K and Akt associated with phosphatidylinositol signaling pathway by inhibiting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, invasion and metastasis could be inhibited by miR-139-5p overexpression and be promoted by SLC7A11 overexpression. MiR-139-5p overexpression could suppress PANC tumor growth and the expressions of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibitory of miR-139-5p to PANC cell proliferation, invasion and metastasis was partly due to its inhibiting effect on SLC7A11 expression., Conclusion: Our study proves that miR-139-5p/SLC7A11 has important functions on PANC, suggesting that miR-139-5p can be used as a biomarker for PANC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The mechanisms underlying metabolic and reproductive dysfunction caused by arrhythmic circadian clock and their involvement in polycystic ovary syndrome (PCOS) are not understood. Here, we addressed this issue using rats with constant light or darkness exposure for 8 weeks and human leukocytes and serum of PCOS and non-PCOS patients. Additionally, we utilized HepG2 cells and KGN cells to verify the molecular mechanisms. The arrhythmic expressions of circadian clock genes due to constant darkness induced the metabolic and reproductive hallmarks of PCOS in rats. After exposure to constant darkness, decreased brain and muscle ARNT-like protein 1 (BMAL1) promoted insulin resistance via glucose transporter 4 (GLUT4), and decreased period (PER) 1 and PER2 promoted androgen excess via insulin-like growth factor-binding protein 4 (IGFBP4) and sex hormone binding globulin (SHBG) in the liver. Hyperinsulinemia and hyperandrogenism shared a bidirectional link promoting aberrant expression of circadian genes and inducing apoptosis of ovarian granulosa cells. Notably, the altered expressions of circadian clock genes in darkness-treated rats matched those of PCOS patients. Furthermore, melatonin treatment relieved the hyperinsulinemia and hyperandrogenism of darkness-treated rats via BMAL1, PER1, and PER2. Restoring normal light/dark exposure for 2 weeks reversed these conditions via BMAL1. In conclusion, our findings elucidated the critical function of circadian clock genes, especially BMAL1, PER1, and PER2 in PCOS, which might aid the development of feasible preventive and therapeutic strategies for PCOS in women with biorhythm disorder., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Increasing evidence indicates a close relationship between HCC and the human microbiota. Herein, we reviewed the important potential of the human microbiota as a diagnostic biomarker of HCC., Data Sources: Several innovative studies have investigated the characteristics of the gut and oral microbiomes in patients with HCC and proposed that the human microbiome has the potential to be a diagnostic biomarker of HCC. Literature from February 1999 to February 2019 was searched in the PubMed database using the keywords "microbiota" or "microbiome" or "microbe" and "liver cancer" or "hepatocellular carcinoma", and the results of clinical and experimental studies were analyzed., Results: Specific changes occur in the human microbiome of patients with HCC. Moreover, the gut microbiome and oral microbiome can be used as non-invasive diagnostic biomarkers for HCC. Furthermore, they also have certain diagnostic potential for precancerous diseases of HCC. The diagnostic potential of the blood microbiota and ascites microbiota in HCC will be gradually discovered in the future., Conclusions: The human microbiome is valuable to the diagnosis of HCC and provides a novel strategy for targeted therapy of HCC. The human microbiome may be widely used in the diagnosis, treatment and prognosis for multiple system diseases or cancers in the future., (Copyright © 2020. Published by Elsevier B.V.)

Objective: With a high incidence of insulin resistance, central obesity and dyslipidemia, women with polycystic ovary syndrome are susceptible to metabolic syndrome (MetS). Our objective was to explore whether metabolic syndrome had an effect on overall female fertility and in vitro fertilization outcomes in infertile women with polycystic ovary syndrome., Study Design: This was a secondary analysis of a multicenter randomized trial in 1508 women with polycystic ovary syndrome, which was originally designed to compare the live birth rate after fresh-embryo transfer vs frozen embryo transfer (Frefro-PCOS). At baseline, metabolic parameters, including body mass index, waist and hip circumference, blood pressure, lipid profile, fasting, and 2 hour glucose and insulin levels after a 75 g oral glucose tolerance test were measured. All subjects were divided into a metabolic syndrome group (metabolic syndrome) and absence of metabolic syndrome group (nonmetabolic syndrome) according to diagnostic criteria. Descriptive statistics and logistic regression models tested the association between metabolic syndrome and overall fertility and in vitro fertilization cycle stimulation characteristics and clinical outcomes., Results: Metabolic syndrome was identified in 410 of 1508 infertile women with polycystic ovary syndrome (27.2%). Patients with metabolic syndrome had longer infertility duration (4.0 ± 2.2 vs 3.7 ± 2.2, P = .004) compared with those without metabolic syndrome. During ovarian stimulation, those with metabolic syndrome required significantly higher and longer doses of gonadotropin and had lower peak estradiol level, fewer retrieved oocytes, available embryos, a lower oocyte utilization rate, and ovarian hyperstimulation syndrome than those with nonmetabolic syndrome. The cumulative live birth rate did not show a significant between-group difference (57.8% vs 62.2%, P = .119). Multivariate logistic regression analysis adjusted for age, duration of infertility, body mass index, thyroid-stimulating hormone, metabolic syndrome group, homeostatic model assessment of insulin resistance, metformin utilization, number of available embryos, and embryos transferred showed that the number of embryos transferred and the number of available embryos were positively but metabolic syndrome negatively associated with the cumulative live birth rate (odds ratio, 2.18, 1.10, and 0.70, respectively, P < .05)., Conclusion: Women with polycystic ovary syndrome with metabolic syndrome have a negative impact from female fecundity, and this suggests an adverse effect on in vitro fertilization cycle stimulation characteristics and clinical outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: This study 1) defines patient involvement from the perspective of patients new to a provider, 2) describes provider communication that patients perceive as promoting involvement, and 3) examines changes in patient definitions of involvement over time., Methods: We enrolled 56 patients at two HIV clinics in Houston, Texas, from August 2013 until March 2015. We interviewed patients three times during the first year of care and analyzed interviews using content analysis., Results: The mean age was 45 years; 54% were men. Patient definitions of involvement ranged from adherence- to decision-oriented. Analysis revealed three provider communication behaviors that patients perceive as promoting involvement: 1) soliciting patient feedback, 2) discussing treatment options and trade-offs, 3) narrating the decision-making process. Definitions of involvement can change over time as providers reframe the patient's illness as manageable and through perceived partnerships with the provider., Conclusion: Provider communication plays a critical role in shaping new patients' perception of involvement and can make patients feel involved even when patients do not actively make medical decisions., Practical Implications: Finding strategies to make patients feel involved in their care is important, particularly for new patients, even if those strategies do not necessarily promote more talk from the patient., (Published by Elsevier B.V.)

Background: Bladder cancer is closely related to occupational carcinogens, and China is undergoing a rapid industrialization. However, trend of bladder cancer incidence and mortality remains unknown in China., Methods: Incidence and mortality rates of bladder cancer (1990-2017) were collected for each 5-year age group stratified by gender (males/females) from the Global Burden of Disease (GBD) 2017 study. The average annual percentage change (AAPC) of rates were analyzed by joinpoint regression analysis; age, period and cohort effects on incidence and mortality were simultaneously estimated by age-period-cohort model., Results: Through 1990-2017, age-standardized incidence rates significantly rose in men (AAPC = 0.72%, 95% CI: 0.5%, 0.9%) while decreased in women (-1.25%: -1.6%, -0.9%); age-standardized mortality rates decreased in both men (-1.09%: -1.2%, -0.9%) and women (-2.48%: -2.8%, -2.2%). The joinpoint regression analysis showed the mortality almost decreased in all age groups; while the incidence increased in men for older age groups (from 45 to 49 to 80-84). Moreover, age effect showed the incidence and mortality increased with age; the incidence and mortality increased with time period, while in women period effect stop decreasing and began to increase since 2007; cohort effect showed them decreased with birth cohorts., Conclusions: The incidence of bladder cancer is increasing in men but mortality decreases in both sexes. Both the incidence and mortality in men substantially increase with age and period, while the rates in women increased with period since 2007. The period effect may indicate the increased risks to bladder cancer in Chinese men. Etiological studies are needed to identify the factors driving these trends of bladder cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Metabolomics provides new insights into disease pathogenesis and biomarker discovery. Samples from large-scale untargeted metabolomics studies are typically analyzed using a liquid chromatography-mass spectrometry platform in several batches. Batch effects that are caused by non-biological systematic biases are unavoidable in large-scale metabolomics studies, even with properly designed experiments. The statistical analysis of large-scale metabolomics data without managing batch effects will yield misleading results. In this study, we propose a novel algorithm, called WaveICA, which is based on the wavelet transform method with independent component analysis, as the threshold processing method to capture and remove batch effects for large-scale metabolomics data. The WaveICA method uses the time trend of samples over the injection order, decomposes the original data into multi-scale data with different features, extracts and removes the batch effect information in multi-scale data, and obtains clean data. The WaveICA method was tested on real metabolomics data. After applying the WaveICA method, scattered quality control samples (QCS) and subject samples in a PCA score plot of the original data were closely clustered, respectively. The average Pearson correlation coefficients for all peaks of the QCS increased from 0.872 to 0.972. Additionally, WaveICA significantly improved the classification accuracy for metabolomics data. The method was compared with three representative methods, and outperformed all of them. To conclude, WaveICA can efficiently remove batch effects while revealing more biological information. This method can be used in large-scale untargeted metabolomics studies to preprocess raw metabolomics data., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Research Question: The prevalence of infertility in couples actively trying to conceive is 25%. What is the consultation-seeking behaviour, diagnosis and related treatment in infertile couples across China?, Design: Large cross-sectional population-based study in 2010-2011, in which 25,270 couples from eight provinces/municipalities in China were approached by a multistage stratified cluster sampling strategy., Results: Among the 2680 couples reporting infertility, 1246 infertile couples consulted a fertility doctor. Age of the couple, man's body mass index and women's educational level were found to be associated with consultation behaviour. After the fertility work-up, diagnoses were tubal infertility (n = 353, 28.3%), unexplained infertility (n = 311, 25.0%), male infertility (n = 234, 18.8%), ovulatory disorder (n = 194, 15.6%) and endometriosis (n = 34, 2.7%), while 8.6% (n = 107) were not classified. Most couples received non-assisted reproductive technology (ART) fertility treatment (n = 906, 89.3%), with a proportion using traditional Chinese medicine (TCM) (n = 298, 29.4%). Intrauterine insemination (n = 62, 6.1%) and IVF/intracytoplasmic sperm injection (n = 57, 5.6%) were less frequent. Medical treatment and outcomes among five subtypes of infertility were also reported: about 30% of couples with unexplained infertility (n = 94, 30.3%) or male infertility (n = 67, 29.0%) used TCM to treat infertility. Apart from patients with endometriosis, of whom 20.6% (n = 7) received ART, patients with other infertility subtypes rarely received ART. For subsequent fertility outcome, 94% of them did not achieve a pregnancy., Conclusion: The prevalence of infertility in China is high, but the uptake of treatment is relatively low., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer., Methods: This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405., Findings: 825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 [50%] vs 329 [40%]; relative risk [RR] 1·26, 95% CI 1·14-1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 [0·5%] in frozen single blastocyst transfer vs nine of 825 [1·1%] in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 [23·0%] vs 124 of 481 [25·8%]; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 [3·1%] vs four of 401 [1·0%]; RR 3·13, 95% CI 1·06-9·30, p=0·029)., Interpretation: Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies., Funding: The National Key Research and Development Program of China., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Observational studies show a beneficial effect of adjuvant metformin therapy on breast cancer survivals, but data from randomized clinical trials are lacking. This study systematically evaluated the evidence from randomized clinical trials currently available. Ten studies were retrieved, comprising 1520 breast cancer patients. Metformin therapy reduced the levels of insulin and HOMA-IR, sex hormones and sex hormone-binding globulin, Ki67, caspase-3, p-Akt, obesity, hs-CRP, blood glucose and lipid profile. Two studies reported conflicting results on survival outcomes. The overall survival was nonsignificantly better in the metformin arm than the control arm (pooled rate ratio 0.89, 95% confidence interval 0.68-1.18, P = 0.43). The progression-free survival was not different between the arms (pooled rate ratio 0.96, 95% confidence interval 0.86-1.06, P = 0.39). These findings provide in vivo evidence in human, supporting an antitumor effect of metformin on breast cancer. Further clinical trials with larger sample size are warranted., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To investigate bioavailability of dissolved organic nitrogen (DON) and its contribution to nitrogen demand for Ulva prolifera, a cruise was conducted during a bloom of U. prolifera in Qingdao coastal waters, China, dissolved inorganic nitrogen (DIN) and DON components were investigated. Uptakes of both DIN and DON by U. prolifera were synchronously measured onboard using stable isotope techniques. The contribution of DON to total dissolved N (TDN) was >50% and that of labile components (urea and to amino acids, AA) to DON exceeded 30%. Both DIN and DON were utilized by U. prolifera, which uptake NH 4 -N preferentially, then urea, NO 3 -N and AA in turn; whereas the ranking of turnover times from short to long was AA, NH 4 -N, urea and NO 3 -N. The high uptake rates and short turnover time of AA and urea indicated that DON may play an important role in the nutrition of U. prolifera., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Increasing epidemiologic evidence suggests that diabetes mellitus (DM) may be associated with a decreased risk of glioma. This systematic review assessed whether DM was associated with glioma risk., Methods: Electronic searches were performed in PubMed, Web of Science, EMBASE, and Cochrane Library databases up to August 30, 2018. A random-effects model was performed to calculate summary effect size with corresponding 95% confidence intervals (CIs)., Results: In total, 10 studies (eight case-control studies and two cohort studies) matched the inclusion criteria. Meta-analyses of case-control studies showed that DM decreased the risk of glioma by 23% (odds ratio: 0.77, 95% CI: 0.61-0.96; P = .02, I 2  = 82.0%). However, no such effect was observed in cohort studies (relative risk: 0.71, 95% CI: 0.10-4.80; P = .72, I 2  = 61.6%). In the subgroup analyses, DM was associated with a decreased risk of glioma in Caucasians but not in Asians; the inverse association was slightly higher in males than in females., Conclusions: Our results indicate that DM decreases the risk of glioma, but the inverse association may vary in subgroups. The present conclusions should be confirmed with further studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this work, a ratiometric fluorescent probe (RF-probe) for highly sensitive and selective detection of uric acid was reported for the first time toward H 2 O 2 based on inner filter effect (IFE) between bimetallic gold/silver nanoclusters (Au/Ag NCs) and 2,3-diaminophenazine (DAP). For this RF-probe, uric acid was degraded to allantoin and H 2 O 2 . Upon the addition of HRP, o-phenylenediamine (OPD) could be catalytically oxidized to DAP in the presence of H 2 O 2 , then the fluorescence intensity corresponding to DAP at 580 nm increased dramatically with a fluorescence quenching of BSA-Au/Ag NCs at 690 nm, resulting in a RF-probe toward uric acid. This RF-probe allowed for the sensitive detection of uric acid in range of 5.0 × 10 -6 M to 5.0 × 10 -5 M with a detection limit (S/N = 3) as low as 5.1 × 10 -6 M. At the same time, it has been successfully used for uric acid levels detection in human serum, and the results are consistent with those of the hospital. RF-probe built may provide a ratiometric fluorescence universal platform for detection of various species involving in the production of H 2 O 2 in other biological systems., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study aimed to elucidate the effect of miR-1306-3p on metastasis of hepatocellular carcinoma (HCC) and potential mechanism involved. miR-1306-3p promoted migration and invasion of HCC in vivo and in vitro. Moreover, miR-1306-3p inhibited snail to enhance its expression via directly targeting FBXL5, thus inducing the epithelial-mesenchymal transition (EMT) in HCC. Intriguingly, miR-1306-3p expression was transcriptionally enhanced by FoxM1. Consistently, miR-1306-3p was upregulated in HCC compared with paracarcinoma and correlated with poor prognosis of HCC patients. Our researches suggest that miR-1306-3p is a tumor enhancer in regulating of HCC metastasis, and miR-1306-3p may be clinically utilized as a factor for the clinical diagnosis and prognosis of HCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To gain insight into the effect of Cu 2+ on the activity and structure of alkaline phosphatase (ALP) from Macrobrachium rosenbergii, the enzyme was purified using ammonium sulfate fractionation, Sephacryl S-200, and DEAE anion exchange chromatography. We studied Cu 2+ -mediated inhibition and aggregation of ALP, and found that Cu 2+ significantly inactivated ALP activity with an IC 50 of 1.47 ± 0.02 mM. We further revealed that Cu 2+ reversibly inhibited ALP in a mixed-type manner with K i  = 0.41 ± 0.02 mM. Time-interval kinetics showed that the inhibition followed first-order reaction kinetics. This process was associated with conformational changes and significant transient free-energy change. Spectrofluorometry results showed that Cu 2+ induced ALP tertiary structural changes, including the exposure of hydrophobic surfaces that directly induced ALP aggregation. The results provide new information regarding ALP from M. rosenbergii., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Neuraminidase (NA) is a glycoside hydrolase that has been proposed as a potential therapeutic target for influenza. Thus, the identification of compounds that modulate NA activity could be of great therapeutic importance. The aim of this study is to develop a drug discovery tool for the identification of novel modulators of NA from both compound libraries and natural plant extracts. NA was immobilized onto the surface of magnetic beads and the inherent catalytic activity of NA-functionalized magnetic beads was characterized. Based on the enzymatic activity (hydrolysis ratio), the inhibitory activities of 12 compounds from plant secondary metabolites were screened, and the desired anti-NA activities of flavonoids were certified. Ligand fishing with the immobilized enzyme was optimized using an artificial test mixture consisting of oseltamivir, lycorine and matrine prior to carrying out the proof-of-concept experiment with the crude extract of Flos Lonicerae. The combination of ligand fishing and HPLC-MS/MS identified luteolin-7-O-β-D-glucoside, luteolin, 3,5-di-O-caffeoylquinic acid and 3,4-di-O-caffeoylquinic acid as neuraminidase inhibitory ligands in Flos Lonicerae. This is the first report on the use of neuraminidase functionalized magnetic beads for the identification of active ligands from a botanical matrix, and it sets the basis for the de novo identification of NA modulators from complex biological mixtures., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The nucleus is one of the most important cellular organelles, where gene encode and transcribe at that location. However, nucleus-targeting gene delivery are rare been reported. It is important to develop a high-efficiency nucleus-targeting gene vector that can deliver targeted gene into nucleus directly for destroy of cancer cells. Here, special nucleus-targeting and size changeable deliver system based on TAT-SS-PAMAM-D3 with TAT functional on the surface and disulfide linked between D2 and D3 is designed to perform highly efficient nucleus-targeting gene delivery for effective cancer cell killing in vitro. CLSM observations reveal that more TAT-SS-PAMAM-D3 are enter into the nucleus when compare to SS-PAMAM-D3. The TAT modified vector can also act as gene deliver to reach high gene transfection efficiencies, high apoptosis and low viability in HeLa cells. This TAT functionalized and disulfide linking in the carrier may become a prospective vector for cancer gene treatment and also offered a different strategy for designing a better gene delivery system., (Copyright © 2018. Published by Elsevier B.V.)

Research Question: Does an association exist between serum anti-Müllerian hormone (AMH) level, the marker of biological ovarian age, and embryonic aneuploidy risk in recurrent spontaneous miscarriage (RSM) patients of reproductive age?, Design: This retrospective study included a total of 422 IVF cycles of 394 unexplained RSM patients undergoing preimplantation genetic testing for aneuploidy (PGT-A), enrolled from January 2014 to December 2016. Subjects were divided into three groups according to the 25th (1.50 ng/ml) and 75th (5.60 ng/ml) percentiles of AMH level (Group 1: low AMH <1.50 ng/ml [N = 107], Group 2: normal AMH 1.50- < 5.60 ng/ml [N = 210] and Group 3: high AMH ≥ 5.60 ng/ml [N = 105])., Results: There was a significant difference in embryonic aneuploid rate between AMH groups (66.7% versus 42.9% versus 50.0%, Groups 1 to 3, respectively, P = 0.006). It was significantly higher in the low AMH group (Group 1) compared with that in the normal AMH group (Group 2, P 1vs2 = 0.002) and high AMH group (Group 3, P 1vs3 = 0.015). After age stratification, embryonic aneuploidy rate was still significantly different among AMH groups with a similar trend in women ≥35 years old (68.2% versus 54.4% versus 51.0%, P = 0.038, P 1vs2 = 0.025, P 1vs3 = 0.035), but not in young subjects., Conclusions: These findings indicate that low AMH level was associated with increased risk of embryo aneuploidy only in women of advanced age. Maternal diminished ovarian reserve along with oocyte ageing may contribute to impaired chromosomal competence of the embryo., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)