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BackgroundPhthalates are ubiquitously used in a variety of products and have an adverse effect on folliculogenesis. However, previous epidemiological studies on the associations between phthalate exposure and antral follicle count (AFC) produced conflicting results. The present study aimed to evaluate the associations between urinary phthalate metabolite concentrations and AFC among women undergoing in vitro fertilization (IVF).MethodsWe collected 525 urine samples and measured 8 phthalate metabolites from IVF patients. Poisson regression models were conducted to evaluate the associations between phthalate metabolite concentrations and AFC. In addition, participants were stratified into a younger group (< 35 years) and an older group (≥ 35 years) to explore the potential effect modification by age. We also performed sensitivity analyses by restricting our analyses to only infertile women diagnosed with tubal factor infertility to test the robustness of the results.ResultsSignificant positive associations were observed among urinary MBP, MEOHP and ∑PAEs concentrations and AFC after adjusting for age, BMI, year of study and infertility diagnosis. Compared with women in the first tertile, women in the third tertile of MBP and MEOHP had 7.02% (95% CI: 1.18%, 12.9%) and 8.84% (95% CI: 2.83%, 14.9%) higher AFC, respectively, and women in the second and third tertiles of ∑PAEs had 6.19% (95% CI: 0.37%, 12.0%) and 9.09% (95% CI: 3.22%, 15.0%) higher AFC, respectively. In addition, MBP, MEOHP and ∑PAEs also had significant positive associations with AFC in trend tests for dose-response. In the age-stratified analysis, we found a stronger relationship between phthalate metabolite concentrations and AFC among older women and an inverse association among younger women. We observed similar results in the sensitivity analyses.ConclusionWe found positive associations between phthalate exposure and AFC, which support the idea that phthalate exposure may accelerate primordial follicle recruitment and lead to higher AFC in women undergoing IVF. More studies are needed to better understand their relationships.

Background: Phthalates have been shown to disrupt the estrous cycle in animal studies. However, epidemiological research investigating their associations with menstrual cycle characteristics is limited. Objective: To explore the relationships between phthalate exposure and menstrual cycle characteristics among women seeking fertility assistance. Methods: We determined the levels of eight phthalate metabolites in both follicular fluid (FF) and urine specimens collected from 441 women in the Tongji Reproductive and Environmental (TREE) cohort, using high-performance liquid chromatography and tandem mass spectrometry. Information about menstrual cycle parameters was obtained through a questionnaire. The impacts of individual and joint exposure to phthalates on menstrual cycle characteristics were assessed using multivariable linear regression, Poisson regression, and quantile g-computation approaches. Results: After adjusting for relevant covariates, we found that per log10-unit increase in mono(2-ethylhexyl) phthalate (MEHP) level in urine specimens was associated with a decrease of 0.20 days (95 % CI: −0.37, −0.03) in bleeding duration. We also observed that mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and the sum of di(2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) concentrations in FF samples were inversely related to cycle length [β = −1.92 (95 % CI: −3.10, −0.75) and −1.87 (95 % CI: −3.56, −0.19), respectively]. However, we generally observed null associations between phthalate metabolites and irregular cycle, dysmenorrhea, hypomenorrhea, or cycle length variation. Furthermore, we also found that phthalate metabolite mixtures in FF and urine were generally unrelated to menstrual cycle characteristics. Conclusion: Our findings suggest that some DEHP metabolites in FF and urine are inversely associated with menstrual cycle length and menstrual bleeding duration in women attending a fertility center.

Doxorubicin is a broad-spectrum chemotherapy drug commonly used in clinical practice. Improving the delivery efficiency of doxorubicin can help improve the therapeutic effect of tumor and reduce the corresponding side effects. The delivery of doxorubicin based on nano-drug loading technology can provide important help for targeted killing of tumor cells. Tumor development is usually accompanied by the changes in the stiffness of extracellular matrix. The effect of substrate stiffness on the endocytic behavior of doxorubicin based on drug-loading nanoparticle technology was explored by the cellular activity regulated by doxorubicin endocytosis and the changes in the expression of important proteins associated with endocytosis. The substrate stiffness can be regulated by adjusting the ratio of PDMS binder and curing agent. The results of the experiment showed that the cell activity on the substrate with appropriate stiffness (Young's modulus of 0.578, 0.815 and 1.986 MPa) was inhibited, indicating that the transport of doxorubicin was more efficient in this range of substrate stiffness. To explore the underlying mechanism of substrate stiffness regulation of doxorubicin endocytosis, we explored the expression of αVβ5 and NUMB, which are closely related to the endocytosis process. From the results of immunofluorescence protein and Western blot experiments, the fluorescence intensity of the αVβ5 protein responsible for anchoring clathrin on the substrate with a Young's modulus of 1.986 MPa was the highest; Within the appropriate stiffness range, the fluorescence intensity of NUMB protein was significantly increased, indicating that increased expression of NUMB and αVβ5 regulated by substrate stiffness mediates doxorubicin transport, thereby affecting cell viability. This work provides a reference for further improving the efficacy of chemotherapy drugs in the treatment of tumors.

Beam position monitor (BPM) characterization has been widely studied at the synchrotron. The characteristic impedance of a stripline BPM was designed using a simulation and measured using the time-domain reflectometer method. The mechanical and electrical parameters of the feedthroughs with the buttons used for the BPMs were measured. Special care was taken in the analysis of the consistency of the four channels of the BPM. The feedthroughs were sorted based on their capacitance values. This paper presents the characterization results of the feedthroughs and BPMs. The electro-mechanical offsets were measured using the Lambertson method, and the calibration coefficients were measured using a stretched wire. The BPM differences introduced during mass production were determined by a statistical analysis of the measurement results.

Background. The prognostic significance of the amino-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) has not been fully elucidated. Major adverse cardiovascular events (MACEs) are clinically viable indicators for the accurate, rapid, and safe evaluation of patients with STEMI. This study was designed to investigate the relationship between NT-proBNP levels and the occurrence of short-term MACEs in patients with STEMI who underwent emergency PCI. Methods. This prospective cohort study included 405 patients with STEMI aged 20–90 years who underwent emergency PCI at the First People’s Hospital of Changde City from April 6, 2017, to May 31, 2019. Stent thrombosis, reinfarction, congestive heart failure, unstable angina, and cardiac death were considered as MACEs in this study. The target-independent and -dependent variables were NT-proBNP at baseline and MACE, respectively. Results. There were 28.25% of MACEs. Age, number of implanted stents, Killip class, infarction-related artery, applied intra-aortic balloon pump (IABP), creatine kinase (CK) peak value, CK-MB peak value, TnI peak value, and ST-segment resolution were independently associated with MACE (P11.66 (NT-proBNP >3.236 pg/mL).

Summary: Focal adhesions anchor cells to extracellular matrix (ECM) and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC) focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM. : Mead et al. identify a proteolytic mechanism that actively maintains a pericellular microenvironment conducive to uterine smooth muscle activation prior to parturition. They show that pericellular matrix proteolysis by the secreted metalloprotease ADAMTS9 is crucial for maintenance of focal adhesions in uterine smooth muscle cells, and its absence impairs parturition. Keywords: metalloprotease, extracellular matrix, smooth muscle, proteoglycan, myometrium, parturition, uterus, focal adhesion, proteolysis, interference reflection microscopy

Based on analysis of the reasons for low efficiency and low production after fracturing of some wells in the ultra-deep fractured tight reservoirs of the Kuqa piedmont zone, Tarim Basin and the matching relationship between the in-situ stress field and natural fractures, technological methods for creating complex fracture networks are proposed. Through theoretical study and large-scale physical simulation experiments, the mechanical conditions for forming complex fracture network in the Kuqa piedmont ultra-deep reservoirs are determined. The effectiveness of temporary plugging and diversion, and multi-stage fracturing to activate natural fractures and consequently realize multi-stage diversion is verified. The coupling effect of hydraulic fractures and natural fractures activating each other and resulting in “fracture swarms” is observed. These insights provide theoretical support for improving fracture-controlled stimulated reservoir volume (FSRV) in ultra-deep tight reservoirs. In addition, following the concept of volume fracturing technology and based on the results of fracture conductivity experiments of different processes, fracturing technologies such as multi-stage fracture-network acid fracturing, “multi-stage temporary plugging + secondary fracturing”, fracturing of multiple small layers by vertically softness-and-hardness-oriented subdivision, and weighted-fluid refracturing are proposed to increase the FSRV. New environment-friendly weighted-fluid with low cost and new fracturing fluid system with low viscosity and high proppant-carrying capacity are also developed. These techniques have achieved remarkable results in field application.

To solve the problems facing the economic development of unconventional oil and gas, a new concept and corresponding technology system of reservoir stimulation based on “fracture-controlled reserves” are put forward. The “fracture-controlled reserves” stimulation technology is to realize the three-dimensional producing and economic and efficient development of unconventional hydrocarbon resources by forming a fracture system that well matches “sweet spots” and “non-sweet spots”. The technical route of the stimulation technology is “three optimizations and controls”, that is, control the scope of sand body through optimizing well spacing, control the recoverable reserves through optimizing fracture system, and control the single well production reduction through optimizing energy complement method. The “fracture-controlled reserves” stimulation emphasizes the maximization of the initial stimulation coefficient, the integration of energy replenishment, stimulation and production, and prolonging the re-fracturing cycle or avoiding re-fracturing. It aims at realizing the three-dimensional full producing and efficient development of reservoir in vertical and horizontal directions and achieving the large-scale, sustainable and high profitable development of unconventional oil and gas resources. The stimulation technology was used to perform 20 pilot projects in five typical tight-oil, shale gas blocks in China. The fracturing and producing effects of tight oil improved and the commercial development for shale gas was realized. Key words: unconventional oil and gas, tight oil and gas, shale oil and gas, fracture-controlled reserves, initial stimulation coefficient, fracture parameters optimization, well pattern optimization, energy complement