The severity of meiotic aneuploidy is associated with altered morphokinetic variables of mouse oocyte maturation.

STUDY QUESTION: Is there an association between morphokinetic variables of meiotic maturation and the severity of aneuploidy following in vitro maturation (IVM) in the mouse? SUMMARY ANSWER: The severity of meiotic aneuploidy correlates with an extended time to first polar body extrusion (tPB1) and duration of meiosis I (dMI). WHAT IS KNOWN ALREADY: Morphokinetic variables measured using time-lapse technology allow for the non-invasive evaluation of preimplantation embryo development within clinical assisted reproductive technology (ART). We recently applied this technology to monitor meiotic progression during IVM of mouse gametes. Whether there is a relationship between morphokinetic variables of meiotic progression and aneuploidy in the resulting egg has not been systematically examined at the resolution of specific chromosomes. Next-generation sequencing (NGS) is a robust clinical tool for determining aneuploidy status and has been reverse-translated in mouse blastocysts and oocytes. Therefore, we harnessed the technologies of time-lapse imaging and NGS to determine the relationship between the morphokinetics of meiotic progression and egg aneuploidy. STUDY DESIGN SIZE DURATION: Cumulus-oocyte complexes were collected from large antral follicles from hyperstimulated CD-1 mice. Cumulus cells were removed, and spontaneous IVM was performed in the absence or presence of two doses of Nocodazole (25 or 50 nM) to induce a spectrum of spindle abnormalities and chromosome segregation errors during oocyte meiosis. Comprehensive chromosome screening was then performed in the resulting eggs, and morphokinetic variables and ploidy status were compared across experimental groups (control, n = 11; 25 nM Nocodazole, n = 13; 50 nM Nocodazole, n = 23). PARTICIPANTS/MATERIALS SETTING METHODS: We monitored IVM in mouse oocytes using time-lapse microscopy for 16 h, and time to germinal vesicle breakdown (tGVBD), tPB1, and dMI were analyzed. Following IVM, comprehensive chromosome screening was performed on the eggs and their matched first polar bodies via adaptation of an NGS-based preimplantation genetic testing for aneuploidy (PGT-A) assay. Bioinformatics analysis was performed to align reads to the mouse genome and determine copy number-based predictions of aneuploidy. The concordance of each polar body-egg pair (reciprocal errors) was used to validate the results. Ploidy status was categorized as euploid, 1-3 chromosomal segregation errors, or ≥4 chromosomal segregation errors. Additionally, aneuploidy due to premature separation of sister chromatids (PSSC) versus non-disjunction (NDJ) was distinguished. MAIN RESULTS AND THE ROLE OF CHANCE: We applied and validated state-of-the-art NGS technology to screen aneuploidy in individual mouse eggs and matched polar bodies at the chromosome-specific level. By performing IVM in the presence of different doses of Nocodazole, we induced a range of aneuploidy. No aneuploidy was observed in the absence of Nocodazole (0/11), whereas IVM in the presence of 25 and 50 nM Nocodazole resulted in an aneuploidy incidence of 7.69% (1/13) and 82.61% (19/23), respectively. Of the aneuploid eggs, 5% (1/20) was due to PSSC, 65% (13/20) to NDJ, and the remainder to a combination of both. There was no relationship between ploidy status and tGVBD, but tPB1 and the dMI were both significantly prolonged in eggs with reciprocal aneuploidy events compared to the euploid eggs, and this scaled with the severity of aneuploidy. Eggs with ≥4 aneuploid chromosomes had the longest tPB1 and dMI (P < 0.0001), whereas eggs with one to three aneuploid chromosomes exhibited intermediate lengths of time (P < 0.0001). LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: We used Nocodazole in this study to disrupt the meiotic spindle and induce aneuploidy in mouse oocytes. Whether the association between morphokinetic variables of meiotic progression and the severity of aneuploidy occurs with other compounds that induce chromosome segregation errors remain to be investigated. In addition, unlike mouse oocytes, human IVM requires the presence of cumulus cells, which precludes visualization of morphokinetic variables of meiotic progression. Thus, our study may have limited direct clinical translatability. WIDER IMPLICATIONS OF THE FINDINGS: We validated NGS in mouse eggs to detect aneuploidy at a chromosome-specific resolution which greatly improves the utility of the mouse model. With a tractable and validated model system for characterizing meiotic aneuploidy, investigations into the molecular mechanisms and factors which may influence aneuploidy can be further elaborated. Time-lapse analyses of morphokinetic variables of meiotic progression may be a useful non-invasive predictor of aneuploidy severity. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Bill & Melinda Gates Foundation (INV-003385). Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. The authors have no conflict of interest to disclose.

Metal Films on Two-Dimensional Materials: van der Waals Contacts and Raman Enhancement.

Electronic devices based on two-dimensional (2D) materials will need ultraclean and defect-free van der Waals (vdW) contacts with three-dimensional (3D) metals. It is therefore important to understand how vdW metal films deposit on 2D surfaces. Here, we study the growth and nucleation of vdW metal films of indium (In) and non-vdW metal films of gold (Au), deposited on 2D MoS2 and graphene. In follows a 2D growth mode in contrast to Au that follows a 3D growth mode. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to image the morphology of metal clusters during growth and quantify the nucleation density. As compared to Au, In atoms exhibit nearly 50 times higher diffusivity (3.65 × 10-6 µm-2 s-1) and half the nucleation density (64.9 ± 2.46 µm-2), leading to larger grain sizes (∼60 nm for 5 nm In on monolayer MoS2). The grain size of In can be further increased by reducing the 2D surface roughness, while the grain size for Au is limited by its high nucleation density due to the creation of interface defects during deposition. The vdW gap between In and MoS2 and graphene leads to strong enhancement (>103) in their Raman signal intensity due to localized surface plasmon resonance. In the absence of a vdW gap, the plasmon-mediated enhancement in Raman does not occur.

Development of Novel Formulation for Sustained Release of Drug to Prevent Swainsonine-Containing Plants Poisoning in Livestock.

Swainsonine-containing plants contain swainsonine which has been shown to cause neurological signs and pathological changes in farm animals. It causes a large number of livestock poisonings every year resulting in economic losses to the livestock industry. At present, "Jifang E" is used in the prevention of swainsonine-containing plants poisoning livestock, and the preventive effects have been well-documented. However, "Jifang E" is typically administered in drinking water, making it difficult to control the administered dosage, because of feeding difficulties and it may cause certain side effects that are unique to the water-dissolved powder. To overcome these difficulties, we developed a temperature-sensitive gel for injection and the optimal ratio of each formula of sustained-release injection is P407 (24%), P188 (6%), Vitamin C (1%), PEG4000 (0.5%), and "Jifang E" (10%). Our results suggest that novel formulation makes the micellar system more stable and the particles are uniformly dispersed. Colloidal morphological studies showed that each group formed a homogeneous pore structure after gelling, and the structure became more dense with the addition of "Jifang E". The rheological study shows that "Jifang E" is a pseudoplastic fluid, and the addition of "Jifang E" reduces the viscosity of the formula, which is beneficial to the injection. In vitro and in vivo release rate studies have shown that the effective concentration of "Jifang E" can be maintained for 3 to 5 days. The acute toxicity test in SPF Kunming mice showed that its LD50 was 828.323 mg/kg, with confidence limits of 676.706-1013.911 mg/kg, which is a safe dosage (LD50 > 200 mg/kg). There were no observed reactions of muscle irritation or subcutaneous tissue irritation with the dosage used for New Zealand rabbits. In summary, we successfully developed the sustained-release injection formulation of "Jifang E" for the prevention of swainsonine-containing plants poisoning livestock, which provides the basis for subsequent field extension trials and the further study of its detoxification mechanism.

Resourcefulness as a mediator in the relationship between self-perceived burden and depression among the young and middle-aged stroke patients: A cross-sectional study.

Objective: To explore the relationships among self-perceived burden, resourcefulness and depression, and to study further whether resourcefulness mediates the effects of self-perceived burden on depression in young and middle-aged stroke patients. Methods: A cross-sectional survey was conducted with 1050 young and middle-aged stroke patients. We used a general demographic questionnaire, Self-Perceived Burden Scale (SPBS), Resourcefulness Scale© (RS) and Hamilton Depression Scale (HAMD) to assess self-perceived burden, resourcefulness, and depression. Statistical methods included correlation analysis, multiple linear regression, and structural equation model. Results: 1018 valid questionnaires were collected with a response rate of 96.95%. Resourcefulness was inversely correlated with self-perceived burden (r = -0.367, p < 0.01) and depression (r = -0.625, p < 0.01); Self-perceived burden was positively associated with depression (r = 0.698, p < 0.01). Multiple linear regression analyses showed that resourcefulness mediated the effects of self-perceived burden on depression; The structural equation model demonstrated that the resourcefulness mediated the relationship between self-perceived burden and depression. Conclusion: Resourcefulness is a mediator between self-perceived burden and depression. Medical staff adjust the psychological state of stroke patients based on the theory of resourcefulness, thereby improving their problem-solving ability, actively encouraging patients to establish problem-solving strategies, providing disease rehabilitation knowledge and skills, and promoting the improvement of resourcefulness level.

Room-Temperature Photoluminescence Mediated by Sulfur Vacancies in 2D Molybdenum Disulfide.

Atomic defects in monolayer transition metal dichalcogenides (TMDs) such as chalcogen vacancies significantly affect their properties. In this work, we provide a reproducible and facile strategy to rationally induce chalcogen vacancies in monolayer MoS2 by annealing at 600 °C in an argon/hydrogen (95%/5%) atmosphere. Synchrotron X-ray photoelectron spectroscopy shows that a Mo 3d5/2 core peak at 230.1 eV emerges in the annealed MoS2 associated with nonstoichiometric MoSx (0 < x < 2), and Raman spectroscopy shows an enhancement of the ∼380 cm-1 peak that is attributed to sulfur vacancies. At sulfur vacancy densities of ∼1.8 × 1014 cm-2, we observe a defect peak at ∼1.72 eV (referred to as LXD) at room temperature in the photoluminescence (PL) spectrum. The LXD peak is attributed to excitons trapped at defect-induced in-gap states and is typically observed only at low temperatures (≤77 K). Time-resolved PL measurements reveal that the lifetime of defect-mediated LXD emission is longer than that of band edge excitons, both at room and low temperatures (∼2.44 ns at 8 K). The LXD peak can be suppressed by annealing the defective MoS2 in sulfur vapor, which indicates that it is possible to passivate the vacancies. Our results provide insights into how excitonic and defect-mediated PL emissions in MoS2 are influenced by sulfur vacancies at room and low temperatures.

Nanoscale Cathodoluminescence and Conductive Mode Scanning Electron Microscopy of van der Waals Heterostructures.

van der Waals heterostructures (vdW-HSs) integrate dissimilar materials to form complex devices. These rely on the manipulation of charges at multiple interfaces. However, at present, submicrometer variations in strain, doping, or electrical breakages may exist undetected within a device, adversely affecting macroscale performance. Here, we use conductive mode and cathodoluminescence scanning electron microscopy (CM-SEM and SEM-CL) to investigate these phenomena. As a model system, we use a monolayer WSe2 (1L-WSe2) encapsulated in hexagonal boron nitride (hBN). CM-SEM allows for quantification of the flow of electrons during the SEM measurements. During electron irradiation at 5 keV, up to 70% of beam electrons are deposited into the vdW-HS and can subsequently migrate to the 1L-WSe2. This accumulation of charge leads to dynamic doping of 1L-WSe2, reducing its CL efficiency by up to 30% over 30 s. By providing a path for excess electrons to leave the sample, near full restoration of the initial CL signal can be achieved. These results indicate that the trapping of charges in vdW-HSs during electron irradiation must be considered, in order to obtain and maintain optimal performance of vdW-HS devices during processes such as e-beam lithography or SEM. Thus, CM-SEM and SEM-CL form a toolkit through which nanoscale characterization of vdW-HS devices can be performed, allowing electrical and optical properties to be correlated.

Metabolomic analysis and antibacterial and antioxidant activities of three species of Artemisia plants in Tibet.

BACKGROUND: Artemisia is important medicinal plants in China and are widely used in medicine, agriculture, and food. Pharmacologically active components of the plants remain to be investigated. METHODS: This study sought to identify and compare the chemical constituents of three species of Artemisia in Tibet using a widely-targeted metabolomics approach and their antibacterial and antioxidant capacities were determined. RESULT: A total of 1109 metabolites within 10 categories were detected from the three species of Artemisia, including lipids, amino acids, nucleotides, flavonoids, terpenes, coumarins, organic acids, and phenolic acids. 732 different metabolites have been identified between Artemisia sieversiana and Artemisia annua, 751 different metabolites were identified between Artemisia wellbyi and A. sieversiana, and 768 differential metabolites were differentially detected from A. wellbyi and A. annua. Differentially identified compounds included flavonoids, phenolic acids, artemisinins and coumarin. A. annua contained the highest relative content of artemisinin among three Artemisia. The antimicrobial experiments showed that the three Artemisia species had strong antibiotic activities against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Proteus mirabilis and Pseudomonas aeruginosa. The biochemical analysis showed that the three species of Artemisia have strong antioxidant capacity. CONCLUSIONS: This is the first reported attempt to comparatively determine the types of the metabolites of the three widely distributed Artemisia species in Tibet. The information should help medicinal research and facilitate comprehensive development and utilization of Artemisia species in Tibet.

swnk plays an important role in the biosynthesis of swainsonine in Metarhizium anisopliae.

OBJECTIVE: Swainsonine (SW) is the principal toxic ingredient of locoweeds, and is produced by multiple fungi. A key enzyme in the SW synthesis pathway is a hybrid swnk/nrps. To analyze the role of swnk in the SW biosynthesis pathway of Metarhizium anisopliae. RESULTS: The concentration of SW and the swnk expression in M. anisopliae fermentation from 1st to 7th day were determined using LC-MS and RT-qPCR, respectively. M. anisopliae had the highest SW content and swnk expression on the 5th day of fermentation; Mutant strain (MT) were obtained by PEG-mediated homologous recombination (HR) which knocked out swnk in the wild-type (WT) strain. Complemented-type (CT) strain were obtained by transforming a modified PUC19 complementation vector containing the geneticin (G418) resistance gene and swnK. SW was not detected in the MT strain and reverted to its original level in the CT strain; A Psilent-1 plasmid with Benomyl (ben)-resistant that was used interfered with swnk of WT strain. The level of SW was markedly diminished in the RNAi strain. RNAi of swnk affects the formation of the cell wall in M. anisopliae. CONCLUSION: These results indicate that swnk plays a crucial role in the SW biosynthesis of M. anisopliae.

Swainsonine-induced vacuolar degeneration is regulated by mTOR-mediated autophagy in HT22 cells.

The indolizidine alkaloid, swainsonine (SW), is the main toxic component of locoweed, which can cause locoism in animals with characteristic neurological dysfunction. Pathological manifestations at cellular level include extensive vacuolar degeneration. Studies have shown that SW can induces autophagy, but the role and mechanism of autophagy in SW-induced vacuolar degeneration is unclear. In this study, we analyzed the role of autophagy in SW-induced cell injury in mouse hippocampal neurons cell line (HT22) using western blotting, qRT-PCR, transmission electron microscopy and immunofluorescence microscopy. The results showed that the expressions of LC3-II, ATG5, Beclin1 and p62 proteins and their mRNAs in HT22 cells were induced by SW treatment. The SW treatment increased the number of autophagosomes with enhanced fluorescence intensity of monodansylcadaverine (MDC) and LC3-II in a time-dose dependent manner. The results of lysosome staining showed that SW could increase the number of lysosomes, increase the intraluminal pH. Transmission electron microscopy results indicate that SW induced autophagosomes, and Baf A1 could effectively alleviate SW-induced vacuolar degeneration. At the molecular level, SW treatment inhibited the expression of p-PI3K, p-AKT, p-ERK, p-AMPK, p-mTOR, p-p70S6K and p-4EBP1 and promoted the expression of p53. Our results collectively suggest, PI3K/AKT/mTOR, ERK/mTOR and p53/mTOR signaling pathways are involved in the regulation of SW-induced autophagy in HT22 cells, while the AMPK/mTOR signaling pathway is not involved in this regulation. Inhibition of autophagic degradation can effectively alleviate SW-induced vacuolar degeneration.

Experiences of health management among people at high risk of stroke in China: A qualitative study.

BACKGROUND: Effective health management of people at high risk of stroke in China is challenging. AIM: To explore and identify the experiences of health management among people at high risk of stroke in order to provide a foundation for a targeted health management strategy for this special group. DESIGN: A qualitative, descriptive study based on interviews. METHODS: Semistructured interviews were conducted with 31 people at high risk of stroke. The interviews were collated and analysed using Colaizzi's seven-step method. RESULTS: A total of 31 people at high risk of stroke were included, and the ages ranged from 40 to 86, with an average age of 60.71 (SD = 11.55). The experiences of health management were categorized into three themes. Theme 1: Facing many ongoing problems in health management, limited knowledge, lack of confidence and poor compliance. Theme 2: Accumulated some value experiences of coping with problems of health management, becoming active learners, promoting social interaction and enhancing self-health management. Theme 3: Sensitivity to multiple influencing factors, the severity of disease and complexity of disease management, family income and economic burden and the value of social support. CONCLUSIONS: This study explored the experiences of health management among people at high risk of stroke, and these findings are of great significance in the primary prevention of stroke.

Hematological and Histopathological Effects of Subacute Aconitine Poisoning in Mouse.

Aconitine is the principal toxic ingredient of Aconitum, which can cause systemic poisoning involving multiple organs and systems after animal ingestion. The purpose of this study was to investigate the effects of aconitine on hematological indices and histological changes in mice. One hundred twenty mice were divided into a control group (normal saline), low-dose group (0.14 µmol/L), middle-dose group (0.28 µmol/L) and high-dose group (0.56 µmol/L), which were continuously lavaged for 30 days. The blood of 10 mice were collected randomly and analyzed by group at the 10th, 20th, and 30th days, and some tissues were collected and stained with hematoxylin-eosin to observe histological changes at the 30th day. Compared with the control group, the organ coefficient (%) of liver, spleen, lungs, and brain of the high-dose group were significantly increased (p < 0.05 or p < 0.01). WBC and Gran initially decreased and then increased in each poisoning group, with significant differences in the high-dose group (p < 0.05 or p < 0.01). RBC, HGB, HCT, and PLT decreased continuously in all groups except the low-dose group at the 20th and 30th days (p < 0.05 or p < 0.01). Moreover, BUN, ALT and AST increased in each poisoning group, in comparison with the control group, with significant differences except for the low-dose group (p < 0.05 or p < 0.01). CRE initially increased and then decreased, the TP and ALB decreased, with significant differences observed in the high-dose and middle-dose groups (p < 0.05). All the mice in the poison-treated groups showed varying degrees of histopathological changes such as degeneration and necrosis of tissues, especially heart and cerebellum. Our data suggest that different doses of aconitine have remarkable effects on hematological and histopathological changes in mice, in a significant time and dose-effect relationship.

Exploring the role of autophagy during early human embryonic development through single-cell transcriptome and methylome analyses.

Early human embryogenesis is a very sophisticated process due to its unique gene regulatory network. Autophagy has been suggested to play an important role in mediating the development of early embryonic cells in mammals. However, evidence showing how autophagy regulates early human embryogenesis remains to be further explored. In this study, we systematically investigated the human transcriptome and methylome patterns of autophagy-related (ATG) genes in early embryonic cells at single-cell resolution. We analyzed the transcriptomic data of 365 cells and methylome data of 265 cells. The results showed that most ATG genes remained epigenetically active and were expressed stably throughout early embryogenesis, whereas the dynamics varied among different developmental stages. This evidence indicated that the autophagy pathway was constitutively activated and exerted a fundamental role in early human embryo development. Our work, for the first time, comprehensively reveals the features of autophagy during early human embryo development.

Ivermectin accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation.

OBJECTIVE: This study aimed to investigate the regulatory effect of ivermectin (IVM) on energy metabolism in glioma progression, and provide a reference for the treatment of glioma. METHODS: Glioma cells were treated with IVM to measure cell viability, autophagy marker protein expression, ATP content, glucose uptake, pyruvate content, and expression of key enzymes of glycolysis. Glucose transporter 4 (GLUT4) or siGLUT4 was transfected in IVM treated U87 cells to investigate the effect of GLUT4 on cellular glycolysis and autophagy. The JAK2 inhibitor AZD-1480 was introduced to explore the specific mechanism by which IVM regulates glycolysis and autophagy. Rat models of glioma xenograft were constructed and treated with 10 mg/kg IVM to observe tumor growth and examine the expression levels of GLUT4 and autophagy marker proteins in tumor tissues. RESULTS: IVM inhibited glioma cell survival and promoted cell death. IVM promoted LC3-II protein expression and inhibited p62/SQSTM1 protein expression in glioma cells. IVM decreased adenosine-triphosphate (ATP) and pyruvate content, promoted glucose uptake, and reduced HK2 and PFK1 protein expression in U87 cells. IVM inhibited GLUT4 protein expression, and overexpression of GLUT4 promoted glycolysis and inhibited autophagic cell death in U87 cells. IVM inhibited glycolysis by blocking GLUT4 mediated the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway activation. IVM inhibited tumor growth in vivo, decreased the protein expression of GLUT4, JAK2, HK2, and PFK1 in tumor tissues, decreased the phosphorylation levels of STAT3/STAT5, and promoted the expression of autophagy marker proteins. CONCLUSIONS: IVM accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation.

Maternal and neonatal outcomes following blastocyst biopsy for PGT in single vitrified-warmed embryo transfer cycles.

RESEARCH QUESTION: Does blastocyst biopsy for preimplantation genetic testing (PGT) increase the risk of adverse maternal and neonatal outcomes? STUDY DESIGN: Retrospective cohort study of 5097 single vitrified-warmed blastocyst transfer cycles from January 2016 to December 2018, with 2061 cycles in the biopsied group and 3036 cycles in the unbiopsied group enrolled in the analyses. Maternal and neonatal outcomes were compared between the two groups. RESULTS: The live birth rate in the biopsied group (41.1%) was significantly higher than that in the unbiopsied group (35.6%, adjusted odds ratio [aOR] 1.27, 95% confidence interval [CI] 1.05-1.54, P = 0.012) after adjusting for maternal age, maternal body mass index, gravidity, parity, infertility diagnosis, timing of blastocyst transfer, blastocyst quality, regimen of endometrial preparation, endometrial thickness before transfer and treatment year. The rates of total pregnancy loss (25.4% versus 32.2%, aOR 0.69, 95% CI 0.52-0.91, P = 0.008) and early miscarriage (12.1% versus 17.3%, aOR 0.56, 95% CI 0.38-0.83, P = 0.004) were significantly lower in the biopsied group than in the unbiopsied group. No significant differences were found in sex ratio or the risks of hypertensive disorders in pregnancy, diabetes in pregnancy, placenta previa, preterm premature rupture of membranes, low birthweight, very low birthweight, macrosomia, small for gestational age, large for gestational age or birth defects between the two groups. When the subgroup analyses were conducted based on different types of PGT, similar patterns were found for all types. CONCLUSION: Blastocyst biopsy might not increase the risks of adverse maternal and neonatal outcomes in the short term.

A Machine Learning Approach for Detecting Vicarious Trial and Error Behaviors.

Vicarious trial and error behaviors (VTEs) indicate periods of indecision during decision-making, and have been proposed as a behavioral marker of deliberation. In order to understand the neural underpinnings of these putative bridges between behavior and neural dynamics, researchers need the ability to readily distinguish VTEs from non-VTEs. Here we utilize a small set of trajectory-based features and standard machine learning classifiers to identify VTEs from non-VTEs for rats performing a spatial delayed alternation task (SDA) on an elevated plus maze. We also show that previously reported features of the hippocampal field potential oscillation can be used in the same types of classifiers to separate VTEs from non-VTEs with above chance performance. However, we caution that the modest classifier success using hippocampal population dynamics does not identify many trials where VTEs occur, and show that combining oscillation-based features with trajectory-based features does not improve classifier performance compared to trajectory-based features alone. Overall, we propose a standard set of features useful for trajectory-based VTE classification in binary decision tasks, and support previous suggestions that VTEs are supported by a network including, but likely extending beyond, the hippocampus.

Association between illness perception and health behaviour among stroke patients: The mediation effect of coping style.

AIMS: This study aims to explore illness perception and coping style in relation to health behaviour and the mediating role of coping style between illness perception and health behaviour among stroke patients. DESIGN: Cross-sectional study. METHODS: This survey was conducted with 515 stroke patients aged ≥18 years from September 2019 to January 2020 in Zhengzhou, China. The demographic and clinical characteristics questionnaire, Stroke Illness Perception Questionnaire-Revised, Simplified Coping Style Questionnaire, and Health Behavior Scale for Stroke Patients were included in this study. Data analysis was performed by correlation analysis, multiple linear regression analysis, and structural equation modelling. RESULTS: The valid questionnaires were 495 (effective response rate: 96.1%). Low negative illness perception, high positive coping style, and low negative coping style are related to high level of health promoting behaviour (all p < 0.01). The results revealed that the effect of illness perception on health behaviour was partly mediated by coping style. It also confirmed that the mediation effect accounts for 43.7% (-0.169/-0.387) of the total effect. CONCLUSION: Illness perception may influence health behaviour partly because of coping style. IMPACT: This study implies that targeted interventions for stroke patients' illness perception are needed to motivate them to take proactive coping strategy to ultimately improve their health behaviours.

Topical Application of Fibroblast Growth Factor 10-PLGA Microsphere Accelerates Wound Healing via Inhibition of ER Stress.

There is a high incidence of acute and chronic skin defects caused by various reasons in clinically practice. The repair and functional reconstruction of skin defects have become a major clinical problem, which needs to be solved urgently. Previous studies have shown that fibroblast growth factor 10 (FGF10) plays a functional role in promoting the proliferation, migration, and differentiation of epithelial cells. However, little is known about the effect of FGF10 on the recovery process after skin damage. In this study, we found that the expression of endogenous FGF10 was increased during wound healing. We prepared FGF10-loaded poly(lactic-co-glycolic acid) (FGF10-PLGA) microspheres, and it could sustain release of FGF10 both in vitro and in vivo, accelerating wound healing. Further analysis revealed that compared with FGF10 alone, FGF10-PLGA microspheres significantly improved granulation formation, collagen synthesis, cell proliferation, and blood vessel density. In the meantime, we found that FGF10-PLGA microspheres inhibited the expression of endoplasmic reticulum (ER) stress markers. Notably, activating ER stress with tunicamycin (TM) reduced therapeutic effects of FGF10-PLGA microspheres in wound healing, whereas inhibition of ER stress with 4-phenyl butyric acid (4-PBA) improved the function of FGF10-PLGA microspheres. Taken together, this study indicates that FGF10-PLGA microspheres accelerate wound healing presumably through modulating ER stress.

Testing Two Student Nurse Stress Instruments in Chinese Nursing Students: A Comparative Study Using Exploratory Factor Analysis.

BACKGROUND: The development and transformation of nursing within professional tertiary education have exerted a great pressure and challenge upon nursing students. Stress experienced by nursing students is a common precursor of psychological distress and attrition. However, no scale is specifically used to evaluate the sources of stress experienced by nursing students in Mainland China. Aims and Objective. This study is aimed at testing and comparing the reliability and validity including sensitivity and specificity of two nursing students' stress instruments, the Chinese version of Student Nurse Stress Index Scale (SNSI-CHI), and the Stressors in Student Nursing Scale (SINS-CN) in Chinese nursing students, and describing the stress status of nursing students in China. METHODS: A cross-sectional survey was conducted in two nursing schools in Henan Province from August 2017 to January 2018. Data were collected by using a questionnaire comprising the Chinese version of SNSI (SNSI-CHI), the Chinese version of SINS (SINS-CN), and the Chinese Perceived Stress Scale (CPSS). Homogeneity and stability, content, construct and concurrent validity, and sensitivity and specificity were assessed. RESULTS: The Cronbach's alpha (α) of SNSI-CHI was 0.90, and the item-to-total correlations ranged from 0.35 to 0.66. The Cronbach's α of SINS-CN was 0.93, and the item-to-total correlations ranged from 0.19 to 0.61. The findings of exploratory factor analysis (EFA) confirmed a good construct validity of SNSI-CHI and SINS-CN. The Pearson's rank correlation coefficients, between total scores of SNSI-CHI and CPSS and SINS-CN and CPSS, were assessed to 0.38 (P < 0.01) and 0.39 (P < 0.01), respectively. Regarding the CPSS, as the criterion, the cut-points of SNSI-CHI and SINS-CN for the area under the receiver operator characteristic (ROC) curve were 0.77and 0.66, respectively. CONCLUSION: Both scales are valid and reliable for evaluating the source of stress of student nurses in China. Each has its own characteristics, but the SNSI-CHI demonstrated marginal advantage over the SINS-CN. The SNSI-CHI is short, is easily understood, and with clear dimension for the nursing students, and the SNSI-CHI is more acceptable for the users in China.

Identification of health behaviour clusters among people at high risk of stroke: A latent class profile analysis.

AIMS: To identify the possible latent classes of health behaviour reported by people at high risk of stroke and to explore the predictors of these different classes of health behaviour. DESIGN: A cross-sectional survey study. METHODS: A stratified cluster random sampling method was used to collect data from 2,500 individuals at high risk of stroke who were from Henan Province, China, from January 2018-January 2019. A latent class profile analysis was used to identify the health behaviour clusters and multinomial logistic regression was used to determine which factors predicted the emergent latent classes of health behaviour. RESULTS: High-risk individuals (N = 2,236) at high risk of stroke replied to the survey (89.44% response rate). Model fit indices (AIC = 257,509.610, BIC = 260,228.733, Entropy = 0.956) supported a three-class model of health behaviours. The latent classes were Class 1 (a good level of adaptive health behaviour, 31%, N = 693), Class 2 (a moderate level of adaptive health behaviour, 36%, N = 805) and Class 3 (a poor level of adaptive health behaviour, 33%, N = 738); Based on physical and belief, behaviour and clinical profiles, the three classes were further labelled self-realization deficiency subgroup, social contact anxiety subgroup and health responsibility absence subgroup respectively. Older age, male gender, no spouse, lower education and household income were risk factors associated with good health behaviour. After controlling these socio-demographic variables, high levels of health-related knowledge and attitude were the main positive predictors of health behaviour. CONCLUSIONS: This study has identified three different latent classes of health behaviour and their predictive factors in people at high risk of stroke in the Chinese setting. IMPACT: This study has significance for the promotion of adaptive health behaviour in individuals at high risk of stroke. It has allowed the identification of specific clusters of health behaviour that vary in terms of their adaptiveness and forms the basis for the development of a targeted intervention to promote health behaviour for each different subgroup.

Is resourcefulness as a mediator between perceived stress and depression among old Chinese stroke patients?

OBJECTIVE: This study aimed to explore whether resourcefulness can serve as a mediator between perceived stress and depression among old Chinese stroke patients. METHODS: A cross-sectional study was conducted in six hospitals during July 2016 to July 2017, from five cities of Henan Province, China. A demographic questionnaire, the Perceived Stress Scale (PSS), the Resourcefulness Scale (RS) and the Center for Epidemiologic Studies Depression Scale (CES-D) were distributed among 3000 old stroke patients, and 2907 of them completed this survey. Correlation analysis, multiple linear regression and structural equation model (SEM) were used for statistical analysis of the study. RESULTS: The total scores of the resourcefulness were negatively correlated with perceived stress (r= -0.795, P<0.01) and depression (r= -0.772, P<0.01); It indicated positive correlation of the total scores of perceived stress and depression (r = 0.820, P<0.01). Multiple regression analyses showed that resourcefulness mediated the relationship between perceived stress and depression, which reduced the effect of perceived stress on depression by 16.3% (from 0.464 to 0.301) on the subscale "sense of being out of control" and by 20.3% (from 0.411 to 0.208) on the subscale "feeling of tension" when resourcefulness was included in the model. Structural equation model validated these findings, and further confirmed that resourcefulness had a partial mediation effect (39.4% of total effect) between perceived stress and depression. LIMITATIONS: This cross-sectional study does not allow for examination of the relationship between pre-stroke resourcefulness and post-stroke depression, or the potential intervening role of perceived stress. CONCLUSION: Resourcefulness was found to be a mediator between perceived stress and depression, suggesting the potential benefit of an intervention to teach resourcefulness skills to decrease depression in highly stressed older Chinese stroke patients.