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Aim: We aim to establish a predictive model for the evaluation of fecundity based on infertility‐related factors. Methods: A total of 410 expectant couples who visited the First Affiliated Hospital of Xinjiang Medical University on January 1, 2017 and June 10, 2019 were included in this study. The 1‐year follow‐up was carried out to investigate the pregnancy of the female. They were divided into model group and test group, respectively. The basic information, life behavior and clinical indices were screened using the Logistics regression analysis and LASSO regression analysis. In addition, the multivariate logistic regression was used to establish the model for the prediction of fecundity risk. Results: The risk factors for the predictive model included female age and occupational pressure, gynecological disease, anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), fasting plasma glucose (FPG), depression, as well as male smoking. The area under the curve (AUC) for the model A and model B was 0.954 (0.931 ~ 0.978) and 0.955 (0.931 ~ 0.979), respectively. The AUC in the test group was 0.917 (0.869 ~ 0.965) and 0.921 (0.873 ~ 0.968). There were no statistical differences in the fitting value and measured values in the model group. Conclusions: We established a predictive model for the evaluation of fecundity, which showed a satisfactory accuracy and discriminatory power. [ABSTRACT FROM AUTHOR]

Aims: This study sought to investigate the association between blood pressure (BP) trajectories from early to middle adulthood and echocardiographic indices of structure and function in middle age. Methods and results: This prospective cohort study included 4717 black and white adults aged 18–30 years at baseline (1985–86) who were followed over 30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Trajectories of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) from the Year 0 examination to Year 30 examination were identified using latent mixture modelling. Echocardiographic indices of myocardial structure, systolic function, and diastolic function were assessed at the Year 30 examination. Five distinct SBP trajectory groups were identified: low‐stable [1110 participants (23.5%)], moderate‐stable [2188 (46.4%)], high‐stable [850 (18.0%)], moderate‐increasing [416 (8.8%)], and high‐increasing [153 (3.2%)]. After adjustment for clinical variables, a significant decreasing trend was observed from the high‐increasing and moderate‐increasing groups through to the low‐stable group for left ventricular (LV) mass index [mean (SE): high‐increasing, 112.3 (3.4); moderate‐increasing, 99.3 (2.6); high‐stable, 88.9 (2.5); moderate‐stable, 86.1 (2.3); low‐stable, 82.1 (2.4), P trend < 0.01], as well as LV end‐diastolic dimension, left atrial volume index, and E/e′, while an increasing trend was apparent for LV longitudinal strain, E/A ratio, and average e′ velocities. Results were generally consistent for trajectories of DBP and PP. Conclusions: Higher BP trajectories from early to middle adulthood were associated with worse indices of myocardial modelling and LV systolic and diastolic function at middle age. [ABSTRACT FROM AUTHOR]

Ligustilide is a phenolic compound isolated from Asian plants of Umbelliferae family. This study was aimed at exploring the neuroprotective effects of Ligustilide from the perspective of endoplasmic reticulum stress (ERS) and autophagy. The Alzheimer's disease (AD) cell models were constructed by SH‐SY5Y cell line, which was exposed to 20 μM Aβ25‐35. CCK‐8 was used to evaluate the cell viability of Ligustilide on AD cell model. Hoechst staining and LysoTracker Red were used to test the cell apoptosis and Lysosome function, respectively. ERS in living cells were detected by Thioflavin T. The expression of autophagy‐related proteins (LC3B‐II/I, P62/SQSTM1, Beclin1, and Atg5), ERS marker proteins (PERK, GRP78, and CHOH), and apoptosis proteins (Bax, Bcl‐2, and Caspase‐12) were analyzed by Western blot analyses. Aβ25‐35 could induce ERS and autophagy in a time‐dependent manner in SH‐SY5Y cells. We demonstrated that Ligustilide significantly decreased the rate of apoptosis, and improved the viability of cells. Simultaneously, Ligustilide effectively modulated ERS via inhibiting the over‐activation of GRP78/PERK/CHOP signaling pathway. In addition, Ligustilide alleviated the accumulation of autophagy vacuoles, reduced the ratio of LC3B‐II/I and the level of P62/SQSTM1. Ligustilide significantly up‐regulated lysosomal acidity and the expression of Cathepsin D (CTSD). Ligustilide could rescue lysosomal function to promote autophagy flux and inhibit the over‐activation of ERS. This finding may contribute to the development of new therapeutic strategies for AD. [ABSTRACT FROM AUTHOR]

Background: Growing evidence indicates that high phosphoserine phosphatase (PSPH) expression is associated with tumor prognosis in many types of cancers. However, the role of PSPH in non‐small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the clinical significance of PSPH in NSCLC. Methods: One hundred forty‐three patients with histologically confirmed NSCLC who underwent surgery were included. Quantitative real‐time PCR and Western blot were used to assess PSPH expression in paired tumor and corresponding adjacent non‐tumorous tissues. The role of PSPH in invasion and cell growth was investigated in vitro. Results: Compared to adjacent normal lung tissues, PSPH messenger RNA and protein levels were significantly higher in NSCLC tissues, and the PSPH expression level was positively related to clinical stage, metastasis, and recurrence. High PSPH expression was predictive of poor overall survival. A549 cells transfected with small interfering‐PSPH showed inhibited cell migration, invasion, and proliferation. We further demonstrated that PSPH might promote the invasive capabilities of NSCLC cells through the AKT/AMPK signaling pathway. Conclusion: Our results indicate that PSPH may act as a putative oncogene in NSCLC, and may be a vital molecular marker for the metastasis and proliferation of NSCLC cells by regulating the AKT/AMPK signaling pathway. [ABSTRACT FROM AUTHOR]

Brain metastasis (BM) is the primary contributor to mortality in non‐small cell lung cancer (NSCLC) patients. Although the findings of NSCLC genetic sequencing studies suggest the potential for personalizing therapeutic approaches, the genetic profiles and underlying mechanisms of BM progression remain poorly understood. Here, we investigated the genetic profiles of brain metastases from NSCLC in six patients with primary tumors and corresponding BM samples via whole exome sequencing and targeted panel sequencing. We have demonstrated considerable genetic heterogeneity between primary lung cancer and corresponding brain metastases specimens. High‐frequency mutations were found in NOTCH2, NOTCH2NL, FANCD2, EGFR, and TP53. Additionally, EGFR and TP53 consistently exhibited high frequencies of mutation between primary tumors and corresponding brain metastases. The implication is that most of the genetic alterations may be acquired or lost during malignant progression, and the stable EGFR and TP53 mutational status between paired primary tumors and metastatic sites confirms that most mutations detected on analysis of the primary tumor or metastases are sufficient for clinical decision‐making, and suggest there is no need to re‐biopsy recurrent tumors or metastases for most NSCLC patients. [ABSTRACT FROM AUTHOR]

Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed cortical function during focal seizures may depend on decreased subcortical cholinergic arousal, which leads to a sleep-like state of cortical slow-wave activity. To test this hypothesis, we sought to directly activate subcortical cholinergic neurons during focal limbic seizures to determine the effects on cortical function. Here we used an optogenetic approach to selectively stimulate cholinergic brainstem neurons in the pedunculopontine tegmental nucleus during focal limbic seizures induced in a lightly anesthetized rat model. We found an increase in cortical gamma activity and a decrease in delta activity in response to cholinergic stimulation. These findings support the mechanistic role of reduced subcortical cholinergic arousal in causing cortical dysfunction during seizures. Through further work, electrical or optogenetic stimulation of subcortical arousal networks may ultimately lead to new treatments aimed at preventing cortical dysfunction during seizures. [ABSTRACT FROM AUTHOR]

Objective Understanding the neural mechanisms that support human consciousness is an important frontier in neuroscience and medicine. We previously developed a rodent model of temporal lobe seizures that recapitulates the human electroencephalography ( EEG) signature of ictal and postictal neocortical slow waves associated with behavioral impairments in level of consciousness. The mechanism of slow-wave production in epilepsy may involve suppression of the subcortical arousal systems including the brainstem and intralaminar thalamic nuclei. We hypothesized that intralaminar thalamic stimulation may lead to electrophysiologic and functional rescue from postictal slow waves and behavioral arrest. Methods We electrically stimulated the central lateral thalamic nucleus (a member of the intralaminar nuclei) under anesthesia and after electrically induced hippocampal seizures in anesthetized and in awake-behaving animal model preparations. Results We demonstrated a proof-of-principle restoration of electrophysiologic and behavioral measures of consciousness by stimulating the intralaminar thalamic nuclei after seizures. We measured decreased cortical slow waves and increased desynchronization and multiunit activity in the cortex with thalamic stimulation following seizures. Functionally, thalamic stimulation produced resumption of exploratory behaviors in the postictal state. Significance Targeting of nodes in the neural circuitry of consciousness has important medical implications. Impaired consciousness with epilepsy has dangerous consequences including decreased school/work performance, social stigmatization, and impaired airway protection. These data suggest a novel therapeutic approach for restoring consciousness after seizures. If paired with responsive neurostimulation, this may allow rapid implementation to improve level of consciousness in patients with epilepsy. [ABSTRACT FROM AUTHOR]

The steep eastern margin of the Tibetan Plateau is thought to have developed in the Cenozoic by brittle crustal thickening or lower crustal flow related to India‐Asia collision. However, our data indicate that Late Triassic crustal shortening and voluminous magmatism contributed to crustal thickening and topography of the region. Sr/Y ratios of intermediate to silicic magmatic rocks reflect mineral assemblages in the magma source and can be used to constrain crustal thickness. The Sr/Y ratios from the Songpan‐Ganzi Fold Belt in the eastern Tibetan Plateau indicate that the eastern margin of the plateau achieved a crustal thickness ranging from 44 ± 6 to 67 ± 9 km during ca. 220 to 190 Ma. An average elevation of 2,600 ± 300 m at ca. 211 Ma is deduced based on average crustal thickness of 55 ± 2 km assuming Airy isostatic compensation. The thickened crust and high topography of the eastern margin of the Tibetan Plateau during the Late Triassic is supported by intense shortening and voluminous magmatism, contemporaneous Barrovian metamorphism, and the development of a foreland basin. Our data indicate that the eastern margin of the Tibetan Plateau was initially built during the Late Triassic, and this area has a long history of crustal thickening and mountain building. Key Points: Eastern margin of the Tibetan Plateau reached an average crustal thickness of 55 ± 2 km during ca. 220 to 190 MaThis margin attained an average elevation of 2,600 ± 300 m due to crustal thickening and magma underplating during this time intervalLate Triassic crustal thickening marks the initial growth of the present‐day eastern margin of the Tibetan Plateau [ABSTRACT FROM AUTHOR]