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Age-associated decreases in follicle number and oocyte quality result in a decline in female fertility, which is associated with increased infertility. Granulosa cells play a major role in oocyte development and maturation both in vivo and in vitro. However, it is unclear whether a reduction in cryptochrome 1 (Cry1) expression contributes to granulosa cell senescence, and further exploration is needed to understand the underlying mechanisms. In this study, we investigated the role of Cry1, a core component of the molecular circadian clock, in the regulation of senescence in ovarian granulosa cells. Western blotting and qRT-PCR showed that Cry1 expression was downregulated in aged human ovarian granulosa cells and was correlated with age and anti-Müllerian hormone (AMH) levels. RNA-seq analysis suggested that ferritinophagy was increased after Cry1 knockdown in KGN cells. MDA, iron, and reactive oxygen species (ROS) assays were used to detect cellular ferritinophagy levels. Ferroptosis inhibitors, iron chelators, autophagy inhibitors, and nuclear receptor coactivator 4 (NCOA4) knockdown alleviated KGN cell senescence induced by Cry1 knockdown. Immunofluorescence, immunoprecipitation, and ubiquitination assays indicated that Cry1 affected NCOA4 ubiquitination and degradation through HERC2, thereby affecting NCOA4-mediated ferritinophagy and causing granulosa cell senescence. KL201, a Cry1 stabilizer, enhanced ovarian function in naturally aged mice by reducing ferritinophagy. Our study reveals the potential mechanisms of action of Cry1 during ovarian aging and provides new insights for the clinical treatment of age-related fertility decline. A proposed molecular model of Cry1 in regulating senescence of human granulosa cells. Cry1 depletion reduced the expression of the E3 ubiquitin ligase HERC2, which reduced the ubiquitination and degradation of NCOA4, thereby promoting ferritinophagy and inducing granulosa cell senescence. [Display omitted] • Cry1 expression is downregulated in aged human ovarian granulosa cells. • Cry1 induces KGN cell senescence through NCOA4-mediated ferritinophagy. • Cry1 affects NCOA4 ubiquitination and degradation through HERC2. • Cry1 stabilizer KL201 enhances ovarian function by reducing ferritinophagy in middle-aged mice. [ABSTRACT FROM AUTHOR]

A growing number of Protestant missionaries engaged in vernacular education in the late nineteenth century. To meet the demands of the new era, Christian church education faced challenges not only in its curriculum design but also in the way it presented new knowledge. Previous studies have focused on church education at the tertiary level while overlooking the elementary level. This article discusses vernacular church education and vernacular textbooks at the elementary level in the late Qing, with specific reference to Youxue baoshen yaoyan 幼學保身要言 (The Human Body for Children). It argues that the demand for spreading new knowledge urged Protestant missionaries to compile vernacular textbooks and present Western knowledge in the local settings. Vernacular church education should be regarded as the precursor of indigenous education proposed by the late Qing Court. The local dialect, Cantonese in this case, bridged the linguistic gap between new terms and children's cognition and became an effective means of presenting new knowledge. Vernacular textbooks had an unparalleled significance in the cultural sphere of dialect writing, since the language of textbooks could drastically influence the writing and reading habits of the young generation and further influence people's attitudes towards dialects and dialect literature. [ABSTRACT FROM AUTHOR]

Bias in perceptual decision making can have both sensory and decisional origins. These distinct sources of bias are typically seen as static and stable over time. However, human behavior is dynamic and constantly adapting. Yet it remains unclear how sensory and decisional biases progress in distinct ways over time. We addressed this question by tracking the dynamics of sensory and decisional biases during a task that involves a visual illusion. Observers saw multiple pairs of peripherally presented faces that induce a strong illusion making the faces appear distorted and grotesque. The task was to judge whether one of the last two faces had true physical distortion (experimentally introduced in half of the trials). Initially, participants classified most faces as distorted as exemplified by a liberal response bias. However, over the course of the experiment, this response bias gradually disappeared even though the distortion illusion remained equally strong, as demonstrated by a separate subjective rating task without artificially distorted faces. The results suggest that the sensory bias was progressively countered by an opposite decisional bias. This transition was accompanied by an increase in reaction times and a decrease in confidence relative to a condition that does not induce the visual illusion. All results were replicated in a second experiment with inverted faces. These findings demonstrate that participants dynamically adjust their decisional bias to compensate for sensory biases, and that these two biases together determine how humans make perceptual decisions. [ABSTRACT FROM AUTHOR]

In this study, we report a novel synthetic strategy to prepare a highly (110)-oriented ZIF-7 film possessing superior anti-corrosion properties via oriented epitaxial growth. Our work provides insights into facile preparation of oriented uniform MOF single seed layers and films with rod-shaped MOF seeds as building blocks. [ABSTRACT FROM AUTHOR]

With the advent of next-generation sequencing, investigators have access to higher quality sequencing data. However, to sequence all samples in a study using next generation sequencing can still be prohibitively expensive. One potential remedy could be to combine next generation sequencing data from cases with publicly available sequencing data for controls, but there could be a systematic difference in quality of sequenced data, such as sequencing depths, between sequenced study cases and publicly available controls. We propose a regression calibration (RC)-based method and a maximum-likelihood method for conducting an association study with such a combined sample by accounting for differential sequencing errors between cases and controls. The methods allow for adjusting for covariates, such as population stratification as confounders. Both methods control type I error and have comparable power to analysis conducted using the true genotype with sufficiently high but different sequencing depths. We show that the RC method allows for analysis using naive variance estimate (closely approximates true variance in practice) and standard software under certain circumstances. We evaluate the performance of the proposed methods using simulation studies and apply our methods to a combined data set of exome sequenced acute lung injury cases and healthy controls from the 1000 Genomes project. [ABSTRACT FROM AUTHOR]

Satellite-derived estimates of the Earth's radiation budget are crucial for understanding and predicting the weather and climate. However, existing satellite products measuring broadband outgoing longwave radiation (OLR) and reflected shortwave radiation (RSR) have spatio-temporal resolutions that are too coarse to evaluate important radiative forcers like aircraft condensation trails. We present a neural network which estimates OLR and RSR based on narrowband radiances, using collocated Cloud and Earth's Radiant Energy System (CERES) and GOES-16 Advanced Baseline Imager (ABI) data. The resulting estimates feature strong agreement with the CERES data products (R 2 = 0.977 for OLR and 0.974 for RSR on CERES Level 2 footprints), and we provide open access to the collocated satellite data and model outputs on all available GOES-16 ABI data for the 4 years from 2018–2021. [Display omitted] • OLR and RSR estimates from GOES-16 ABI without radiative transfer simulation dataset. • Strong agreement with CERES data products (R 2 = 0.977 for OLR and 0.974 for RSR). • 4 years of flux estimates for GOES-16 viewing extent made publicly available. [ABSTRACT FROM AUTHOR]

WeChat business is an emerging way of doing business in China, which can be considered as a marriage between traditional e-business and social networking communications. In WeChat business, firms have developed customer relationships along two distinct ways: business relationships and friendships. However, research on the combination of business relationships and friendships is relatively nascent, and there are contradictory findings. In this study, we examine the effectiveness of the two relationship strategies using data from a field experiment through the WeChat platform by an apparel firm. Results from the field experiment suggest that development of friendships with new customers can help the strategy of developing business relationships; but developing friendships and business relationships with experienced customers negates each other. The study contributes to the literature on relationship marketing and role theory, and helps WeChat managers clarify how new social networking relationships with customers can be effectively leveraged. [ABSTRACT FROM PUBLISHER]

Concurrent manipulation of orientation and thickness of MOF membranes has become a reliable approach for improving their separation performances. In terms of oriented seeded growth, oriented deposition of MOF nanosheets during seeding process and sealing all intergranular gaps with no discernible increase in membrane thickness during secondary growth have become indispensable. In this study, we pioneered the fabrication of uniform hexagonal-shaped, 20–40 nm thick MIL-96 nanosheets through solvent composition optimization (V H2O /V FA = 1/2). Subsequently, spin coating was employed for c -oriented deposition of uniform MIL-96 seed layer, during which the addition of PVP in the suspension was found to be critical for obtaining qualified seed layer. Finally, well-intergrown, highly c -oriented ultrathin MIL-96 membrane was prepared upon employing NMF as the solvent during secondary growth. Gas permeation results implied that prepared MIL-96 membrane exhibited superior gas separation performance compared with that of a -& b -oriented counterpart. [Display omitted] • Uniform 20–40 nm thick MIL-96 nanosheets were synthesized via solvent optimization. • Solvent type affected preferred orientation and thickness of the MIL-96 membrane. • c -Oriented ultrathin MIL-96 membrane showed superior H 2 /CO 2 separation performance. [ABSTRACT FROM AUTHOR]

Metal‐organic framework (MOF), which possesses stable framework structure constructed by highly connected metal‐oxo cluster nodes and organic linkers, has shown great promise in gas storage, adsorption, and separation, owing to the high surface areas, tunable pore aperture, and rich functional groups. In this review article, we summarized recent progress made in synthesizing high‐valence MOF (e. g. UiO‐66, MIL‐125, PCN‐22, and MIP‐207) with metal‐oxo cluster as metal source. Of particular note, recent breakthroughs in the preparation of UiO‐66 and MIL‐125 membranes with the corresponding Zr6‐oxo and Ti8‐oxo cluster sources (e. g. Zr6O4(OH)4(OAc)12 and Ti8O8(OOCR)16 clusters) possessing superior separation performance were highlighted. In the end, an outlook on the preparation of versatile high‐valence MOF membranes with the corresponding metal‐oxo clusters as metal sources was highlighted. [ABSTRACT FROM AUTHOR]

Required for meiotic nuclear division 5 homolog A (RMND5A) functions as an E3 ubiquitin ligase. To date, few studies have investigated the role of RMND5A in cancer. In the present study, the expression levels of RMND5A in multiple types of cancer were analyzed using the Gene Expression Profiling Interactive Analysis platform. The results revealed that RMND5A was highly expressed and associated with overall survival in patients with pancreatic adenocarcinoma (PAAD). A wound-healing assay revealed that RMND5A overexpression significantly increased cell migration in the PAAD cell lines AsPC-1 and PANC-1. In silico analysis predicted that RMND5A was a potential target of microRNA(miR)-590-5p. Further in vitro experiments demonstrated that overexpression of miR-590-5p downregulated the expression levels of RMND5A and decreased the migratory ability of the AsPC-1 and PANC-1 cell lines. In addition, overexpression of miR-590-5p attenuated the promoting effects of RMND5A on the migration of AsPC-1 and PANC-1 cells. The results of the present study may further elucidate the mechanisms underlying PAAD progression and provide novel targets for the treatment of PAAD. [ABSTRACT FROM AUTHOR]

Network models are applied in numerous domains where data arise from systems of interactions among pairs of actors. Both statistical and mechanistic network models are increasingly capable of capturing various dependencies among these actors. Yet, these dependencies pose statistical challenges for analyzing such data, especially when the data set comprises only a single observation of one network, often leading to intractable likelihoods regardless of the modeling paradigm and limiting the application of existing statistical methods for networks. We explore a subsampling bootstrap procedure to serve as the basis for goodness of fit and model selection with a single observed network that circumvents the intractability of such likelihoods. Our approach is based on flexible resampling distributions formed from the single observed network, allowing for more nuanced and higher dimensional comparisons than point estimates of quantities of interest. We include worked examples for model selection, with simulation, and assessment of goodness of fit, with duplication-divergence model fits for yeast (S.cerevisiae) protein-protein interaction data from the literature. The proposed approach produces a flexible resampling distribution that can be based on any network statistics of one's choosing and can be employed for both statistical and mechanistic network models. [ABSTRACT FROM AUTHOR]

Concurrent regulation of crystallographic orientation and thickness of zirconium metal–organic framework (Zr‐MOF) membranes is challenging but promising for their performance enhancement. In this study, we pioneered the fabrication of uniform triangular‐shaped, 40 nm thick UiO‐66 nanosheet (NS) seeds by employing an anisotropic etching strategy. Through innovating confined counter‐diffusion‐assisted epitaxial growth, highly (111)‐oriented 165 nm‐thick UiO‐66 membrane was prepared. The significant reduction in thickness and diffusion barrier in the framework endowed the membrane with unprecedented CO2 permeance (2070 GPU) as well as high CO2/N2 selectivity (35.4), which surpassed the performance limits of state‐of‐the‐art polycrystalline MOF membranes. In addition, highly (111)‐oriented 180 nm‐thick NH2‐UiO‐66 membrane showing superb H2/CO2 separation performance with H2 permeance of 1230 GPU and H2/CO2 selectivity of 41.3, was prepared with the above synthetic procedure. [ABSTRACT FROM AUTHOR]

Concurrent regulation of crystallographic orientation and thickness of zirconium metal–organic framework (Zr‐MOF) membranes is challenging but promising for their performance enhancement. In this study, we pioneered the fabrication of uniform triangular‐shaped, 40 nm thick UiO‐66 nanosheet (NS) seeds by employing an anisotropic etching strategy. Through innovating confined counter‐diffusion‐assisted epitaxial growth, highly (111)‐oriented 165 nm‐thick UiO‐66 membrane was prepared. The significant reduction in thickness and diffusion barrier in the framework endowed the membrane with unprecedented CO2 permeance (2070 GPU) as well as high CO2/N2 selectivity (35.4), which surpassed the performance limits of state‐of‐the‐art polycrystalline MOF membranes. In addition, highly (111)‐oriented 180 nm‐thick NH2‐UiO‐66 membrane showing superb H2/CO2 separation performance with H2 permeance of 1230 GPU and H2/CO2 selectivity of 41.3, was prepared with the above synthetic procedure. [ABSTRACT FROM AUTHOR]

Loss or absence of hearing is common at both extremes of human lifespan, in the forms of congenital deafness and age-related hearing loss. While these are often studied separately, there is increasing evidence that their genetic basis is at least partially overlapping. In particular, both common and rare variants in genes associated with monogenic forms of hearing loss also contribute to the more polygenic basis of age-related hearing loss. Here, we directly test this model in the Penn Medicine BioBank–a healthcare system cohort of around 40,000 individuals with linked genetic and electronic health record data. We show that increased burden of predicted deleterious variants in Mendelian hearing loss genes is associated with increased risk and severity of adult-onset hearing loss. As a specific example, we identify one gene–TCOF1, responsible for a syndromic form of congenital hearing loss–in which deleterious variants are also associated with adult-onset hearing loss. We also identify four additional novel candidate genes (COL5A1, HMMR, RAPGEF3, and NNT) in which rare variant burden may be associated with hearing loss. Our results confirm that rare variants in Mendelian hearing loss genes contribute to polygenic risk of hearing loss, and emphasize the utility of healthcare system cohorts to study common complex traits and diseases. Author summary: Age-related hearing loss is relatively common and has a genetic component to risk, though little is known about specific genes that are involved. Here, we study participants in the Penn Medicine BioBank to identify factors that increase risk of hearing loss. We show that loss-of-function variants in genes that are known to cause Mendelian forms of hearing loss also increase risk of age-related hearing loss. Because many such genes have been identified, they can be used to interpret the results of genome-wide association studies and to investigate the biological basis of age-related hearing loss. Our results also emphasize that many reported Mendelian hearing loss variants are incompletely penetrant and may act cumulatively. Finally, our study shows how hospital-recruited biobank cohorts can aid in the study of common conditions like hearing loss, even when those conditions are not the primary reason for contact with the health system. [ABSTRACT FROM AUTHOR]

Although having shown great promise for efficient gas separation, relevant study of Ti‐MOF membranes remains very scarce, owing to limited Ti source types and uncertain factors which dominate the separation properties. In this work, we pioneered the use of the Ti8(μ2‐O)8(OOCC6H5)16 cluster as the Ti source of MIL‐125 membranes, which led to lower reaction temperature and higher missing‐linker number within the framework and therefore, enhanced CO2/N2 adsorption selectivity. The MIL‐125 membrane prepared by combining single‐mode microwave heating with tertiary growth displayed an ideal CO2/N2 selectivity of 38.7, which ranked the highest among all pristine pure MOF membranes measured under comparable conditions. In addition, the ideal H2/N2 and H2/CH4 selectivity was as high as 64.9 and 40.7, thus showing great promise for versatile utility in gas separation. [ABSTRACT FROM AUTHOR]

Although having shown great promise for efficient gas separation, relevant study of Ti‐MOF membranes remains very scarce, owing to limited Ti source types and uncertain factors which dominate the separation properties. In this work, we pioneered the use of the Ti8(μ2‐O)8(OOCC6H5)16 cluster as the Ti source of MIL‐125 membranes, which led to lower reaction temperature and higher missing‐linker number within the framework and therefore, enhanced CO2/N2 adsorption selectivity. The MIL‐125 membrane prepared by combining single‐mode microwave heating with tertiary growth displayed an ideal CO2/N2 selectivity of 38.7, which ranked the highest among all pristine pure MOF membranes measured under comparable conditions. In addition, the ideal H2/N2 and H2/CH4 selectivity was as high as 64.9 and 40.7, thus showing great promise for versatile utility in gas separation. [ABSTRACT FROM AUTHOR]

Although challenging, multi-scale structure tailoring has been proven to significantly enhance the separation performance of MOF membranes. In this study, through engineering seed morphology and innovating metal source, highly c -oriented MIL-125 membrane with tailored missing-linker defects was facilely prepared. Experimental results indicated that iron (III) acetylacetonate could serve as competent modulator for preparing uniform NH 2 -MIL-125(Ti/Fe) nanosheet seeds, while employing Ti 6 -oxo cluster source warranted precise tailoring of missing-linker defects in the framework. Through combining with single-mode microwave heating during secondary growth, we prepared highly c-oriented defect-rich MIL-125 membrane with CO 2 /N 2 separation factor of 47.7 ± 1.8 and CO 2 permeance of 720.6 ± 24.3 GPU, which remarkably surpassed the separation performance limit of state-of-the-art MOF membranes, demonstrating significant potential for energy-efficient CO 2 capture from flue gas. [Display omitted] • Defect-rich MIL-125 nanosheets were prepared with Ti 6 -oxo cluster as titanium source and Fe (acac) 3 as modulator. • Defect-rich, highly c-oriented and ultrathin MIL-125 membrane was prepared by facile oriented epitaxial growth. • Obtained MIL-125 membrane exhibited unprecedented CO 2 /N 2 separation performance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Highly reactive NH 4 F-mediated gel was employed as nutrient during epitaxial growth. • Both ammonium ions and fluorine ions were vital for enhancing the gel reactivity. • Fabrication of b -oriented MFI film over a broad temperature window of 30 ∼ 210 °C. • Synthetic procedure works well for the substrates with different surface properties. Despite that oriented MFI zeolite films exhibit significant prospects for a wide range of applications due to microstructural superiority, their precise orientation control entails rigorous demands on reaction conditions (e.g., reaction temperature). In this work, we achieved facile synthesis of continuous b -oriented MFI zeolite films with few twins over a wide crystallization temperature range of 30–210 °C through adopting NH 4 F-mediated gel as nutrient during epitaxial growth. Both ammonium ions and fluorine ions were found crucial for enhancing the gel reactivity, endowing epitaxial growth with higher crystallization rates; moreover, the above morphology could be maintained even under fluctuating temperature conditions during film processing, thereby showing great potential for their bath production in a facile and reproducible manner. [ABSTRACT FROM AUTHOR]

Background: Cardiac damage triggered by severe hypocalcemia is well known. However, the role of chronic hypoparathyroidism (HP) and pseudohypoparathyroidism (PHP) in cardiac health is still unclear. We investigated the effect of chronic HP and PHP on cardiac structure and conductive function in patients compiling with treatment. Methods: The study included 18 patients with HP and eight with PHP aged 45.4 ± 15.4 and 22.1 ± 6.4 years, respectively with a previously regular follow-up. In addition, 26 age- and sex-matched healthy controls were included. General characteristics and biochemical indices were recorded. Cardiac function and structure were assessed by estimation of myocardial enzymes, B-type natriuretic peptide (BNP), and echocardiography. The 12-lead electrocardiogram and 24-h Holter electrocardiography were performed to evaluate the conductive function. Results: Levels of serum calcium in HP and PHP were 2.05 ± 0.16 mmol/L and 2.25 ± 0.19 mmol/L, respectively. The levels of myocardial enzyme and BNP were within the normal range. Adjusting for age at evaluation and body mass index, all M-mode measurements, left ventricular mass (LVM), LVM index (LVMI) and relative wall thickness (RWT) were comparable between patients and controls. Prolongation of corrected QT (QTc) intervals occurred in 52.6% (10/19) of patients, and 6.7% (1/15) of patients manifested more than 100 episodes of supraventricular and ventricular extrasystoles, as well as supraventricular tachycardia. None of the above arrhythmias was related to a severe clinical event. Conclusions: From this pilot study, patients diagnosed with HP and PHP and well-controlled serum calcium levels manifested normal cardiac morphology and ventricular function, except for prolonged QTc intervals, and a small percentage of mild arrhythmias needing further investigation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Continuous carbon membranes were prepared via simple mechanical rubbing of pencil graphite. • Carbon membranes prepared from 2B pencil graphite showed the highest dye rejection rates. • The spent membranes could be recycled by erasing, enabling complete recycling and reuse of substrates. Although having shown great promise in gas separation, reverse osmosis, and nanofiltration, preparation of carbon membranes, which commonly involves elaborate high-temperature pyrolysis or exfoliation-reassembly, still suffers from complicated fabrication procedure and/or high production cost. In this study, we pioneered the preparation of continuous asymmetric carbon membrane through facile mechanical rubbing of a pencil graphite. Among them, 2B-type pencil with 64 wt% graphite exhibited superior nanofiltration performance (Congo Red rejection rate of 99.4% and water flux of 21.91 L·m−2·h−1·bar−1). Long-time operation confirmed its excellent stability. Of particular note, the spent membrane could be facilely recovered by erasing, resulting in not only zero pollutant discharge but also full recovery and reutilization of the substrate. The above protocol is anticipated to pave an avenue for facile and sustainable production of versatile carbon membranes with superior separation performances. [ABSTRACT FROM AUTHOR]

The framework dimension has been proven to exert significant influence on the separation performance of molecular sieve membranes (MSMs). Compared with the flourishing research on three-dimensional (3D) and two-dimensional (2D) membranes, relevant studies on one-dimensional (1D) membranes remained rarely explored to date. In this study, well-intergrown 1D VS 4 membranes were facilely prepared by in situ solvothermal growth. Among various synthetic parameters, the pH value of the precursor solution was found to play a crucial role in modulating the membrane microstructure, so that uniform and continuous 1D VS 4 membrane could be obtained at the pH value of 10 in ethylene glycol-H 2 O (EG-H 2 O) binary solvent. Relying on regular interchain space and great hydrophilicity, our membrane displayed excellent dye rejection efficiency (>99.0%), thus holding great promise for energy-efficient separation. [Display omitted] • The fabrication of polycrystalline 1D membranes comprising VS 4 nanochains was first reported in this study. • The solvent type and the pH value were found to exert significant influence on final morphology of 1D VS 4 membranes. • Obtained 1D VS 4 membranes exhibited excellent dye rejection performance (dye rejection rate >99%). [ABSTRACT FROM AUTHOR]