Identification and analysis of key genes related to efferocytosis in colorectal cancer.

The impact of efferocytosis-related genes (ERGs) on the diagnosis of colorectal cancer (CRC) remains unclear. In this study, efferocytosis-associated biomarkers for the diagnosis of CRC were identified by integrating data from transcriptome sequencing and public databases. Finally, the expression of biomarkers was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Our study may provide a reference for CRC diagnosis. BACKGROUND: It has been shown that some efferocytosis related genes (ERGs) are associated with the development of cancer. However, it is still uncertain how ERGs may influence the diagnosis of colorectal cancer (CRC). METHODS: In our study, the CRC cohorts were gained from transcriptome sequencing and the gene expression omnibus (GEO) database (GSE71187). Efferocytosis related biomarkers with diagnostic utility for CRC were identified through combining differentially expressed analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Then, infiltration abundance of immune cells between CRC and control was evaluated. The regulatory networks (including mRNA-miRNA-lncRNA and miRNA/transcription factors (TF)-mRNA networks) were created. Finally, the expression of biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: There were 3 biomarkers (ELMO3, P2RY12, and PDK4) related diagnosis for CRC patients gained. ELMO3 was highly expressed in CRC group, while P2RY12 and PDK4 was lowly expressed. Besides, the infiltrating abundance of 3 immune cells between CRC and control groups was significantly differential, namely activated CD4 memory T cells, macrophages M0, and resting mast cells. We then constructed a mRNA-miRNA-lncRNA network containing 3 mRNAs, 33 miRNAs, and 22 lncRNAs, and a miRNA/TF-mRNA network including 3 mRNAs, 33 miRNAs, and 7 TFs. Additionally, RT-qPCR results revealed that the expression trends of all biomarkers were consistent with the transcriptome sequencing data and GSE71187. CONCLUSION: Taken together, this study provides three efferocytosis related biomarkers (ELMO3, P2RY12, and PDK4) for diagnosis of CRC, providing a scientific reference for further studies of CRC.

Transplantation of human endometrial perivascular stem cells with hydroxy saffron yellow A promotes uterine repair in rats.

BACKGROUND: Intrauterine adhesions (IUAs) jeopardise uterine function in women, which is a great challenge in the clinic. Previous studies have shown that endometrial perivascular cells (En-PSCs) can improve the healing of scarred uteri and that hydroxysafflor yellow A (HSYA) promotes angiogenesis. The purpose of this study was to observe whether the combination of En-PSCs with HSYA could improve the blood supply and fertility in the rat uterus after full-thickness injury. METHODS: En-PSCs were sorted by flow cytometry, and the effect of HSYA on the proliferation and angiogenesis of the En-PSCs was detected using CCK-8 and tube formation assays. Based on a previously reported rat IUA model, the rat uteri were sham-operated, spontaneously regenerated, or treated with collagen-loaded PBS, collagen-loaded HSYA, collagen-loaded En-PSCs, or collagen-loaded En-PSCs with HSYA, and then collected at both 30 and 90 days postsurgery. HE staining and Masson staining were used to evaluate uterine structure and collagen fibre deposition, and immunohistochemical staining for α-SMA and vWF was used to evaluate myometrial regeneration and neovascularization in each group. A fertility assay was performed to detect the recovery of pregnancy function in each group. RNA-seq was performed to determine the potential mechanism underlying En-PSCs/HSYA treatment. Immunofluorescence, tube formation assays, and Western blot were used to validate the molecular mechanism involved. RESULTS: The transplantation of Collagen/En-PSCs/HSYA markedly promoted uterine repair in rats with full-thickness injury by reducing fibrosis, increasing endometrial thickness, regenerating myometrium, promoting angiogenesis, and facilitated live births. RNA sequencing results suggested that En-PSCs/HSYA activated the NRG1/ErbB4 signaling pathway. In vitro tube formation experiments revealed that the addition of an ErbB inhibitor diminished the tube formation ability of cocultured En-PSCs and HUVECs. Western blot results further showed that elevated levels of NRG1 and ErbB4 proteins were detected in the Collagen/En-PSCs/HSYA group compared to the Collagen/En-PSCs group. These collective results suggested that the beneficial effects of the transplantation of Collagen/En-PSCs/HSYA might be attributed to the modulation of the NRG1/ErbB4 signaling pathway. CONCLUSIONS: The combination of En-PSCs/HSYA facilitated morphological and functional repair in rats with full-thickness uterine injury and may promote endometrial angiogenesis by regulating the NRG1/ErbB4 signaling pathway.

The impact of education and occupation on cognitive impairment: a cross-sectional study in China.

Background and objectives: Education, occupation, and cognitive activity are key indicators of cognitive reserve and are thought to influence cognitive impairment. However, the individual and combined impacts of these factors are not fully understood. This study aims to investigate the roles of education and occupation in cognitive impairment while controlling for brain reserve and cognitive activity. Methods: This cross-sectional study involved 369 participants aged 50 years or older from urban outpatient clinics in Jilin Province, China. Cognitive impairment was assessed using neuropsychological scales and brain imaging. Cognitive activity was evaluated with the Cognitive Reserve Scale (CRS). Covariance analysis and logistic regression models were used to analyze the associations, adjusting for age, sex, education, and occupation. Results: Higher education was significantly associated with a lower risk of cognitive impairment (p < 0.001), regardless of occupation. In contrast, occupational complexity and cognitive activity did not show a significant relationship with cognitive impairment (p > 0.05). Conclusion: Education, rather than occupation or cognitive activities, is a significant predictor of cognitive impairment, highlighting the importance of educational attainment in cognitive health.

Barriers and Stimulus in Shared Decision Making Among Aesthetic Dermatologists in China: Findings from a Cross-Sectional Study.

Introduction: Shared decision making (SDM) is a collaborative process involving both healthcare providers and patients in making medical decisions, which gains increasing prominence in healthcare practice. But evidence on the level of SDM in medical practice and barriers as well as stimulus during the SDM implementation among aesthetic dermatologists is limited in China. Methods: From July to August 2023, 1938 dermatologists were recruited online in China. Data were collected through an electronic questionnaire covering: (1) demographic features; (2) SDM questionnaire physician version (SDM-Q-Doc); and (3) stimulus and barriers in SDM implementation. Logistic regression was applied to explore factors associated with SDM practice, barriers, and stimulus of SDM implementation, respectively. Results: The 1938 dermatologists included 1329 females (68.6%), with an average age of 35 years. The total SDM score ranged from 0 to 45, with a median value of 40 (IQR: 35-44), and the median stimulus score and barriers scores were 28 (IQR: 24-32) and 19 (IQR: 13-26), respectively. The prevalence of good SDM was 27.2%, logistic regression indicated that female dermatologists (odds ratio, OR=1.21, 95% confidence interval, CI: 0.96-1.51), and dermatologists with more years of aesthetic practice had a higher proportion of good SDM practice (OR was 1.44 for 5-9 years, 1.58 for 10-15 years and 1.77 for over 15 years). Moreover, female dermatologists and dermatologists with higher education level and serviced in private settings had lower barrier scores; female dermatologists and dermatologists with more years of aesthetic practice had higher stimulus scores. Conclusion: Chinese aesthetic dermatologists appear to implement SDM at an active level, with more stimulus and less barriers in SDM implementation. The integration of SDM into clinical practice among dermatologists is beneficial both for patients and dermatologists. Moreover, SDM practice should be strongly promoted and enhanced during medical aesthetics, especially among male dermatologists, dermatologists with less working experience, and those who work at public institutions.

The impact mechanism of telework on job performance: a cross-level moderation model of digital leadership.

Traditional enterprise management believes that telecommuting activities are out of the enterprise's control, which may reduce staff performance. We use the extension of job demand-resource theory and work embeddedness theory to develop and test the intermediary mechanism of embedded in and out of work in telework. Moreover, it judges the mediating effect of job embeddedness on telecommuting → job performance. With the help of family conflict theory, we have revealed the possible performance changes in telework and the impact of family on telework. We predict embedding outside of work may reduce job performance. However, this worry will not happen under the adjustment of digital leadership and job insecurity. We collected survey data from 36 enterprise teams and 328 members. We have confirmed that work performance will not be reduced by telecommuting. Digital leadership magnifies the embedding of telecommuting resources into employees' work to a certain extent and inhibits the embedding problem outside work caused by telecommuting requirements. The telecommuting requirement may become a positive factor for employees staying home and avoiding workplace conflicts. We confirmed the inhibitory effect of job embeddedness on turnover rate and expanded the antecedent model of job embeddedness theory.

Microfluidic Encapsulation of Exosomes Derived from Lipopolysaccharide-Treated Mesenchymal Stem Cells in Hyaluronic Acid Methacryloyl to Restore Ovarian Function in Mice.

Premature ovarian failure (POF) features an upward incidence nowadays, and the human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived exosomes (MSC-Exos) have shown applied values in the recovery of ovarian function. Here, a novel exosome-encapsulated microcarrier prepared by microfluidic technology for ovarian repair after chemotherapy damage is presented. The exosomes derived from lipopolysaccharide (LPS)-preconditioned hUC-MSCs are encapsulated with hyaluronic acid methacryloyl (HAMA) via microfluidic electrospray, which is named HAMA/MSC-Exos. Attributing to the biocompatibility and semipermeable property of HAMA, the encapsulated exosomes show great viability and controllable release behavior from HAMA. It is demonstrated that in situ transplantation of HAMA/MSC-Exos can rescue ovarian functions of cyclophosphamide-induced ovarian failure in mice by increasing ovarian volume, improving the number of antral follicles and restoring fertility. It is believed that the transplantation of HAMA/MSC-Exos will provide a new concept for the treatment of POF in clinical practice.

Application potential of senolytics in clinical treatment.

Of the factors studied in individual ageing, the accumulation of senescent cells has been considered as an essential cause of organ degeneration to eventually initiate age-related diseases. Cellular senescence is attributed to the accumulation of damage for an inducement in the activation of cell cycle inhibitory pathways, resulting the cell permanently withdraw from the cell proliferation cycle. Further, senescent cells will activate the inflammatory factor secretion pathway to promote the development of various age-related diseases. Senolytics, a small molecule compound, can delay disease development and extend mammalian lifespan. The evidence from multiple trials shows that the targeted killing of senescent cells has a significant clinical application for the treatment of age-related diseases. In addition, senolytics are also significant for the development of ageing research in solid organ transplantation, which can fully develop the potential of elderly organs and reduce the age gap between demand and supply. We conclude that the main characteristics of cellular senescence, the anti-ageing drug senolytics in the treatment of chronic diseases and organ transplantation, and the latest clinical progress of related researches in order to provide a theoretical basis for the prevention and treatment of ageing and related diseases.

Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy.

With aging, abnormalities during oocyte meiosis become more prevalent. However, the mechanisms of aging-related oocyte aneuploidy are not fully understood. Here we performed Hi-C and SMART-seq of oocytes from young and old mice and reveal decreases in chromosome condensation and disrupted meiosis-associated gene expression in metaphase I oocytes from aged mice. Further transcriptomic analysis showed that meiotic maturation in young oocytes was correlated with robust increases in mevalonate (MVA) pathway gene expression in oocyte-surrounding granulosa cells (GCs), which was largely downregulated in aged GCs. Inhibition of MVA metabolism in GCs by statins resulted in marked meiotic defects and aneuploidy in young cumulus-oocyte complexes. Correspondingly, supplementation with the MVA isoprenoid geranylgeraniol ameliorated oocyte meiotic defects and aneuploidy in aged mice. Mechanically, we showed that geranylgeraniol activated LHR/EGF signaling in aged GCs and enhanced the meiosis-associated gene expression in oocytes. Collectively, we demonstrate that the MVA pathway in GCs is a critical regulator of meiotic maturation and euploidy in oocytes, and age-associated MVA pathway abnormalities contribute to oocyte meiotic defects and aneuploidy.

CRISPR-Cas12-Based Diagnostic Applications in Infectious and Zoonotic Diseases.

Rapid detection of infectious and zoonotic diseases is very important for pathogen identification and infection control. Molecular diagnostic assays are well-known for high accuracy and sensitivity; however, conventional methods such as real-time PCR may require professional instruments and operations, preventing their wide applications in scenarios including animal quarantine. The recently developed CRISPR diagnostic (CRISPR-Dx) methods, employing the trans-cleavage activities of either Cas12 (e.g., HOLMES) or Cas13 (e.g., SHERLOCK), have shown great potential in rapid and convenient nucleic acid detection. Guided by specially designed CRISPR RNA (crRNA), Cas12 binds target DNA sequences and trans-cleaves ssDNA reporters, generating detectable signals, while Cas13 recognizes target ssRNA and trans-cleaves ssRNA reporters. To achieve high detection sensitivity, both HOLMES and SHERLOCK systems can be combined with pre-amplification procedures including both PCR and isothermal amplifications. Here, we present the employment of the HOLMESv2 method for convenient detection of the infectious and zoonotic diseases. Specifically, target nucleic acid is first amplified by LAMP or RT-LAMP, and the products are then detected by the thermophilic Cas12b. In addition, Cas12b reaction can be combined with LAMP amplification to achieve one-pot reaction systems. In this chapter, we provide a step-by-step description of the HOLMESv2-mediated rapid and sensitive detection of Japanese encephalitis virus (JEV), an RNA pathogen as an example.

Shape-Factor Impact on a Mass-Based Hybrid Nanofluid Model for Homann Stagnation-Point Flow in Porous Media.

This paper studies the impact of shape factor on a mass-based hybrid nanofluid model for Homann stagnation-point flow in porous media. The HAM-based Mathematica package BVPh 2.0 is suitable for determining approximate solutions of coupled nonlinear ordinary differential equations with boundary conditions. This analysis involves discussions of the impact of the many physical parameters generated in the proposed model. The results show that skin friction coefficients of Cfx and Cfy increase with the mass of the first and second nanoparticles of the hybrid nanofluids w1 and w2 and with the coefficient of permeability in porous media. For the axisymmetric case of γ = 0, when w1 = w2 = 10 gr, wf = 100 gr and Cfx = Cfy = 2.03443, 2.27994, 2.50681, and 3.10222 for σ = 0, 1, 2, and 5. Compared with w1 = w2 = 10 gr, wf = 100 gr, and σ = 0, it can be found that the wall shear stress values increase by 12.06%, 23.21%, and 52.48%, respectively. As the mass of the first and second nanoparticles of the mass-based hybrid nanofluid model increases, the local Nusselt number Nux increases. Values of Nux obviously decrease and change with an increase in the coefficient of permeability in the range of γ < 0; otherwise, Nux is less affected in the range of γ > 0. According to the calculation results, the platelet-shaped nanoparticles in the mass-based hybrid nanofluid model can achieve maximum heat transfer rates and minimum surface friction.

Sheep and goat pathogen database: a pathogen data integration and analysis database of sheep and goat infectious diseases.

The prevalence of infectious diseases in sheep and goats has a significant impact on the development of the sheep and goat industry and public health security. The identification and analysis of pathogens are crucial for infectious disease research; however, existing databases pay little attention to sheep and goat diseases, and pathogen data are relatively scattered. Therefore, the effective integration, analysis and visualization of these data will help us conduct in-depth research on sheep and goat infectious diseases and promote the formulation of disease prevention and control strategies. This article considered the pathogens of 44 infectious diseases in sheep and goats as the main research objects and collected and downloaded relevant scientific literature, pathogen genomes, pathogen transcriptomes, pathogen occurrence records, and other data. The C# programming language and an SQL Server database were used to construct and realize the functions of the Sheep and Goat Pathogen Database (SGPD) within a B/S architecture based on the ASP.NET platform. The SGPD mainly provides an integrated platform for sheep and goat pathogen data retrieval, auxiliary analysis, and user upload, including several functionalities: (1) a Disease Introduction module that queries basic information regarding the 44 recorded sheep and goat infectious diseases, such as epidemiology, clinical characteristics, diagnostic criteria, and prevention and control measures; (2) an Omics Information module that allows users to query and download the genome and transcriptome data related to the pathogens of sheep and goat infectious disease, and provide sequence alignment functionality; (3) a Pathogen Structure module that enables users to view electron micrographs of pathogen structure and tissue sections related to sheep and goat disease from publicly published research; (4) a Literature Search module based on the "Pathogen Dictionary" search strategy that facilitates searches for published research related to pathogens of infectious disease; (5) a Science Popularization module that allows users to view popular science materials related to sheep and goat infectious diseases; and (6) a Public Health module that allows users to query the risk factors of zoonotic disease transmission and the corresponding related literature, and realize the visualization of pathogen distribution. The SGPD is a specialized sheep and goat pathogen information database that provides comprehensive resources and technical support for sheep and goat infectious disease research, prevention, and control.

Screen-based sedentary behaviors but not total sedentary time are associated with anxiety among college students.

Objective: The purpose of the study was to investigate the associations of device-measured total sedentary time and screen-based sedentary time with anxiety in college students. Methods: Three hundred and twenty-one college students (mean age = 19.72 ± 1.18, 55.8% females) were recruited from Shanghai, China. Total sedentary time was objectively measured using accelerometry, while screen-based sedentary time was self-reported. Anxiety symptom was evaluated using the Self-Rating Anxiety Scale. Linear regression modeling was used to assess the associations of total sedentary time and screen-based sedentary time with anxiety symptom. Results: Accelerometer-assessed total sedentary time was not associated with anxiety symptom. Prolonged sedentary time on TV and movie viewing (>2 h on weekdays) and social media using (>2 h on weekdays and weekend) were associated with a higher level of anxiety. However, time on video gaming and recreational reading was not associated with anxiety symptom. Conclusion: The findings indicated that screen-based sedentary behaviors but not total sedentary time were associated with anxiety symptom among college students. The associations of screen-based sedentary behaviors with anxiety symptom varied by the types of screen time.

Lnc-SELPLG-2:1 enhanced osteosarcoma oncogenesis via hsa-miR-10a-5p and the BTRC cascade.

BACKGROUND: To investigate the potential role of Long Non-coding RNAs (lncRNAs) in the progression of osteosarcoma. METHODS: The candidate lncRNAs were screened with RNA-seq and confirmed with quantitative real-time PCR. Using MTS, transwell assay, and flow cytometric analysis, the effects of overexpressed lnc-SELPLG-2:1 on cell functions were determined. Immunohistochemical staining, fluorescence in situ hybridization, and luciferase reporter assay were used to evaluate the potential mechanism of lnc-SELPLG-2:1 in vivo and in vitro using a tumor model. Moreover, the effects of overexpression of hsa-miR-10a-5p on the functions of SaOS2 cells were determined using functional cell analysis. A response test was used to confirm the mechanism by which lnc-SELPLG-2:1 sponge hsa-miR-10a-5p promotes the expression of BTRC to regulate osteosarcoma. RESULTS: Lnc-SELPLG-2:1 was highly expressed in osteosarcoma compared to normal cells and bone and marrow samples. Inhibition of lnc-SELPLG-2:1 accelerated cell apoptosis and suppressed cell proliferation, migration, and invasion, whereas lnc-SELPLG-2:1 overexpression had the opposite effect. Moreover, inhibiting lnc-SELPLG-2:1 in an in vivo model decreased tumor size and suppressed the expression of cell migration-related proteins. The prediction, dual luciferase assay, and response test results indicated that hsa-miR-10-5p and BTRC were involved in the lnc-SELPLG-2:1 cascade. Unlike lnc-SELPLG-2:1, hsa-hsa-miR-10a-5p had opposite expression and function. Competitive binding of lnc-SELPLG-2:1 to hsa-hsa-miR-10a-5p prevented BTRC from miRNA-mediated degradation, thereby activating the expression of VIM, MMP9, and MMP2, promoting osteosarcoma cell proliferation, migration, and invasion, and inhibiting apoptosis. CONCLUSION: Lnc-SELPLG-2:1 is an oncogenesis activator in osteosarcoma, and its functions are performed via hsa-miR-10a-5p /BTRC cascade.

Changes in working memory performance and cortical activity during acute aerobic exercise in young adults.

This study aimed to examine the concurrent performance of working memory and cortical activity during acute aerobic exercise in young adults. In a crossover study design, 27 young adults (mean age = 22.7 ± 3.4 years, 15 women) participated in two experimental conditions in a randomized order: (1) sitting condition (without exercise) and (2) cycling condition (moderate-intensity exercise). Working memory was measured with a modified version of the n-back task. A functional near-infrared spectroscopy (fNIRS) was used to measure cortex activation. In the cycling condition, response time (RT) for the n-back task was significantly faster (p < 0.05). No differences in accuracy were observed between the sitting and cycling conditions. The fNIRS results showed that the oxygenated hemoglobin (oxy-Hb) concentrations in the bilateral frontopolar area (p < 0.05), dorsolateral prefrontal cortex (p < 0.05), and right premotor and supplementary cortex (p < 0.05) were decreased while cycling. The findings indicated that the concurrent performance of working memory was improved during acute aerobic exercise, whereas cortical activity was decreased in some brain regions.

Human Endometrium-Derived Adventitial Cell Spheroid-Loaded Antimicrobial Microneedles for Uterine Regeneration.

Asherman's syndrome (AS) occurs as a consequence of severe damage to the endometrial basalis, usually leading to menstrual abnormalities, infertility, and recurrent miscarriage in women. Currently, human endometrium-derived adventitial cells (En-ADVs) are considered ideal seed cells with high pluripotency for regenerative medicine. However, critical issues such as noninvasive repair of tissues, targeting of native stem cells, and continuous action in the injured sites are not well resolved. Herein, En-ADV spheroid-loaded hierarchical microneedles (MN/En-ADV) for in situ intrauterine repair are developed. The flexible microneedles are fabricated with gelatin methacryloyl and lactoferrin, imparting the characteristics of rapid degradation and antimicrobial activity. Benefiting from an array of microwells on microneedles, En-ADVs can rapidly form 3D cell spheroids, which display higher potential for cell proliferation, differentiation, and migration than dissociated cells. With the application of MN/En-ADV, the repaired uteri show well-defined myometrial regeneration, angiogenesis, and an increase of endometrial receptivity in a rat AS model. Notably, embryos are able to implant in the reconstructed sites and remain viable, indicating that this system promotes the restoration of both normal morphology and reproductive function in the injured uterus. It is anticipated that multifunctional MN/En-ADV can be an ideal candidate for versatile in situ tissue regeneration.

Empirical Analysis and Suggestions on the Selection of City Leading Industries based on SSM Algorithm.

City leading industries are the pillars of urban economic development and are constantly changing as urban economic development enters different stages. The weight setting of many factors in the existing leading industry selection methods and means is mainly set by humans, which is highly subjective and lacks dynamics, integrity, and quantification, and the accuracy of prediction results is not high. Therefore, starting from respecting objective data, the SSM selection method with both dynamic and quantifiable properties is introduced. Based on the SSM mathematical model and principles, 35 manufacturing industries in Guangzhou in 2015 and 2020 are selected as initial variables and stage variables, respectively, taking 35 corresponding industrial sectors in the province as reference variables at the same time point and using the SSM algorithm as an analytical tool to conduct an empirical analysis of the share deviation component, structural deviation component, and competitiveness deviation component of the 35 manufacturing industry sectors in Guangzhou. After drawing the Shift-share analysis chart, it was found that there are 12 industrial sectors most likely to become the city leading industries in Guangzhou, and 4 suggestions for the development planning of city leading industries were put forward; they are, respectively, ➀ accelerate traditional industries technological upgrading, ➁ focus on optimizing automobile manufacturing industry, ➂ promote leading industries independent innovation, and ➃ create leading industry sharing platform.

Is Sedentary Behavior Associated With Executive Function in Children and Adolescents? A Systematic Review.

BACKGROUND: Prolonged time on sedentary behavior, especially screen-based sitting time, is associated with unfavorable health indicators in children and adolescents. However, the effects of sedentary behavior on cognitive function remain to be elucidated. OBJECTIVE: The purpose of this systematic review was to synthesize the evidence on the associations of sedentary behavior with executive function in children and adolescents. METHODS: Four electronic databases (i.e., PubMed, Web of Science, PsycINFO, and SPORTDiscus) were searched for studies examining the associations between sedentary behavior and executive function in children and adolescents. Study quality was assessed by the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: A total of 1,151 records were initially identified through database searches and other searches. Twelve cross-sectional and four longitudinal studies met the inclusion criteria. Of the 16 studies, seven studies found significant negative associations between sedentary behavior and executive function, and two studies presented positive associations. Eight studies measured sedentary time using accelerometers and showed varied associations between objectively measured sedentary time and executive function. Nine studies measured screen-based sedentary behavior, of which five studies found negative associations of sedentary time with executive function. CONCLUSION: The available evidence on the associations between sedentary behavior and executive function is not conclusive in children and adolescents. However, screen-based sedentary behavior may be negatively associated with executive function.

The mitochondrial protease LONP1 maintains oocyte development and survival by suppressing nuclear translocation of AIFM1 in mammals.

BACKGROUND: Oogenesis is a fundamental process of human reproduction, and mitochondria play crucial roles in oocyte competence. Mitochondrial ATP-dependent Lon protease 1 (LONP1) functions as a critical protein in maintaining mitochondrial and cellular homeostasis in somatic cells. However, the essential role of LONP1 in maintaining mammalian oogenesis is far from elucidated. METHODS: Using conditional oocyte Lonp1-knockout mice, RNA sequencing (RNA-seq) and coimmunoprecipitation/liquid chromatography-mass spectrometry (Co-IP/LC-MS) technology, we analysed the functions of LONP1 in mammalian oogenesis. FINDINGS: Conditional knockout of Lonp1 in mouse oocytes in both the primordial and growing follicle stages impairs follicular development and causes progressive oocyte death, ovarian reserve loss, and infertility. LONP1 directly interacts with apoptosis inducing factor mitochondria-associated 1 (AIFM1), and LONP1 ablation leads to the translocation of AIFM1 from the cytoplasm to the nucleus, causing apoptosis in mouse oocytes. In addition, women with pathogenic variants of LONP1 lack large antral follicles (>10 mm) in the ovaries, are infertile and present premature ovarian insufficiency. INTERPRETATION: We demonstrated the function of LONP1 in regulating oocyte development and survival, and in-depth analysis of LONP1 will be crucial for elucidating the mechanisms underlying premature ovarian insufficiency. FUNDING: This work was supported by grants from the National Key Research and Development Program of China (2018YFC1004701), the National Nature Science Foundation of China (82001629, 81871128, 81571391, 81401166, 82030040), the Jiangsu Province Social Development Project (BE2018602), the Jiangsu Provincial Medical Youth Talent (QNRC2016006), the Youth Program of the Natural Science Foundation of Jiangsu Province (BK20200116) and Jiangsu Province Postdoctoral Research Funding (2021K277B).