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).

Spatiotemporal distribution of human brucellosis in Inner Mongolia, China, in 2010-2015, and influencing factors.

Human brucellosis is caused by Brucella species and remains a major burden in both human and domesticated animal populations, especially in Inner Mongolia, China. The aims of this study were to analyze the spatiotemporal trends in human brucellosis in Inner Mongolia during 2010 to 2015, to explore the factors affecting the incidence of brucellosis. The results showed that the annual incidence was 29.68-77.67 per 100,000, and peaked from March to June. The majority of human brucellosis was male farmers and herdsmen, aged 40-59 years. The high-risk areas were mainly Xilin Gol League and Hulunbeier City. The incidence of human brucellosis in Inner Mongolia decreased during 2010 to 2015, although the middle and eastern regions were still high-risk areas. The regions with larger number of sheep and cattle, lower GDP per capita, less number of hospital beds, higher wind speed, lower mean temperature more likely to become high-risk areas of human brucellosis.

Plant Dehydrins: Expression, Regulatory Networks, and Protective Roles in Plants Challenged by Abiotic Stress.

Dehydrins, also known as Group II late embryogenesis abundant (LEA) proteins, are classic intrinsically disordered proteins, which have high hydrophilicity. A wide range of hostile environmental conditions including low temperature, drought, and high salinity stimulate dehydrin expression. Numerous studies have furnished evidence for the protective role played by dehydrins in plants exposed to abiotic stress. Furthermore, dehydrins play important roles in seed maturation and plant stress tolerance. Hence, dehydrins might also protect plasma membranes and proteins and stabilize DNA conformations. In the present review, we discuss the regulatory networks of dehydrin gene expression including the abscisic acid (ABA), mitogen-activated protein (MAP) kinase cascade, and Ca2+ signaling pathways. Crosstalk among these molecules and pathways may form a complex, diverse regulatory network, which may be implicated in regulating the same dehydrin.

An iteration model for identifying essential proteins by combining comprehensive PPI network with biological information.

BACKGROUND: Essential proteins have great impacts on cell survival and development, and played important roles in disease analysis and new drug design. However, since it is inefficient and costly to identify essential proteins by using biological experiments, then there is an urgent need for automated and accurate detection methods. In recent years, the recognition of essential proteins in protein interaction networks (PPI) has become a research hotspot, and many computational models for predicting essential proteins have been proposed successively. RESULTS: In order to achieve higher prediction performance, in this paper, a new prediction model called TGSO is proposed. In TGSO, a protein aggregation degree network is constructed first by adopting the node density measurement method for complex networks. And simultaneously, a protein co-expression interactive network is constructed by combining the gene expression information with the network connectivity, and a protein co-localization interaction network is constructed based on the subcellular localization data. And then, through integrating these three kinds of newly constructed networks, a comprehensive protein-protein interaction network will be obtained. Finally, based on the homology information, scores can be calculated out iteratively for different proteins, which can be utilized to estimate the importance of proteins effectively. Moreover, in order to evaluate the identification performance of TGSO, we have compared TGSO with 13 different latest competitive methods based on three kinds of yeast databases. And experimental results show that TGSO can achieve identification accuracies of 94%, 82% and 72% out of the top 1%, 5% and 10% candidate proteins respectively, which are to some degree superior to these state-of-the-art competitive models. CONCLUSIONS: We constructed a comprehensive interactive network based on multi-source data to reduce the noise and errors in the initial PPI, and combined with iterative methods to improve the accuracy of necessary protein prediction, and means that TGSO may be conducive to the future development of essential protein recognition as well.

Research on Decomposition of Offset in MEMS Capacitive Accelerometer.

In a MEMS capacitive accelerometer, there is an offset due to mechanical and electrical factors, and the offset would deteriorate the performance of the accelerometer. Reducing the offset from mechanism would benefit the improvement in performance. Yet, the compositions of the offset are complex and mix together, so it is difficult to decompose the offset to provide guidance for the reduction. In this work, a decomposition method of offset in a MEMS capacitive accelerometer was proposed. The compositions of the offset were first analyzed quantitatively, and methods of measuring key parameters were developed. Based on our proposed decomposition method, the experiment of offset decomposition with a closed-loop MEMS capacitive accelerometer was carried out. The results showed that the offset successfully decomposed, and the major source was from the fabricated gap mismatch in the MEMS sensor. This work provides a new way for analyzing the offset in a MEMS capacitive accelerometer, and it is helpful for purposefully taking steps to reduce the offset and improve accelerometer performance.

The Relationship between Physical Activity, Mobile Phone Addiction, and Irrational Procrastination in Chinese College Students.

The aim of the current study was to examine the associations between physical activity, mobile phone addiction, and irrational procrastination after adjustment for potential confounding variables. The participants were 6294 first- and second-year students recruited as a cluster sample from three public universities in Shanghai, China. Physical activity, mobile phone use, and irrational procrastination were assessed using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the mobile phone addiction index scale (MPAI), and the irrational procrastination scale (IPS). The participants were divided into four groups according to their mobile phone usage status and physical activity level. The binary logistic regression model was used to predict the probability of serious irrational procrastination among different groups. The emergence of serious of irrational procrastination under physical activity of different intensity and different mobile phone addiction statuses was predicted by a multiple linear regression model. In this study, the combination of insufficient physical activity and mobile phone addiction is positively associated with high levels of irrational procrastination. Furthermore, students who exhibited both mobile phone addiction behaviors and insufficient physical activity tended to have significantly higher odds of reporting high levels of irrational procrastination than those students who exhibited one behavior or neither behavior. After adjusting for the effects of age, BMI, tobacco, alcohol use, and sedentary time, the result is consistent with previous outcomes. These findings suggest that intervention efforts should focus on the promotion of physical activity and reduction of mobile phone addiction.