Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress

BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanofiller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

Create an International Environment for the Peaceful and Steady Development to Boost the Sound Development of Human Rights on the International Stage——An Address at the Opening Ceremony of the 7th Beijing Forum on Human Rights, Spet. 17, 2014

Since its initiation in 2008, the Beijing Forum on Human Rights has been bent on promoting our mutual understanding and expanding our common grounds. It has carried out very fruitful exchanges and researches around many important questions concerning human rights development, and hence attained great achievements. It has played avery constructive role in promoting exchanges about and cooperation in human rights between China and other countries, becoming an important and influential platform for international dialogs over human rights.

Taking a Path of Human Rights Development Suitable to the Economic Basis and Humanistic Environment of China, Realizing“Chinese Dream”

The Sixth Beijing Forum on Human Rights is opened today, which is co-spon- sored by the China Society for Human Rights Studies and the China Foundation for Human Rights Development. First, on behalf of the China Foundation for Human Rights Development, I would like to express warm congratulations to the opening of the Forum, and heartfelt thanks tothe friends who have always cared for and supported for the development and progress of human rights cause of China.

The Rapid Development of the Cause of Human Rights in China

As early as in 2002, the China Society for Human Rights Studies and the China Foundationfor Human Rights Development co-sponsored an international symposium titled ＂Oriental Culture and Human Rights Development,＂ marking an important milestone for the human rights organizations of China to confidently open themselves to the world and voluntarily perform mul- tilateral cooperation. In the past tenyears, the exchanges and cooperation in human rights between China and other countries in the world have been increasingly extended and deepened, and the world human rights cause has increasingly shown a positive trend of close contact, mutual dependence and collective development for all countries.

The Powerful Role of Mothers in Adolescent Purpose Development

Adolescence is a critical time for the cultivation of life purpose,also known as a meaningful long-term aim focused on contribution to others.Youth with purpose,especially marginalized youth,report a number of positive outcomes.Relationships with caring adults appear to be particularly helpful in guiding young people on their path to purpose,but little work has focused specifically on the role of mothers.This qualitative study,approved by a Institutional Review Board,examines how twenty adolescents from marginalized communities describe their sense of purpose and its relationship to their caregivers.The sample size was determined based on saturation,a process in qualitative research when the researchers begin to observe redundancy in the data.Through content analysis,a major theme emerged:the role of mothers and their impact on purpose development on their children.Results showed that mothers helped their adolescents develop their sense of purpose through serving as a sense of inspiration,providing the adolescents with support,sparking a desire for the adolescents to make their mothers proud,and through the mothers and adolescents in engaging in conversations about one’s future.

Apigenin ameliorates imiquimod-induced psoriasis in C57BL/6J mice by inactivating STAT3 and NF-κB

Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.

Optimality of Group Testing with Differential Misclassification

Group testing is a method that can be used to estimate the prevalence of rare infectious diseases,which can effectively save time and reduce costs compared to the method of random sampling.However,previous literature only demonstrated the optimality of group testing strategy while estimating prevalence under some strong assumptions.This article weakens the assumption of misclassification rate in the previous literature,considers the misclassification rate of the infected samples as a differentiable function of the pool size,and explores some optimal properties of group testing for estimating prevalence in the presence of differential misclassification conforming to this assumption.This article theoretically demonstrates that the group testing strategy performs better than the sample by sample procedure in estimating disease prevalence when the total number of sample pools is given or the size of the test population is determined.Numerical simulation experiments were conducted to evaluate the performance of group tests in estimating prevalence in the presence of dilution effect.

Advancing PCB Quality Control:Harnessing YOLOv8 Deep Learning for Real-Time Fault Detection

Printed Circuit Boards(PCBs)are materials used to connect components to one another to form a working circuit.PCBs play a crucial role in modern electronics by connecting various components.The trend of integrating more components onto PCBs is becoming increasingly common,which presents significant challenges for quality control processes.Given the potential impact that even minute defects can have on signal traces,the surface inspection of PCB remains pivotal in ensuring the overall system integrity.To address the limitations associated with manual inspection,this research endeavors to automate the inspection process using the YOLOv8 deep learning algorithm for real-time fault detection in PCBs.Specifically,we explore the effectiveness of two variants of the YOLOv8 architecture:YOLOv8 Small and YOLOv8 Nano.Through rigorous experimentation and evaluation of our dataset which was acquired from Peking University’s Human-Robot Interaction Lab,we aim to assess the suitability of these models for improving fault detection accuracy within the PCB manufacturing process.Our results reveal the remarkable capabilities of YOLOv8 Small models in accurately identifying and classifying PCB faults.The model achieved a precision of 98.7%,a recall of 99%,an accuracy of 98.6%,and an F1 score of 0.98.These findings highlight the potential of the YOLOv8 Small model to significantly improve the quality control processes in PCB manufacturing by providing a reliable and efficient solution for fault detection.

Pregnancy stressors and postpartum symptoms of depression and anxiety:the moderating role of a cognitivebehavioural therapy(CBT)intervention

Background Little is known about the association between stressors(especially positive stressors)during pregnancy and postpartum depression and anxiety.Aims We investigated the association between positive and negative stress events during different stages of pregnancy and postpartum mental health outcomes among low-income pregnant women with symptoms of anxiety in Pakistan and evaluated whether an intervention based on cognitive behavioural therapy(CBT)had a regulatory effect.Methods Participants were 621 pregnant Pakistani women with mild anxiety.Using the Pregnancy Experience Scale-Brief Version,six scores were created to assess positive and negative stressors.We performed a multivariate linear regression to examine whether these six scores,measured both at baseline and in the third trimester,were associated with postpartum anxiety and depressive symptoms.The effect of the intervention on this relationship was examined by adding an interaction term to the regression model.Results Hassles frequency measured in the third trimester was positively associated with depression(B=0.22,95%confidence interval(Cl):0.09 to 0.36)and anxiety(B=0.19,95%Cl:0.08to 0.30).At the same timepoint,uplifts intensity was negatively associated with symptoms of depression(B=-0.82,95%Cl:1.46 to-0.18)and anxiety(B=-0.70,95%Cl:-1.25 to-0.15),whereas hassles intensity was positively related to symptoms of depression(B=1.02,95%Cl:0.36 to 1.67)and anxiety(B=0.90,95%Cl:0.34 to 1.47).The intensity ratio of hassles to uplifts reported in the third trimester was positively related to both depression(B=1.40,95%Cl:0.59 to 2.20)and anxiety(B=1.26,95%Cl:0.57 to 1.96).The intervention strengthened the overall positive effects of uplfts and the negative effects of hassles.Pregnancy experiences at baseline during early pregnancy to mid-pregnancy were not associated with mental health outcomes.Conclusions Stressors in the third trimester but not earlier in pregnancy were associated with postpartum symptoms of anxiety and depression.The CBT intervention modified the association between pregnancy stressors and postpartum mental health outcomes.Programmes that promote positive experiences and reduce negative experiences,especially in late pregnancy,may mitigate postpartum mental health consequences.

Anomaly Detection Using Data Rate of Change on Medical Data

The identification and mitigation of anomaly data,characterized by deviations from normal patterns or singularities,stand as critical endeavors in modern technological landscapes,spanning domains such as Non-Fungible Tokens(NFTs),cyber-security,and the burgeoning metaverse.This paper presents a novel proposal aimed at refining anomaly detection methodologies,with a particular focus on continuous data streams.The essence of the proposed approach lies in analyzing the rate of change within such data streams,leveraging this dynamic aspect to discern anomalies with heightened precision and efficacy.Through empirical evaluation,our method demonstrates a marked improvement over existing techniques,showcasing more nuanced and sophisticated result values.Moreover,we envision a trajectory of continuous research and development,wherein iterative refinement and supplementation will tailor our approach to various anomaly detection scenarios,ensuring adaptability and robustness in real-world applications.

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

Examining the Hypothesis of Common Factors Shared by Different Addictive Behaviors and Gender Effects on Propensity to Addiction Type

Background: From the two facts reported by previous research: 1) frequent co-occurrence of more than one addictive behavior, 2) childhood adversities identified as origins of different types of addictive behaviors, it is assumed that all types of addictive behaviors, regardless of substance, behavioral, or relationship, share common factors which have not yet been proven by epidemiological research. The Shorter PROMIS Questionnaire (SPQ) was previously developed to assess 16 types of addictive behaviors. Its factor structure, however, has not been fully investigated. Confirming the factor structure will enable us to hypothesize the common factor(s) shared by all, or if not all, most types of addictive behaviors. Aims: This study aimed at 1) examining the factor structure of the SPQ, 2) confirming the reliability of the questionnaire, and 3) examining the impacts of gender and age on each addictive behavior. Methods: Data obtained from 232 Japanese adults who completed all items of the SPQ were used for the analyses. After confirming the one-factor structure model for each of the 16 subscales, the validity of the one-factor structure of the SPQ was evaluated using Confirmatory Factor Analysis (CFA), by adapting 16 subscale scores as observed variables. If its validity was not confirmed, another model which showed better compatibility to the data was explored. The reliability of the SPQ as well as that of all 16 subscales was evaluated. Also, the impacts of gender and age on each subscale score were examined. Results: The one-factor structure for each of the 16 subscales was confirmed. The compatibility of the SPQ one-factor model was not acceptable. The best fit model was a bi-factor model in which one main factor was shared by all 16 subscales, and three factors were shared by some specific addictive behaviors. Male respondents were more likely than female respondents to show high scores in Alcohol, Tobacco, Gambling, Sex, and Recreational Drugs, and low scores only in Shopping. Respondents’ age did not impact any of the 16 subscale scores. Conclusion: It was demonstrated that there are common factors shared by all different types, as well as selected types of addictive behaviors, by conducting CFAs of the SPQ. Reliability was proven for the SPQ and for all 16 subscales. Male respondents were more likely to show physically hedonic addictive behaviors.

The Impact of Urban and Rural Education Gap on Student Achievement Differences

With our country’s social development,the gap between urban and rural education has become increasingly obvious,especially the difference in student achievement.This study aims to explore the impact of the urban-rural education gap on student achievement.The study adopts a quantitative analysis method to collect and analyze the academic performance,learning resources,and social resources of urban and rural students.The results show that the unbalanced distribution of educational resources in urban and rural areas is the key factor leading to the gap in students’achievement.For example,urban education resources are abundant while rural education resources are relatively scarce.At the same time,the difference in social environment and family economic status also have a significant impact on student achievement.The differences between urban and rural areas,particularly in terms of family economic conditions and their ability to invest in education,further widen the gap between urban and rural education.The results of this study can provide a reference for reducing the gap between urban and rural education and improving the academic performance of rural students.A fair education policy is essential to narrow the gap between urban and rural education resources distribution,so as to improve the equality of education in society.

Application of Cooperative Learning and Flipped Classrooms in University Basketball Courses in China

This study investigates the application of the teaching model combining cooperative learning and flipped classrooms in university basketball courses in China.By analyzing the advantages and disadvantages of the traditional basketball teaching model and students’satisfaction with the course,the necessity of implementing cooperative learning and flipped classrooms is proposed.The study planned in detail the implementation strategies before class,in the classroom,and after class,and compared them with the control group through an experimental design.The experimental results showed that the new teaching mode demonstrated significant advantages in terms of learning outcomes,student satisfaction,and teacher evaluation.This study provides a valuable reference for the future reform of the physical education curriculum.

Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

Background Psychiatric comorbidities are common in patients with epilepsy.Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy.We then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression.Finally,we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions.For example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions.Conclusions Psychiatric comorbidities are common in patients with epilepsy.Genetic correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions.These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.

Androgen effects on skeletal muscle： implications for the development and management of frailty

Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well-tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators （SARMs） suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies.

Use of hybrid chitosan membranes and human mesenchymal stem cells from the Wharton jelly of umbilical cord for promoting nerve regeneration in an axonotmesis rat model

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to assess the effect on nerve regeneration, associating a hybrid chitosan membrane with non-differentiated human mesenchymal stem cells isolated from Wharton＇s jelly of umbilical cord, in peripheral nerve reconstruction after crush injury. Chromosome analysis on human mesenchymal stem cell line from Wharton＇s jelly was carried out and no structural alterations were found in metaphase. Chitosan membranes were previously tested in vitro, to assess their ability in supporting human mesenchymal stem cell survival, expansion, and differentiation. For the in vivo testing, Sasco Sprague adult rats were divided in 4 groups of 6 or 7 animals each： Group 1, sciatic axonotmesis injury without any other intervention （Group 1-Crush）; Group 2, the axonotmesis lesion of 3 mm was infiltrated with a suspension of 1 250 -1 500 human mesenchymal stem cells （total volume of 50 pL） （Group 2-CrushCell）; Group 3, axonotmesis lesion of 3 mm was enwrapped with a chitosan type Ill membrane covered with a monolayer of non-differentiated human mesenchymal stem cells （Group 3-CrushChitlllCell） and Group 4, axonotmesis lesion of 3 mm was enwrapped with a chitosan type III membrane （Group 4-CrushChiUll）. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index, static sciatic index, extensor postural thrust, and withdrawal reflex latency. Stereological analysis was carded out on regenerated nerve fibers. Results showed that infiltration of human mesenchymal stem cells, or the combination of chitosan membrane enwrapment and human mesenchymal stem cell enrichment after nerve crush injury provide a slight advantage to post-traumatic nerve regeneration. Results obtained with chitosan type III membrane alone confirmed that they significantly improve post-traumatic axonal regrowth and may represent a very promising clinical tool in peripheral nerve reconstructive surgery. Yet, umbilical cord human mesenchymal stem cells, that can be expanded in culture and induced to form several different types of cells, may prove, in future experiments, to be a new source of cells for cell therapy, including targets such as peripheral nerve and muscle.

Building a Database for the Future:Humans and Lakes within Ecosystems

1 Introduction Fresh or saline,lakes constantly exchange with other water bodies on the Earth.Together,they form a crucial part of the water cycle–one of the most important ecosystem functions supporting humans and other biological communities.Lakes have provided invaluable and irreplaceable ecosystem services(benefits)for the

The Contribution of the Belt and Road Initiative to the World's Right to Development

The Belt and Road Initiative makes an important contribution to the right to development in theory and practice in the current world. Since the reform and opening-up, the Chinese government puts the rights to subsistence and development before any other human rights, which effectively guarantees and accelerates a rapid economic development in China. Nowadays, countries along the Belt and Road have joined a "community of common destiny". Inside the "community of common destiny," countries have enjoyed not only the responsibility, rights and benefit of the right to development, but also a win-win cooperation that ensured the right to development. Therefore, the Belt and Road initiative enriches the UN Declaration on the Right to Development, and "community of common destiny" of countries becomes a higher form of the right to development.