Progress Research Articles

Filamin A is involved in human intrahepatic cholangiocarcinoma aggressiveness and progression.

Intrahepatic cholangiocarcinoma (iCCA) is a primary liver tumour, characterized by poor prognosis and lack of effective therapy. The cytoskeleton protein Filamin A (FLNA) is involved in cancer progression and metastasis, including primary liver cancer. FLNA is cleaved by calpain, producing a 90 kDa fragment (FLNACT ) that can translocate to the nucleus and inhibit gene transcription. We herein aim to define the role of FLNA and its cleavage in iCCA carcinogenesis. We evaluated the expression and localization of FLNA and FLNACT in liver samples from iCCA patients (n = 82) revealing that FLNA expression was independently correlated with disease-free survival. Primary tumour cells isolated from resected iCCA patients expressed both FLNA and FLNACT , and bulk RNA sequencing revealed a significant enrichment of cell proliferation and cell motility pathways in iCCAs with high FLNA expression. Further, we defined the impact of FLNA and FLNACT on the proliferation and migration of primary iCCA cells (n = 3) and HuCCT1 cell line using silencing and Calpeptin, a calpain inhibitor. We observed that FLNA silencing decreased cell proliferation and migration and Calpeptin was able to reduce FLNACT expression in both the HuCCT1 and iCCA cells (p < .05 vs. control). Moreover, Calpeptin 100 μM decreased HuCCT1 and primary iCCA cell proliferation (p <.00001 vs. control) and migration (p < .05 vs. control). These findings demonstrate that FLNA is involved in human iCCA progression and calpeptin strongly decreased FLNACT expression, reducing cell proliferation and migration.

OPTIMIZATION OF PUBLIC SPEAKING SKILLS FOR IMPROVEMENT OF HUMAN RESOURCES MANAGEMENT OF RPTRA &amp; PKK KELURAHAN PETUKANGAN UTARA

A community engagement initiative conducted in collaboration between Budi Luhur University's Faculty of Communication and Creative Design and North Petukangan Subdistrict, Jakarta, has yielded significant results. The program focused on enhancing public speaking skills and has left a notable impact. Participants in the Public Speaking Workshop reported substantial improvements in their ability to communicate effectively in public. They gained practical speaking techniques, overcame stage fright, and developed a better understanding of their audience, resulting in a boost in self-confidence. Participants expressed increased confidence and motivation to address audiences, a valuable asset in their roles at RPTRA and PKK North Petukangan Subdistrict.&#x0D; Furthermore, the positive community response indicated a growing interest in similar programs, emphasizing the increasing awareness of the significance of public speaking skills for human resource development and community progress. The most significant impact was observed in human resource management at RPTRA and PKK, where enhanced speaking skills enable leaders and facilitators to communicate, motivate, and lead more effectively. In conclusion, this community engagement program has brought about positive changes in human resource development and community management in North Petukangan Subdistrict. It illustrates how higher education can benefit local communities, enabling them to realize their full potential.

Implementing of Restorative Justice to Build the Criminal Justice System in Indonesia: A Study of the Batak Toba Justice System

The pursuit of fairness and harmony between the realization of rights and duties is a cornerstone of human progress. Restorative justice case resolution represents an endeavor to introduce a non-punitive procedure into Indonesia's criminal justice system as part of its ongoing effort to modernize its legal framework. Restorative justice focuses on healing criminal behavior's harm and shattered relationships. This study examined the feasibility of implementing restorative justice aspects into a national criminal justice system, gaining inspiration from the Toba Batak Indigenous People. The methodology was socio-legal. Dalihan Natolu is recognized as an alternative conflict settlement method for Toba Batak. The traditional leader mediates in this conflict resolution. By Batak customary law, the imposition of sanctions is decided by customary judges or kings. Dalihan Natolu then tells the culprit not to repeat his behavior. Dalihan Natolu involves offenders, victims, families of offenders and victims, and other parties in seeking a fair settlement that emphasizes repair above retribution. This helps Dalihan Natolu solve criminal concerns. In indigenous cultures, customary institutions convene the parties engaged in a crime to provide counsel and find solutions that do not harm or profit only one side. Justice is served, and the victim is not harmed.

Fast multiple-trait genome-wide association analysis for correlated longitudinal measurements

Large-scale longitudinal biobank data can be leveraged to identify genetic variation contributing to human diseases progression and traits trajectories. While methods for genome-wide association studies (GWAS) of multiple correlated traits have been proposed, an efficient multiple-trait approach to model longitudinal phenotypes is not currently available. We developed GAMUT, a genome-wide association approach for multiple longitudinal traits. GAMUT employs a mixed-effects model to fit longitudinal outcomes where a fast algorithm for inversion by recursive partitioning of the random effects submatrix is introduced. To evaluate performance of the algorithms introduced and assess their statistical power and type I error, stochastic simulation was conducted. Consistent with our expectation, power was greater for cross-sectional (CS) than longitudinal (LT) effects, particularly with a diminishing LT/CS ratio. With a minimum minor allele count of 3 within genotype by time categories, observed type I error was roughly equal to theoretical genome-wide significance. Additionally, 28 blood-based biomarkers measured at 2 time points on participants of the UK Biobank were used to compare GAMUT against single-trait standard and longitudinal GWAS (including rate of change). Across all biomarkers, we observed 539 (CS) and 248 (LT) significant independent variants for the GAMUT method, and 513 (CS) and 30 (LT) for single-trait longitudinal GWAS, respectively. Only 37 variants were identified by modeling rates of change using standard GWAS.

Numerical Simulation and Analysis of Hydraulic Turbines Based on BIM for Sustainable Development

Hydropower is considered to be an important way to achieve the sustainable development goal of human progress. The performance of turbines is very important to the safety and stability of hydropower stations. Most of the hydraulic turbine performance studies only use Computational Fluid Dynamics (CFD) for performance simulation, lacking the integration of Building Information Modeling (BIM) technology and CFD. Therefore, a performance analysis model of a Francis turbine based on BIM was put forward in this paper. The BIM software OpenBuildings Designer CONNECT Edition Update 10 was used to build the hydraulic turbine model, and then the BIM model was transferred to the CFD numerical simulation platform ANSYS through the intermediate format conversion. In the ANSYS environment, the numerical simulation of different working conditions was carried out with the help of Fluent 2021 R1 software. The numerical simulation results show that the fluid velocity gradient in the volute was 2~3 m/s under the three working conditions, which was relatively stable. The water flow could progress the guide vane mechanism at a higher speed, and the drainage effect of the volute was better. There were some negative pressure areas at the back of the runner blades and the inlet of draft tube, and the negative pressure value was as high as −420,000 Pa and −436,842 Pa under maximum head conditions, which were prone to cavitation erosion. It is proven that BIM supported the hydraulic turbine performance analysis and provided a geometric information model for hydraulic turbine CFD numerical simulation, meaning that the performance analysis model based on BIM is feasible. This study can expand the application value of BIM and provide guidance for the study of hydraulic turbine numerical simulation using BIM technology in combination with CFD methods.

The Relationship Between Effects of Extrinsic Motivation and Intrinsic Motivation in Children's Educational Development

Education stands as a globally paramount subject, a cornerstone of human development and progress. In an increasingly competitive world, parents often grapple with how to instill a genuine love for learning in their children. The notion of extrinsic and intrinsic motivation in childrens educational development presents a compelling avenue for exploration. its essential to delve into the intricate interplay between these two types of motivation, shedding light on their effects and implications. As parents and educators navigate the realm of childrens education, a nuanced understanding of motivation is paramount. Extrinsic motivation, with its assortment of verbal and tangible rewards, can be a potent tool to catalyze learning engagement. However, the potential risks of dampening intrinsic motivation must be approached with caution. Striking a balance between extrinsic incentives and the inherent joy of learning is crucial for nurturing well-rounded, intrinsically motivated learners. The intricate interplay between extrinsic and intrinsic motivation underscores the need for a holistic approachone that encourages a genuine passion for knowledge while harnessing the positive aspects of rewards. In the pursuit of optimal educational development, acknowledging and harmonizing these motivational dynamics is an essential step toward fostering lifelong learners poised for success in an ever-evolving world.

Sino-futurism and alternative imaginaries of Digital China

This paper investigates the role of digital technologies in transforming China's self-image. It focuses on the use of extended reality (XR) in ceremonial events and art exhibitions. The paper offers two case studies. The first study, Beijing 8-Minute Show (2018), a multimedia performance at the closing ceremony of the Pyeongchang Winter Olympic Games, set the scene for what was called the Science and Technology Winter Olympics in 2022. The second study, Blueprints (2020), was a multimedia exhibition in the UK by the artist Cao Fei, which drew attention to a future of increased alienation, loss of privacy and digital surveillance. In the paper, the framework of a ‘techno-cultural imaginary’ shows how China's self-image is increasingly tied to modernisation. The paper demonstrates how the ‘two cultures’, science and the arts, have converged in policy thinking. In this reset, China's so-called cultural confidence is re-energised by digital platforms, echoing the description of Digital China. Sino-futurism, originally used in relation to Chinese sci-fi literature, provides a stepping-off point to imagine the future, which is alternatively characterised as techno-utopian (within China) and dystopian (in the West). Drawing on the qualitative analysis of publicly available interviews, media reports, online comments and close reading of the art content, the paper argues that XR allows the government to present Digital China as a positive blueprint for human progress. Meanwhile, XR is capable of generating critical stories about China, which contradict the message the government seeks to cultivate with its public diplomacy and propaganda campaigns.

Fetal health screening model and element analysis

The United Nations Sustainable Development Goals has mentioned to reduce child mortality. That is also a crucial indicator of human progress. The UN hopes that all countries will eradicate preventable deaths of newborns at the end of 2030. Cardiotocogram (CTG) can be used to identify in-danger women during pregnancy. The aim of this article is to apply machine learning algorithm techniques on CTG data to ensure fetal well-being. CTG data of 2126 samples and 22 variables were obtained from the CTG exams on Kaggle. Two different classification models were trained through the data. In order to predict Normal, Suspect, and Pathological fetal states, each class had its own sensitivity, precision and F1 score. Each model has its overall accuracy. Determined by obstetricians interpretation of CTG, Normal state accounted for 57%, Suspect state accounted for 23% and Pathological state accounted for 20%. The classification models generated by Logistic Regression and Random Forest to predict the suspect and pathological state of the fetus by tracing CTG. They had high precision of 86% and 94% respectively. However, the classification model developed by Random Forest had higher prediction accuracy for a negative fetal outcome. Healthcare workers without professional training in low-income countries have the opportunity to utilize this model for the purpose of prioritizing pregnant women in hard-to-reach regions, ensuring they receive timely referrals and appropriate follow-up care.

Peran Penting Pendidikan Islam dalam Kehidupan Manusia

The purpose of this research is to determine the role of Islamic education in human life. while the method used in this research is qualitative, namely a scientific method that emphasizes collecting references. The importance of education is widely agreed upon by every element of society. Islamic education, which in its historical movement has always aimed at the progressivity and transformativeness of human life, so that its existence must also contain everything that humans need, not only has a pragmatic dimension, but also idealistic, not only profane, but also sacred, and not only full of content. knowledge, but also morals. The essence of Islamic education is carried out as an effort towards changes in behavior that are "better", and necessitates changes as desired, in accordance with the goals outlined by an educational institution. Changes intended by an educational institution. The changes in question can have nuances in the progress of humanity, both in the context of one's relationship with society, nature and God. The meaning of physical and spiritual education is very important, whether seen from the education system, educational environment, educational social interaction, educational access, educational facilities.

Type 2 Cystatins and Their Roles in the Regulation of Human Immune Response and Cancer Progression.

Cystatins are a family of intracellular and extracellular protease inhibitors that inhibit cysteine cathepsins-a group of lysosomal cysteine proteases that participate in multiple biological processes, including protein degradation and post-translational cleavage. Cysteine cathepsins are associated with the development of autoimmune diseases, tumor progression, and metastasis. Cystatins are categorized into three subfamilies: type 1, type 2, and type 3. The type 2 cystatin subfamily is the largest, containing 10 members, and consists entirely of small secreted proteins. Although type 2 cystatins have many shared biological roles, each member differs in structure, post-translational modifications (e.g., glycosylation), and expression in different cell types. These distinctions allow the type 2 cystatins to have unique biological functions and properties. This review provides an overview of type 2 cystatins, including their biological similarities and differences, their regulatory effect on human immune responses, and their roles in tumor progression, immune evasion, and metastasis.

Are the later Mohists preference-satisfaction consequentialists? A discussion of Daniel Stephens’ “Later Mohist ethics and philosophical progress in ancient China”

ABSTRACT The Mohists may have been the first consequentialists on earth. Their most important principles are that right action is what benefits the world and that the underlying outlook for benefiting the world is inclusive care, whereby each person receives equal consideration. The early Mohists are clearly objective-list consequentialists, whereby benefiting the world amounts to promoting the most basic goods. Stephens argues that the later Mohists shift to a preference-satisfaction consequentialism whereby benefiting the world amounts to promoting what happens to please individual people. Stephens argues that while the direct texts are ambiguous between an objective-list interpretation and a preference-satisfaction interpretation, the latter better explains later Mohist engagement with opponents. I argue that the direct texts actually preclude Stephens’ preference-satisfaction interpretation, which moreover has the later Mohists concede an implausible amount to their opponents.

Outdoor artificial light at night and cardiovascular disease in adults: a Chinese nationwide cohort study

Abstract Background Although the electric light is a significant promotion in the human progress and civilization, its adverse effects of outdoor artificial light at night (ALAN) are being extensively studied. However, the association of outdoor ALAN and cardiovascular disease (CVD) has never been confirmed in large nationwide studies, especially in urban areas with high exposure levels and in rural areas with low exposure levels, respectively. Purpose To explore the association between outdoor ALAN and CVD. Methods This national study enrolled 12,686 adults ≥ 40 years across China. The outdoor ALAN exposure (nW/cm2/sr) with the resolution of the 500 meters around each participant's location was obtained from satellite image data via Visible Infrared Imaging Radiometer Suite day-night band on board the Joint Polarorbiting Satellite System. CVD was defined by a doctor's record of diagnoses, including heart disease and stroke. Poisson regression model and restricted cubic spline models were used to estimate the relationship between outdoor ALAN and CVD in urban and rural areas, respectively. Subgroup analysis was also conducted using Poisson models for each subgroup. Results At a median follow-up of 7 years, 1,732 cases of CVD were identified. The mean age of the participants was 58 years and 49% were males. In urban areas, outdoor ALAN exposure at the highest quartile (Q4) increased the incidence of CVD among participants by 34% compared to those exposure at the lowest quartile (Q1) (incident rate ratio, IRR: 1.34,95% CI: 1.07—1.69, p = 0.01), adjusting for age, sex, BMI, education, smoke ever, alcohol consumption, physical activity and household consumption. In rural areas, compared with those at the Q1 of outdoor ALAN exposure, exposure at the Q4 reduced the incidence of CVD by 17% (IRR: 0.83, 95% CI: 0.70—0.98, p = 0.028) after full adjustment. Dose-response relationship indicated that outdoor ALAN levels were linearly associated with decreased CVD in rural area (p for non-linearity = 0.370), while the association between outdoor ALAN levels and CVD was shown as an inverse "U" shape in urban area (p for non-linearity ≤ 0.001). Subgroup analysis shown that the CVD risk of middle-aged people, people with history of alcohol consumption, or people with low levels of physical activity were susceptible to outdoor ALAN exposure. Conclusions Outdoor ALAN exposure was associated with the risk of CVD, which was heterogeneous with different levels of exposure range. In rural areas with low outdoor ALAN exposure settings, outdoor ALAN exposure was negatively correlated with the risk of developed CVD, while the association was reverse in urban areas with high outdoor ALAN exposure settings. We call for a reduction in the use of high-intensity ALAN and to pay attention to the effects of emotional, psychological, and biological changes associated with outdoor ALAN exposure on cardiovascular health.Figure 1

Abstract 14313: A Proteomic Atlas of Human Coronary Artery Reveals the Pathological Progression of Atherosclerosis

Introduction: The key molecular mechanisms associated with human atherosclerotic plaque progression, atherosclerotic lesion initiation and plaque destabilization are not fully understood. Hypothesis: Different stages of atherosclerosis (AS) progression have distinct pathological processes. Some key proteins induce AS progression. Methods: We employed 20 coronary artery samples among 4 explanted hearts from coronary heart disease patients. Each heart contains stages of unaffected control (NC), pathological intimal thickening (PIT), fibroatheroma (FA), transition to thin-cap fibroatheroma (TCFA) and ruptured plaque (RP), which were validated by hematoxylin and eosin (H&amp;E) staining. We performed quantitative proteomics in each of the samples based on tandem-mass-tags and liquid chromatography-tandem mass spectrometry. Furthermore, we measured proteins in human coronary artery tissue via immunofluorescence. Results: Proteomics revealed that extracellular matrix (ECM) organization was the most significantly enriched pathway in PIT. FA exhibited an enrichment of immunologic processes, such as neutrophil degranulation, myeloid leukocyte activation and innate immune response. Molecular profiles of TCFA and RP are similar, with complement and coagulation cascades pathway as a hallmark of these stages. Clustering analysis of DEPs displayed 4 clusters, notably cluster 2 had a precipitous elevation from FA to TCFA. Within this cluster, we identified a high-rank molecule: macrophage-capping protein (CAPG). Immunohistochemistry and immunofluorescence revealed that CAPG is highly elevated in plaque compared to NC and is specifically expressed in the plaque. Conclusions: ECM organization was continuously dysregulated in AS progression. Immune response might initiate the atherosclerotic plaque. Complement and coagulation cascades pathway was a hallmark of TCFA and RP. CAPG might be a therapeutic target for AS progression.

Abstract 18753: Dynamic Phenotypic Transition of Smooth Muscle Cells During Human Ascending Thoracic Aortic Disease Progression: From Compensation in Aortic Aneurysm to Decompensation in Aortic Dissection

Introduction: Although ascending thoracic aortic aneurysm (ATAA) and ascending thoracic aortic dissection (ATAD) share common pathologic features of aortic degeneration, the specific elements that lead to rapid disease progression in ATAD remain poorly understood. We examined the molecular and cellular dynamics in smooth muscle cells (SMCs) of aortic tissues from ATAA and ATAD patients and further examined mechanisms in a mouse model. Methods: Single-cell RNA sequencing (scRNA-seq) analyses were performed in ascending aortic tissues from individuals without aortic disease (n=8), patients with ATAA without dissection (n=9), and patients with acute ATAD (n=9). Further, scRNA-seq and scATAC-seq were performed in ascending aortic tissues from mice infused with angiotensin II (AngII) or control mice; scRNA-seq analyses were performed on SMC-specific Tgfbr2 -/- mice. Results: Six SMC subtypes were identified in human aortic tissues. Cluster proportion and trajectory analyses indicated a profound SMC transition from contractile in control to extracellular matrix (ECM)-contractile phenotype in ATAA, however, was reduced in ATAD tissues. Instead, ATAD showed significant SMC transition to inflammatory phenotype. Consistently, many genes in ECM organization and muscle contraction, collectively termed compensatory response, were upregulated in ATAA but downregulated in ATAD tissues compared with controls, whereas inflammatory response and cell death pathway genes were significantly upregulated in ATAD compared with control and ATAA tissues. Cell-cell interaction, regulatory network, and motif analysis suggested that TGF-beta-MEF2C signaling contributed to the induction of the ECM-contractile SMC phenotype. MEF2C + SMCs exhibited the capacity of transition towards ECM-producing SMCs in both mouse and human aorta. SMC-specific Tgfbr2 -/- mice showed compromised SMC transition to ECM-producing phenotype. Conclusions: Our study reveals SMC phenotypic transitions to ECM-producing SMCs in ATAA and to inflammatory and pro-death SMCs in ATAD, which represent a compensatory response in ATAA and a decompensatory status in ATAD. TGF-beta-MEF2C, a novel regulatory axis, promoted the compensatory response in SMCs of the ascending aorta.

Lagrange Multiplier-Based Optimization for Hybrid Energy Management System with Renewable Energy Sources and Electric Vehicles

The issues of energy scarcity and environmental harm have become major priorities for both business and human progress. Hence, it is important and useful to focus on renewable energy research and efficient utilization of distributed energy sources (DERs). A microgrid (MG) is a self-managed system that encompasses these energy resources as well as interconnected consumers. It has the flexibility to function in both isolated and grid-connected configurations. This study aims to design an effective method of power management for a MG in the two operating modes. The proposed optimization model seeks to strike a balance between energy usage, protecting the life of batteries, and maximizing economic benefits for users in the MG, with consideration of the real-time electricity price and constraints of the power grid. Furthermore, in order to accurately account for the dynamic nature of not only the stationary battery banks used as the energy storage systems (ESS) but also the built-in batteries of electric vehicles (EVs), the model is presented as a multi-objective, multiparametric and constrained problem. The solution is proposed to be found using the Lagrange multiplier theory, which helps to achieve good performance with less computational burden. Lastly, simulation results from both the isolated and grid-connected modes also demonstrate the effectiveness of the designed method.

Tubular dysfunction impairs renal excretion of pseudouridine in diabetic kidney disease.

Plasma nucleosides-pseudouridine (PU) and N2N2-dimethyl guanosine (DMG) predict the progression of type 2 diabetic kidney disease (DKD) to end-stage renal disease, but the mechanisms underlying this relationship are not well understood. We used a well-characterized model of type 2 diabetes (db/db mice) and control nondiabetic mice (db/m mice) to characterize the production and excretion of PU and DMG levels using liquid chromatography-mass spectrometry. The fractional excretion of PU and DMG was decreased in db/db mice compared with control mice at 24 wk before any changes to renal function. We then examined the dynamic changes in nucleoside metabolism using in vivo metabolic flux analysis with the injection of labeled nucleoside precursors. Metabolic flux analysis revealed significant decreases in the ratio of urine-to-plasma labeling of PU and DMG in db/db mice compared with db/m mice, indicating significant tubular dysfunction in diabetic kidney disease. We observed that the gene and protein expression of the renal tubular transporters involved with nucleoside transport in diabetic kidneys in mice and humans was reduced. In conclusion, this study strongly suggests that tubular handling of nucleosides is altered in early DKD, in part explaining the association of PU and DMG with human DKD progression observed in previous studies.NEW & NOTEWORTHY Tubular dysfunction explains the association between the nucleosides pseudouridine and N2N2-dimethyl guanosine and diabetic kidney disease.

Prevalence and genomic characterization of Salmonella isolates from commercial chicken eggs retailed in traditional markets in Ghana.

Salmonella enterica are important foodborne bacterial pathogens globally associated with poultry. Exposure to Salmonella-contaminated eggs and egg-related products is a major risk for human salmonellosis. Presently, there is a huge data gap regarding the prevalence and circulating serovars of Salmonella in chicken eggs sold in Ghana. In this study, 2,304 eggs (pools of six per sample unit) collected from informal markets in Accra, Kumasi and Tamale, representing the three ecological belts across Ghana, were tested for Salmonella. Antimicrobial susceptibility testing and Whole Genome Sequencing (WGS) of the isolates were performed using standard microdilution protocols and the Illumina NextSeq platform, respectively. The total prevalence of Salmonella was 5.5% with a higher rate of contamination in eggshell (4.9%) over egg content (1.8%). The serovars identified were S. Ajiobo (n = 1), S. Chester (n = 6), S. Hader (n = 7), S. enteritidis (n = 2); and S. I 4:b:- (n = 8). WGS analysis revealed varied sequence types (STs) that were serovar specific. The S. I 4:b:- isolates had a novel ST (ST8938), suggesting a local origin. The two S. enteritidis isolates belonged to ST11 and were identified with an invasive lineage of a global epidemic clade. All isolates were susceptible to ampicillin, azithromycin, cefotaxime, ceftazidime, gentamicin, meropenem, and tigecycline. The phenotypic resistance profiles to seven antimicrobials: chloramphenicol (13%), ciprofloxacin (94%), and nalidixic acid (94%), colistin (13%), trimethoprim (50%) sulfamethoxazole (50%) and tetracycline (50%) corresponded with the presence of antimicrobial resistance (AMR) determinants including quinolones (gyrA (D87N), qnrB81), aminoglycosides (aadA1), (aph(3")-Ib aph(6)-Id), tetracyclines (tet(A)), phenicols (catA1), trimethoprim (dfrA14 and dfrA1). The S. enteritidis and S. Chester isolates were multidrug resistant (MDR). Several virulence factors were identified, notably cytolethal distending toxin (cdtB gene), rck, pef and spv that may promote host invasion and disease progression in humans. The findings from this study indicate the presence of multidrug resistant and virulent strains of Salmonella serovars in Ghanaian chicken eggs, with the potential to cause human infections. This is a critical baseline information that could be used for Salmonella risk assessment in the egg food chain to mitigate potential future outbreaks.

CircPTEN suppresses human clear cell renal carcinoma progression and resistance to mTOR inhibitors by targeting epigenetic modification.

Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.

ROUSSEAU AND HO CHI MINH'S VIEWS ON THE CONSTITUTIONAL AND LAWFUL STATE – FROM THEORY TO PRACTICE IN VIETNAM

Inheriting the humanistic and revolutionary spirit of the French Enlightenment, especially from Rousseau, in the twentieth century, President Ho Chi Minh, on the foundation of Marxism-Leninism, solved the problem of the liberated nation, human rights, and civil rights with realistic social revolutions, contributing to the common progress of humanity according to the ideals of freedom and equality for all people and peoples. The socialist state of Vietnam, from the first days of its founding, has been a constitutional and legal state in accordance with all principles of a legitimate state. Thanks to its legitimacy, the Vietnamese state had gained the strength and legitimacy needed in the struggle to protect national independence from hostile forces. Facing the requirements of socio-political reality, Vietnam, on the theoretical basis of Ho Chi Minh's thoughts, has made efforts to consolidate and perfect the state to ensure civil and human rights in the country, contributing to promoting peace, cooperation, and progress of the world. Researching a variety of thoughts from Rousseau's views on the legal and constitutional state to Ho Chi Minh's thoughts and drawing out the core values and orientations for building the administrative system in Vietnam today is the purpose of the article.&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt; Article visualizations:&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;img src="/-counters-/soc/0032/a.php" alt="Hit counter" /&gt;&lt;/p&gt;

Towards a low-carbon society: spatial distribution, characteristics and implications of digital economy and carbon emissions decoupling

Reducing carbon emissions and attaining sustainable economic, social, and environmental development are vital components of the 2030 Agenda for Sustainable Development. Previous research has overlooked the influence of the digital economy on urban carbon decoupling. To bridge this gap, this study employs GIS software and econometric models for analyzing the spatial distribution and characteristics of the digital economy and carbon decoupling and also investigates the direct, heterogeneous, and spatial effects of the digital economy on carbon decoupling. This study reveals: (1) A lesser digital economy presence in the northeast and northwest, while more developed in the Southeast Coast and municipalities directly under the Central Government. Cities with weak carbon decoupling are concentrated in Northeast and North China. (2) The digital economy and the decoupling of urban carbon emissions have spatial correlation and agglomeration characteristics. (3) The digital economy can contribute to decoupling carbon emissions in cities. (4) Improved urban carbon decoupling by the digital economy in central, eastern, and non-resource-based cities. (5) Spatial spillover effect in urban carbon emissions decoupling, yet the digital economy worsens nearby cities’ carbon decoupling due to a siphon effect. That research indicates that the digital economy holds significant promise not only in advancing human progress, bridging the digital divide, and fostering social development but also in driving the decoupling of urban carbon emissions.