Indirect Role Research Articles

The role of ceRNAs in breast cancer microenvironmental regulation and therapeutic implications.

The tumor microenvironment, which is the tailored physiological milieu of heterogeneous cancer cell populations surrounded by stromal and immune cells as well as extracellular matrix components, is a leading modulator of critical cancer hallmarks and one of the most significant prognostic indicators in breast cancer. In the last few decades, with the discovery of the interactions of ncRNAs with diverse cellular molecules, considerable emphasis has been devoted to understanding their direct and indirect roles in specific functions in breast cancer. Collectively, all of these have revealed that the competitive action of protein-coding RNAs and ncRNAs such as circRNAs and lncRNAs, which have a shared affinity for miRNAs, play a vital role in the molecular regulation of breast cancer. This phenomenon, termed as competing endogenous RNAs (ceRNAs), facilitates modeling the microenvironment through intercellular shuttles. Microenvironment ceRNA interactions have emerged as a frontier in the deep understanding of the complex mechanisms of breast cancer. In this review, we first discuss cellular ceRNAs in four key biological processes critical for microenvironmental regulation in breast cancer tissues: hypoxia, angiogenesis, immune regulations, and ECM remodeling. Further, we draw a complete portrait of microenvironment regulation by cell-to-cell cross-talk of shuttled ceRNAs and offer a framework of potential applications and challenges in overcoming the aggressive phenotype of the breast cancer microenvironment.

How is the concept of charisma used in the academic literature about biodiversity conservation? A systematic map protocol

BackgroundThe extinction of species is a multifaceted phenomenon shaped by the complex interplay between biological and socio-cultural factors. Public and academic preferences for different species often play a direct or indirect role in influencing the conservation outlook of these species. The “charisma” of species and other components of biodiversity is often mentioned as an important factor in shaping human preferences, determining both the scope of scientific studies and justifications for such scope. Here, we present a protocol for systematically mapping the use of the concept of “charisma” in relation to biodiversity peer-reviewed academic literature focused on biodiversity conservation.MethodsThe search targeting academic peer-reviewed research articles and reviews will be conducted in three publication databases, The Lens, Scopus and Web of Science (Core Collection and SciELO), and will be supplemented by search engine results from Google Scholar. Broad-scope searches will be performed in 3 different languages (English, Portuguese, and Spanish) and article screening will be performed at two stages to ensure the relevance of each entry and consistency amongst reviewers in their use of the defined inclusion criteria. The resulting systematic map of the literature will be summarised by employing a narrative synthesis approach, and through descriptive statistics and analysis of temporal trends.

Parenting style profiles and adolescents’ creativity: the indirect role of regulatory focus

Parenting style profiles and adolescents’ creativity: the indirect role of regulatory focus

Exploring the impact of university-driven supplier development interventions on supplier performance: a case of the garment industry

PurposeThe purpose of this study is to investigate the effectiveness of university-driven knowledge transfer initiatives in enhancing the capabilities and performance of local suppliers in the garment industry. By focusing on the impact of UDIs in Myanmar, this research aims to provide empirical evidence on how these initiatives can foster supplier development and performance improvement through targeted capability enhancement strategies.Design/methodology/approachThis study utilizes a combination of surveys and an experimental design to evaluate the impact of university-driven supplier development interventions (UDIs) based on Lean principles in Myanmar’s garment industry. Nine garment suppliers were assessed before and after the UDI program. The research employed partial least squares structural equation modeling (PLS-SEM) to analyze the direct, indirect and mediating effects of UDIs on supplier performance, focusing on the role of supplier capability enhancement as a mediating factor.FindingsThe study found that the UDI program significantly improved supplier capabilities, which in turn led to enhanced performance. The analysis revealed partial mediation, indicating that while UDIs directly impact supplier performance, their effect is significantly amplified through the enhancement of supplier capabilities. These findings highlight the critical role of targeted capability development in achieving substantial performance improvements among local suppliers.Originality/valueThis research contributes to the literature by providing empirical evidence on the effectiveness of university-driven supplier development initiatives in a developing country context. It validates the indirect role of UDIs in boosting supplier performance via capability enhancement, emphasizing the importance of industry-specific and capability-focused development strategies. The findings underscore the value of structured knowledge transfer programs in supporting local suppliers, offering practical insights for policymakers and educational institutions aiming to enhance industrial performance through strategic interventions.

China–ASEAN Tourism Economic Relationship Network: A Geopolitical Risk Perspective

Despite extensive research on the network structure of tourism destinations, literature on the spatial network structure of cross-border tourism–economic connections is relatively limited, specifically the complex geopolitical relationship between China and the Association of Southeast Asian Nations (ASEAN). Thus, in this study we explored the relevant characteristics and influencing factors of the spatial structure of tourism economic networks. The results first indicate that the China–ASEAN tourism economic network exhibits distinct stage characteristics, with an ‘N’-shaped fluctuating growth trend, evolving from a point-like network to a multipolar development in spatial structure. In addition, China demonstrates a distinctive personality in the network and occupies a central leadership position. Secondly, an analysis of influencing factors shows that institutional distance and geographic distance have a significant impact on the network. Geopolitical risk plays a notable indirect moderating role in the network through its association with tourism policies and regulations, tourism promotion, and cooperation. This further reveals the diverse pathways through which geopolitical risk affects the network, providing a novel perspective for research on the tourism economic network.

Local Governance and School-based Approaches to English Language Acquisition: A Comparative Analysis

In order to improve the effectiveness of English acquisition, it is necessary to discuss it in conjunction with local governance policies. Local governments should conduct an analysis of English acquisition from the aspects of policies, systems, and social participation. This paper puts forward three hypotheses: local policies and systems can improve the effectiveness of English learning, which are related. Public attention can promote the improvement of English acquisition effect and play a supervisory role; Laws and regulations can ensure the foundation of basic conditions for English acquisition and promote the improvement of school infrastructure. The results show that local policies and institutions are the conditions for improving English acquisition methods, social attention is the condition for verification, and school infrastructure is the key condition. Social issues, local policies and institutions all play an indirect role in promoting English language acquisition, while infrastructure plays a direct role. Therefore, local governments should improve English acquisition policies and systems, promote the introduction of English acquisition laws and regulations, and guide the public to supervise.

Acceptance of Digital Health Care Technology and the Role of Nursing Education.

As digital health care technology develops, the use of technology in the nursing field has become an essential part of nursing education. However, few studies have linked nurses' awareness of digital health care with nursing education. This study examines the direct effects and mediating effects of factors in technology acceptance on nurses' intention to accept digital health care technology. To empirically investigate these relationships, a survey was conducted among nurses in South Korea. This study emphasizes the importance of a multifaceted approach that considers personal, organizational, and innovation-related factors in understanding nurses' intentions toward acceptance of digital health care technologies. The findings confirm that performance expectancy and facilitating conditions play crucial roles in nurses' acceptance of digital health care technologies. The mediating effects of performance expectancy and facilitating conditions on intentions to accept technologies suggest that these factors can also play vital indirect roles. [J Contin Educ Nurs. 202x;5x(x):xx-xx.].

The chlorine evolution of arc magmas and the crustal water filter

Degassing of water from magmatic systems is key to transporting metals from magmas to form ore deposits, but elements like chlorine, through the formation of anion complexes, can be important in solubilizing and mobilizing these metals into water-rich fluids. Reconstructing the Cl systematics of evolving magmas is thus an important step towards understanding the origins of ore deposits, but the magmatic record is not well preserved because Cl can be lost during degassing. Here, we reconstruct the pre-degassing history of Cl in subduction zone (arc) magmas through amphiboles, which incorporate Cl directly into their crystal structures, preserving pre-eruptive magmatic signatures. Amphibole-reconstructed Cl contents indicate that magmatic differentiation can lead to a 4-fold increase in concentration due to Cl's incompatible behavior. The amphibole-reconstructed Cl contents of arc magmas are also significantly higher than values reported from melt inclusions, suggesting that many melt inclusions may have been trapped after magmas had already lost some Cl. We show that such Cl loss is likely associated with preferential partitioning of Cl into hydrous fluids degassed from the magma during crustal storage or ascent. The extent of Cl depletion can thus be used to estimate how much water was lost during early degassing. If Cl is important to certain ore deposits, magmatic water content may play an indirect role. Magmas too rich in water will lose water and hence Cl at greater depths, rendering such magmas less able to transport metals to the upper crust. By contrast, drier magmas may not produce enough Cl-rich fluids to mobilize metals. Thus, magmas with intermediate water contents may produce enough Cl-rich fluids at the right depths for certain types of ore deposits.

Decoding the genomic terrain: functional insights into 14 chemosensory proteins in whitefly Bemisia tabaci Asia II-1

Genome-wide analysis of Bemisia tabaci Asia II-1 unravelled for the first-time full-length sequences of 14 chemosensory proteins (CSPs), their exon-intron boundaries, insertion sites of retrotransposons, and clustering patterns on chromosomes. All the CSPs sans CSP6 have an N-terminal signal peptide. The presence of OS-D superfamily and PhBP domains in different CSPs suggests their roles in chemosensory signal transduction and pheromone binding. Motif analysis reveals the conservation and cohesiveness of CSPs in hemiptera. The phylogenetic analysis uncovers the evolutionary lineages of Hemipteran CSPs. RT-qPCR analysis showed spatial expression of CSPs in different body tissues of B. tabaci adults. In-silico docking analysis showed high-affinity binding of CSP 1 and 5 with two insecticides, imidacloprid and fipronil, with energy values ranging from − 5.8 to -9.3 kcal/mol, along with the details of interacting aminoacidic residues in the hydrophobic binding pockets of these two CSPs. Further functional validation was done through insecticide bioassays and RNAi. This study provides novel insights into the genomic architecture of CSPs in B. tabaci Asia II-1, and functional characterisation suggests that CSP1 and 5 genes may have indirect roles in insecticide resistance. It lays the foundation for further research on developing new control strategies for B. tabaci.

A new look at TFPI inhibition of factor X activation.

Blood coagulation is a vital physiological process involving a complex network of biochemical reactions, which converge to form a blood clot that repairs vascular injury. This process unfolds in three phases: initiation, amplification, and propagation, ultimately leading to thrombin formation. Coagulation begins when tissue factor (TF) is exposed on an injured vessel's wall. The first step is when activated factor VII (VIIa) in the plasma binds to TF, forming complex TF:VIIa, which activates factor X. Activated factor X (Xa) is necessary for coagulation, so the regulation of its activation is crucial. Tissue Factor Pathway Inhibitor (TFPI) is a critical regulator of the initiation phase as it inhibits the activation of factor X. While previous studies have proposed two pathways-direct and indirect binding-for TFPI's inhibitory role, the specific biochemical reactions and their rates remain ambiguous. Many existing mathematical models only assume an indirect pathway, which may be less effective under physiological flow conditions. In this study, we revisit datasets from two experiments focused on activated factor X formation in the presence of TFPI. We employ an adaptive Metropolis method for parameter estimation to reinvestigate a previously proposed biochemical scheme and corresponding rates for both inhibition pathways. Our findings show that both pathways are essential to replicate the static experimental results. Previous studies have suggested that flow itself makes a significant contribution to the inhibition of factor X activation. We added flow to this model with our estimated parameters to determine the contribution of the two inhibition pathways under these conditions. We found that direct binding of TFPI is necessary for inhibition under flow. The indirect pathway has a weaker inhibitory effect due to removal of solution phase inhibitory complexes by flow.

Tracking Employee Lifetime Value: Strategically Leveraging Metrics to Grow Your Talent Pipeline and Bottom Line

This practitioner-oriented research brief examines why and how companies can strategically track employee lifetime value (ELV) metrics. ELV refers to the total financial contributions and indirect cost savings an employee provides over their career both within and beyond their tenure at an organization. After outlining the scholarly foundation demonstrating ELV as a key driver of competitive advantage, productivity, revenue and firm performance, the brief delves into methods for quantifying ELV. Two primary components are contribution value from direct compensation and indirect support roles, as well as retention value from avoided replacement expenses and future referral potential. Examples are given of calculating ELV through estimating average tenure, forecasting contribution streams, incorporating various rates and modeling knowledge depreciation. The brief then analyzes how leveraging robust ELV insights supports strategic decisions around talent deployment, succession planning, training investments, and evaluating alignment of strategies to sustain ELV. Finally, real-world case studies from the technology and financial services industries demonstrate multi-billion dollar impacts achieved by companies that proactively track and maximize employee lifetime value through workforce planning and positive engagement of employee networks.

Role of Complexin 2 in the regulation of hormone secretion from the islet of Langerhans.

Regulated secretion of insulin from β-cells, glucagon from α-cells, and somatostatin from δ-cells is necessary for the maintenance of glucose homeostasis. The release of these hormones from pancreatic islet cells requires the assembly and disassembly of the SNARE protein complex to control vesicle fusion and exocytosis. Complexin 2 (Cplx 2) is a small soluble synaptic protein that participates in the priming and release steps of vesicle fusion. It plays a dual role as a molecular switch that first clamps and prevents fusion pore opening, and subsequently undergoes a conformational change upon Ca 2+ binding to synaptotagmin to facilitate exocytosis. Using a Cplx 2 knockout (KO) mouse model, we show a direct inhibitory role of Cplx 2 for glucagon and somatostatin secretion, along with an indirect role in the paracrine inhibition of insulin secretion by somatostatin. Deletion of Cplx 2 increases glucagon and somatostatin secretion from intact mouse islets, while there is no difference in insulin secretion between WT and Cplx 2 KO islets. The normal paracrine inhibition of insulin secretion by somatostatin is disrupted in Cplx 2 KO islets. On the contrary, deletion of Cplx 2 did not affect the known role of somatostatin in the paracrine inhibition of glucagon at elevated glucose levels, since the paracrine inhibition of glucagon secretion by somatostatin is similar for both WT and Cplx 2 KO islets. In both β- and α-cells, the secretion profiles are parallel to Ca 2+ activity changes following somatostatin treatment of WT and Cplx 2 KO islets. The loss of paracrine inhibition of insulin secretion is substantiated by direct measurements of insulin vesicle fusion events in Cplx 2 KO islets. Together, these data show a differential role for Cplx 2 in regulating hormone secretion from pancreatic islets.

The impact of digital technology use on adolescents' subjective well-being: The serial mediating role of flow and learning engagement.

While existing research has established the influence of digital technology use, flow, and learning engagement on students' subjective well-being, there remains a gap in understanding the interrelationships among these factors and the serial mediating role of flow and learning engagement in the relationship between digital technology use and adolescents' subjective well-being. This study examined the potential indirect roles of flow and learning engagement in the association between digital technology use and adolescents' subjective well-being. A paper-based survey was conducted among 1289 adolescents (M = 16.33, SD = 1.688) in Shandong Province. All participants completed a structured self-report questionnaire, including measures of digital technology use, flow, learning engagement, and subjective well-being. Data analyses were conducted using structural equation modeling via Amos 24.0 and SPSS 24.0. The results are as follows: (1) digital technology use has a significant and positive effect on adolescents' subjective well-being; (2) digital technology use significantly and positively affects adolescents' subjective well-being through flow; (3) digital technology use significantly and positively affects adolescents' subjective well-being through learning engagement; (4) digital technology use significantly and positively affects the subjective well-being of adolescents through both flow and learning engagement. This study underscores the benefits of digital technology in boosting adolescents' well-being and identifies flow and learning engagement as key mediators. Our findings equip educators and policymakers with insights to craft interventions that optimize digital technology's role in fostering adolescent development, presenting a fresh view on the intricate dynamics linking digital interaction with psychological health.

Kinetics and Mechanism of PPh3/Ni-Catalyzed, Zn-Mediated, Aryl Chloride Homocoupling: Antagonistic Effects of ZnCl2/Cl.

The Ni/PPh3-catalyzed homocoupling of aryl chlorides in DMF using Zn as the stochiometric reducing agent is one of a general class of Ni-catalyzed processes, where the mechanism has been a matter of long-standing debate. This study re-evaluates prior conclusions and insights. NMR spectroscopy is used to identify [(PPh3)2NiII(Ar)Cl] as a key intermediate and to explore the indirect roles of using Zn as the reductant. The [ZnCl2] coproduct is responsible for several features, including a sequential transmetalation pathway involving [ArZnCl]. [ZnCl2] also abstracts halide from [(PPh3)2NiCl2] to generate [NiIICl(DMF)5]+[ZnCl3(DMF)]-, and in doing so, affects the NiII + Ni0 ↔ 2 NiI speciation. [ZnCl2] thus acts as an accelerator and inhibitor, resulting in mildly sigmoidal reaction profiles. When the [ZnCl2] concentration becomes too high or the phosphine ligand concentration too low, catalysis stalls. Turnover is restored by the addition of further phosphine ligand, or chloride ion. In the presence of an exogenous chloride ion, turnover is rapid, again proceeding via [(PPh3)2NiII(Ar)Cl] but via dinuclear metathesis. The generation of [ZnCl3(DMF)]- results in mutually antagonistic effects between [ZnCl2] and [Cl]- such that turnover proceeds via one mechanism or the other, depending on which species is in excess. The intermediacy of [ArZnCl] suggests a solution to the long-standing anomaly that many other reductants were found to be much less effective than Zn in inducing turnover of Ni/PPh3 catalyzed aryl chloride homocoupling in DMF. The use of DMAc as a solvent in place of DMF inhibits stalling through the steric inhibition of mixed metalate generation.

Taking what you get or Getting what you Need: A Qualitative Study on Experiences with Mental Health and Welfare Services in Long-Term Recovery in First-Episode Psychosis.

How people in long-term recovery (clinical and personal) in first-episode psychosis (schizophrenia and bipolar spectrum disorders) experience the mental health and welfare services they interact with is not frequently studied but has significant implications. We therefore aimed to explore which aspects of these services people with FEP evaluate as important for their long-term recovery. Twenty participants in clinical and/or personal recovery from two Norwegian long-term follow-up studies after FEP (TOP 10-year and TIPS 20-year) were sampled for this interview-based qualitative study. The research-team included service user experience. A deductive analysis based on personal accounts of recovery generated five service aspects. Few specific types of interventions were reported to promote recovery although medications, psychotherapy and employment support were mentioned. Participants valued services based in collaboration and that focused on their resources rather than limitations. The importance of long-term follow-up with a consistent aim was highlighted, as was the inclusion of caregivers and peers. Welfare services contributed to recovery by supporting basic needs and safety, but some experienced social exclusion when not participating in the labor market. This study is unique in exploring the role of services, including welfare, in long-term FEP recovery from service user perspectives. Participants evaluated that services played a more indirect role in long-term recovery by supporting their personal resources, although what they needed from services had frequently not been offered. Their expertise by experience contributes valuable knowledge. Better service coordination and consistent implementation of this knowledge are crucial to support recovery in FEP.

Pharmaceutical Agents for Targeting Autophagy and Their Applications in Clinics

Autophagy is the process by which damaged regions of the cytoplasm and intracellular pathogens are degraded. This mechanism often serves an adaptive role in cells, enhancing their survival. It plays a direct or indirect role in the development of various pathological conditions within the body. This phenomenon is common in various malignant diseases, where autophagy is associated with the resistance of transformed cells to chemotherapy. Conversely, abnormal activation of autophagy can trigger cell death, a process often seen in neurodegenerative conditions. Given that dysregulation of autophagy is associated with the progression of numerous pathological conditions, this is of significant interest to the developers of drugs that can effectively modulate autophagy for both basic research and clinical applications. Here, we provide a brief description of the mechanism of macroautophagy, the most prevalent form of autophagy identified in humans. We also discuss the clinical potential of drugs that can modulate autophagy, highlighting their use in combating diseases associated with direct or indirect dysregulation of this essential process.

INSTRUCTIONAL LEADERSHIP AND TEACHER SELF-EFFICACY ON JOB SATISFACTION: THE MEDIATING EFFECT OF SCHOOL CLIMATE IN INDONESIAN ISLAMIC SENIOR HIGH SCHOOLS

This study explores the impact of instructional leadership and teacher self-efficacy on job satisfaction among teachers in Indonesian Islamic Senior High Schools (Madrasah Aliyah), focusing on the mediating role of school climate. Instructional leadership plays a crucial role in shaping a positive school environment, which can enhance teacher job satisfaction by providing necessary guidance, resources, and support. A mixed-method approach was employed, with data collected from 219 teachers using validated survey instruments. The Content Validity Index (CVI) was used to ensure instrument reliability. Data analysis was conducted using Partial Least Squares Structural Equation Modeling (PLS-SEM) to assess relationships between variables and the mediating effect of school climate. The results show that instructional leadership significantly impacts both school climate and teacher job satisfaction, with path coefficient values of .463 and .818, respectively. However, school climate did not significantly mediate the relationship between instructional leadership and job satisfaction. Teacher self-efficacy, while positively influencing school climate (p < .05), did not have a substantial direct effect on job satisfaction (ß = -0.058). This research provides fresh insights into the nuanced interplay between leadership, teacher self-efficacy, and job satisfaction in the context of Islamic schools. The findings highlight school climate's indirect yet pivotal role in educational leadership dynamics. By integrating these variables, the study offers practical recommendations for improving leadership strategies and enhancing teacher well-being in faith-based educational settings.

Consolidating building greening: Integrating mobile modular vertical greening systems into prefabricated building

Vertical greening systems increase green plant coverage within built environments, enhancing urban air quality while reducing building energy consumption. But they encounter challenges related to intensive maintenance and significant costs. As a mainstream future building form, the characteristics of modularization and factory customization inherent in prefabricated buildings can effectively address the demands of vertical greening system. This study employs structural equation model and cloud model to examine the feasibility of integrating mobile modular vertical greening system into prefabricated structures, based on a survey of 403 respondents in Shandong Province, China. The study highlights the supportive roles and mediating effects of two maintenance management measures. It confirms the strong correlations between cost control strategies and the successful integration of mobile modular vertical greening system into prefabricated building. The results indicate that integrating intelligent technology and plant-microalgae combined systems are essential exogenous and endogenous maintenance management strategies. They exert a positive influence on prefabricated modular vertical greening systems. A positive interconnection exists between integrating intelligent technology and the plant-microalgae combined system. Carbon credit trading incentive proves more advantageous in reducing mobile modular vertical greening system costs. Plant-microalgae combined system playing a partial mediating role. Although crowdfunding-community participation does not significantly reduce the costs of mobile modular vertical greening system, integrated intelligent technology mediates this relationship. This highlights the indirect role of crowdfunding-community participation in facilitating cost control for these systems.

The relationships between discrimination and academic help-seeking: the indirect effects of the impostor phenomenon among undergraduates students

Academic help-seeking behaviors, such as asking peers or instructors to clarify academic topics, are important behaviors contributing to the academic success of college students. However, environmental factors such as experiences of discrimination (e.g., exclusion, being subjected to negative stereotypes) and individual psychological factors, such as the impostor phenomenon or feelings of intellectual incompetence, may dissuade students from seeking academic help. The current study utilized social cognitive theory as a guide to investigate the relationship between perceived discrimination and academic help-seeking attitudes, as well as the indirect role of the impostor phenomenon. Survey responses from 460 racially diverse undergraduates were analyzed using confirmatory factor analyses and structural equation modeling. Results indicated that perceptions of discrimination directly and indirectly – via the impostor phenomenon – influenced academic help-seeking. Specifically, greater experiences of discrimination contributed to higher levels of the impostor phenomenon, which predicted more positive attitudes toward academic help-seeking. These findings demonstrate the influence of discrimination on academic help-seeking among a diverse sample of learners. Particularly, increased academic help-seeking may serve as a compensatory reaction to experiencing discrimination in an educational context. Implications for how institutions can better promote more equitable learning environments and theory-based interpretations of findings are discussed.

Ostracism and Sense of Coherence: The Mediating Role of Social Media Addiction in Adolescents

Social belonging is of vital importance for adolescents. However, ostracism in the digital age may negatively affect adolescents’ sense of coherence through social media addiction. The main objective of the current study was to investigate the associations between ostracism and sense of coherence and to conduct mediation analysis including social media addiction. The sample consisted of 425 Turkish adolescents aged between 14 and 18 years (Mage= 15.53, SD = 1.26). Data were collected through the Ostracism Experience Scale for Adolescents, the Bergen Social Media Addiction Scale, and the Sense of Coherence Scale-Revised. The results showed that ostracism increased social media addiction, which in turn negatively affected adolescent’s sense of coherence. Besides, an indirect role of social media addiction was found between ostracism and sense of coherence. Overall, these results suggest that ostracism is a risk factor for sense of coherence and that social media addiction increases this risk. Elucidating the indirect role of social media addiction between ostracism and sense of coherence is believed to shed light on the requirement for policies and intervention programmes to address ostracism and social media addiction to maintain adolescents’mental health.