Extrinsic Factors Research Articles

One health: the impact of environment, detergents and hygiene on barrier, microbiome and allergy

SummaryA variety of body surfaces, such as skin and mucosal membranes—from the nasopharyngeal area to the lungs, uterus, vaginal area, and digestive tract—contain complex microbial ecosystems that are tailored to the specifics of the respective niche [1].The so-called dysbiosis—a disadvantageous change in the composition of the microbiome—is associated with the pathogenesis of a variety of diseases [2]. Gastrointestinal as well as cardiovascular, metabolic, neurodegenerative, psychological, oncological, and also allergic diseases have been linked to microbial dysbiosis. Susceptibility to allergies can be due to genetic predisposition; in addition, extrinsic factors from today’s lifestyle increasingly contribute to microbiome changes, but also to the disruption of the skin and mucosal barrier and thus to the development of allergies [3].Gisela, a fictional farmer, guides us through this review. She is representative of adults and children of all genders in industrialized countries. During her daily routine, the skin and mucosal microbiome is influenced by a variety of exogenous factors. These include everyday personal hygiene products, detergents for laundry and dishes, food, medication, animal contact, and exposure to various outdoor environments. Gisela’s daily routine will illustrate how the human microbiome and the skin barrier are modified in positive or negative ways, and how this could influence the development of allergies. Furthermore, potential measures for the prevention and management of dysbiosis will be discussed in terms of examples of alternative products and behaviors.

Oral Wound Healing in Aging Population

Background: Oral wound healing in the aging population is a multifaceted issue requiring a comprehensive approach, considering the physiological changes that come with aging and the frequent presence of comorbidities. Methods: This descriptive review summarizes the factors influencing oral wound healing in aging patients, including age-related physiological changes, hormonal modifications, multimorbidities, polypharmacy, oralome alterations, and nutritional status. Results: The aging population encounters numerous challenges in oral wound healing due to intrinsic factors, such as biological aging and hormonal changes, and extrinsic factors, such as medication use and lifestyle. Conclusion: Understanding these factors and their combined impact is essential for effective clinical management and improved outcomes in older adults.

Green voices in digital spaces: exploring the impact of knowledge sharing on sustainable engagement and eWOM in tourism

PurposeThis study explores the dynamics of companies’ green knowledge sharing (GKS) within the tourism sector, focusing on its influence on green electronic word-of-mouth (eWOM) intention via the mediation of tourists’ green engagement behaviour. Additionally, the study considers the moderating effects of green destination psychological ownership and perceived injunctive norms of green self-expression online on the pathway from green knowledge sharing to tourists’ green engagement behaviour to green eWOM.Design/methodology/approachThe primary dataset, consisting of 902 valid responses obtained through time-lagged surveys administered to environmentally conscious tourists, was analysed using structural equation modelling (SEM) by PROCESS package for R.FindingsFindings indicate that green destination psychological ownership enhances the mediation effect of tourists’ green engagement behaviour on green eWOM intention, reinforcing the sense of personal investment and belonging among tourists. Conversely, perceived injunctive norms of green self-expression online moderate this pathway by shaping the social norms and acceptability of green behaviours online.Practical implicationsTo effectively spread green knowledge, tourism businesses should focus on enhancing tourists' psychological ownership of green destinations and align their communications with the perceived norms of green expression online. This strategy not only deepens tourists' environmental commitment but also stimulates active participation in spreading sustainable practices.Originality/valueThis study contributes to the green marketing literature by revealing how intrinsic and extrinsic motivational factors interact to influence green engagement and eWOM intention in the tourism industry, aiding marketers in strategically fostering green value co-creation and enhancing sustainable practices through targeted green knowledge sharing.

7587 The Estrogen Receptors and ARE/Nrf2 are Involved in Protecting Human Dermal Fibroblasts from Damage Caused by Mitochondrial Disfunction

Abstract Disclosure: A. Darawshe: None. A. Trachtenberg: None. Y. Sharoni: None. Skin ageing is influenced by several factors including environmental exposure and hormonal changes. Reactive oxygen species (ROS), which mediate many of the effects of these factors, can be formed by extrinsic factors, such as sun exposure, or can result from mitochondrial dysfunction as occurs during ageing. Several studies have shown the protective role of estrogens on skin health. The aim of the current study was to examine the damage to dermal fibroblasts by mitochondrially generated ROS, and to study the mechanism of the protective effects of estradiol. Rotenone, a complex I inhibitor, was used to cause mitochondrial dysfunction in human dermal fibroblasts and its effects on mitochondrial and cytosolic ROS levels, mitochondrial respiration, cell death, apoptosis, matrix metalloproteinase-1 (MMP1) and pro-collagen secretion were determined as markers of skin damage. Rotenone caused substantial reduction of respiration, followed by increased mitochondrial and cytosolic ROS which resulted in apoptotic cell death, increased MMP1 secretion and decreased collagen secretion. Pretreatment with estradiol recovered more than 50% of the respiratory activity, reduced mitochondrial and cytosolic ROS levels and MMP1 secretion and increased cell number and collagen secretion. These effects can be partially explained by a cooperative effect of estradiol and rotenone on Antioxidant Response Element (ARE/Nrf2) transcriptional activity, which leads to upregulation of antioxidant proteins such as NQO1 and Trxr1. To determine if estrogen receptors (ER) are involved in the protective effects, we used the ER inhibitor, Fulvestrant. This inhibitor, which completely inhibited ER Response Element reporter activity, partially prevented the protective effects of estradiol. The protective effects of estradiol were Similarly reduced by ML385 and Ochratoxin A, that are inhibitors of the ARE/Nrf2 transcription system. Incubating the cells with Fulvestrant and Ochratoxin A, which inhibit both pathways, completely blocked the protective effect of estradiol. These results suggest that the estrogen receptors and the ARE/Nrf2 signaling pathways are involved in the protective effects of estradiol against the damage caused by rotenone-induced mitochondria generated oxidative stress. Presentation: 6/3/2024

12391 When Pressure Drops, Consequences Rise: A Case Of Pituitary Apoplexy And Watershed Infarcts

Abstract Disclosure: D. Moreno Watashi: None. H.R. Alkaissi: None. M.B. Sharma: None. Introduction: Pituitary apoplexy (PA) results from sudden hemorrhaging and infarction of the pituitary gland, typically within a pituitary adenoma. The primary symptom is a sudden, severe headache, often followed by acute endocrine dysfunction, ophthalmoplegia and visual or neurological disturbances. Case Description: A 68-year-old male with a past medical history of hypertension presented to the emergency department with acute chest and upper back pain, beginning one day prior. No history of smoking, alcohol intake or drug use. Blood pressure (BP) on arrival was 180/95 mmHg. Initial labs revealed mild electrolyte abnormalities. Troponins were normal, but ECG showed diffuse T wave inversion and ST depression. CT angiography revealed a type B aortic dissection. He was managed in the critical care unit with continuous esmolol intravenous (IV) infusion and planned for endovascular repair. During his stay, he became disoriented and hypotensive. MRI from the brain incidentally discovered a pituitary macroadenoma measuring 2.9x2.2x3cm and recent infarcts, with a distribution concerning for hypoperfusion. Fundoscopy concerning for optic chiasm compression. Labs indicated secondary hypothyroidism and hypogonadism (TSH 0.3 uUI/ml, free T4 0.88 ng/dL, total testosterone 56.3 ng/dL). Neurosurgical intervention was deferred until after aortic repair. Endovascular aortic repair was performed with episodes of hypotension. Post-procedure, the patient developed fever (39.5°C) and worsening mental status. Head CT revealed an increased suprasellar extension of the pituitary macroadenoma and vasogenic edema, consistent with hemorrhage of the lesion. He was started on stress doses of hydrocortisone, levothyroxine 125mcg and managed conservatively due to a high surgical risk. Discussion: PA's extrinsic risk factors include angiographic procedures, endocrinological dynamic tests, anticoagulation therapy, exogenous estrogen administration, orthopedic and cardiac surgeries (due to BP fluctuations). The intrinsic risk factors are non-functioning adenomas, macroadenomas and suprasellar extension. Treatment is focused on immediate correction of endocrine derangements and relieving local compression. Stress dosage of corticosteroids should be administered IV as soon as the diagnosis is confirmed to prevent life-threatening corticotropic deficiency. Neurosurgical decompression via a transsphenoidal approach is the definitive therapy to relieve local compression with severe visual loss, obtundation or rapidly progressive course. The potential outcomes are based on the extent of hemorrhage, necrosis, and edema. PA should be treated as a medical emergency in the setting of hemodynamic changes from acute corticotropic deficiency and irreversible neurological damage from acute intracranial compression. The risk factors for PA should be known to assist in early diagnosis. Presentation: 6/1/2024

Experiences of a controlled early exercise intervention following a sport-related concussion: A qualitative study of rugby union student-athletes

BackgroundEarly aerobic exercise is associated with improved outcomes following recovery from sport-related concussion (SRC) and is now recommended in guidance for clinicians managing athletes return-to-play. ObjectivesTo explore student-athlete experiences of a novel early aerobic exercise intervention. DesignQualitative study using semi-structured interviews. SettingLoughborough University, UK. ParticipantsTen rugby union university aged student-athletes (6 men) that had been medically diagnosed with an SRC sustained playing rugby. ResultsThree themes divided into eight supporting subthemes were generated. Main findings were: 1) Experience: despite some apprehension over the novel approach, most had a positive experience, 2) Adherence: Participants suggested reasonably good overall adherence to the prescribed exercises but intrinsic and extrinsic factors for non-adherence were identified, 3) Outcomes: the intervention was perceived to help rehabilitation, improve confidence, support retention of athletic identity and, for some, influenced more cautious attitudes toward brain health. ConclusionsThe novel early exercise intervention was reasonably well received and adhered to. Unintended benefits included supporting retainment of athletic identity and encouraging precautious health behaviours. As early exercise protocols are refined, these findings will help inform the design and delivery of future interventions, particularly in relation to intensity and diversity of exercises and supporting education.

Current Strategies for Optic Nerve Protection and Repair

Damage to the optic nerve and its functioning is referred to as optic neuropathy, unlike the peripheral nervous system (PNS), the optic nerve is part of the central nervous system (CNS), which presents limitations in its regenerative abilities. Both intrinsic and extrinsic factors contribute to these limitations. Strategies for neuroprotection and neuroregeneration have been studied and implemented to address these challenges. While there is no definite treatment in the past two decades there have been many advances in the modulation of inflammation, apoptosis, neurotrophic factors and stem cell replacement strategies. The advances in these areas could transform our approach to optic nerve impairment in the future.

Population Pharmacokinetics Modeling and Simulation of Deutenzalutamide, A Novel Androgen Receptor Antagonist, in Patients With Metastatic Castration-Resistant Prostate Cancer.

Deutenzalutamide is a new molecular entity androgen receptor antagonist. The primary aim of this study was to develop a population pharmacokinetic model of deutenzalutamide and evaluate effects of intrinsic and extrinsic factors on pharmacokinetics. A nonlinear mixed-effects modeling approach was performed to develop the population pharmacokinetic of deutenzalutamide using data from 1 Phase I trial of deutenzalutamide. Goodness-of-fit plots, prediction-corrected visual predictive check, and bootstrap analysis were carried out to evaluate the final model. Simulation for the developed model was used to evaluate the covariate effects on the pharmacokinetics of deutenzalutamide. A 2-compartment model with first-order absorption and elimination from the central compartment was established for deutenzalutamide. The final covariate included body weight on peripheral compartment volume. This is the first research developing the population pharmacokinetic model of deutenzalutamide in patients with metastatic castration-resistant prostate cancer, and it is expected to support the future clinical administration of deutenzalutamide.

Paternal age, de novo mutations, and offspring health? New directions for an ageing problem.

This Directions article examines the mechanisms by which a father's age impacts the health and wellbeing of his children. Such impacts are significant and include adverse birth outcomes, dominant genetic conditions, neuropsychiatric disorders, and a variety of congenital developmental defects. As well as age, a wide variety of environmental and lifestyle factors are also known to impact offspring health via changes mediated by the male germ line. This picture of a dynamic germ line responsive to a wide range of intrinsic and extrinsic factors contrasts with the results of trio studies indicating that the incidence of mutations in the male germ line is low and exhibits a linear, monotonic increase with paternal age (∼two new mutations per year). While the traditional explanation for this pattern of mutation has been the metronomic plod of replication errors, an alternative model pivots around the 'faulty male' hypothesis. According to this concept, the genetic integrity of the male germ line can be dynamically impacted by age and a variety of other factors, and it is the aberrant repair of such damage that drives mutagenesis. Fortunately, DNA proofreading during spermatogenesis is extremely effective and these mutant cells are either repaired or deleted by apoptosis/ferroptosis. There appear to be only two mechanisms by which mutant germ cells can escape this apoptotic fate: (i) if the germ cells acquire a mutation that by enhancing proliferation or suppressing apoptosis, permits their clonal expansion (selfish selection hypothesis) or (ii) if a genetically damaged spermatozoon manages to fertilize an oocyte, which then fixes the damage as a mutation (or epimutation) as a result of defective DNA repair (oocyte collusion hypothesis). Exploration of these proposed mechanisms should not only help us better understand the aetiology of paternal age effects but also inform potential avenues of remediation.

Factors Influencing Employee Job Commitment in the Public Sector: A Case Study of Temeke Municipal Council, Tanzania

The study aims to assess the factors influencing employee Job commitment Case study Temeke Municipal Council, Tanzania. The main objective was to examine factors which influence employees Job commitment at work place in public sector Temeke Municipal. The specific objectives were to examine the relationship between communication practices within public sector, to examine various leadership styles within public sector organizations, to analyse the association between job satisfaction levels among public sector employees, to investigate the role of employee engagement initiatives in influencing job commitment within public sector organization. This research was guided by Social Exchange Theory and Agency Theory. The study adopted a descriptive research design and a quantitative approach. Data was collected structured questionnaires from a purposive sample of 50 and descriptively analyzed. The study found that both intrinsic and extrinsic factors significantly influence employee job commitment at Temeke Council. Key findings revealed that effective communication practices, transformational leadership styles, high job satisfaction, and robust employee engagement initiatives are positively correlated with increased job commitment. Employees who experienced clear and frequent communication, recognized and supportive leadership and opportunities for professional growth reported higher levels of engagement and loyalty to the organization. The study concludes that retaining and enhancing employee’s commitment relies on deliberate efforts of the management to improve job satisfaction, quality selection of leadership styles, communication practices as well as employee’s engagement. The study recommends the management of Temeke Municipal Council to invest in leadership development programs to enhance managers' skills in communication, conflict resolution, and team building. Effective leadership is crucial for fostering a supportive and motivating work environment.

Impact of Motivational Factors on Employee Performance on Banking Industry in Nepal

This research investigates the impact of motivational factors on employee performance within the Nepalese banking industry, a sector critical for the nation's financial stability and economic growth. Recent growth in Nepal's banking sector, driven by factors such as increased financial inclusion and technological advancements, underscores the need for a highly motivated and productive workforce. Employee performance, defined as the measurable contribution of an individual to organizational goals, is crucial for maintaining a competitive edge. This study explores the relationship between motivation and performance, drawing on need-based theories, goal-setting theory, and social cognitive theory, while considering Nepal's unique socio-cultural context. This study investigates the impact of intrinsic and extrinsic motivational factors on employee performance within the banking sector in Nepal. Data were collected from 350 respondents across various banks through online surveys, with a pilot test conducted to ensure clarity and reliability. The survey assessed both types of motivational factors and their influence on employee performance. Demographic analysis provided key insights into the participant pool, enhancing the understanding of the sample's characteristics. The findings underscore the importance of both intrinsic factors, such as job satisfaction and professional development, and extrinsic factors, including competitive salaries and job security, as key motivators for employee performance. Additionally, the study highlights the influence of cultural values, such as collectivism and respect for hierarchy, in shaping employee motivation in Nepal. By employing a descriptive research design and rigorous methodological steps, including statistical analysis using SPSS, this study provides a comprehensive understanding of the motivational landscape in Nepal's banking sector. The insights gained can guide banks in developing effective strategies to enhance employee motivation and performance, contributing to the overall success and growth of the industry.

FAKTOR YANG MEMPENGARUHI MINAT MAHASISWA DALAM BERWIRAUSAHA

To support and enhance the human resources of students in entrepreneurship and their ability to create new job opportunities, good preparation and individual business interest are required. This study aims to identify the intrinsic and extrinsic factors that influence the entrepreneurial interest of students in the Social Studies Education Program at FKIP Universitas Tanjungpura. The research employs a qualitative approach with a case study on five Social Studies students from the 2020-2022 cohorts who have been involed in entrepreneurial activities. The main findings highlight the backgrounds of these individuals in starting their businesses, which include intrinsic factors such as personal experience, internal motivation, a sense of enjoyment, and mental preparedness, as well as extrinsic factors such as the family environment and residential surroundings. The impact of this research is a deep understanding of the motivations behind the entrepreneurial interest of Social Studies student, which can provide valuable insights for the development of entrepreneurship programs in academic settings.

Extrinsic rather than intrinsic factors determine microbial colonization of deadwood

Deadwood decomposition is primarily attributed to wood-colonizing fungi and bacteria, driven mainly by intrinsic (e.g. tree species identity) rather than by extrinsic factors. A recent cross-ecosystem study, using gamma-sterilized wood blocks of different coniferous and deciduous tree species placed at 150 forest and 150 grassland sites, revealed that intrinsic factors most strongly influenced rate of decomposition. These results raised the question of whether the wood-colonizing microbial biodiversity follows similar assembly patterns. For this purpose, we used metabarcoding to analyse the fungal and bacterial communities colonizing the wood blocks. We discovered that the wood-colonizing communities were more strongly determined by extrinsic factors such as the ecosystem type and microclimate (air humidity, soil pH, soil moisture, soil temperature) than by intrinsic factors (tree species identity, wood pH, wood mass loss). Although overall these results seem to be more pronounced for fungi, both communities comprised highly specialized wood colonizers in both ecosystems. For instance, the fungal genus Mycena and the bacterial genus Granulicella were detected more frequently in forests, whereas Exophiala and Sphingomonas were more abundant in grasslands. Wood mass loss exhibited a stronger correlation with reduced fungal diversity, while bacterial richness displayed no association with mass loss, both within and across forest and grassland sites. However, the composition of both colonizers’ communities was consistently linked to wood mass loss. Our study suggests that the environment selects distinct wood-colonizing communities that differ greatly in their decomposition efficiency; this result highlights the importance of cross-ecosystem analyses to assess ecological patterns.

Lemming and Vole Cycles: A New Intrinsic Model.

It is 100 years since the first paper described the multiannual cycles in Arctic rodents and lagomorphs. The mechanisms driving population cycles in animals like lemmings and voles are complex, often attributed to extrinsic factors, such as food availability and quality, pathogens, parasites and/or predators. While extrinsic factors provide insights into population cycles, none fully explain the phenomenon. We propose an underlying innate, intrinsic mechanism, based on epigenetic regulation, that drives population cycles under harsh arctic conditions. We propose that epigenetically driven phenotypic changes associated with sexual development, growth and behaviour accumulate over time in offspring, eventually producing a phase change from rising population density to eventual population collapse. Under this hypothesis, and unlike previous hypotheses, extrinsic factors modify population cycles but would not be primary drivers. The interaction between our intrinsic cycle and extrinsic factors explains established phenomena like delayed-density dependence, whereby population growth is controlled by time-dependent negative feedback. We advocate integrating a century of field research with the latest epigenetic analysis to better understand the drivers of population cycles.

Asia-inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler.

With the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guidelines in effect from 2018, the design of Asia-inclusive multiregional clinical trials (MRCTs) has been streamlined, thereby enabling efficient simultaneous global development. Furthermore, with the recent regulatory reforms in China and its drug administration joining the ICH as a full regulatory member, early participation of China in the global clinical development of novel investigational drugs is now feasible. This would also allow for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E5 and E17. Herein, we describe recent case examples of model-informed Asia-inclusive global clinical development in the EMD Serono portfolio, as applied to the ataxia telangiectasia and Rad3-related inhibitors, tuvusertib and berzosertib (oncology), the toll-like receptor 7/8 antagonist, enpatoran (autoimmune diseases), the mesenchymal-epithelial transition factor inhibitor tepotinib (oncology), and the antimetabolite cladribine (neuroimmunological disease). Through these case studies, we illustrate pragmatic approaches to ethnic sensitivity assessments and the application of a model-informed drug development toolkit including population pharmacokinetic/pharmacodynamic modeling and pharmacometric disease progression modeling and simulation to enable early conduct of Asia-inclusive MRCTs. These examples demonstrate the value of a Totality of Evidence approach where every patient's data matter for de-risking ethnic sensitivity to inter-population variations in drug- and disease-related intrinsic and extrinsic factors, enabling inclusive global development strategies and timely evidence generation for characterizing benefit/risk of the proposed dosage in Asian populations.

Sticky Science: Using Complex Coacervate Adhesives for Biomedical Applications.

Tissue adhesives are used for various medical applications, including wound closure, bleeding control, and bone healing. Currently available options often show weak adhesion or cause adverse effects. Recently, there has been an increasing interest in complex coacervates as medical adhesives. Complex coacervates are formed by mixing oppositely charged macromolecules that associate and undergo liquid-liquid phase separation, in which the dense bottom phase is the complex coacervate. Complex coacervates are strong and often biocompatible, and show strong underwater adhesion. The properties of the resulting materials are tunable by intrinsic factors such as polymer chemistry, molecular weight, charge density, and topology of the macromolecules, as well as extrinsic factors such as temperature, pH, and salt concentration. Therefore, complex coacervates are interesting new candidates for medical adhesives. In this review, it is described how complex coacervates form and how different factors influence their behavior. Next, an overview of recent studies on complex coacervates in the context of medical adhesives is presented. The application of complex coacervates as hemostatic or embolic agents, skin or bone repair adhesives, and soft tissue sealants is discussed. Lastly, additional possibilities for utilizing these materials in the future are discussed.

"Optical Properties and Translucency of ImplantSupported PEEK Crowns: Spectrophotometric Evaluation"

AIM- To evaluate the difference in optical properties and translucency parameters of implant supported PEEK crowns at different time intervals. MATERIAL AND METHODS: Optical properties and translucency parameters of implant supported PEEK crowns were assessed in 35 patients using spectrophotometer RESULT: Results revealed noticeable changes in translucency parameters and optical properties of implant supported PEEK crowns at 3 months. CONCLUSION- Our study on 35 patients on implant-supported PEEK crowns revealed that glazing improves surface roughness and opalescence, enhancing aesthetic appeal. Although, oral fluids containing intrinsic and extrinsic factors still adversely affect PEEK's color stability and surface quality

Mechanisms and Prevention Strategies of Anterior Cruciate Ligament Injuries in Alpine Skiers

Alpine skiing is a sport enjoyed by more than 50 million people across the world every year. However, despite advancements in safety practices and technology, anterior cruciate ligament (ACL) injuries remain a significant concern. This narrative review investigates the prevalence and mechanisms of ACL injuries in alpine skiing and differentiates between intrinsic (e.g., age, sex, and skill level) and extrinsic factors (e.g., equipment design and environmental conditions) that contribute to the risk of ACL injuries. This article outlines 4 primary mechanisms through which ACL injuries occur, highlighting the complex physical demands of skiing and the role of skier behavior and environmental interactions in injury occurrence. Based on these findings, this article advocates for neuromuscular training (NMT) as a possible effective prevention strategy. NMT enhances muscular coordination and strength, balance, and agility through exercises that mimic skiing movements, potentially lowering the risk of ACL injuries. By providing a detailed analysis of ACL injury risk factors and prevention strategies in the sport, this review offers valuable insights for reducing injury rates and underscores the importance of NMT to mitigate the high incidence of ACL injuries in alpine skiing.

Long-Term Exposure of Fresh and Aged Nano Zinc Oxide Promotes Hepatocellular Carcinoma Malignancy by Up-Regulating Claudin-2.

Tumor development and progression is a long and complex process influenced by a combination of intrinsic (eg, gene mutation) and extrinsic (eg, environmental pollution) factors. As a detoxification organ, the liver plays an important role in human exposure and response to various environmental pollutants including nanomaterials (NMs). Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and remains a serious threat to human health. Whether NMs promote liver cancer progression remains elusive and assessing long-term exposure to subtoxic doses of nanoparticles (NPs) remains a challenge. In this study, we focused on the promotional effects of nano zinc oxide (nZnO) on the malignant progression of human HCC cells HepG2, especially aged nZnO that has undergone physicochemical transformation. In in vitro experiments, we performed colony forming efficiency, soft agar colony formation, and cell migration/invasion assays on HepG2 cells that had been exposed to a low dose of nZnO (1.5μg/mL) for 3 or 4 months. In in vivo experiments, we subcutaneously inoculated HepG2 cells that had undergone long-term exposure to nZnO for 4 months into BALB/c athymic nude mice and observed tumor formation. ZnCl2 was administered to determine the role of zinc ions. Chronic low-dose exposure to nZnO significantly intensified the malignant progression of HCC cells, whereas aged nZnO may exacerbate the severity of malignant progression. Furthermore, through transcriptome sequencing analysis and in vitro cellular rescue experiments, we demonstrated that the mechanism of nZnO-induced malignant progression of HCC could be linked to the activation of Claudin-2 (CLDN2), one of the components of cellular tight junctions, and the dysregulation of its downstream signaling pathways. Long-term exposure of fresh and aged nZnO promotes hepatocellular carcinoma malignancy by up-regulating CLDN2. The implications of this work can be profound for cancer patients, as the use of various nanoproducts and unintentional exposure to environmentally transformed NMs may unknowingly hasten the progression of their cancers.

What motivates knowledge sharing? Evaluating the quality of answer contribution in online Q&A communities

The Online Q&A community provides platforms for Internet users to exchange and share knowledge. Its rapid development has caused the problem of information overload, which promotes users' demand for precise and personalized information. In light of this, we innovatively analyze the correlation between knowledge quality and user behaviors. First, we propose a novel approach method to evaluate the answer quality through a machine learning approach, which applies the information adoption theory to the design of a text classification model. Hereafter, with applications of motivation crowding theory, this paper introduces the classification results of answer quality by machine learning algorithms into the empirical research model to explore the factors that motivate users in both participation and high-quality user-generated content creation. Results show that both extrinsic and intrinsic factors determine the quality of knowledge contributors' answers. Further, certain external interventions (monetary rewards) can crowd out the effects of knowledge contributors’ intrinsic motivations (knowledge self-efficacy). It enriches the research on user knowledge contribution behavior in online Q&A communities and also provides theoretical guidance and suggestions for community operation.