Apoptotic Janus-faced mycotoxins against thoracal and breast metastases.

Abdominal organs (liver, kidney, spleen) are frequent targets of cancer cell invasion but their primary tumours are less known for their metastatic potential to other organs e.g. to the breast. Despite the known connection of the pathogenesis from breast cancer to liver metastasis, the study of the spread in the opposite direction has been neglected. The notion that breast cancer could be a metastasis besides being a primary tumour is based on rodents' tumour models upon implantation of tumour cells under the capsule of the kidney or under the Glisson's capsule of the liver of rats and mice. Tumour cells develop into a primary tumour at the site of subcutaneous implantation. The metastatic process starts with peripheral disruptions of blood vessels near the surface of primary tumours. Tumour cells released into the abdomen cross the apertures of the diaphragm, enter the thoracal lymph nodes and accumulate in parathymic lymph nodes. Abdominal colloidal carbon particles injected into the abdomen faithfully mimicked the migration of tumour cells and deposited in parathymic lymph nodes (PTNs). An explanation is provided why the connection between abdominal tumours and mammary tumours escaped attention, notably, parathymic lymph nodes in humans were referred to as internal mammary or parasternal lymph nodes. The apoptotic effect of Janus-faced cytotoxins is suggested to provide a new approach against the spread of abdominal primary tumours, and metastatic development.

ROS in hepatocellular carcinoma: What we know.

Hepatocellular carcinoma (HCC), which is a primary liver cancer subtype, has a poor prognosis due to its high degree of malignancy. The lack of early diagnosis makes systemic therapy the only hope for HCC patients with advanced disease; however, resistance to drugs is a major obstacle. In recent years, targeted molecular therapy has gained popularity as a potential treatment for HCC. An increase in reactive oxygen species (ROS), which are cancer markers and a potential target for HCC therapy, can both promote and inhibit the disease. At present, many studies have examined targeted regulation of ROS in the treatment of HCC. Here, we reviewed the latest drugs that are still in the experimental stage, including nanocarrier drugs, exosome drugs, antibody drugs, aptamer drugs and polysaccharide drugs, to provide new hope for the clinical treatment of HCC patients.

The double-edged sword role of TGF-ß signaling pathway between intrauterine inflammation and cranial neural crest development.

Intrauterine infection would harm a developing embryo/fetus, thereby increasing the risk of developmental malformation. But, whether or not the infection-induced inflammation affects neural crest development still remains obscure. In this study, we employed meta-analysis to demonstrate the potential correlation between infection-induced inflammation and craniofacial anomalies, which was usually derived from the problems in neural crest cell development. The correlation was further verified by inflammatory cytokine release and the activation of nuclear factor kappa-light-chain enhancer of activated B cells signaling in lipopolysaccharide-treated HH10 chicken embryos. In such an inflammatory condition, AP-2α- and Pax7-labeled pre-migratory and migratory neural crest cells in HH10 chicken embryos were significantly less than the ones in control. The bioinformatics analysis of RNA-seq data demonstrated that the principal differential gene expression occurred in transforming growth factor-beta (TGF-ß) signaling pathway, which was confirmed by the subsequent experimental results of quantitative PCR and immunofluorescent staining. Under this inflammatory circumstance, whole-mount in situ hybridization, immunofluorescence, and quantitative PCR showed the gene expression changes of key EMT-related transcription factors including upregulated Msx1, downregulated Slug, and FoxD3, as well as adhesion molecules and extracellular matrix protein including upregulated Cadherrin6B, E-cadherin, N-cadherin, and Laminin at the dorsal portion of neural tube of HH10 chicken embryos. Meanwhile, the bioinformatics analysis of RNA-seq data also manifested the differential gene expressions relevant to cell proliferation, which was confirmed by proliferating cell nuclear antigen Western blot data and co-immunofluorescence staining of human natural killer-1 and phosphorylated histone H3. In brief, this study revealed for the first time that the double-edged sword role of TGF-ß signaling pathway between intrauterine inflammation (protective role) and cranial neural crest development (harmful role).

The current existence of ChatGPT in education: a double-edged sword?

The authors in this article would like to invite related parties to carry out updates in the world of education, that the existence of ChatGPT can provide new enthusiasm for all of us to improve in a better direction.

Netherton syndrome in a Bulgarian patient : Presentation of a case and an update of therapeutic options.

Comel-Netherton syndrome, or Netherton syndrome (NS), is a rare chronic genetic skin condition affecting the daily life of patients, which often results in poorly developed social skills and anxiety. Genetic predisposition plays a key role alongside the clinical findings, and clinicians must be aware of it as it can mimic other well-known skin conditions. Diagnosis is challenging both clinically and histologically. Clinically, it can mimic a severe form of atopic dermatitis, psoriasiform dermatitis overlapping with atopic dermatitis, or erythrokeratodermia variabilis. The difficulties in making histological diagnosis are similar, and it is often necessary to take several biopsies in order to clarify the diagnosis. Although retinoids are used for both psoriasis, erythrokeratodermia variabilis, and other congenital forms of keratodermia, the recommended treatment doses are different. This often results in poor treatment outcome. We present a 16-year-old patient previously diagnosed as erythrokeratodermia variabilis and treated with little to no improvement. Systemic therapy with acitretin 10 mg daily, local pimecrolimus 1%, emollients, and bilastine 20 mg once daily was initiated. Due to the limited application of retinoids and the difficulties in achieving permanent remission, modern medicine is faced with the challenge of seeking innovative therapeutic solutions. New hopes are placed on targeted or anti-cytokine therapy, based on inhibiting the inflammatory component of the disease. This article is mainly focused on innovative therapeutic options, including modern medications such as dupilumab, infliximab, secukinumab, anakinra, omalizumab, and others.

The Double-Edged Impact of the COVID-19 Pandemic on Chinese Family Relationships.

To comprehensively understand the Chinese family relationships (i.e., marital relationship, parent-child relationship, sibling relationship, and grandparent-grandchild relationship) during the COVID-19 pandemic, this study investigated the changes of family relationships and the individual differences related to knowledge of the COVID-19, personality traits (i.e., neuroticism and optimism), and emotional characteristics (i.e., emotion regulation and negative emotional reactions). From March 1 to April 5, 2020, 8821 participants were involved, including 3995 teenagers, 1146 unmarried young adults, 3571 married adults, and 109 grandparents. Results revealed a double-edged pattern that people experienced both positive changes and negative changes during the pandemic. Teenagers reported significant negative changes in the relationships with their parents. Peoples' knowledge of the COVID-19, neuroticism, optimism, emotion regulation, and negative emotional reactions were in varying extents to which accounted for the individual differences in the changes of family relationships. These findings help recognize the overall Chinese family relationships during the hard period.

Promising targets based on pattern recognition receptors for cancer immunotherapy.

Pattern recognition receptors (PRRs) recognize pathogen-associated as well as endogenous damage-associated molecular patterns. Once ligand binding occurs, signaling cascades develop within the cells to activate effector molecules. Thus, PRRs play key roles in immune surveillance and immune tolerance. Due to their differences in cell localization, stage of action, and ligand recognition, PRRs form a defense network from the cell membrane to the cytoplasm, constituting the regulatory networks of the innate and adaptive immune systems in cancer. However, the activation of PRRs cannot only recruit and activate anti-tumor immune cells, but also promote the release of inflammatory cytokines, which may lead to the formation of the local inflammatory microenvironment in tumors, thus promoting the development of cancer. Therefore, the dual regulation of PRRs in the immune system has attracted much attention, with current research being focused on maximizing their anti-tumor immune activity. In addition to their expression in host cells, PRRs are also expressed in tumor cells; this is closely related to the occurrence and development of cancer. This review attempts to clarify the feasibility and directions for the development of PRR-based applications in cancer immunotherapy by elaborating on the mechanisms underlying the action of PRRs and the current status of immunotherapies.

Revealing the Double-Edged Sword Role of Graphene on Boosted Charge Transfer versus Active Site Control in TiO2 Nanotube Arrays@RGO/MoS2 Heterostructure.

Charge separation/transfer is generally believed to be the most key factor affecting the efficiency of photocatalysis, which however will be counteracted if not taking the active site engineering into account for a specific photoredox reaction. Here, a 3D heterostructure composite is designed consisting of MoS2 nanoplatelets decorated on reduced graphene oxide-wrapped TiO2 nanotube arrays (TNTAs@RGO/MoS2 ). Such a cascade configuration renders a directional migration of charge carriers and controlled immobilization of active sites, thereby showing much higher photoactivity for water splitting to H2 than binary TNTAs@RGO and TNTAs/MoS2 . The photoactivity comparison and mechanistic analysis reveal the double-edged sword role of RGO on boosted charge separation/transfer versus active site control in this composite system. The as-observed inconsistency between boosted charge transfer and lowered photoactivity over TNTAs@RGO is attributed to the decrease of active sites for H2 evolution, which is significantly different from the previous reports in literature. The findings of the intrinsic relationship of balanced benefits from charge separation/transfer and active site control could promote the rational optimization of photocatalyst design by cooperatively manipulating charge flow and active site control, thereby improving the efficiency of photocatalysis for target photoredox processes.

Theoretical and Numerical Study on Stress Intensity Factors for FRP-Strengthened Steel Plates with Double-Edged Cracks.

This paper presents a theoretical and numerical study on the stress intensity factors for double-edged cracked steel plates strengthened with fiber reinforced polymer (FRP) plates. Based on the stress intensity factor solution for infinite center-cracked steel plates strengthened with FRP plates, expressions of the stress intensity factors were proposed for double-edged cracked steel plates strengthened with FRP plates by introducing two correction factors: ß and f. A finite element (FE) simulation was carried out to calculate the stress intensity factors of the steel plate specimens. Numerous combinations of the specimen width, crack length, FRP thickness and Young's modulus, adhesive thickness, and shear modulus were considered to conduct the parametric investigation. The FE results were used to investigate the main influencing factors of the stress intensity factors and the correction factor, ß. The expression of the correction factor, ß, was formulated and calibrated based on the FE results. The proposed expressions of the stress intensity factors were a function of the applied stress, the crack length, the ratio between the crack length and the width of the steel plate, the stiffness ratio between the FRP plate and steel plate, the adhesive thickness, and the shear modulus. Finally, the theoretical results and numerical results were compared to validate the proposed expressions.

The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.

(1) Background: The neddylation pathway assumes a pivotal role in the initiation and progression of cancer. MLN4924, a potent small-molecule inhibitor of the NEDD8-activating enzyme (NAE), effectively intervenes in the early stages of the neddylation pathway. By instigating diverse cellular responses, such as senescence and apoptosis in cancer cells, MLN4924 also exerts regulatory effects on non-malignant cells within the tumor microenvironment (TME) and tumor virus-infected cells, thereby impeding the onset of tumors. Consequently, MLN4924 has been widely acknowledged as a potent anti-cancer drug. (2) Recent findings: Nevertheless, recent findings have illuminated additional facets of the neddylation pathway, revealing its active involvement in various biological processes detrimental to the survival of cancer cells. This newfound understanding underscores the dual role of MLN4924 in tumor therapy, characterized by both anti-cancer and pro-cancer effects. This dichotomy is herein referred to as the "double-edged effects" of MLN4924. This paper delves into the intricate relationship between the neddylation pathway and cancer, offering a mechanistic exploration and analysis of the causes underlying the double-edged effects of MLN4924-specifically, the accumulation of pro-cancer neddylation substrates. (3) Perspectives: Here, the objective is to furnish theoretical support and novel insights that can guide the development of next-generation anti-cancer drugs targeting the neddylation pathway.

The "double-edged sword effect" of nicotine.

As the main effect substances of tobacco products, the physiological effects of nicotine have attracted the attention of researchers, especially in recent years, the discussion on the benefits and harms of nicotine (or tobacco products) has become increasingly fierce. In this review, the structure, distribution and physiological effects of nicotinic acetylcholine receptor (nAchR) are summarized. The absorption, distribution, metabolism and excretion of nicotine in the body were introduced. Further, the positive effects of low-dose and short-term nicotine exposure on mitochondrial function regulation, stem cell proliferation and differentiation, nervous system protection and analgesia were elucidated. At the same time, it is also discussed that high-dose and long-term nicotine exposure can activate the oxidative stress effect, mediate abnormal epigenetic modification, and enhance the immune inflammatory response, and then produce negative effects on the body. To sum up, this review suggests that there is a "double-edged sword" effect of nicotine, which on the one hand helps people to understand the physiological effects of nicotine more comprehensively and carefully, and on the other hand provides some theoretical basis for the rational use of nicotine and the innovative development of related products.

The double-edged nature of nicotine: toxicities and therapeutic potentials.

Nicotine is the primary addictive component of cigarette smoke and is associated with various smoking-related diseases. However, recent research has revealed its broader cognitive-enhancing and anti-inflammatory properties, suggesting its potential therapeutic applications in several conditions. This review aims to examine the double-edged nature of nicotine, encompassing its positive and negative effects. We provide a concise overview of the physiochemical properties and pharmacology of nicotine, including insights into nicotine receptors. Therefore, the article is divided into two main sections: toxicity and therapeutic potential. We comprehensively explored nicotine-related diseases, focusing on specific signaling pathways and the underlying mechanisms that contribute to its effects. Furthermore, we addressed the current research challenges and future development perspectives. This review aims to inspire future researchers to explore the full medical potential of nicotine, which holds significant promise for the clinical management of specific diseases.

How the interplay of monitoring-enabled digital technologies and human factors facilitates or hinders metro systems' resilient response to operational disruptions.

The metro is susceptible to disruption risks and requires a system response capability to build resilience to manage disruptions. Achieving such resilient response state requires readiness in both the technology side, e.g., utilizing digital technologies (DTs) to monitor system components, and the human factors side, e.g., fostering positive human coping capabilities; however, these two sides are usually considered independently, without sufficient integration. This paper aims to develop and empirically test a model in which monitoring-enabled DTs, employees' reactions, and their positive capabilities are simultaneously considered in terms of their interplay and impact on system response capability. The results showed that while DTs for monitoring physical components enhanced perceived management commitment and fostered collective efficacy, DTs for monitoring human components increased psychological strain and inhibited improvisation capability, creating a "double-edged sword" effect on system response capability. Additionally, explicit management commitment buffered the adverse effect of DTs-induced psychological strain on individual improvisation.

Double-Edged Network Effects on Disclosing Traumatic Experiences Among Korean "Comfort Women".

This study examines the effects of social networks on the disclosure of stigmatizing and traumatic sexual assault experiences. We analyzed publicly archived oral histories of Korean "comfort women" from World War II, employing an innovative method combining word embedding analysis, word frequency comparison, and grounded theory. By extracting their significant social relationships from narrated survivor stories, we parsed two distinctive disclosure patterns according to timing of disclosure: early disclosers and late disclosers. The latter were more socially embedded than the former, indicating the constraining aspect of social networks, in which the size of social networks was positively associated with delayed disclosure. Qualitative findings further elaborated that social networks have double-edged effects. Survivors' familial networks functioned as both social constraints and social support for public disclosure. Yet, the late disclosers tend to exploit it more as constraints for the fear of transgenerational transmission of social scorn and stigma. The findings contribute to enhancing a culturally relevant understanding of trauma and the repercussions of human trafficking.

A step toward inclusive green growth: can digital finance be the main engine?

Inclusive green growth (IGG) has become a worldwide consensus to achieve the target of sustainable development goals. Although the prominent role of digital finance (DF) against the pandemic has drawn considerable attention from policymakers, its plausible effect on IGG and underlying mechanisms have not been distinctly explored in academia. The aim of the study is to explore the causal effect of DF on IGG based on prefecture city-level data from 2011 to 2019 in China. To this end, we employed the non-radial direction distance function approach within the global production technology to evaluate the aggregate IGG performance and its three sub-dimensions. The empirical results demonstrate that DF exerts a significant promotional effect on urban IGG. This finding continues to survive in an extensive set of robustness checks using an alternative dependent variable, model specifications, instrumental variable, and difference-in-difference approaches to address the endogeneity concerns. Meanwhile, sub-dimensional regressions show that this positive effect is driven predominantly by the scale economy of DF, while the depth of usage and digitalization playing a minor role. Moreover, we uncover that DF enhances IGG by leveraging greater marginal product of labor rather than capital, improving environmental externalities, increasing fuller employment, and reducing rural-urban income inequality. However, we also reveal the dark side of DF on imbalanced regional development. The promotional effect of DF on IGG is only prominent for cities with better inherent comparative advantages, and we are thus likely to see a widening digital divide resulting from the "Matthew effect" on regional disparity without timely policy interventions.

The Important Double-Edged Role of Astrocytes in Neurovascular Unit After Ischemic Stroke.

In recent years, neurovascular unit (NVU) which is composed of neurons, astrocytes (Ast), microglia (MG), vascular cells and extracellular matrix (ECM), has become an attractive field in ischemic stroke. As the important component of NVU, Ast closely interacts with other constituents, which has been playing double-edged sword roles, beneficial or detrimental after ischemic stroke. Based on the pathophysiological changes, we evaluated some strategies for targeting Ast in treating ischemic stroke. The present review is focused on the roles of Ast in NVU and its complex signaling molecular network after ischemic stroke, which may be a prospective approach to the treatment of ischemic diseases in central nervous system.

Macrophages in melanoma: A double­edged sword and targeted therapy strategies (Review).

Melanoma, which evolves from melanocytes, is the most malignant skin cancer and is highly fatal, although it only accounts for 4% of all skin cancers. Numerous studies have demonstrated that melanoma has a large tumor mutational burden, which means that melanoma has great potential to achieve immune evasion. Tumor-associated macrophages (TAMs) are an important component of both the immune system and tumor microenvironment. Several studies have demonstrated their double-edged sword effects on melanoma. The present review focuses on the role of TAMs in melanoma development, including regulation of proliferation, invasion, metastasis, angiogenesis and chemical resistance of melanoma. Furthermore, the existing mechanisms of action of the TAM-targeting treatments for melanoma are reviewed. More broadly, the weak points of existing research and the direction of future research are finally identified and described.

An update on the role of tumor necrosis factor alpha stimulating gene-6 in inflammatory diseases.

At present, the occurrence and development of inflammatory diseases are closely related to the abnormal changes of the content and function of many cytokines. At the same time, targeting related cytokines to prevent and treat diseases has also achieved good results. Therefore, it is very important to explore the role of various cytokines in inflammatory diseases. As an inflammation related protein, Tumor necrosis factor alpha stimulating gene-6 (TSG-6) has attracted more and more attention. In the process of disease, it's like a double-edged sword, showing different responses. It is constitutively expressed in some tissues with high metabolic activity and barrier protection. The diversity of its functions depends on the binding of TSG-6 with a variety of ligands, including matrix molecules, autoimmune regulatory factors and growth factors, participating in extracellular matrix remodeling and regulating protease network. This paper reviews the structure, biological function and research progress of TSG-6 in inflammatory diseases, in order to provide reference for drug development in the future.

The double-edged sword effect of ethical leadership on constructive deviance: An integrated model of two approaches based on organizational identification and normative conflict.

Based on the normative conflict model, this study proposes a dual-pathway model that is constituted of organizational identification and normative conflict, and examines the double-edged sword effect of ethical leadership on subordinates' constructive deviance. According to the analysis of 449 questionnaires collected from Chinese employees, the results show that ethical leadership can promote employees' constructive deviance by improving their constructive intention (Organizational identification), and it can weaken employees' deviance motivation (normative conflict) to prevent their constructive deviance. Moreover, ethical leadership has different effects on different types of constructive deviance. This research further enriches the formation mechanism of constructive deviance and provides practical guidance to exert the effectiveness of constructive deviance in organizational management.

The Impact of Social Media on Employee Mental Health and Behavior Based on the Context of Intelligence-Driven Digital Data.

With the rapid development and widespread popularity of the Internet, employee social media use at work has become an increasingly common phenomenon in organizations. This paper analyzes 105 related papers from the Social Science Citation Index in Web of Science through Scoping Review to clarify the definition and characteristics of employee social media use and the types of social media and summarizes the current research methods. Then, the reasons for employees' willingness and refusal to use social media and the positive and negative effects of employee social media use on employees' work attitudes, behaviors, and performance are discussed. Then, the mediating variables, moderating variables, and theoretical frameworks used in the relevant studies are described, and a comprehensive model of employee social media use is constructed. Finally, this paper indicates future research directions based on the latest research results in 2020-2022, i.e., improving research methods, increasing antecedent studies, expanding consequence research, and expanding mediating variables, moderating variables, and theoretical perspectives.