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Abstract In the historically male-dominated world of Go—a game with a rich history and a current global player base of 46 million—recent years have marked a significant shift in gender dynamics, highlighted by Choi Jeong’s historic achievement as the first female to reach the open major world tournament finals. This study investigates the rise of female Go players in Korea through multiple lenses: descriptive analyses cover demographic data, Elo ratings, and competition statistics, while social representation analyses employ in-depth interviews and core-periphery analysis. A core finding is the profound transformation within the Korean Go community, where female players are not just witnessing increased representation but also significant enhancements in performance, opportunities, and financial rewards. Narratives from the players unravel the intricate web of performance disparities, community engagement, and evolving infrastructures. Economic incentives, societal and cultural shifts, and institutional support are identified as key contributors to their success. Beyond its application to professional Go, this research underscores a paradigmatic shift, illuminating strategies for fostering gender inclusivity in fields traditionally overshadowed by male dominance.

Abstract Our ability to predict, control, or design biological function is fundamentally limited by poorly annotated gene function. This can be particularly challenging in non-model systems. Accordingly, there is motivation for new high-throughput methods for accurate functional annotation. Here, we used complementation of auxotrophs and DNA barcode sequencing (Coaux-Seq) to enable high-throughput characterization of protein function. Fragment libraries from eleven genetically diverse bacteria were tested in twenty different auxotrophic strains of Escherichia coli to identify genes that complement missing biochemical activity. We recovered 41% of expected hits, with effectiveness ranging per source genome, and observed success even with distant E. coli relatives like Bacillus subtilis and Bacteroides thetaiotaomicron. Coaux-Seq provided the first experimental validation for 53 proteins, of which 11 are less than 40% identical to an experimentally characterized protein. Among the unexpected function identified was a sulfate uptake transporter, an O-succinylhomoserine sulfhydrylase for methionine synthesis, and an aminotransferase. We also identified instances of cross-feeding wherein protein overexpression and nearby non-auxotrophic strains enabled growth. Altogether, Coaux-Seq’s utility is demonstrated, with future applications in ecology, health, and engineering.

Abstract Chemical genomics is a powerful and increasingly accessible technique to probe gene function, gene–gene interactions, and antibiotic synergies and antagonisms. Indeed, multiple large-scale pooled datasets in diverse organisms have been published. Here, we identify an artifact arising from uncorrected differences in the number of cell doublings between experiments within such datasets. We demonstrate that this artifact is widespread, show how it causes spurious gene–gene and drug–drug correlations, and present a simple but effective post hoc method for removing its effects. Using several published datasets, we demonstrate that this correction removes spurious correlations between genes and conditions, improving data interpretability and revealing new biological insights. Finally, we determine experimental factors that predispose a dataset for this artifact and suggest a set of experimental and computational guidelines for performing pooled chemical genomics experiments that will maximize the potential of this powerful technique.

Abstract This study explores the potential mechanisms by which neighbourhood isolation is created and reinforced in non-home activity locations. The existing discussion on neighbourhood isolation, its consequences, and the subsequent reproduction of interactions between individuals and their environment has focused on their residential locations. However, the vitality of a neighbourhood depends not only on its own socioeconomic conditions but also on the conditions of the other neighbourhoods its residents visit and are visited by. Residential locations are only one of the many spaces in which individuals engage in their activities; therefore, to fully comprehend people’s everyday experiences of integration and isolation, it is imperative to look at interactions within both home and non-home activity spaces. Building on this extended perspective, we examine: (1) whether residential neighbourhood isolation is intensified by socioeconomic conditions individuals’ encounter in consumption and commuting activity spaces; and (2) which socioeconomic group drives the association between residential neighbourhood isolation and activity spaces—whether both disadvantaged and privileged groups contribute to isolation through the differential use of urban space or either group predominantly leads this association. We use Seoul as a case study, characterised as a city that is highly populated, contains multiple economic centres, functions with a highly affordable and efficient public transportation system, and suffers from increasing socioeconomic segregation. The results suggest that mobility patterns in activity spaces tend to reinforce neighbourhood isolation through potential forces driven by neighbourhood homophily. Isolation in the use of urban spaces appears to be driven mainly by the self-seclusion of the most advantaged neighbourhood group, while neighbourhoods in the lower socioeconomic status groups indicate broader cross-interactions across status groups, probably because of Seoul’s transit-friendly environment. Our study contributes to enhancing the understanding of spatial-societal inequalities in Korea and beyond and could assist in formulating policies for a more balanced provision of diverse urban social services and infrastructure.

Abstract This article aims to analyze the impact of economic freedom on economic growth, considering the influence of varying regulatory qualities (RQ) among nations. Analyzing data from 54 countries from 2008 to 2022, Bayesian linear regression results on two sample groups, categorized based on RQ, reveal that economic freedom positively affects economic growth regardless of high or low RQs. Additionally, separate regression analyses for Vietnam indicate no significant difference from other countries. However, control variables uncover differences between the two groups, particularly in corruption control and financial development, with their effects varying across nations. Notably, in Vietnam, government expenditure on education, inflation, fixed capital formation, and population growth rate exhibit regression outcomes contrary to those of other countries in the two groups. The suggested policy implications align with the regression results, aiming to strengthen economic freedom. They support policymakers in achieving this.

Abstract This article seeks to argue that although AI language has developed to the level where it can answer human questions, AI language cannot yet contain the truth. In the AI era, humans who speak their minds will no longer express their thoughts directly in words and will depend more on AI’s artificial language. However, it is only a question for now whether AI will be able to substitute for human speech and whether such a fact will contribute to the expansion of human thinking and the state of being. Accordingly, in this paper, we try to identify the limitations of artificial intelligence language by precisely clarifying the meaning of human language and discourse. Foucault and Heidegger’s discussion of discourse deals with issues of language, subject, existence, and authentic discourse. We use their discussions as a tool to illuminate our own perspectives. Therefore, we will re-analyze the language produced in the AI environment in relation to the issue of truth.

Abstract Prohibitive voice behavior plays a crucial role in organizational effectiveness by signaling previously undetected issues. However, individuals paradoxically perceive this behavior as difficult due to its emphasis on identifying harmful factors, which may lead to misinterpretation and other undesirable social consequences. Based on social learning theory, this study aims to identify how the leader’s prohibitive voice behavior affects the follower’s prohibitive voice behavior. We employed a quantitative research design, collecting and analyzing questionnaires from 317 leader-follower dyads in 59 Chinese companies. To test our hypotheses, we used mediation and moderation analyses, hierarchical regression analysis, and the PROCESS macro. The results partially supported the research hypothesis, indicating that leader prohibitive voice behavior positively influenced follower prohibitive voice behavior. Additionally, leader identification mediated this relationship, whereas follower political skill moderated the mediated relationship. Notably, the mediation’s direction contradicted our hypothesis; the mediated effect through leader identification was pronounced when follower political skill was at lower levels. This study proposes that the leader’s role as a role model is crucial in motivating followers’ prohibitive voice behavior. It highlights the significance of considering followers’ political skills when they emulate their leader’s behavior. From both theoretical and practical perspectives, we discussed these findings and highlighted their implications for organizational behavior and leadership development.

Abstract Language mindsets, which are beliefs about personal qualities relevant to language learning and perceived as either fixed or malleable, have become a focus in understanding their roles in shaping language learning processes. Several studies show how they are related to language learning, along with important variables such as self-efficacy. Although research on language mindsets is growing, most studies have focused on their isolated effects, leaving a critical gap in understanding how these mindsets interact with other significant factors to influence language learning in a motivational aspect. This study aimed to address this gap by exploring the interplay between language mindsets, self-efficacy, engagement, and perceived proficiency (PP)—a construct that reflects an individual’s subjective perception of their language skills and is linked to their motivation to learn. A total of 257 students enrolled in English language courses from three universities in Korea joined the study by responding to questionnaires. The results of the path analysis show that a growth mindset did not predict self-PP; notably, however, it predicted PP with the full mediation of self-efficacy. In addition, the indirect effect of the relationship between self-efficacy, engagement, and proficiency was significant but weak. However, the inclusion of a growth mindset strengthened the indirect effect. Conversely, the link between a fixed mindset and PP showed no significant indirect effect through self-efficacy and engagement. The findings highlight the importance of a growth mindset in initiating the process of language learning and underscore the mediating role of self-efficacy in this context, contributing to the development of more effective and pedagogically informed guidance in L2 classrooms.

Abstract Do cities have a collective identity? The latest advancements in generative artificial intelligence (AI) models have enabled the creation of realistic representations learned from vast amounts of data. In this study, we test the potential of generative AI as the source of textual and visual information in capturing the place identity of cities assessed by filtered descriptions and images. We asked questions on the place identity of 64 global cities to two generative AI models, ChatGPT and DALL·E2. Furthermore, given the ethical concerns surrounding the trustworthiness of generative AI, we examined whether the results were consistent with real urban settings. In particular, we measured similarity between text and image outputs with Wikipedia data and images searched from Google, respectively, and compared across cases to identify how unique the generated outputs were for each city. Our results indicate that generative models have the potential to capture the salient characteristics of cities that make them distinguishable. This study is among the first attempts to explore the capabilities of generative AI in simulating the built environment in regard to place-specific meanings. It contributes to urban design and geography literature by fostering research opportunities with generative AI and discussing potential limitations for future studies.

Abstract This paper explores the dynamic relationship between income and the willingness to pay (WTP) a premium for organic food across regions with varying levels of environmental development in South Korea. It is widely recognized that income significantly influences consumers’ decisions to purchase organic products. Using the Environmental Kuznets Curve (EKC) hypothesis as a contextual framework, we confirm that income leads to a higher WTP for organic foods once a specific income threshold is reached. This threshold marks the transition to the “environmental improvement stage,” where regional economic development begins to reduce environmental degradation. Below this threshold, economic priorities often overshadow environmental concerns, resulting in a “pollution-intensive stage” where rising income exacerbates environmental degradation and negatively impacts WTP for organic foods. Our results indicate that the influence of income on organic food demand is sensitive to the level of environmental development. Specifically, the effect of income on WTP varies: it is negative in the pollution-intensive stage and positive in the environmental improvement stage. The magnitude of these effects intensifies with increasing pollution, thereby widening the sustainability gap between these regions. Our findings underscore the importance of addressing economic inequality as a crucial step toward achieving environmental sustainability.

Abstract Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)+ metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD+ metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD+ precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy.

Abstract The General Data Protection Regulation (GDPR) of the European Union has established regulations on automated decisions in Article 22 with the proliferation of artificial intelligence. In response, the Personal Information Protection Act (PIPA) of South Korea, serving as a counterpart to the GDPR, has recently incorporated provisions for automated decisions under Article 37-2 through an amendment. Although the PIPA follows a distinct legal framework from the GDPR, it is crucial to ensure an equivalent level of protection for fundamental rights. Recognising this concern, this study analyses the differences between the PIPA and GDPR regarding automated decisions, focusing on three aspects: format, target, and content. This analysis identifies that the PIPA lacks comprehensive safeguards for data subjects in certain aspects compared to the GDPR. First, regarding the format, the PIPA grants the right to object rather than establishing a general prohibition to automated decisions, posing limitations in protecting individuals who are unable to effectively exercise their rights. Second, in terms of the target, the PIPA regulates a completely automated status at the overall system level, creating a regulatory vacuum for a multi-stage profiling system. Third, concerning the content, the PIPA faces several technical and practical limitations that remain unresolved in delineating the content of the right to explanation. Building upon this analysis, this study proposes potential legislation and interpretation remedies to address these concerns based on each aspect.

Abstract The need for novel antibiotics to combat emerging multi-drug resistant bacterial strains is widely acknowledged. The development of new therapeutic agents relies on small and medium-sized biotechnology enterprises (SMEs), representing 75% of the late-stage pipeline. However, most SME sponsors of an antibacterial approved by the FDA since 2010 have gone bankrupt, or exited at a loss, below investment cost. Uncovering financial flows related to the development and commercialisation of a single drug is complex and typically untransparent. There is therefore a lack of empirical research on the financial vulnerabilities of these critical SMEs. The development of plazomicin by Achaogen (2004–2019) entailed financial disclosures as a public company enabling application of financial analysis methods to: determine quantum and timing of public and private investments; quantify development costs; and provide a deeper understanding of the role of capital market dependency in exacerbating pipeline fragility. Achaogen’s widely cited bankruptcy, and plazomicin’s commercialisation failure, created a perception that novel antibiotics have zero market value, causing investors to question the SME developer business model. Our analysis of Achaogen’s inability to fund commercialisation suggests three key implications for the antibiotic investment ecosystem: (1) novel antibiotics with narrow approval for small patient populations affected by severe resistant infections cannot be successfully commercialised in the current US antibiotic market; (2) SMEs need incentive payments structured to enable them to survive the commercialisation cashflow drought, and (3) these changes are necessary to restore industry and financial investor confidence in the antibiotic SME development model. Achaogen’s demise demonstrates that proposals to incentivise innovation, e.g. by providing one-off payments at registration, may be insufficient to ensure access to novel antibiotics developed by SMEs. In plazomicin’s case, moreover, US government biosecurity investments have not resulted in access, as the Indian and Chinese companies which bought post-bankruptcy rights have not widely commercialised the drug. This study is timely as new market-based incentives are currently being proposed by the US, EU, Canada and Japan. In order to make further government funding effective, ensuring access, not only innovation, these must support sustainable financial models for the SMEs critical to novel antibiotic development.

Abstract With the growing number of individuals seeking to improve their living conditions abroad, social networking sites are becoming indispensable to their daily existence for acculturation. However, the nature of the contribution of social networking sites in fulfilling migrants’ acculturation needs remains unclear and inadequately addressed in literature. This scoping review aims to synthesise the current literature examining the role of social networking sites in meeting migrants’ acculturation needs. Following the Joanna Briggs Institute (JBI) Methodological Guidelines and the most recent modifications to the PRISMA-ScR framework, this study synthesised 48 empirical articles published between 2019 and 2023. An automated search was conducted using multiple database platforms (Web of Science, ScienceDirect, Scopus, Google Scholar and ABDC’s Journal Ranking) with sorted results using a variety of search term combinations. The synthesis of the past studies found five common acculturation needs, namely, the cognitive, social integration, personal integration, affective and tension release needs that migrants have sought and obtained from social networking sites. All of these needs are included in the uses and gratifications theory as media consumption needs. Among the identified needs, social integration and cognitive ones are the most crucial for international students, migrant workers, immigrants, refugees and other categories of migrants to overcome the difficulties that they face in the host society and to maintain connections with the ethnic community. Nevertheless, the utilisation of social networking sites to fulfil those needs differs because of various socio-demographic and psychological determinants. Many of the studies focused on identifying needs associated with integration, thus neglecting those associated with other acculturation strategies, such as separation, marginalisation and assimilation. Mismatches and inconsistencies in the acculturation requirements that migrants obtain or seek from social network sites have also not been investigated in empirical studies. Therefore, this area is potentially viable and is likely to be the subject of subsequent research. The results of the current study are useful for formulating government policies and for recruiting agencies, rights activists, social workers and administrators who are working for migrant populations.

Abstract Despite the proliferation of tools available to search for information online, such as search engines and generative artificial intelligence (AI), many people still actively use social question-and-answer (Q&A) platforms. This study examines the best answerers on Korean social Q&A platforms as key content producers and potential entrepreneurs. The characteristics of the best answerers, who are the core contributors to social Q&A platforms, were analysed based on the 903 best answerers from the social Q&A platform Naver Knowledge-iN, a leading social Q&A platform in South Korea. Research hypotheses were formulated based on three key dimensions: the intrinsic characteristics of the answers (length, immediacy, and similarity with the question), attributes of the answerer (self-introduction, credentials beyond the social Q&A platform), and level of engagement of the answerer on the platform (variety in the field of answers, diversity in role activities on the platform). An in-depth analysis using a multiple regression model was conducted to test the hypotheses. The findings of the analysis results indicate that enhanced user performance is positively correlated with several factors. Specifically, longer answers, high similarity between questions and answers, additional credentials beyond the social Q&A platform, a broader range of fields answered, and active participation as both asker and answerer all contribute to improved user performance. These findings highlight what sets social Q&A platforms apart from other search tools such as search engines or generative AI chatbots. This study has practical implications for social Q&A platforms seeking to identify the best contributors who are likely to produce quality content and are potential entrepreneurs.

Abstract Carbon source-dependent control of bacterial growth is fundamental to bacterial physiology and survival. However, pinpointing the metabolic steps important for cell growth is challenging due to the complexity of cellular networks. Here, the elastic net model and multilayer perception model that integrated genome-wide gene-deletion data and simulated flux distributions were constructed to identify metabolic reactions beneficial or detrimental to Escherichia coli grown on 30 different carbon sources. Both models outperformed traditional in silico methods by identifying not just essential reactions but also nonessential ones that promote growth. They successfully predicted metabolic reactions beneficial to cell growth, with high convergence between the models. The models revealed that biosynthetic pathways generally promote growth across various carbon sources, whereas the impact of energy-generating pathways varies with the carbon source. Intriguing predictions were experimentally validated for findings beyond experimental training data and the impact of various carbon sources on the glyoxylate shunt, pyruvate dehydrogenase reaction, and redundant purine biosynthesis reactions. These highlight the practical significance and predictive power of the models for understanding and engineering microbial metabolism.

Abstract This study aims to estimate the net effect of China’s entrepreneurship policy on back-home migrant workers since 2015. Using survey data from the provinces of; Zhejiang, Henan, and Guizhou with propensity score matching to control selection bias, the study indicates that the overall entrepreneurship policy has a significant positive impact on the probability of entrepreneurial entry. The poverty alleviation effect of the overall policy is greater than its industrial development effect, while the employment effect is not significant. The infrastructure policy’s effect on employment, industrial development, and poverty alleviation is greater than the other policies, and the financial policy’s effect on these three aspects is not significant. This study contributes to the existing literature by addressing a well-defined gap regarding the net effect of entrepreneurship policy on entrepreneurship entry and provides well-supported and plausible explanations for the inconsistencies among previous studies on policy effect indicators. As a practical contribution, this study provides China and other developing economies with compelling empirical evidence to support the design and amendment of entrepreneurship policy at the national level.

Abstract Global scientific output is expanding exponentially, which in turn calls for a better understanding of the science of science and especially how the boundaries of scientific fields expand through processes of emergence. The present study proposes the application of embedded topic modeling techniques to identify new emerging science via knowledge recombination activities as evidenced through the analysis of research publication metadata. First, a dataset is constructed from metadata derived from the Web of Science Core Collection database. The dataset is then used to generate a global map representing a categorical scientific co-occurrence network. A research field is defined as interdisciplinary when multiple science categories are listed in its description. Second, the co-occurrence networks are subsequently compared between periods to determine changing patterns of influence in light of interdisciplinarity. Third, embedded topic modeling enables unsupervised association of interdisciplinary classification. We present the results of the analysis to demonstrate the emergence of global interdisciplinary sciences and further we perform qualitative validation on the results to identify what the sources of the emergent areas are. Based on these results, we discuss potential applications for identifying emergence through the merging of global interdisciplinary domains.

Abstract Vaccination with infectious Plasmodium falciparum (Pf) sporozoites (SPZ) administered with antimalarial drugs (PfSPZ-CVac), confers superior sterilizing protection against infection when compared to vaccination with replication-deficient, radiation-attenuated PfSPZ. However, the requirement for drug administration constitutes a major limitation for PfSPZ-CVac. To obviate this limitation, we generated late liver stage-arresting replication competent (LARC) parasites by deletion of the Mei2 and LINUP genes (mei2 – /linup – or LARC2). We show that Plasmodium yoelii (Py) LARC2 sporozoites did not cause breakthrough blood stage infections and engendered durable sterilizing immunity against various infectious sporozoite challenges in diverse strains of mice. We next genetically engineered a PfLARC2 parasite strain that was devoid of extraneous DNA and produced cryopreserved PfSPZ-LARC2. PfSPZ-LARC2 liver stages replicated robustly in liver-humanized mice but displayed severe defects in late liver stage differentiation and did not form liver stage merozoites. This resulted in complete abrogation of parasite transition to viable blood stage infection. Therefore, PfSPZ-LARC2 is the next-generation vaccine strain expected to unite the safety profile of radiation-attenuated PfSPZ with the superior protective efficacy of PfSPZ-CVac.

Abstract The aims of this study are to predict the stock price trend in the stock market in an emerging economy. Using the Long Short Term Memory (LSTM) algorithm, and the corresponding technical analysis indicators for each stock code include: simple moving average (SMA), convergence divergence moving average (MACD), and relative strength index (RSI); and the secondary data from VN-Index and VN-30 stocks, the research results showed that the forecasting model has a high accuracy of 93% for most of the stock data used, demonstrating the appropriateness of the LSTM model and the test set data is used to evaluate the model’s performance. The research results showed that the forecasting model has a high accuracy of 93% for most of the stock data used, demonstrating the appropriateness of the LSTM model in analyzing and forecasting stock price movements on the machine learning platform.

Abstract Prior research shows that political uncertainty affects general economic and firm-related outcomes. However, little is known about how firm-specific political uncertainty is related to corporate risk-taking. Taking advantage of a recent construct and using a large sample of non-financial U.S. firms covering the period between 2002 and 2021, we find compelling evidence that firm-specific political uncertainty is positively related to corporate risk-taking, especially for larger firms. On average, a one standard deviation rise in the level of political risk at the firm-level results in a 2.53% increase in risk-taking. Further analysis shows that the impact of firm-level political uncertainty on corporate risk-taking is more pronounced for firms that spend more on corporate lobbying. Our results are significant and robust to alternative risk-taking measures and endogeneity tests.

Abstract Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis.

Abstract The global epidemic of obesity remains a daunting problem. Here, we report hexamethylene bisacetamide (HMBA) as a potent anti‐obesity compound. Peripheral and central administration of HMBA to diet‐induced obese mice regulated the expression of hypothalamic neuropeptides critical for energy balance, leading to beneficial metabolic effects such as anorexia and weight loss. We found that HMBA bound to MYH9 and ACTG1, which were required for the anti‐obesity effects of HMBA in both NPY‐expressing and POMC‐expressing neurons. The binding of HMBA to MYH9 and ACTG1 elevated the expression of HEXIM1 and enhanced its interaction with MDM2, resulting in the dissociation of the HEXIM1–p53 complex in hypothalamic cells. Subsequently, the free HEXIM1 and p53 translocated to the nucleus, where they downregulated the transcription of orexigenic NPY, but p53 and acetylated histone 3 upregulated that of anorexigenic POMC. Our study points to a previously unappreciated efficacy of HMBA and reveals its mechanism of action in metabolic regulation, which may propose HMBA as a potential therapeutic strategy for obesity.

Abstract This study investigates the social distancing measures necessary for participants to safely engage in leisure sports activities and comply with social distancing requirements during epidemics. Based on crowding and risk perception in public spaces in this context of an epidemic, this investigation was conducted in terms of distance in Edward T. Hall’s concept of ‘proxemics’. The participants were males aged 20–65 who used spaces for leisure sports during COVID-19 in South Korea. An online survey was conducted from September 20 to October 20, 2021, and data from 391 participants were used for the final analysis. Measures of perceived crowding, risk perception, and Hall’s proxemics were used as tools after they were modified and validated. The results show that perceived crowding according to space for leisure sports activities during COVID-19 affected individual risk perception in indoor leisure sports and social risk perception in outdoor leisure activities. Perceived crowding, according to proxemics, influenced (1) personal, social, and public distances in individual risk perception and (2) public and social distances in social risk perception. Therefore, it is necessary to re-examine the scope of social distance in developing risk perception and reducing the perceived crowding of participants in leisure sports to prevent the spread of infectious diseases such as COVID-19. Moreover, individuals must make efforts to maintain a minimum distance from one another. Further, media education and warning messages must be disseminated to reduce crowding and prevent infection spread.

Abstract Based on user-related data, an algorithmic news recommendation service (ANRS) predicts users’ reading preferences and selectively recommends news. Given the double-edged opinions on ANRS, identifying and managing crucial factors influencing users’ satisfaction and trust in this service will be essential for service providers and developers. However, few studies have tried to find these factors or develop a more precise understanding of users’ perceptions of this service. Therefore, this study aims to examine factors affecting users’ loyalty to ANRS with partial least squares structural equation modelling (PLS-SEM). This study conducted an online survey for users of “My News”, the free mobile ANRS of NAVER, Korea’s dominant online portal site, and analyzed the data from 483 responses. This analysis verified that both satisfaction and trust positively affect loyalty to ANRS, and trust positively affects satisfaction. Moreover, it was found that perceived accuracy positively affects satisfaction. The result also showed that perceived news value and perceived transparency positively affect trust, and privacy concerns negatively affect it. Lastly, it was found that perceived usability and pre-existing attitude toward the service provider positively affect satisfaction and trust. The results and discussions will be helpful for service providers and developers to manage ANRS effectively based on users’ responses and perceptions of this service.

Abstract Although blockchain has often been perceived as a game-changer that can revolutionize the music industry, it also retains possible challenges regarding the practicality of such innovative adoption. This study seeks to construe the realistic thoughts raised by artists regarding the new revenue opportunities arising from the adoption of blockchain in the Korean music industry. This involves the disintermediation of the obsolete music royalty distribution system and a new revenue channel from the Non-fungible Token market. Based on social representation theory and interviews with Korean artists, this study found ambivalent perceptions towards the adoption of blockchain in the music industry - hoping for new possibilities while also perceiving the impracticality of such innovation. Indeed, it may be too good to be true for artists who have observed the local domain with little change regardless of their continuous cries for help. After thorough discussion, the study provides key implications to induce sound settlement of an innovative technology.

Abstract Vietnam as a nation is deeply rooted in the wet-rice agricultural civilization, which is characterized by the Yin (female) principle and the religion worshiping Mother Goddess. However, Chinese Confucianism significantly influenced Vietnam throughout the feudal dynasties (10–19th centuries). Confucian kingship propagates symbols of virtuous women to establish the moral order of a male-dominated society. In contrast, by practicing lived religion and spreading folk narratives, Vietnamese people turn virtuous women into Mother Goddess with a liberal, creative and patronage identity. This study, thus, examines the position of women in Confucian Nguyễn Dữ’s The Young Woman from Nam Xuong, a canonical story reconstructed from legend. It is important to address the main concern about metaphors of a duality culture and a conflict discourse of Confucian politics and Vietnamese lived religion through the issue of Goddess spirituality. This article uses an interdisciplinary approach to demonstrate that resistance to Chinese Dominance and anti-Sinicization were significant issues of Vietnamese medieval literature and culture.

Abstract The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection.

Abstract Governments around the world attempted to suppress the spread of COVID-19 using restrictions on social and economic activity. This study presents the first global analysis of job and income losses associated with those restrictions, using Gallup World Poll data from 321,000 randomly selected adults in 117 countries from July 2020 to March 2021. Nearly half of the world’s adult population lost income because of COVID-19, according to our estimates, and this outcome and related measures of economic harm—such as income loss—are strongly associated with lower subjective well-being, financial hardship, and self-reported loss of subjective well-being. Our primary analysis uses a multilevel model with country and month-year levels, so we can simultaneously test for significant associations between both individual demographic predictors of harm and time-varying country-level predictors. We find that an increase of one-standard deviation in policy stringency, averaged up to the time of the survey date, predicts a 0.37 std increase in an index of economic harm (95% CI 0.24–0.51) and a 14.2 percentage point (95% CI 8.3–20.1 ppt) increase in the share of workers experiencing job loss. Similar effect sizes are found comparing stringency levels between top and bottom-quintile countries. Workers with lower-socioeconomic status—measured by within-country income rank or education—were much more likely to report harm linked to the pandemic than those with tertiary education or relatively high incomes. The gradient between harm and stringency is much steeper for workers at the bottom quintiles of the household income distribution than it is for those at the top, which we show with interaction models. Socioeconomic status is unrelated to harm where stringency is low, but highly and negatively associated with harm where it is high. Our detailed policy analysis reveals that school closings, stay-at-home orders, and other economic restrictions were strongly associated with economic harm, but other non-pharmaceutical interventions—such as contact tracing, mass testing, and protections for the elderly were not.

Abstract The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases (NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi‐layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK‐3β), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell‐based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long‐term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.

Abstract Prolyl‐tRNA synthetase 1 (PARS1) has attracted much interest in controlling pathologic accumulation of collagen containing high amounts of proline in fibrotic diseases. However, there are concerns about its catalytic inhibition for potential adverse effects on global protein synthesis. We developed a novel compound, DWN12088, whose safety was validated by clinical phase 1 studies, and therapeutic efficacy was shown in idiopathic pulmonary fibrosis model. Structural and kinetic analyses revealed that DWN12088 binds to catalytic site of each protomer of PARS1 dimer in an asymmetric mode with different affinity, resulting in decreased responsiveness at higher doses, thereby expanding safety window. The mutations disrupting PARS1 homodimerization restored the sensitivity to DWN12088, validating negative communication between PARS1 promoters for the DWN12088 binding. Thus, this work suggests that DWN12088, an asymmetric catalytic inhibitor of PARS1 as a novel therapeutic agent against fibrosis with enhanced safety.

Abstract Treatment of sensitive bacteria with beta‐lactam antibiotics often leads to two salient population‐level features: a transient increase in total population biomass before a subsequent decline, and a linear correlation between growth and killing rates. However, it remains unclear how these population‐level responses emerge from collective single‐cell responses. During beta‐lactam treatment, it is well‐recognized that individual cells often exhibit varying degrees of filamentation before lysis. We show that the cumulative probability of cell lysis increases sigmoidally with the extent of filamentation and that this dependence is characterized by unique parameters that are specific to bacterial strain, antibiotic dose, and growth condition. Modeling demonstrates how the single‐cell lysis probabilities can give rise to population‐level biomass dynamics, which were experimentally validated. This mapping provides insights into how the population biomass time‐kill curve emerges from single cells and allows the representation of both single‐ and population‐level responses with universal parameters.

Abstract DNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the temporal trajectory of blood epigenetic remodeling in 133 participants in a prospective study of young adults before, during, and after asymptomatic and mildly symptomatic SARS‐CoV‐2 infection. The differential methylation caused by asymptomatic or mildly symptomatic infections was indistinguishable. While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow‐up, with a pattern resembling autoimmune or inflammatory disease. We leveraged these responses to construct methylation‐based machine learning models that distinguished samples from pre‐, during‐, and postinfection time periods, and quantitatively predicted the time since infection. The clinical trajectory in the young adults and in a diverse cohort with more severe outcomes was predicted by the similarity of methylation before or early after SARS‐CoV‐2 infection to the model‐defined postinfection state. Unlike the phenomenon of trained immunity, the postacute SARS‐CoV‐2 epigenetic landscape we identify is antiprotective.

Background: In breast cancer, ErbB receptors play a critical role, and overcoming drug resistance remains a major challenge in the clinic. However, intricate regulatory mechanisms of ErbB family genes are poorly understood. Here, we demonstrate SON as an ErbB-regulatory splicing factor and a novel therapeutic target for ErbB-positive breast cancer. Methods: SON and ErbB expression analyses using public database, patient tissue microarray, and cell lines were performed. SON knockdown assessed its impact on cell proliferation, apoptosis, kinase phosphorylation, RNA splicing, and in vivo tumour growth. RNA immunoprecipitation was performed to measure SON binding. Results: SON is highly expressed in ErbB2-positive breast cancer patient samples, inversely correlating with patient survival. SON knockdown induced intron retention in selective splice sites within ErbB2 and ErbB3 transcripts, impairing effective RNA splicing and reducing protein expression. SON disruption suppressed downstream kinase signalling of ErbB2/3, including the Akt, p38, and JNK pathways, with increased vulnerability in ErbB2-positive breast cancer cells compared to ErbB2-negative cells. SON silencing in ErbB2-positive breast cancer xenografts led to tumour regression in vivo. Conclusion: We identified SON as a novel RNA splicing factor that plays a critical role in regulating ErbB2/3 expression, suggesting SON is an ideal therapeutic target in ErbB2-positive breast cancers. [ABSTRACT FROM AUTHOR]

The brain helps us survive by forming internal representations of the external world1,2. Excitatory cortical neurons are often precisely tuned to specific external stimuli3,4. However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective5. PV interneurons differ from excitatory neurons in their neurotransmitter receptor subtypes, including AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs)6,7. Excitatory neurons express calcium-impermeable AMPARs that contain the GluA2 subunit (encoded by GRIA2), whereas PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable (CP-AMPARs). Here we demonstrate a causal relationship between CP-AMPAR expression and the low feature selectivity of PV interneurons. We find low expression stoichiometry of GRIA2 mRNA relative to other subunits in PV interneurons that is conserved across ferrets, rodents, marmosets and humans, and causes abundant CP-AMPAR expression. Replacing CP-AMPARs in PV interneurons with calcium-impermeable AMPARs increased their orientation selectivity in the visual cortex. Manipulations to induce sparse CP-AMPAR expression demonstrated that this increase was cell-autonomous and could occur with changes beyond development. Notably, excitatory–PV interneuron connectivity rates and unitary synaptic strength were unaltered by CP-AMPAR removal, which suggested that the selectivity of PV interneurons can be altered without markedly changing connectivity. In Gria2-knockout mice, in which all AMPARs are calcium-permeable, excitatory neurons showed significantly degraded orientation selectivity, which suggested that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type. Moreover, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, which indicated that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality. These results reveal a new role of CP-AMPARs in maintaining low-selectivity sensory representation in PV interneurons and implicate a conserved molecular mechanism that distinguishes this cell type in the neocortex. Calcium-permeable AMPA receptors are identified to have a role in maintaining low feature selectivity in a specific population of inhibitory interneurons, and this function is conserved across ferrets, rodents, marmosets and humans. [ABSTRACT FROM AUTHOR]

Opportunistic fish pathogen Vibrio scophthalmi frequently infects olive flounder and turbot, which are primary marine species cultured for seafood production in Far East Asia. These infections cause substantial yield reductions and significant economic losses. Although quorum sensing (QS) genes were previously reported in V. scophthalmi, the impacts of QS on genome-wide gene expression and consequent behaviors and physiological traits have remained largely unexplored. In this study, we conducted genomic and transcriptomic analyses to uncover the global regulatory network governed by LuxRVs, a QS master regulator in V. scophthalmi. By comparing the wild-type strain and a luxRVs deletion mutant strain, we found that LuxRVs positively regulates biosynthetic genes for poly-hydroxyalkanoate (PHA) while negatively controlling genes for biofilm formation. Quantification of intracellular PHAs and biofilm biomass on borosilicate tubes confirmed these results. Gene set enrichment analyses further demonstrated that LuxRVs also governs genes related to osmoprotection and defense against reactive oxygen species. Overall, these findings indicate that LuxRVs acts as a global transcriptional regulator, controlling a wide range of physiological processes in V. scophthalmi. Targeting LuxRVs could therefore be a promising strategy for improving seafood production by disrupting diverse physiological and pathogenic traits in this fish pathogen. [ABSTRACT FROM AUTHOR]

Melon thrips, Thrips palmi, represent a significant threat to plants, inducing necrosis and acting as vectors for numerous plant viruses. Entomopathogenic fungi present a promising avenue for the management of melon thrips populations resistant to conventional chemical treatments. In this work, an adult colony of melon thrips was exposed to Beauveria bassiana strain JEF-350, and the ensuing transcriptional response of the infected thrips was scrutinized to elucidate their reactions during fungal pathogenesis. Utilizing Illumina sequencing, RNA samples were extracted from untreated thrips as well as from thrips continuously infected for 2 and 4 days, each with three biological replicates. While no notable alterations in gene expression were observed between the untreated control and thrips infected for 2 days, those infected for 4 days exhibited a plethora of differentially expressed genes. Specifically, in the thrips infected for the extended period, pathways associated with lysosomal function and insect hormone biosynthesis were notably repressed, while others such as serine and glycine metabolism, Toll and Imd, and circadian rhythm pathways displayed heightened activity. Noteworthy downregulation was observed in numerous lysosomal hydrolase genes encoding glycosidases, sulfatases, and lipases, particularly glycosidases. Furthermore, certain genes related to hydrolase precursors within the Golgi apparatus exhibited heightened expression levels but failed to progress toward hydrolase biosynthesis. Upstream regulation of juvenile hormone biosynthesis was augmented, yet downstream genes were significantly downregulated, leading to a disruption in juvenile hormone production. Similarly, while cytochrome P450 genes in the downstream of ecdysone biosynthesis were upregulated, expressions of cholesterol desaturase and cytochrome P450 genes in the upstream were inhibited, consequently dampening ecdysone biosynthesis. The observed differential targeting of organs or pathways by B. bassiana JEF-350, in contrast to conventional chemicals primarily affecting neurotransmission and energy production, suggests its potential efficacy in managing resistant thrips populations. Consequently, integrating JEF-350 into the chemical spray regimen or incorporating it into tank-mix formulations with chemical insecticides emerges as a pragmatic approach within the realm of integrated pest management strategies. Key points: • Beauveria treatment inhibited lysosomal function and hormone synthesis in thrips. • Thrips serine/glycine metabolism, Toll and Imd, and circadian rhythm pathways were activated. • Upstream functions of thrips hormone biosynthesis increased, while downstream functions were suppressed. • Regarding biosynthesis of metabolites, this fungus targets other pathways with resistance management. [ABSTRACT FROM AUTHOR]

Adsorption-based atmospheric water harvesting (AWH) has the potential to address water scarcity in arid regions. However, developing adsorbents that effectively capture water at a low relative humidity (RH < 30%) and release it with minimal energy consumption remains a challenge. Herein, we report a fluorophenyl oligomer (FO)-incorporated metal-organic framework (MOF), HKUST-1 (FO@HK), which exhibits fast adsorption kinetics at low RH levels and facile desorption by sunlight. The incorporated fluorophenyl undergoes vapor-phase polymerization at the metal center to generate fluorophenyl oligomers that enhance the hydrolytic stability of FO@HK while preserving its characteristic water sorption behavior. The FO@HK exhibited vapor sorption rates of 8.04 and 11.76 L kg−1MOF h−1 at 20 and 30% RH, respectively, which are better than the state-of-the-art AWH sorbents. Outdoor tests using a solar-driven large-scale AWH device demonstrate that the sorbent can harvest 264.8 mL of water at a rate of 2.62 L kg−1MOF per day. This study provides a ubiquitous strategy for transforming water-sensitive MOFs into AWH sorbents. In arid regions, effective atmospheric water harvesting (AWH) is essential. The fluorophenyl oligomer (FO)-incorporated HKUST-1 (FO@HK) shows impressive performance. F3@HK achieves up to 11.76 L kg−1MOF h−1 at 30% RH and can harvest 2.62 L kg−1MOF of water daily with solar energy. [ABSTRACT FROM AUTHOR]

Plant pathogens secrete nuclear effectors into the host nuclei to modulate the host immune system. Although several nuclear effectors of fungal pathogens have been recently reported, the molecular mechanism of NLS-associated transport vehicles of nuclear effectors and the roles of NLS in transcriptional reprogramming of host immunity genes remain enigmatic. We previously reported the MoHTR1, a nuclear effector of the rice blast fungus, Magnaporthe oryzae. MoHTR1 is translocated to rice nuclei but not in fungal nuclei. Here, we identify the core NLS (RxKK) responsible for MoHTR1's nuclear localization. MoHTR1 is translocated in the host nucleus through interaction with rice importin α. MoHTR1 NLS empowers it to translocate the cytoplasmic effectors of M. oryzae into rice nuclei. Furthermore, other nuclear effector candidates of the blast pathogen and rice proteins which have RxKK also exhibit nuclear localization, highlighting the crucial role of RxKK in this process. We also unveil the importance of SUMOylation in the stability of MoHTR1 and translocation of MoHTR1 to host nuclei. Moreover, MoHTR1 NLS is essential for the pathogenicity of M. oryzae by reprogramming immunity-associated genes in the host. Our findings provide insights into the significance of plant-specific NLS on fungal nuclear effectors and its role in plant-pathogen interactions. Nuclear effectors of plant pathogens modulate the host immunity. Here, Lim et al. unveiled the core sequence and mechanism for nuclear localization of the rice blast fungal effector, MoHTR1, revealing its role in regulating the host immune system. [ABSTRACT FROM AUTHOR]

Alkali-free aluminoborosilicate glasses without (GDMC-Si) and with La2O3 addition (GDMC-La) were fabricated with an aim to develop low dielectric glass fibers for use in printed circuit boards (PCBs) as a reinforcing material in high-speed 5G/6G telecommunications application. This study presents the structural, thermo-physical, and dielectric properties of the glasses. The decrease in glass transition temperature (Tg) and the increase in coefficient of thermal expansion (CTE) were found by the addition of SiO2 and La2O3 in the present glass system, which are due to the depolymerization of the glass networks confirmed by the FTIR analysis. The dielectric constants (Dk) and the dissipation factors (Df) of the glasses were investigated at a high frequency of 10 GHz. The Dk values of the GDMC-Si and GDMC-La glass systems reached a minimum of 4.50 and 4.75, while their Df values reached a minimum of 2.86 × 10−3 and 3.01 × 10−3, respectively. Notably, the Dk and Df values of the present glasses were lower than the commercial E-glass (Dk: 6.9, Df: 7.0 × 10−3 at 10 GHz) and L-glass (Dk: 4.8, Df: 3.0 × 10−3 at 10 GHz). Glass fibers with a diameter of 10 μm were successfully drawn by the continuous melt-spinning process and their mechanical properties were investigated. [ABSTRACT FROM AUTHOR]

Gene therapy is a promising method for treating inherited diseases by directly delivering the correct genetic material into patient cells. However, the limited packaging capacity of vectors poses a challenge. Minimizing promoter size is a viable strategy among various approaches to address this issue. This study aims to optimize the bovine myostatin (MSTN) promoter, enhancing its utility in gene therapy applications. We identified the primary driver of activity as the proximal regulatory region. Isolated from the native promoter and termed M243, this 243-bp sequence was assessed for its potential as a ubiquitous promoter. In a variety of cell types, including bovine embryos and embryonic stem cells, the M243 promoter showed consistent expression, highlighting its suitability for applications requiring compact promoters. The isolation of a highly conserved, compact 243-bp sequence serving as a promoter suggests a solution for overcoming the size constraints of AAV vectors, suggesting potential contributions to the field of gene therapy. [ABSTRACT FROM AUTHOR]

The anisotropic nature of granite, a key factor affecting its mechanical properties, is inherently governed by its mineral alignment and the presence of orthogonal cleavage planes: rift, grain, and hardway. This study examines how these cleavage planes influence anisotropy, particularly in the context of microcracking formation and acoustic properties. A new measurement procedure for the acoustic nonlinearity parameter () is developed to address the well-known limitations of conventional linear ultrasound methods, including wave velocity and attenuation coefficient, in detecting microstructural changes induced by existing cleavage planes. Unlike other parameters, exhibits remarkable changes depending on the plane type, highlighting its high sensitivity to the mineral distribution in each cleavage plane and to the microcracks. A correlation between the linear and nonlinear parameters provides further evidence of the superiority of in detecting inherent microscale defects that develop in each plane and affect the anisotropic characteristics of granite. The findings of this study confirm that nonlinear ultrasound is capable of elucidating the mechanisms underlying the origin of anisotropy in granite due to microcracks, with broader implications for understanding unidentified chemical and mechanical phenomena in geological materials. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients. [ABSTRACT FROM AUTHOR]

Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC. [ABSTRACT FROM AUTHOR]

Histone post-translational modifications play pivotal roles in eukaryotic gene expression. To date, most studies have focused on modifications in unstructured histone N-terminal tail domains and their binding proteins. However, transcriptional regulation by chromatin-effector proteins that directly recognize modifications in histone globular domains has yet to be clearly demonstrated, despite the richness of their multiple modifications. Here, we show that the ATP-dependent chromatin-remodeling BAF complex stimulates p53-dependent transcription through direct interaction with H3K56ac located on the lateral surface of the histone globular domain. Mechanistically, the BAF complex recognizes nucleosomal H3K56ac via the DPF domain in the DPF2 subunit and exhibits enhanced nucleosome-remodeling activity in the presence of H3K56ac. We further demonstrate that a defect in H3K56ac–BAF complex interaction leads to impaired p53-dependent gene expression and DNA damage responses. Our study provides direct evidence that histone globular domain modifications participate in the regulation of gene expression. The authors suggest that histone globular domain modifications participate in the regulation of gene expression. The ATP-dependent chromatin-remodeling BAF complex enhances transcription through direct interaction with H3K56ac located on the lateral surface of the histone globular domain. [ABSTRACT FROM AUTHOR]

KRAS is one of the most frequently mutated oncogenes across various cancers. Oncogenic KRAS mutations rewire cellular signaling, leading to significant alterations in gene expression. RNA-binding proteins (RBPs) play a pivotal role in gene expression regulation by post-transcriptionally controlling various aspects of RNA metabolism. It has become clear that interactions between RBPs and RNA are frequently dysregulated in numerous cancers. However, how oncogenic KRAS mutations reshape the post-transcriptional regulatory network mediated by RBPs remains poorly understood. In this study, we systematically dissected oncogenic KRAS-driven alterations of RNA-RBP networks. We identified 35 cancer-associated RBPs with either increased or decreased RNA binding upon oncogenic KRAS activation, including PDCD11, which is essential for the viability of KRAS mutant cancers, and ELAVL2, which regulates cell migration in KRAS mutant lung cancers. Our study serves as a crucial resource for elucidating RBP regulatory networks in KRAS mutant cancers and may provide new avenues for therapeutic strategies targeting KRAS mutant malignancies. [ABSTRACT FROM AUTHOR]

Decompensated cirrhotic patients experience severely increased intestinal permeability and bacterial translocation. Thus, autologous blood salvaged during deceased donor liver transplantation (DDLT) may be contaminated with enteric bacteria. We aimed to evaluate bacterial contamination of autologous blood salvaged during DDLT and its association with post-transplant bacteremia. In 30 patients undergoing DDLT, bacterial culture was performed in salvaged autologous blood samples: one before graft reperfusion (non-leukoreduced) and two after graft reperfusion (non-leukoreduced and leukoreduced). The primary outcome was bacterial contamination of salvaged autologous blood. Seven of 30 patients (23.3%) were positive for bacteria (3 enteric/4 non-enteric) before graft reperfusion while 11 patients (36.7%) were positive (5 enteric/6 non-enteric) after graft reperfusion. Six of 7 patients who were positive for bacteria before graft reperfusion were positive after graft reperfusion with the same bacteria. Only 4 of 11 contaminated blood samples were converted to negative after leukoreduction. Post-transplant bacteremia risk was insignificantly greater in patients who received autologous blood with bacteria than in patients without bacteria (30.0% vs. 5.0%, P = 0.06). We found contamination of salvaged autologous blood with enteric bacteria throughout DDLT and incomplete performance of leukoreduction, indicating high bacterial load. The potential association between contaminated autotransfusion and post-transplant bacteremia warrants further validation in a larger prospective study. Clinical trial notation: This study was registered at the Clinical Research Information Service (CRiS; https://cris.nih.go.kr; No. KCT0007223; principal registration investigator: Sangbin Han, date of registration: April 25, 2022). [ABSTRACT FROM AUTHOR]

Aromatherapy using essential oils (EOs) is well known for its beneficial effects on mental health and neuroprotection. However, the significant molecular mechanisms have not yet been identified. Recent studies have identified a decrease in glucose uptake as a common feature across various neurodegenerative diseases (NDDs), leading to mitochondrial dysfunction and excessive autophagy. This suggests that glucose may serve not only as an energy source but also as a therapeutic target for NDDs. Using SH-SY5Y neuroblast-like cells and the glucose uptake inhibitor BAY-876, we demonstrated that glucose depletion promoted autophagy. To discover the potential therapeutics that modulate glucose metabolism, we obtained EO from Pinus koraiensis Siebold & Zucc. (PKSZ) using steam distillation. PKSZ-EO upregulated mRNA expression of SLC2A2, SLC2A3, and SLC2A4, leading to increased glucose uptake in SH-SY5Y cells. Furthermore, PKSZ-EO protected SH-SY5Y cells from BAY-876-induced mitochondrial dysfunction, cytostasis, autophagy, and inflammation. Using gas chromatography-mass spectrometry, we confirmed the high levels of α-pinene, an inducer of GLUT4 expression, in PKSZ-EO. These results suggest that PKSZ-EO exerts a protective effect against glucose depletion stress, highlighting its potential as a therapeutic agent for NDDs. [ABSTRACT FROM AUTHOR]