Endogenous Interaction Research Articles

Effects of Cimetidine and Dolutegravir on the Endogenous Drug-Drug Interaction Biomarkers for Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Protein 1 in Healthy Volunteers.

This study was designed to assess the quantitative performance of endogenous drug-drug interaction (DDI) biomarkers (N1-methylnicotinamide (1-NMN), N1-methyladenosine (m1A), and creatinine) for the organic cation transporters, OCT2 and MATE1/2K in the kidney. Ten healthy volunteers received cimetidine (400 and 800 mg, single dose) or dolutegravir (50 mg, twice a day) together with metformin (500 mg). Cimetidine and dolutegravir were considered to act mainly as MATE1/2K and OCT2 inhibitors, respectively. The renal clearance (CLr) of metformin was decreased by 15.5% and 42.5% by cimetidine 400 and 800 mg, and by 26.8% and 56.9% by dolutegravir first and fifth doses, respectively. CLr ratio (CLrR) of 1-NMN were 0.93 and 0.64 for cimetidine 400 and 800 mg, and 0.87 and 0.47 for dolutegravir first and fifth doses, respectively. CLrR of m1A was less than that of 1-NMN: 1.0 and 0.80 for cimetidine 400 and 800 mg, and 0.77 and 0.71 for dolutegravir first and fifth doses, respectively. CLr of creatinine was significantly decreased only by cimetidine 800 mg. Individual CLrR of 1-NMN and m1A showed a positive correlation with the corresponding CLrR of metformin with r2 of 0.58 and 0.55, respectively. When evaluated individually, m1A showed a better correlation during cimetidine periods (r2 0.64) than 1-NMN (r2 0.36), but vice versa during dolutegravir periods (r2 1-NMN, 0.80; m1A, 0.32). These results suggest that 1-NMN and m1A might be more promising than creatinine as endogenous biomarkers for quantitatively assessing the DDI potential of investigational drugs for OCT2 and MATE1/2K based on their CLrR change.

Phenotypic homogenization and potential fitness constraints following non-native introgression in an endemic sportfish.

Introgressive hybridization may lead to contrasting evolutionary outcomes that are difficult to predict, since they depend on the fitness effects of endogenous genomic interactions and environmental factors. Conservation of endemic biodiversity may be more effective with require direct measurement of introgressed ancestry and fitness in wild populations, especially for keystone taxa at risk of hybridization following species introductions. We assessed the relationship of non-native ancestry with growth and body condition in the basin-restricted Neosho Bass (Micropterus velox; NB), focusing on two streams in the NB native range that are admixed extensively with non-native Smallmouth Bass (M. dolomieu; SMB). We quantified genetic composition of 116 fish from Big Sugar Creek (N=46) and Elk River (N=70) at 14 microsatellite loci. Using back-calculated total length-at-age estimated from sagittal otoliths, we assessed whether genetic ancestry explained variation in von Bertalanffy growth model parameters, accounting for sex and stream effects. We then assessed the relationship of ancestry and body condition. We found no differences in growth parameters by sex, stream, or ancestry, suggesting phenotypic homogenization which could be mediated by selection on body size. We found a negative correlation between SMB ancestry and condition, including lower condition in Big Sugar Creek, possibly reflecting a trade-off between maximum length and condition with respect to overall fitness. We show that ongoing non-native introgression, which may be augmented by anthropogenic SMB introductions, may attenuate evolutionary differentiation between species and directly influence fitness, possibly having critical implications for long-term persistence and management of adaptive potential in a popular and ecologically important endemic sportfish.

The role of social interaction in farmers’ water-saving irrigation technology adoption: testing farmers’ interaction mechanisms

In rural areas, neighborly relationships are complex, and farmers’ behaviors are largely influenced by neighborly interactions. The promotion of agricultural technologies should not overlook the social interactions between farmers. Based on survey data from farmers in Minqin, China, this paper explores the role of overall social interaction and its various dimensions in farmers’ adoption of water-saving irrigation technology, focusing on the testing of three interactive mechanisms during the technology adoption process. The goal is to provide scientific policy suggestions for government when promoting agricultural technologies. The results show the following: social interaction promotes the adoption of water-saving irrigation technology among farmers; among the four dimensions of social interaction, the depth and frequency of social interaction facilitate the adoption of these technologies; social interaction promotes technology adoption through endogenous interaction mechanism, situational interaction mechanism, and social norm mechanism, with situational interaction mechanism and social norm mechanism playing a more significant role; social interaction has a stronger impact on farmers with longer farming experience and higher irrigation costs. Therefore, the government should emphasize the important role of social interaction in the adoption of agricultural technologies and accelerate the diffusion of these technologies through fostering technical exchanges among farmers, cultivating demonstration households, and implementing differentiated promotion strategies.

USP24 promotes autophagy-dependent ferroptosis in hepatocellular carcinoma by reducing the K48-linked ubiquitination of Beclin1.

Ubiquitination is a post-translational modification (PTM), which is critical to maintain cell homeostasis. Ubiquitin-specific protease 24 (USP24) plays roles in various diseases, the mechanisms by which USP24 regulates hepatocellular carcinoma (HCC) remain poorly understood. In this study, USP24 is found to be significantly downregulated in HCC. Knocking down USP24 promotes HCC proliferation and migration, whereas USP24 overexpression inhibits HCC in vitro and in vivo. The endogenous interaction between USP24 and Beclin1 is confirmed. Mechanically, USP24 delays Beclin1 degradation by reducing its K48-linked ubiquitination, the effects of overexpressing USP24 on HCC proliferation can be partially reversed by silencing Beclin1. We find that increased autophagy is accompanied by ferroptosis in USP24 overexpressed HCC cells and USP24 increases the susceptibility of HCC to sorafenib. Collectively, this study highlights the critical role of USP24 in regulating autophagy-dependent ferroptosis by decreasing Beclin1 ubiquitination, suggesting that targeting USP24 may be a strategy for treating HCC.

Pooled endogenous protein tagging and recruitment for systematic profiling of protein function

The emerging field of induced proximity therapeutics, which involves designing molecules to bring together an effector and target protein-typically to induce target degradation-is rapidly advancing. However, its progress is constrained by the lack of scalable and unbiased tools to explore effector-target protein interactions. We combine pooled endogenous gene tagging using a ligand-binding domain with generic small-molecule-based recruitment to screen for induction of protein proximity. We apply this methodology to identify effectors for degradation in two orthogonal screens: using fluorescence to monitor target levels and a cellular growth that depends on the degradation of an essential protein. Our screens revealed new effector proteins for degradation, including previously established examples, and converged on members of the C-terminal-to-LisH (CTLH) complex. We introduce a platform for pooled induction of endogenous protein-protein interactions to expand our toolset of effector proteins for protein degradation and other forms of induced proximity.

ORF48 is required for optimal lytic replication of Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes persistent infection in the host by encoding a vast network of proteins that aid immune evasion. One of these targeted innate immunity pathways is the cGAS-STING pathway, which inhibits the reactivation of KSHV from latency. Previously, we identified multiple cGAS/STING inhibitors encoded by KSHV, suggesting that the counteractions of this pathway by viral proteins are critical for maintaining a successful KSHV life cycle. However, the detailed mechanisms of how these viral proteins block innate immunity and facilitate KSHV lytic replication remain largely unknown. In this study, we report that ORF48, a previously identified negative regulator of the cGAS/STING pathway, is required for optimal KSHV lytic replication. We used both siRNA and deletion-based systems to evaluate the importance of intact ORF48 in the KSHV lytic cycle. In both systems, loss of ORF48 resulted in defects in lytic gene transcription, lytic protein expression, viral genome replication and infectious virion production. ORF48 genome deletion caused more robust and global repression of the KSHV transcriptome, possibly due to the disruption of RTA promoter activity. Mechanistically, overexpressed ORF48 was found to colocalize and interact with endogenous STING in HEK293 cells. Endogenous ORF48 and STING interactions were also detected in reactivated iSLK.219 cells. Compared with the control cell line, HUVEC cells stably expressing ORF48 exhibited repressed STING-dependent innate immune signaling upon ISD or diABZI treatment. However, the loss of ORF48 in our iSLK-based lytic system failed to induce IFNβ production, suggesting a redundant role of ORF48 on STING signaling during the KSHV lytic phase. Thus, ORF48 is required for optimal KSHV lytic replication through additional mechanisms that need to be further explored.

High-sensitivity in situ capture of endogenous RNA-protein interactions in fixed cells and primary tissues

RNA-binding proteins (RBPs) have pivotal functions in RNA metabolism, but current methods are limited in retrieving RBP-RNA interactions within endogenous biological contexts. Here, we develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), circumventing the challenges through in situ RNA labeling by precisely directing a purified APOBEC1-nanobody fusion to the RBP of interest. This method enables highly specific RNA-binding site identification across a diverse range of fixed biological samples such as HEK293T cells and mouse brain tissue and accurately identifies the canonical binding motifs of RBFOX2 (UGCAUG) and TDP-43 (UGUGUG) in native cellular environments. Applicable to any RBP with available primary antibodies, INSCRIBE enables sensitive capture of RBP-RNA interactions from ultra-low input equivalent to ~5 cells. The robust, versatile, and sensitive INSCRIBE workflow is particularly beneficial for precious tissues such as clinical samples, empowering the exploration of genuine RBP-RNA interactions in RNA-related disease contexts.

Regional drivers of industrial decarbonisation: a spatial econometric analysis of 238 EU regions between 2008 and 2020

ABSTRACT The European context of socio-economic integration and physical proximity likely plays an essential role in explaining the decarbonisation outcomes of industrial sectors. However, there is hardly any spatial regional analysis on CO2 emissions drivers in European countries. This study investigates the role of geographical space and regional determinants in industrial decarbonisation by analysing how socio-economic drivers and their interregional relationships impact industrial carbon emissions in European regions. We employ a spatial panel data econometric model to a novel panel dataset comprising 13 years (2008–20) of carbon emissions from hard-to-abate industrial sectors from 238 NUTS-2 regions across 27 European Union countries. Results indicate the presence of endogenous spatial interactions and high-time persistence between CO2-eq emissions in European Union regions. As such, industrial carbon emissions of regions follow similar patterns to their neighbours, supporting the evolutionary economic geography and growth theory assumptions of the spatial interaction of carbon emissions between regions. Furthermore, the use of a spatial econometric model illustrates the negative direct and spillover effects that higher levels of education and regional investment in research and development have on industrial CO2-eq emissions.

Exchange rate dynamics and the central bank's balance sheet

Are nominal exchange rate variations linked to the central bank's balance sheet, in particular to remunerated domestic liabilities? We use two metrics of implied exchange rates based on central bank balance sheet data: one is a traditional metric that includes the monetary base, and the other adds remunerated domestic liabilities. We first estimate a VAR model to investigate the endogenous interactions between central bank balance sheet components for a set of seven Latin American countries for the 2006:01-2019:12 period. Then, we use a pairwise cointegration framework to compare these two metrics of implied exchange rate with the spot (observed) exchange rate. We find that the implied exchange rates and the spot exchange rate are cointegrated for most of the set of Latin American countries. We also find that for a subset of our sample, the spot exchange rate adjusts to the metric that adds remunerated domestic liabilities. We conclude that remunerated domestic liabilities matter for understanding exchange rate dynamics, and explore a simple theoretical setup to better understand the mechanism.

A longitudinal analysis of local innovation in Italy: How do proximity measures matter?

ABSTRACT This paper investigates the factors influencing local innovation from a longitudinal perspective while assessing geographical, economic and technological proximity. The research hypotheses concern spatial interactions, spillover effects and proximity measures that best fit innovation patterns and territorial interactions in Italy. The estimation strategy is the spatial Durbin panel model. The optimal specification to handle cross-sectional dependence in the data was derived from statistical tests evaluating (i) individual-specific effects, (ii) time-specific effects and (iii) both individual and time effects. The model was estimated using data from 107 Italian provinces over 2010–2019. The results show that both endogenous and exogenous interaction effects drive innovation processes and the underlying spillovers are global. Economic proximity explains local innovation patterns more effectively than geographical contiguity and technological proximity.

The Effect of Crime on Foreign Investment and Economic Development in Sub-Saharan Africa: A Panel Data Analysis

This study investigates the effect of crime on economic development in 22 sub-Saharan African countries between 2000 and 2020, using data from global sources. The study utilized a panel vector autoregression (VAR) approach to analyze the dynamic correlations between variables. This was achieved through the examination of impulse response functions and error variance decomposition. The study established a definitive cause-and-effect connection between the crime rate and growth indicators. The panel vector autoregression (VAR) technique resolves the issue of endogeneity by permitting endogenous interaction among the variables in the system. The findings indicate that the crime rate has a significant effect on economic growth in sub-Saharan countries, though with very low magnitude. The economic prosperity of most sub-Saharan African countries may be attributed to the abundant availability of natural resources in the region. The causality test findings indicate a diverse causal connection between the crime rate and growth indicators. While there is no direct causal relationship between economic growth and the crime rate, there is a one-way causality between economic growth and foreign investment. This means that economic growth can enhance foreign investment, suggesting that in sub-Saharan countries, economic growth plays a crucial role in improving foreign investment. However, as indicated by the findings, there exists a bidirectional causal relationship between foreign investment and crime rates. In summary, it is clear that the crime rate in sub-Saharan African nations has a significant impact. In the future, countries with higher crime rates are likely to see slow economic growth and less foreign investment.

Unraveling the spatial dynamics of regional economic disparities in East Java

The objective of this research was to analyze the determinants of regional disparities in East Java Province. This study utilized panel data, incorporating research locations across 38 regencies in East Java, with a data series spanning from 2016 to 2020. Spatial panel data models were employed to address the research objective, specifically examining the impact of spatial and non-spatial factors on disparities in East Java. The study's findings indicated that the Spatial Autoregressive (SAR) model was the most effective for estimating disparities in the region. The effects of each variable are as follows: the average duration of schooling and investment had positive and significant effects on disparities, while the variable of open unemployment rate did not exhibit any significant effect. Additionally, there is a spatial effect in the form of an endogenous interaction effect, signifying that the extent of disparities is influenced by the disparities in neighboring areas.

Spatial dependence and poverty factors: A study of Pantura Regions in East Java Province, Indonesia

Poverty is still a problem in various countries in the world, so eradicating poverty and hunger by 2030 is the backbone of the goals of the sustainable development agenda. Poverty, which is the main goal of the Millennium Development Goals (MDGs), is again the main goal in the Sustainable Development Goals (SDGs). This research aims to determine the spatial dependence of poverty in the Pantura Region of East Java Province and to determine the influence of economic growth, education, unemployment, natural resources, health and accessibility on poverty in the Pantura Region of East Java Province. This research uses a quantitative approach, with data analysis methods using Moran’s index analysis, and spatial panel regression by selecting the best model from four models, namely the spatial autoregressive model (SAR), the spatial error model (SEM), the spatial Durbin model (SDM), and spatial autoregressive combined (SAC) model. The research results show that there is spatial interaction between coastal areas through endogenous and exogenous interactions between independent variables. Based on the selection of the best model, the spatial Durbin model (SDM) was selected for the Pantura Region. Economic growth has a negative effect on poverty. Education has a negative effect on poverty. Unemployment has no effect on poverty. Natural resources have a positive effect on poverty. Health has no effect. Accessibility has a negative effect on poverty in the Pantura Region. This research provides a new and important contribution in understanding the spatial patterns of poverty and the factors that influence it in the Pantura Region, which is a strategic and vulnerable area in East Java. This research also faces several limitations and challenges, such as data quality, model assumptions, and spatial validity. Future research could expand this analysis using more complete data, more flexible models, and more sophisticated techniques.

Evaluation of synbiotic combinations of commercial probiotic strains with different prebiotics in in vitro and ex vivo human gut microcosm model.

Exploring probiotics for their crosstalk with the host microbiome through the fermentation of non-digestible dietary fibers (prebiotics) for their potential metabolic end-products, particularly short-chain fatty acids (SCFAs), is important for understanding the endogenous host-gut microbe interaction. This study was aimed at a systematic comparison of commercially available probiotics to understand their synergistic role with specific prebiotics in SCFAs production both in vitro and in the ex vivo gut microcosm model. Probiotic strains isolated from pharmacy products including Lactobacillus sporogenes (strain not labeled), Lactobacillus rhamnosus GG (ATCC53103), Streptococcus faecalis (T-110 JPC), Bacillus mesentericus (TO-AJPC), Bacillus clausii (SIN) and Saccharomyces boulardii (CNCM I-745) were assessed for their probiotic traits including survival, antibiotic susceptibility, and antibacterial activity against pathogenic strains. Our results showed that the microorganisms under study had strain-specific abilities to persist in human gastrointestinal conditions and varied anti-infective efficacy and antibiotic susceptibility. The probiotic strains displayed variation in the utilization of six different prebiotic substrates for their growth under aerobic and anaerobic conditions. Their prebiotic scores (PS) revealed which were the most suitable prebiotic carbohydrates for the growth of each strain and suggested xylooligosaccharide (XOS) was the poorest utilized among all. HPLC analysis revealed a versatile pattern of SCFAs produced as end-products of prebiotic fermentation by the strains which was influenced by growth conditions. Selected synbiotic (prebiotic and probiotic) combinations showing high PS and high total SCFAs production were tested in an ex vivo human gut microcosm model. Interestingly, significantly higher butyrate and propionate production was found only when synbiotics were applied as against when individual probiotic or prebiotics were applied alone. qRT-PCR analysis with specific primers showed that there was a significant increase in the abundance of lactobacilli and bifidobacteria with synbiotic blends compared to pre-, or probiotics alone. In conclusion, this work presents findings to suggest prebiotic combinations with different well-established probiotic strains that may be useful for developing effective synbiotic blends.

Subtle Structural Differences Affect the Inhibitory Potency of RGD-Containing Cyclic Peptide Inhibitors Targeting SPSB Proteins.

The SPRY domain-containing SOCS box proteins SPSB1, SPSB2, and SPSB4 utilize their SPRY/B30.2 domain to interact with a short region in the N-terminus of inducible nitric oxide synthase (iNOS), and recruit an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in the proteasomal degradation of iNOS. Inhibitors that can disrupt the endogenous SPSB-iNOS interactions could be used to augment cellular NO production, and may have antimicrobial and anticancer activities. We previously reported the rational design of a cyclic peptide inhibitor, cR8, cyclo(RGDINNNV), which bound to SPSB2 with moderate affinity. We, therefore, sought to develop SPSB inhibitors with higher affinity. Here, we show that cyclic peptides cR7, cyclo(RGDINNN), and cR9, cyclo(RGDINNNVE), have ~6.5-fold and ~2-fold, respectively, higher SPSB2-bindng affinities than cR8. We determined high-resolution crystal structures of the SPSB2-cR7 and SPSB2-cR9 complexes, which enabled a good understanding of the structure-activity relationships for these cyclic peptide inhibitors. Moreover, we show that these cyclic peptides displace full-length iNOS from SPSB2, SPSB1, and SPSB4, and that their inhibitory potencies correlate well with their SPSB2-binding affinities. The strongest inhibition was observed for cR7 against all three iNOS-binding SPSB proteins.

Political uncertainty and macro-financial dynamics in the BRICS

We empirically study the impact of political uncertainty on macro-financial variables (stock prices, inflation, consumption) and behavioral dynamics (consumer confidence, anxiety) in the BRICS over the period 1990–2022. To this end, we applied a panel vector autoregressive (PVAR) model that tests further endogenous interactions between the variables in the model. Accordingly, we find that political uncertainty increases inflation while reducing consumer spending and stock prices. In addition, we find that consumer confidence and investor anxiety are negatively affected by political uncertainty. Our results have different implications, especially for policymakers who have to tackle political uncertainty in order to protect householders and investors more effectively.

Endogenous Protein-Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex.

NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein-protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics. The current study investigated protein-protein interactions specific to the wild-type and the most prevalent NPC1 mutation (NPC1I1061T) while filtering out any protein interactor identified in the Npc1-/- mouse model. Additionally, the results were matched across the two species to map the parallel interactome of wild-type and mutant NPC1I1061T. Most of the identified wild-type NPC1 interactors were related to cytoskeleton organization, synaptic vesicle activity, and translation. We found many putative NPC1 interactors not previously reported, including two SCAR/WAVE complex proteins that regulate ARP 2/3 complex actin nucleation and multiple membrane proteins important for neuronal activity at synapse. Moreover, we identified proteins important in trafficking specific to wild-type and mutant NPC1I1061T. Together, the findings are essential for a comprehensive understanding of NPC1 biological functions in addition to its classical role in sterol efflux.

Abstract 487: Peptide amphiphiles hitchhike on endogenous biomolecules for enhanced drug delivery

Abstract Peptide amphiphiles (PAs) have been applied as building blocks for self-assembled nanostructures with various morphologies. These self-assembled nanostructures are promising drug delivery platforms as they are naturally biodegradable and biocompatible with low immunogenicity. One primary focus in drug delivery using the PA nanostructures has been to develop strongly assembled structures to avoid disassembly in the blood and allow them to carry payloads to their intended targets. In this work, rather than developing stable self-assembled PA structures, we focused on weakly assembled PA nanostructures to investigate their interactions with blood components and to understand how these interactions affect their biodistribution. We found that weakly assembled PA nanostructures (SA-E) quickly disassembled in plasma and reassembled with lipoproteins (LPs), which significantly prolonged the blood circulation of SA-E in mice. We showed that SA-E crossed the endothelial barriers through transcytosis only when they were assembled with LPs. Cellular uptake studies showed that SA-E accumulated in cancer cells through lipid-raft-mediated uptake. Interestingly, their cellular internalization was independent of LP receptors, suggesting that SA-E assembles with different endogenous biomolecules in vivo. By exploiting these endogenous interactions, SA-E demonstrated high tumor accumulation in a myriad of small animal tumor models of breast, colon, pancreatic, brain, skin, prostate, or lung cancers. SA-E demonstrated large tumor-to-background signal ratios in live animals (>5), extended retention (>2 weeks), and excellent tissue distribution (tumor to liver signal >3) in these tumor models. Encouraged by the excellent tumor accumulation of SA-E, we prepared SA-E drug conjugate using a highly potent and toxic chemotherapeutic agent, Monomethyl auristatin E (MMAE). SA-E-MMAE conjugate demonstrated strong antitumor efficacy in aggressive breast and glioma models in mice with reduced side effects. With its simple and modular design and universal tumor accumulation mechanism, SA-E represents a promising platform for broad applications in cancer therapy. Citation Format: Jared M. Fischer, Morgan Stewart, Mingchong Dai, Samuel Drennan, Sinan Sabuncu, Benjamin Kingston, Isabel Dengos, Li Xiang, Karla Bonic, Xin Yi, Srivathsan Ranganathan, Bruce Branchaud, Adem Yildirim. Peptide amphiphiles hitchhike on endogenous biomolecules for enhanced drug delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 487.

Unleashing digital empowerment: Pioneering low-carbon development through the broadband China strategy

Low-carbon development has emerged as an imperative in the pursuit of carbon peak and neutrality. To this end, the intersection of digital empowerment and the quest for innovative solutions in developing countries has taken center stage, particularly in exploring the network infrastructure construction potential. This research delves into the intricate relationship between network infrastructure construction expansion and low-carbon development in developing countries, drawing insights from a comprehensive analysis of panel data collected from 282 Chinese cities. Leveraging the quasi-natural experiment presented by “Broadband China” and employing a rigorous multi-period difference-in-difference (DID) model, our study uncovers significant findings. First, it reveals that the expansion of the network infrastructure construction directly amplifies the prospects of low-carbon development, a result consistently upheld through meticulous assessments of the multi-period DID approach and validation through the robust synthetic control DID method. Second, the study elucidates how network infrastructure construction expansion fosters low-carbon development by optimizing industrial structure and promoting investments in cutting-edge technologies. Third, it unveils the impact of network infrastructure construction expansion on the efficiency of low-carbon technology, concurrently encouraging its enhancement while imposing specific inhibitory effects. Remarkably, the policy outcomes exhibit variations among cities of differing sizes and between cities with old and non-old industrial bases. Finally, the research underscores the spatially endogenous interaction effects within low-carbon development. In sum, this study not only enriches comprehension of innovative avenues for low-carbon development within the sphere of digital empowerment but also provides empirical evidence to refine policy recommendations specifically tailored to the unique context of developing countries.

Gender- and Age-Group Specific Association of Persistent Organic Pollutants (POPs) Exposure with Diabetes Mellitus: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

Exposure to persistent organic pollutants (POPs) has been reported as a potential risk factor for diabetes in adults. However, effect modifications by sex and age, especially among Asian populations, have seldom been investigated. In the present study, we assessed associations of major POPs exposure including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), with diabetes in Korean adults (n = 1,295), a subset of the Korean National Environmental Health Survey (KoNEHS) Cycle 3 (2015-2017). In the adult population, serum levels of dichlorodiphenyltrichloroethanes (DDTs) and PCB167 showed an increased odds ratio (OR) for diabetes. When stratified by gender, associations became stronger and more consistent in women: In women, serum levels of OCPs including p,p'-DDT, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and ΣOCPs and mono-ortho PCBs, such as PCB118 and PCB157, were significantly associated with diabetes. In the male participants, however, no significant positive associations were detected. When stratified by a cutoff age of 50 years, most studied POPs except PBDEs, i.e., p,p'-DDT, p,p'-DDE, PCB118, PCB157, PCB167, PCB138, and PCB153, showed significant associations with diabetes, in the older adults. In the younger group, however, no measured POPs showed a significant positive association. Effects of endogenous sex hormones or interaction of POPs on aryl hydrocarbon receptors may partly explain the observed differences by gender and age, although further experimental confirmations should follow. Our findings show that POPs exposure at the current levels is associated with diabetes among general Korean adults, and such associations could be modified by gender and age.