Governing artificial intelligence has emerged as a policy challenge. However, scholarly understanding of the AI-policy interface remains fragmented. This study synthesizes 82 peer-reviewed articles through a systematic literature review and topic modeling. Five thematic clusters are identified, including algorithms, antitrust, and institutional trust; data rights, market power, and responsible deployment; national AI strategies; AI ethics and education; and AI, work, and society. A structured extraction framework maps governance levels, policy domains, regulatory instruments, and governance outcomes, showing how AI policy responses differ across contexts and outcomes. The study develops the AI-Policy Interface Model, examines policy implications, and suggests future research directions.
Post-war recovery requires investment incentives that are targeted, disciplined and transparent. We model the socially optimal subsidy as a function of a project’s investment volume and show that its curvature is inherited from the sector’s externality profile and additionality: concave for traditional sectors, linear for creative sectors, and convex (capped) for socio-ecological sectors. Evidence from Ukraine’s thirty largest investment projects (2015–2025) shows that real projects cluster into these three archetypes. A portfolio simulation shows that, for the same fiscal budget, differentiated schedules mobilise about 27 % more induced investment than a flat subsidy by concentrating support where additionality is highest.
This paper provides an ex-ante evaluation of Korea’s Yellow Envelope Law using a reduced-form segmented labor market Diamond–Mortensen–Pissarides (DMP) framework calibrated to recent Korean data. The analysis explicitly accounts for the country’s pronounced labor market duality between large firms and small and medium-sized enterprises (SMEs).The reform is modeled through simultaneous increases in vacancy posting costs, worker bargaining power, and separation rates, together with a modest decline in matching efficiency. Stronger effects are assumed for the small-firm sector. Under the benchmark Moderate scenario, simulations indicate that the law may weaken overall labor market tightness and raise unemployment, with disproportionately adverse effects on SMEs.Although the reform aims to strengthen worker protections and collective bargaining rights, the results also point to clear trade-offs with job creation. Under the welfare measure used in this study, social welfare declines in every simulated scenario. We therefore treat the findings strictly as scenario-based stress tests, not as point predictions. Policies that ease the burden on SMEs, particularly short-term hiring support and simpler compliance procedures, will likely be needed if the law is to protect workers without unduly weakening employment incentives.
This study builds an economic model to investigate how key oil market participants, specifically OPEC and Rest of the World (ROW) producers, respond to energy and environmental policies designed to curb oil demand under the Net-Zero 2050 scenario. The model predicts a sustained decline in oil supply by 2050. Furthermore, it suggests that if oil demand remains inelastic and annual demand falls below 24 billion barrels, OPEC achieves a Nash equilibrium within a competitive market structure. Under these conditions, OPEC undergoes a major strategic pivot in 2043, ramping up its capacity utilization to 99 % (up from 49 % in 2042) to capture 42 % of the global market, driving prices down to $34.1 per barrel. These findings indicate that stringent climate targets may intensify competition among producers, creating downward price pressure that could strengthen the relative competitiveness of fossil fuels. Consequently, maintaining the effectiveness of renewable subsidies and feed-in tariffs will require significantly higher budget allocations, emphasizing the necessity of policies that explicitly constrain oil consumption or current policy amendments.
Deoxysphingolipids (dSLs) are atypical sphingolipids that accumulate in several pathological settings, yet their impact on hematologic malignancies is poorly understood. Here, we investigate the pathways and mechanisms of deoxysphinganine (dSA) cytotoxicity in lymphoma cells and its potential as a therapeutic agent. dSA exhibited markedly greater cytotoxicity than canonical sphingoid bases in lymphoma cell lines, yet induced only cytostatic effects in normal human T cells, indicating a therapeutically exploitable window. Inhibition of ceramide synthase blocked the generation of deoxy(dihydro)ceramides, prevented mitochondrial depolarization, caspase activation, ER stress, and DNA damage, establishing CerS-dependent deoxysphingolipids as essential mediators of dSA-induced death. Mechanistically, dSA engaged a mitochondrial apoptotic pathway, with DNA damage occurring downstream of mitochondrial permeabilization and caspase activation, while PERK-driven ER stress occurred in parallel and was dispensable for cytotoxicity. Subtype-specific engagement of ER stress and DNA damage further suggests that dSL signaling is shaped by lineage context. The differential sensitivity between malignant lymphoid cells and normal T cells, together with the central role of CerS-derived deoxy(dihydro)ceramides, highlights deoxysphingolipid metabolism as a druggable vulnerability in lymphoma. These findings support further exploration of dSA-based strategies and targeted modulation of dSL synthesis as a novel therapeutic avenue for non-solid hematologic malignancies.
Whether the fecal metabolome differs according to intensive low-density lipoprotein cholesterol (LDL-C) target achievement among statin-treated patients is unclear. In this cross-sectional study, 124 statin-treated adults with chronic disease were stratified by fasting LDL-C into a target-achieved group (< 70 mg/dL, n = 52) and a target-not-achieved group (≥ 70 mg/dL, n = 72). Stool samples were profiled by untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry, and multivariable models adjusted for age, sex, chronic kidney disease, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were used to identify metabolites independently associated with target achievement. Statin dose, treatment duration and glucose-lowering therapy were also compared between the groups. Paired 16S rRNA gene sequencing data available for a subset (n = 86) were used for integrative correlation and network analyses. Partial least-squares discriminant analysis showed separation between the two groups. Eight annotated metabolites-glutamine, glutamate, phenylalanine, N-acetyl-L-phenylalanine, L-methionine, N-acetyl-L-methionine, lysine, and N-methyl-D-aspartic acid, predominantly amino acids and their derivatives-were present at lower fecal levels in participants who achieved the LDL-C target. Metabolite set enrichment analysis implicated amino acid and nitrogen metabolism, and multiomics network analysis identified an Anaerotruncus-centered amino acid module with high degree centrality. In conclusion, LDL-C target achievement under statin therapy was associated with a coherent "low fecal amino acid" signature and an Anaerotruncus-linked microbe-metabolite hub. These findings suggest that intestinal nutrient handling and gut microbial amino acid metabolism may contribute to variability in LDL-C response, and they warrant prospective mechanistic evaluation.
Metabolic dysfunction-associated liver disease (MASLD) arises from the accumulation of triglycerides within the liver. MASLD can advance to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma. Monoacylglycerol acyltransferase 2 (MOGAT2) is essential for triglyceride synthesis and plays a significant role in regulating lipid metabolism. Here, we demonstrate the ability of a new human MOGAT 2 inhibitor, VB-85387, to inhibit the development of MASLD/MASH and further define its effects on the key metabolic pathways that progress MASH development. MASLD/MASH was induced using a methionine, choline-deficient diet (LMCD) or by streptozotocin treatment combined with high fat diet feeding (STAM-HFD). VB-85387 significantly mitigated the severity of MASLD and reduced signs of MASH in mice subjected to these two distinct diets. VB-85387-treated mice exhibited decreased fibrosis, evidenced by reduced hepatic triglyceride concentrations, hydroxyproline levels, and collagen deposition. NAS scores were consistently lower in VB-85387-treated mice across both models. VB-85387-treated mice showed induced PPARα signaling and reduced SREBP transcription, demonstrating a likely role for VB-85387 in regulating lipogenesis and fatty acid β-oxidation. STAM-HFD treated mice showed lower NF-κBp65 activation, which was associated with lower TNFα expression. IL-1β and IFNβ levels were also both reduced, suggesting VB-85387 can reduce pro-inflammatory pattern recognition receptor signaling. In addition, treatment suppressed IL-4/IL-6-dependent JAK activation. Overall, VB-85387 inhibited MASLD development by reducing liver triglyceride levels, fibrosis, and meta-inflammatory signaling. VB-85387 was as effective or superior to the MOGAT2 inhibitor phase I clinical trial drug BMS-963272 in reducing MASLD and fibrosis. VB-85387 has considerable potential for developing therapeutics targeting MASLD/MASH.
Glioma represents one of the most aggressive tumors in the central nervous system, with clinical management facing significant challenges including high recurrence rates and therapeutic resistance. Ferroptosis, an iron-dependent form of cell death, holds potential for glioma treatment, yet tumor cells frequently develop evasion mechanisms. This study elucidates the molecular mechanisms by which hypoxic microenvironment confers ferroptosis resistance in glioma cells, focusing on the pivotal role of the HIF-1α/SREBP1 signaling axis and its downstream effectors FASN and SCD1. Our experimental results demonstrate that hypoxic conditions significantly upregulate HIF-1α expression and confer resistance to RSL3-induced ferroptosis. Mechanistic studies reveal that HIF-1α promotes SREBP1 activation, which subsequently upregulates FASN and SCD1 expression to suppress lipid peroxidation.Furthermore, the HIF-1α-specific inhibitor PX-478 effectively reverses hypoxia-induced ferroptosis resistance and significantly enhances tumor cell sensitivity to ferroptosis inducers. In vivo experiments confirm the potent antitumor effects of PX-478 combined with RSL3. This study systematically elucidates the role of the HIF-1α-SREBP1-FASN/SCD1 signaling axis in ferroptosis regulation in glioma, providing important theoretical foundations and experimental support for developing HIF-1α-targeted ferroptosis therapies.
BACKGROUND:Lipoprotein(a) [Lp(a)] reflects inherited atherothrombotic risk, whereas the C-reactive protein-triglyceride-glucose index (CTI) integrates systemic inflammation, triglyceride-related lipid disturbance, and glucose-related metabolic stress. Their individual and joint association with angiographic coronary lesion burden in acute coronary syndrome (ACS) remain incompletely defined. We examined whether CTI complements Lp(a) in characterizing coronary lesion burden in ACS. MATERIALS AND METHODS:This retrospective, single-center study included 2,836 consecutive patients with ACS who underwent coronary angiography. Coronary lesion burden was assessed using continuous Gensini score, a high Gensini score, and multivessel disease (MVD). Multivariable regression, restricted cubic spline analyses, CTI-stratified analyses, incremental receiver operating characteristic analyses, and internally validated machine-learning analyses with SHAP interpretation were performed. RESULTS:Higher Lp(a) and CTI level were both associated with greater coronary lesion burden. Compared with Lp(a) <75 nmol/L, Lp(a) ≥175 nmol/L was associated with high Gensini score (OR, 1.51 [95% CI, 1.17-1.96]) and MVD (OR, 1.69 [95% CI, 1.27-2.26]). Each 1-SD increase in CTI was associated with high Gensini score (OR, 1.47 [95% CI, 1.35-1.60]) and MVD (OR, 1.18 [95% CI, 1.08-1.28]). Among inflammatory-lipid indices, CTI showed the most consistent associations and provided the largest numerical incremental discrimination beyond Lp(a). The associaton between ver high Lp(a) and coronary lesion burden was more pronounced at higher CTI levels, particular for MVD. Machine-learning analyses further supported the relevance of both CTI and Lp(a). CONCLUSIONS:In patients with ACS, higher Lp(a) and CTI level were associated with greater angiographic coronary lesion burden. CTI may complement Lp(a) by capturing inflammatory-metabolic status, supporting their joint assessment for more refined characterization of lesion-burden risk in ACS.
Lipoprotein metabolism is significantly different between mice and humans thus making it difficult to model disorders of human lipid metabolism in transgenic mice. Systemic lipoprotein metabolism is predominantly governed by hepatocytes, and mice with humanized livers display human-like lipid profiles. Here we report a highly efficient method to knock out genes in human hepatocytes while retaining their ability to repopulate immune deficient rodents. As proof-of-principle Fah deficient, immune compromised mice were repopulated with Apolipoprotein B (APOB) knockout human hepatocytes. Mice humanized with knockout cells recapitulated typical features of human hypobetalipoproteinemia. We conclude that at least some human lipid metabolism disorders can be modeled in liver chimeric mice using human knockout hepatocytes.
This paper analyses the development of micro-entrepreneurship in India through the Common Services Centres initiative under the policy-driven Digital India programme. Using Sen’s capability approach, it evaluates how this policy bridges the digital divide, creates entrepreneurial opportunities for the poor, and advances women’s empowerment. Primary data from urban districts in Karnataka are analysed using two-period panel regressions to assess the roles of inputs, conversion factors, and agency in enterprise performance. Findings show that women have strengthened their capabilities and agency over time, achieving higher returns to scale than men. The study offers policy lessons for India and other developing countries to enhance women’s effective participation.
This paper evaluates a constant stepwise rule (CSR) for monetary policy, under which the policy rate rises in fixed increments until rate targets begin to fall. Using a calibrated three-equation, backward-looking New Keynesian model with adaptive expectations, we compare the CSR to standard and smoothed Taylor rules across 540 inflation–growth conditions, scoring performance by the RMSE of inflation and output-growth gaps. The CSR delivers lower losses when inflation is elevated and growth is weak, avoiding the contractionary shocks of front-loaded tightening; Taylor rules dominate in overheating regimes. The CSR requires no estimate of the natural rate, reducing model-misspecification sensitivity.
This paper examines the impact of public debt on economic growth, emphasizing the role of governance quality in OECD countries over the period 2007–2024. Using panel threshold models and dynamic estimators, the study identifies significant nonlinearities and declining debt thresholds, particularly in the post-pandemic period. The results show that high debt levels negatively affect growth, while moderate levels have limited impact. Governance factors, especially regulatory quality, influence the debt–growth relationship by mitigating adverse effects. The findings highlight the importance of sustainable debt management, efficient public spending, and strong institutions in supporting long-term economic growth in an increasingly uncertain global environment.
Menstrual health and hygiene are essential in the life of women and remains a significant public health challenge in India. Identification of population groups that require targeted policy interventions, remains limited. In this study, data is taken from the National Family Health Survey- V to examine the socioeconomic and informational factors associated with the use of hygienic menstrual practices among women aged 15–49 years. A logistic regression model is employed. Results shows that women with media exposure have 65 per cent higher odds of adopting hygienic practices than those women with no media exposure. The results also highlight the need for targeted support and interventions through awareness campaigns and menstrual health programmes. Such interventions may prioritise disadvantaged populations to promote more equitable access to hygienic menstrual practices.
In this paper, we shed new light on the intended destabilizing effect of sanctions in the target country. A prevailing assumption in international political economy, based on studies of non-hyperinflationary periods, suggests that sanctions contribute to inflationary pressures. Contrary to this view, our empirical results find no evidence of such an effect during the hyperinflation in Venezuela. While higher sanction intensity is associated with a short run deceleration in money growth, we find also no evidence of a lasting contraction in the regime’s financing capacity. Although the complexities of sanctions’ impact are not well-understood, our findings call into question the effectiveness of sanctions. Nevertheless, relying on monthly and weekly time series the well-known money supply-price level nexus also holds for the Venezuelan hyperinflation.
High-altitude polycythemia (HAPC) remains prevalent among Tibetans despite genetic adaptations, including EPAS1/HIF2A. Excessive erythrocytosis elevates blood viscosity and increases cardiopulmonary risk, yet erythrocyte metabolic and membrane-lipid mechanisms of HAPC and of therapeutic erythrocytapheresis (TE) remain incompletely defined. We conducted integrated metabolomic and lipidomic profiling of washed erythrocytes from HAPC patients and non-HAPC (NHAPC), and from patients with HAPC after TE. Relative to NHAPC, HAPC showed coordinated erythrocyte remodeling spanning amino acid and purine metabolism together with membrane phospholipid and lipid structure (unsaturation and chain length) changes. The disease contrast was multiomic, whereas the acute post-TE contrast was lipid-dominant, consistent with apheresis acting primarily through erythrocyte removal. K-means stratification revealed clinically meaningful TE response heterogeneity, but erythrocyte omics did not define stable responder subtypes. These findings point to erythrocyte membrane lipids as a persistent molecular feature of HAPC and of the acute TE response.
Clinically, acute kidney injury (AKI) is one of the most frequent complications of Naja atra (N. atra) envenomation, primarily attributed to snake venom phospholipase A2 (SVPLA2). Although the SVPLA2 inhibitor varespladib shows great therapeutic promise, the underlying mechanisms remain incompletely understood. Herein, we integrated multi-omics and molecular biology approaches to investigate the critical role of SVPLA2 in N. atra venom-induced AKI as evidenced by pharmacological inhibition with varespladib. Proteomic profiling identified HRAS and CCND1 as key mediators of SVPLA2-induced nephrotoxicity. Mechanistically, SVPLA2 disrupts lipid raft integrity, impairing HRAS palmitoylation-dependent plasma membrane localization and GTPase activity. This defect suppresses phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, causing apoptosis and cell cycle arrest in renal tubular epithelial cells, enforced activation of PI3K-AKT signaling effectively rescued cells from injury. Beyond direct cytotoxicity, SVPLA2 profoundly remodels the renal immune microenvironment. SVPLA2 enhances glycolysis by upregulating hexokinase 2 (HK2) while suppressing fatty acid oxidation through downregulation of carnitine palmitoyltransferase IA, thereby metabolically driving M1 polarization. This metabolic shift impairs macrophage efferocytosis and sustains inflammatory injury. HK2 knockdown reverses these effects in macrophages. Taken together, this study reveals a dual epithelial-immune mechanism by which SVPLA2 activity critically contributes to N. atra venom-induced AKI, as evidenced by pharmacological inhibition with varespladib. These findings highlight PI3K-AKT signaling and HK2 as potential therapeutic targets for N. atra-triggered AKI.
Pancreatic lipase is the major enzyme responsible for breaking down dietary triglycerides in the intestines. A previous report suggested that intestinal angiopoietin-like 4 (ANGPTL4) might serve as an endogenous inhibitor of pancreatic lipase and thus regulate fat absorption. As ANGPTL4 expression is reportedly induced by high-fat-diet feeding, we hypothesized that induction of ANGPTL4 by a high-fat diet would lead to an increased inhibition of pancreatic lipase, less breakdown of dietary triglycerides, and ultimately a reduced rate of postprandial triglyceride absorption. To test this hypothesis, we generated intestinal epithelial cell-specific ANGPTL4 knockout mice, fed them diets with varying levels of fat, and measured postprandial triglyceride absorption and intestinal triglyceride lipase activity. As we hypothesized, we found that chronic high-fat feeding reduced the rate of postprandial triglyceride absorption in mice. However, this regulation of postprandial triglyceride absorption appeared to be largely independent of ANGPTL4, as similar decreases were observed in both wild-type and intestinal epithelial cell-specific ANGPTL4 knockout mice. We conclude that there is mechanism by which chronic high-fat feeding reduces the rate of secretion of dietary triglycerides into the circulation, but that this mechanism does not require intestinal ANGPTL4.
