N-lactoyl-phenylalanine (Lac-Phe), an exercise-induced metabolite that suppresses appetite, has quickly emerged as a key molecule in metabolic signaling networks. Lac-Phe, following its CNDP2-mediated synthesis, mediates key appetite- and weight-modulating effects of metformin, which acts primarily by mitochondrial inhibition in gut epithelial cells. Both Lac-Phe and related N-lactoyl-amino acids serve as potent biomarkers of mitochondrial dysfunction. Elevated levels of these metabolites are found in genetic mitochondrial diseases, offering potentially superior prognostic value compared to lactate in conditions alike. Despite uncertainties regarding its specific receptor(s) and signaling mechanisms, the expanding roles of Lac-Phe underscore its critical position at the intersection of exercise physiology, pharmacology, energy metabolism, and disease pathology, suggesting significant potential for future diagnostics and therapeutics in mitochondrial and metabolic disorders.

Recent studies showed ferritin increase and hemoglobin decrease to COVID‐19 severity and sepsis mortality. However, the potential relationship between iron metabolism disorders and susceptibility to pneumonia remains unclear. This study explores the association between iron metabolism disorder and susceptibility to bacterial pneumonia, viral pneumonia, and sepsis. GWAS data from the FinnGen and UK biobank is used for a two‐sample Mendelian randomization (MR) analysis, followed by MR meta‐analysis. Low serum iron levels were negatively associated with the risk of bacterial pneumonia (OR, 0.85; p = 0.04), influenza pneumonia (OR, 0.86; p = 0.03), and sepsis (OR, 0.81; p = 0.0004). Increased transferrin saturation and decreased total iron‐binding capacity were linked to higher risks of bacterial pneumonia and sepsis. Elevated liver iron content correlated positively with susceptibility to bacterial pneumonia (OR, 1.11; p = 0.007), influenza pneumonia (OR, 1.08; p = 0.03), and sepsis (OR, 1.13; p = 0.0007), but negatively with pneumococcal pneumonia (OR, 37.62; p = 0.0013). Neutrophils mediated the impact of serum iron and transferrin saturation on susceptibility to bacterial pneumonia and sepsis. This MR study confirms that disruptions in iron metabolism, including low serum iron levels and elevated liver iron content, increase susceptibility to bacterial and viral pneumonia as well as sepsis by affecting neutrophil function and cytokine levels. The findings emphasize the need for monitoring iron metabolism indicators in high‐risk populations and provide valuable insights for further mechanistic research and clinical intervention.

The spectre of ‘Disease X,’1 a pathogen currently unknown but with the potential to cause a serious international epidemic, has shifted from a hypothetical scenario to an acknowledged reality, urging a fundamental change in our approach to global health security and urban resilience.2 When outbreak data remain confined within discrete institutional silos, essential insights for tracking disease spread and optimising interventions are lost or delayed.3 In the USA, the absence of a national public health system and centralised leadership forced state, local, tribal and territorial health departments to operate in isolated silos, resulting in critical gaps in COVID-19 data tracking, ineffective guidance development and a torrent of falsehoods.4 While past decades have seen us react to specific named threats like SARS, MERS, Ebola, and most recently COVID-19, the core challenge lies in preparing for an undefined future, demanding not just reactive countermeasures but proactive, networked and deeply integrated systems.5 This requires moving beyond traditional, siloed approaches to embrace innovative strategies that acknowledge the hyperconnected and complex nature of our modern world.

We evaluated the reading characteristics of normal-sighted young adults using C-Read to provide baseline healthy population values. We also investigated the relationship between the National Eye Institute’s Visual Functioning Questionnaire (VFQ-25) score and reading ability, myopia, and hours of screen use, focusing on the extent to which these factors affect participants’ visual function and, ultimately, their vision-related quality of life (QoL). Overall, 207 young, healthy participants (414 eyes) aged 18–35 years were tested for reading speed using C-Read connected to a smartphone-based application between December 2022 and January 2023. Each participant received a VFQ-25 questionnaire to evaluate vision-related QoL. Data on daily e-screen usage hours were collected. Among the participants, 91 (44.0%) were women; their mean (SD) age was 22.45 (4.01) years. The mean (SD) reading acuity (RA) was 0.242 (0.124), 0.249 (0.120), and 0.193 (0.104) logarithmic minimum angle of resolution (logMAR) for the right, left, and both eyes, respectively. The mean (SD) maximum reading speed (MRS) was 171.65 (46.27), 168.59 (45.68), and 185.16 (44.93) words per minute (wpm) with the right, left, and both eyes, respectively. The mean (SD) critical print size (CPS) was 0.412 (0.647), 0.371 (0.229), and 0.419 (1.05) logMAR per the right, left, and both eyes, respectively. The RA and CPS were significantly different between sexes (p = 0.002 and p = 0.001). MRS was significantly different between the education level (p = 0.005) and myopia level groups (p = 0.010); however, it was not clear whether this difference was confounded by age. The myopic power in diopters significantly affected RA (coefficient, −0.012; 95% CI, −0.018 to −0.006; p = 0.001); screen time significantly affected MRS (coefficient, 0.019; 95% CI, 0.57 to 6.33; p = 0.019). RA (coefficient, −21.41; 95% CI, −33.74 to −9.08; p = 0.001) and duration of screen use (coefficient, -0.86; 95% CI, −1.29 to −0.43; p < 0.001) independently had a significantly negative correlation with VFQ-25 scores. Our findings provide a baseline value for C-Read in normal-sighted young adults. Refractive status significantly affected RA, while screen time significantly affected MRS. Interventions aimed at enhancing RA may have the potential to maximize vision-related QoL and enable older adults with impaired vision to achieve greater outcomes. Future, larger-scale, C-Read experiments will help provide newer, more optimal methods for the early diagnosis of visual impairment.

Background/Objectives: Patients with type 2 diabetes face heightened risks of lower respiratory tract infections, but whether distinct glucose-lowering drug targets differentially alter pulmonary susceptibility remains unclear. We investigated how genetically proxied perturbations of major antidiabetic targets relate to respiratory infection and sepsis risks. Methods: Using two-sample drug-target Mendelian randomization, we examined genetic instruments proxying six antidiabetic pathways: insulin (INSR), sulfonylureas (KCNJ11/ABCC8), thiazolidinediones (PPARG), GLP-1 receptor agonists (GLP1R), SGLT2 inhibitors (SLC5A2), and metformin (GPD1, GPD2, PRKAG2). Associations were calibrated to standardized glycemic decrements and tested across 13 respiratory infection and sepsis GWAS outcomes. Analyses incorporated functional-variant comparisons, a type 2 diabetes positive control, and linkage disequilibrium adjustment. Results: Genetically proxied glucose lowering through PPARG showed consistent nominal associations with increased respiratory infection risk. Per 0.1 mmol/L lower glucose, the primary proxy and Pro12Ala functional variant were associated with higher odds of influenza and pneumonia (odds ratio [OR] 1.53, 95% CI 1.16–2.02, p = 0.003; and OR 1.53, 95% CI 1.13–2.06, p = 0.006) and other acute lower respiratory infections (OR 1.78, 95% CI 1.14–2.77, p = 0.011; and OR 1.87, 95% CI 1.16–3.01, p = 0.010). PPARG primary and functional proxies agreed in direction for 10/13 outcomes, whereas potassium-channel proxies agreed for only 3/13. Other targets showed distinct, heterogeneous patterns. Crucially, all signals were nominal and none survived false discovery rate correction (q ≥ 0.05). Conclusions: Genetically proxied glucose-lowering pathways exhibit divergent associations with respiratory infection susceptibility. While findings do not support class-wide causal risks, the repeated PPARG pattern highlights target-specific pulmonary immune mechanisms warranting functional and clinical investigation.