Thrombin is increased in diabetic retinal pathology in the STZ mice model, and its attenuation by a specific inhibitor, PARIN5, is associated with preserved function.

Sweetness is among the earliest gustatory qualities perceived by humans. During lactation, infants are exposed to sweet taste through lactose, the principal sugar in human milk (~6–7%), which may help shape early sweet preference. During childhood, consumption of energy-dense foods helps meet the high energetic demands of growth, and the reward value of sweetness further reinforces such ingestive behavior. Sweet taste not only underpins palatability, but also activates brain reward circuits, eliciting pleasurable responses that promote continued consumption of sweet foods. Carbohydrates are a fundamental energy source in the human diet and serve as the primary metabolic fuel for blood and tissues. Although glucose (Glu) and fructose (Fru) share the same chemical formula (C₆H₁₂O₆) and gross energy content (≈400 kcal/100 g), they differ markedly in perceived sweetness, glycemic index, satiety effects, and in absorption and metabolic pathways. Sucrose (Suc), a disaccharide composed of Glu and Fru, is a principal dietary source of Fru alongside high-Fru corn sirup (HFCS), honey, whole fruit, and fruit juices. In whole foods, sugars are typically embedded within a matrix of dietary fiber, vitamins, and minerals and are released more slowly; even diets high in fruits and vegetables rarely contribute fructose energy exceeding ~5% of total intake. Consequently, moderate consumption of sugars within intact food matrices is generally not associated with adverse health outcomes in otherwise healthy adults. By contrast, structural changes in modern food systems have substantially increased the intake of free sugars. Sugar-sweetened beverages (SSB), i.e., beverages to which caloric sweeteners such as HFCS (≈55% Fru, 42% Glu) or fruit juice concentrates have been added, have become major contributors to population-level free sugar intake. Global SSB consumption has risen rapidly over the past three decades, increasing by >40% between 1990 and 2016. In the United States, roughly 6.5% of adult energy intake (≈145 kcal/day) is derived from SSB, exceeding recommended limits from national dietary guidelines and the World Health Organization‌ (WHO). In China, about 50% of adults consume SSB; per-capita SSB consumption reached 119 kg in 2014 (~300 mL/day), nearly a tenfold increase relative to a decade earlier, and the prevalence of SSB consumption among children rose from 7.8% to 18.9%. The mean sugar concentration of SSB is ~10.7 g/100 mL; a single 500-mL bottle thus commonly exceeds the WHO recommended daily limit for free sugars (50 g). Rapid absorption of free sugars from SSB can provoke large postprandial glycemic excursions and increase metabolic burden. A large body of evidence links chronic high SSB intake to increased risks of obesity, type 2 diabetes (T2DM), cardiovascular disease (CVD), and nonalcoholic fatty liver disease (NAFLD). The population health burden attributable to SSB consumption has risen concomitantly. In 2020, approximately 2.2 million new cases of T2DM and 1.2 million new cases of CVD were attributed to SSB consumption worldwide, accounting for 9.8% and 3.1% of all cases, respectively. SSB were responsible for 12.5 million disability-adjusted life years. Of additional concern, higher SSB intake has been associated with adverse mental-health correlates, including depressive and anxiety symptoms and increased suicidal ideation among adolescents, indicating potential impacts on psychological well-being. As mechanistic and epidemiological evidence of SSB-associated harms has accumulated, reducing free sugar content in the food supply has emerged as a priority for public health agencies, the food industry, and consumers. In recent years, the WHO and many national authorities have issued policy recommendations and implemented interventions, such as sugar taxation, front-of-pack nutrition labeling, and marketing restrictions, aiming at reducing population sugar consumption. From a food-science perspective, however, consumer dependence on the characteristic flavor and hedonic texture of sweetened beverages makes sugar reduction a multidimensional challenge that spans sensory science and formulation engineering. Research and industry practice are therefore shifting from single-axis sugar replacement toward integrated, “smart” sugar-reduction technologies that combine precision use of non-caloric and low-caloric sweeteners, food-structure optimization, and multisensory enhancement to realize “less sugar, same sweetness” product profiles.