Inhibition of Ferroptosis Enables Safe Rewarming of HEK293 Cells following Cooling in University of Wisconsin Cold Storage Solution

The prolonged cooling of cells results in cell death, in which both apoptosis and ferroptosis have been implicated. Preservation solutions such as the University of Wisconsin Cold Storage Solution (UW) encompass approaches addressing both. The use of UW improves survival and thus extends preservation limits, yet it remains unclear how exactly organ preservation solutions exert their cold protection. Thus, we explored cooling effects on lipid peroxidation and adenosine triphosphate (ATP) levels and the actions of blockers of apoptosis and ferroptosis, and of compounds enhancing mitochondrial function. Cooling and rewarming experiments were performed in a cellular transplantation model using Human Embryonic Kidney (HEK) 293 cells. Cell viability was assessed by neutral red assay. Lipid peroxidation levels were measured by Western blot against 4-Hydroxy-Nonenal (4HNE) and the determination of Malondialdehyde (MDA). ATP was measured by luciferase assay. Cooling beyond 5 h in Dulbecco's Modified Eagle Medium (DMEM) induced complete cell death in HEK293, whereas cooling in UW preserved ~60% of the cells, with a gradual decline afterwards. Cooling-induced cell death was not precluded by inhibiting apoptosis. In contrast, the blocking of ferroptosis by Ferrostatin-1 or maintaining of mitochondrial function by the 6-chromanol SUL150 completely inhibited cell death both in DMEM- and UW-cooled cells. Cooling for 24 h in UW followed by rewarming for 15 min induced a ~50% increase in MDA, while concomitantly lowering ATP by &gt;90%. Treatment with SUL150 of cooled and rewarmed HEK293 effectively precluded the increase in MDA and preserved normal ATP in both DMEM- and UW-cooled cells. Likewise, treatment with Ferrostatin-1 blocked the MDA increase and preserved the ATP of rewarmed UW HEK293 cells. Cooling-induced HEK293 cell death from hypothermia and/or rewarming was caused by ferroptosis rather than apoptosis. UW slowed down ferroptosis during hypothermia, but lipid peroxidation and ATP depletion rapidly ensued upon rewarming, ultimately resulting in complete cell death. Treatment throughout UW cooling with small-molecule Ferrostatin-1 or the 6-chromanol SUL150 effectively prevented ferroptosis, maintained ATP, and limited lipid peroxidation in UW-cooled cells. Counteracting ferroptosis during cooling in UW-based preservation solutions may provide a simple method to improve graft survival following cold static cooling.</p

Effects of near-infrared light on well-being and health in human subjects with mild sleep-related complaints:A double-blind, randomized, placebo-controlled study

Modern urban human activities are largely restricted to the indoors, deprived of direct sunlight containing visible and near-infrared (NIR) wavelengths at high irradiance levels. Therapeutic exposure to doses of red and NIR, known as photobiomodulation (PBM), has been effective for a broad range of conditions. In a double-blind, randomized, placebo-controlled study, we aimed to assess the effects of a PBM home set-up on various aspects of well-being, health, sleep, and circadian rhythms in healthy human subjects with mild sleep complaints. The effects of three NIR light (850 nm) doses (1, 4, or 6.5 J·cm−2) were examined against the placebo. Exposure was presented five days per week between 9:30 am and 12:30 pm for four consecutive weeks. The study was conducted in both summer and winter to include seasonal variation. The results showed PBM treatment only at 6.5 J·cm−2 to have consistent positive benefits on well-being and health, specifically improving mood, reducing drowsiness, reducing IFN-γ, and resting heart rate. This was only observed in winter. No significant effects on sleep or circadian rhythms were noted. This study provides further evidence that adequate exposure to NIR, especially during low sunlight conditions, such as in the winter, can be beneficial for human health and wellness.</p

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

The Role of Body Mass Index, Insulin, and Adiponectin in the Relation Between Fat Distribution and Bone Mineral Density

Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio. Analyses were stratified by gender and median age (48.0 years in women and 49.2 years in men) and were performed with and without adjustment for BMI, fasting insulin, and adiponectin. Using linear regression (adjusting for age, height, smoking, and use of alcohol), most relationships between fat distribution and BMD and BMC were positive, except for WTR. After BMI adjustment, most correlations were negative except for trunk-to-leg fat ratio in both genders. No consistent influence of age or menopausal status was found. Insulin and adiponectin levels did not explain either positive or negative associations. In conclusion, positive associations between android fat distribution and BMD/BMC are explained by higher BMI but not by higher insulin and/or lower adiponectin levels. Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone

YAG:Ce 3+ Phosphor: From Micron-Sized Workhorse for General Lighting to a Bright Future on the Nanoscale

The renowned yellow phosphor yttrium aluminum garnet (YAG) doped with trivalent cerium has found its way into applications in many forms: as powder of micron sized crystals, as a ceramic, and even as a single crystal. However, additional technological advancement requires providing this material in new form factors, especially in terms of particle size. Where many materials have been developed on the nanoscale with excellent optical properties (e.g., semiconductor quantum dots, perovskite nanocrystals, and rare earth doped phosphors), it is surprising that the development of nanocrystalline YAG:Ce is not as mature as for these other materials. Control over size and shape is still in its infancy, and optical properties are not yet at the same level as other materials on the nanoscale, even though YAG:Ce microcrystalline materials exceed the performance of most other materials. This review highlights developments in synthesis methods and mechanisms and gives an overview of the state of the art morphologies, particle sizes, and optical properties of YAG:Ce on the nanoscale

Eu3+ Sensitization via Nonradiative Interparticle Energy Transfer Using Inorganic Nanoparticles

Phosphors have been used successfully for both research and commercial applications for decades. Eu3+-doped materials are especially promising, because of their extremely stable, efficient, and narrow red emission lines. Although these emission properties are ideal for lighting applications, weak absorption in the blue spectral range has until now prevented the use of Eu3+-based phosphors in applications based on blue light-emitting diodes. Here, we demonstrate a sensitization mechanism of Eu3+ based on interparticle Förster resonance energy transfer (IFRET) between lanthanide-doped inorganic nanocrystals (NCs). Compared to co-doping different lanthanides in the same host crystal, IFRET allows an independent choice of host lattices for Eu3+ and its sensitizer while potentially greatly reducing metal-to-metal charge transfer quenching. We demonstrate IFRET between NCs, resulting in red Eu3+ emission upon blue excitation at 485 nm using LaPO4:Tb/LaPO4:Eu and LaPO4:Tb/YVPO4:Eu NC mixtures. These findings pave the way toward engineering blue-sensitized line emitters for solid-state lighting applications

Saturation Mechanisms in Common LED Phosphors

Commercial lighting for ambient and display applications is mostly based on blue light-emitting diodes (LEDs) combined with phosphor materials that convert some of the blue light into green, yellow, orange, and red. Not many phosphor materials can offer stable output under high incident light intensities for thousands of operating hours. Even the most promising LED phosphors saturate in high-power applications, that is, they show decreased light output. The saturation behavior is often poorly understood. Here, we review three popular commercial LED phosphor materials, Y3Al5O12 doped with Ce3+, CaAlSiN3 doped with Eu2+, and K2SiF6 doped with Mn4+, and unravel their saturation mechanisms. Experiments with square-wave-modulated laser excitation reveal the dynamics of absorption and decay of the luminescent centers. By modeling these dynamics and linking them to the saturation of the phosphor output intensity, we distinguish saturation by ground-state depletion, thermal quenching, and ionization of the centers. We discuss the implications of each of these processes for LED applications. Understanding the saturation mechanisms of popular LED phosphors could lead to strategies to improve their performance and efficiency or guide the development of new materials

YAG:Ce 3+ Phosphor: From Micron-Sized Workhorse for General Lighting to a Bright Future on the Nanoscale

The renowned yellow phosphor yttrium aluminum garnet (YAG) doped with trivalent cerium has found its way into applications in many forms: as powder of micron sized crystals, as a ceramic, and even as a single crystal. However, additional technological advancement requires providing this material in new form factors, especially in terms of particle size. Where many materials have been developed on the nanoscale with excellent optical properties (e.g., semiconductor quantum dots, perovskite nanocrystals, and rare earth doped phosphors), it is surprising that the development of nanocrystalline YAG:Ce is not as mature as for these other materials. Control over size and shape is still in its infancy, and optical properties are not yet at the same level as other materials on the nanoscale, even though YAG:Ce microcrystalline materials exceed the performance of most other materials. This review highlights developments in synthesis methods and mechanisms and gives an overview of the state of the art morphologies, particle sizes, and optical properties of YAG:Ce on the nanoscale