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Investigative Ophthalmology & Visual... Jul 2024Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood...
PURPOSE
Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization.
METHODS
Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed.
RESULTS
Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss.
CONCLUSIONS
Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.
Topics: Animals; Mice; Disease Models, Animal; Oxygen; Retinal Neovascularization; Animals, Newborn; Retinopathy of Prematurity; Intravitreal Injections; Mice, Inbred C57BL; Membrane Glycoproteins; Hyperoxia; Vascular Endothelial Growth Factor A; Humans
PubMed: 38958972
DOI: 10.1167/iovs.65.8.10 -
Environmental Science & Technology Jul 2024Southern Hemisphere humpback whales accumulate persistent and toxic chemicals, which are transported to Antarctica through distant sources and usage. The extreme...
Southern Hemisphere humpback whales accumulate persistent and toxic chemicals, which are transported to Antarctica through distant sources and usage. The extreme seasonal migration-associated fast of humpback whales results in the remobilization of persistent and lipophilic environmental contaminants from liberated fat stores. Mitochondria play a key role in lipid metabolism, and any disruption to mitochondrial function is expected to influence whole-organism bioenergetics. It is therefore of interest to advance understanding of the impact of known contaminants of the Antarctic sea-ice ecosystem upon humpback whale cellular bioenergetics. Using cell line-based testing, this study employed the Seahorse Extracellular Flux Analyzer to study cellular metabolic activity in live humpback whale fibroblast cells. The assay, based on oxygen consumption rate, provides insights into the cause of cellular bioenergetic disruption. Immortalized skin fibroblasts were exposed to four priority environmental chemicals found in the Antarctic sea-ice ecosystem. Our findings reveal chemical-dependent functional alterations and varying bioenergetic profile responses. Chlorpyrifos was observed to decrease mitochondrial basal oxygen consumption; dieldrin increased basal oxygen consumption; trifluralin's impact was dose-specific, and endosulfan displayed no effect. Our results provide unique insights into environmental chemical mechanisms of action on cellular bioenergetics, generating much-needed taxa-specific chemical effect data in support of evidence-based conservation policy and management.
PubMed: 38958666
DOI: 10.1021/acs.est.3c10595 -
Small (Weinheim An Der Bergstrasse,... Jul 2024In P2-type layered oxide cathodes, Na site-regulation strategies are proposed to modulate the Na distribution and structural stability. However, their impact on the...
In P2-type layered oxide cathodes, Na site-regulation strategies are proposed to modulate the Na distribution and structural stability. However, their impact on the oxygen redox reactions remains poorly understood. Herein, the incorporation of K in the Na layer of NaNiCuMnO is successfully applied. The effects of partial substitution of Na with K on electrochemical properties, structural stability, and oxygen redox reactions have been extensively studied. Improved Na diffusion kinetics of the cathode is observed from galvanostatic intermittent titration technique (GITT) and rate performance. The valence states and local structural environment of the transition metals (TMs) are elucidated via operando synchrotron X-ray absorption spectroscopy (XAS). It is revealed that the TMO slabs tend to be strengthened by K-doping, which efficiently facilitates reversible local structural change. Operando X-ray diffraction (XRD) further confirms more reversible phase changes during the charge/discharge for the cathode after K-doping. Density functional theory (DFT) calculations suggest that oxygen redox reaction in NaKNiCuMnO cathode has been remarkably suppressed as the nonbonding O 2p states shift down in the energy. This is further corroborated experimentally by resonant inelastic X-ray scattering (RIXS) spectroscopy, ultimately proving the role of K incorporated in the Na layer.
PubMed: 38958092
DOI: 10.1002/smll.202402991 -
Resuscitation Plus Sep 2024An 18-year-old drowning victim was successfully resuscitated using prehospital veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite 24 min of submersion...
An 18-year-old drowning victim was successfully resuscitated using prehospital veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite 24 min of submersion in water with a surface temperature of 15 °C, the patient was cannulated on-scene and transported to a trauma center. After ICU admission on VA-ECMO, he was decannulated and extubated by day 5. He was transferred to a peripheral hospital on day 6 and discharged home after 3.5 weeks with favorable neurological outcome of a Cerebral Performance Categories (CPC) score of 1 out of 5. This case underscores the potential of prehospital ECMO in drowning cases within a well-equipped emergency response system.
PubMed: 38957704
DOI: 10.1016/j.resplu.2024.100685 -
Chemistry, An Asian Journal Jul 2024The introduction of phosphorous (P), and oxygen (O) heteroatoms in the natural honeydew chemical structure is one of the most effective, and practical approaches to...
The introduction of phosphorous (P), and oxygen (O) heteroatoms in the natural honeydew chemical structure is one of the most effective, and practical approaches to synthesizing activated carbon for possible high-performance energy storage applications. The performance metrics of supercapacitors depend on surface functional groups and high-surface-area electrodes that can play a dominant role in areas that require high-power applications. Here, we report a phosphorous and oxygen co-doped honeydew peel-derived activated carbon (HDP-AC) electrode with low surface area for supercapacitor via H3PO4 activation. This activator form phosphorylation with cellulose fibers in the HDP. The formation of heteroatoms stabilizes the cellulose structure by preventing the formation of levoglucosan (C6H10O5), a cellulose combustion product, which would otherwise offer a pathway for a substantial degradation of cellulose into volatile products. Therefore, heteroatom doping has proved effective, in improving the electrochemical properties. The improved performance is attributed to the high phosphorous doping with a hierarchical porous structure, which enables the transportation of ions at higher current rates. The high specific capacitance of 486, and 478 F/g at 0.6, and 1.3 A/g in 1M H2SO4 electrolyte with a prominent retention of 98% is observed for 2M H3PO4 having an impregnation ratio of 1:4.
PubMed: 38956831
DOI: 10.1002/asia.202400622 -
European Journal of Sport Science Jul 2024To investigate the effects of 8-week hiking bench training on cardiorespiratory and muscular responses of highly trained sailors during hiking emulation. Twenty-four...
To investigate the effects of 8-week hiking bench training on cardiorespiratory and muscular responses of highly trained sailors during hiking emulation. Twenty-four sailors were assigned into two groups: the hiking bench training group (HTG, n = 12) and the control group (CG, n = 12). Both groups maintained their regular training with the HTG performed two additional hiking bench training sessions per week for 8 weeks, while the CG performed an equivalent duration of on-water sailing training. Physiological responses were assessed by performing four successive 3-min hiking bouts on a sailing emulation ergometer before and after the 8-week training period. Comparing the pretest, both groups exhibited a significant decrease (p < 0.05) in the percentage of maximal oxygen uptake (%VOmax) and maximal heart rate (%HRmax); the HTG experienced a greater decrease in %VOmax in bouts 2 and 3. The root mean square (RMS) of rectus femoris (RF), vastus lateralis (VL), rectus abdominis (RA), and external oblique decreased significantly (p < 0.05), whereas the mean power frequency (MPF) of RF, VL, and RA exhibited an increasing trend. The RMS of RF and RA in HTG were lower than those in CG in the initial three bouts; VL and EA in HTG were lower than those in CG in bouts 1 and 2 (p < 0.05). The MPF of RA in HTG was significantly increased in bouts 2, 3, and 4 (p < 0.05). Eight-week hiking bench training could improve hiking economy and the activation of lower limb and trunk muscles delaying the onset of fatigue in sailors.
Topics: Humans; Water Sports; Oxygen Consumption; Heart Rate; Male; Young Adult; Ships; Adult; Physical Conditioning, Human; Muscle, Skeletal; Cardiorespiratory Fitness; Quadriceps Muscle
PubMed: 38956795
DOI: 10.1002/ejsc.12118 -
Military Medical Research Jul 2024
Topics: Humans; Blood Volume; Oxygen Consumption; Lung; Pulmonary Gas Exchange
PubMed: 38956634
DOI: 10.1186/s40779-024-00546-3 -
Environmental Management Jul 2024Despite significant advancements in ichthyoplankton collection and data processing, challenges persist in the taxonomic identification of these organisms, particularly...
Despite significant advancements in ichthyoplankton collection and data processing, challenges persist in the taxonomic identification of these organisms, particularly their eggs. To overcome these challenges, a novel technique has been developed to facilitate the identification of live eggs collected directly in wild. This user-friendly technique includes the collection, processing of the material, and field incubation. Sampling must be conducted using a pelagic net towed at low speed, preferably during early evening. The material processing involves pre-sorting and sorting to remove eggs and larvae. The separated eggs, kept in an aerated bowl, can be identified based on their morphological and meristic characteristics. Unidentified eggs can be placed in plastic bags with oxygen and incubated directly in the aquatic environment for 48-72 h. After this incubation period, the hatched larvae at the yolk-sac or preflexion stage, are identified to the lowest possible taxonomic level. Depending on the study's purpose, hatched larvae and field-collected larvae can be transported to research centers for further development, released back into the natural environment, or fixed to complete the collection. The application of this technique supports management and monitoring programs by identifying spawning areas through egg identification, forming broodstock, and replenishing threatened species, thereby enhancing scientific collections of ichthyoplankton. Additionally, it reduces mortality in ichthyoplankton techniques, including endangered species. Therefore, we believe that this novel taxonomic technique for identifying live ichthyoplankton represents a paradigm shift in the monitoring, management, and conservation of fish, as well as in ecological stewardship and advances in this area of research.
PubMed: 38955870
DOI: 10.1007/s00267-024-02010-3 -
Journal of the American Chemical Society Jul 2024The messenger RNA (mRNA) vaccines hold great significance in contagion prevention and cancer immunotherapy. However, safely and effectively harnessing innate immunity to...
The messenger RNA (mRNA) vaccines hold great significance in contagion prevention and cancer immunotherapy. However, safely and effectively harnessing innate immunity to stimulate robust and durable adaptive immune protection is crucial, yet challenging. In this study, we synthesized a library of stimuli-responsive bivalent ionizable lipids (srBiv iLPs) with smart molecular blocks responsive to esterase, HO, cytochrome P450, alkaline phosphatase, nitroreductase, or glutathione (GSH), aiming to leverage physiological cues to trigger fast lipid degradation, promote mRNA translation, and induce robust antitumor immunity via reactive oxygen species (ROS)-mediated boosting. After subcutaneous immunization, esterase-responsive vaccine (eBiv-mVac) was rapidly internalized and transported into the draining lymph nodes. It then underwent fast decaging and self-immolative degradation in esterase-rich antigen-presenting cells, releasing sufficient mRNA for antigen translation and massive reactive quinone methides to elevate ROS levels. This resulted in broad activation of innate immunity to boost T cell response, prompting a large number of primed antigen-specific CD8 T cells to circulate and infiltrate into tumors (>1000-fold versus unvaccinated control), thereby orchestrating innate and adaptive immunity to control tumor growth. Moreover, by further combining our vaccination strategy with immune checkpoint blockade, we demonstrated a synergism that significantly amplified the magnitude and function of antigen-specific CD8 T cells. This, in turn, caused potent systemic antitumor efficacy and prolonged survival with high complete response rate in xenograft and metastasis models. Overall, our generalized stimuli-responsive mRNA delivery platform promises a paradigm shift in the design of potent vaccines for cancer immunotherapy, as well as effective and precise carriers for gene editing, protein replacement, and cell engineering.
PubMed: 38955767
DOI: 10.1021/jacs.4c04331 -
Nursing in Critical Care Jul 2024Critical patients may experience various adverse events during transportation within hospitals. Therefore, quickly evaluating and classifying patients before...
BACKGROUND
Critical patients may experience various adverse events during transportation within hospitals. Therefore, quickly evaluating and classifying patients before transporting them from the emergency department and focusing on managing high-risk patients are critical. At present, no unified classification method exists; all the current approaches are subjective.
AIMS
To ensure transportation safety, we conducted a cluster analysis of critically ill patients transferred from the emergency department to the intensive care unit.
STUDY DESIGN
Single-centre cohort study. This study was conducted at a comprehensive first-class teaching hospital in Beijing. Convenience sampling and continuous enrolment were employed. We collected data from 1 January 2019, to 31 December 2021. All patients were transferred from the emergency department to the intensive care unit, and cluster analysis was conducted using five variables.
RESULTS
A total of 584 patients were grouped into three clusters. Cluster 1 (high systolic blood pressure group) included 208 (35.6%) patients. Cluster 2 (high heart rate and low blood oxygen group) included 55 (9.4%) patients. Cluster 3 (normal group) included the remaining 321 (55%) patients. The oxygen saturation levels of all the patients were lower after transport, and the proportion of adverse events (61.8%) was the highest in Cluster 2 (p < .05).
CONCLUSIONS
This study utilized data on five important vital signs from a cluster analysis to explore possible patient classifications and provide a reference for ensuring transportation safety.
RELEVANCE TO CLINICAL PRACTICE
Before transferring patients, we should classify them and implement targeted care. Changes in blood oxygen levels in all patients should be considered, with a focus on the occurrence of adverse events during transportation among patients with high heart rates and low blood oxygen levels.
PubMed: 38955501
DOI: 10.1111/nicc.13099