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Purpose: TRIMP and sRPE are both representative indicators of training load(TL), and the correlation between two has been widely demonstrated across various sports. The aim of this study was to investigate the reliability of sRPE-TRIMP correlation across different intensities/duration of training in cross-country skiing, and whether sRPE can serve as an validity supplement to TRIMP data in cases of lost heart rate data. Method: 10 athletes were used as the experimental objects. The intensity, duration and RPE of 273 different types of training sessions were collected, and statistical methods were used for data analysis. Results: 1. There was a significant correlation between sRPE and TRIMP (r = 0.68, p < 0.05), but the correlation differs among the LIT, MIT and HIT groups (r = 0.70, 0.46, r = 0.31, p < 0.05) 2. sRPE-TRIMP correlation among three different time duration in the LIT group (0-60 min, 60-120 min and 120-180 min), are all highly significant (r = 0.70, 0.67, 0.69, p < 0.05) and the LRsRPE-TRIMP of 3 duration have no significant differences (chow test, p > 0.05). 3. The difference in actual training duration between samples was the main reason for the difference in the application effect of sRPE, because the actual training duration ratio of LIT was 89.7 ± 16.4%; MIT, 98.5 ± 6.2%; and HIT, 94.4 ± 13.5%. Conclusion: 1. The linear relationship between sRPE and TRIMP (LRsRPETRIMP) is more significant in LIT compared to that in MIT and HIT. 2. Variations in the duration of LIT sessions do not affect the consistency of the relationship between sRPE and TRIMP. 3. Discrepancies between actual and planned training durations directly impact the significance of the LRsRPE-TRIMP. [ABSTRACT FROM AUTHOR]

Ceramic sherds from the archaeological site of Suta, Leyva Valley, Colombia, have been dated by the electron paramagnetic resonance (EPR). The Ti-H center, generated by radiation in quartz, was detected by EPR and used to determine the age of the ceramic sherds studied here. The annual dose rate (AD) received by the pottery was evaluated from the contributions of external and internal radiation sources. Two dates were obtained from the absolute chronological data of the samples taken from the excavated archaeological units: 665.3 ± 130 and 1048.8 ± 110 AD years. This indicates an extended settlement period of 380 years for the two excavated sites. [ABSTRACT FROM AUTHOR]

To report long-term results from a phase 1/2a clinical trial assessment of a scaffold-based human embryonic stem cell-derived retinal pigmented epithelium (RPE) implant in patients with advanced geographic atrophy (GA). A single-arm, open-label phase 1/2a clinical trial approved by the United States Food and Drug Administration. Patients were 69-85 years of age at the time of enrollment and were legally blind in the treated eye (best-corrected visual acuity [BCVA], ≤ 20/200) as a result of GA involving the fovea. The clinical trial enrolled 16 patients, 15 of whom underwent implantation successfully. The implant was administered to the worse-seeing eye with the use of a custom subretinal insertion device. The companion nonimplanted eye served as the control. The primary endpoint was at 1 year; thereafter, patients were followed up at least yearly. Safety was the primary endpoint of the study. The occurrence and frequency of adverse events (AEs) were determined by scheduled eye examinations, including measurement of BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were collected to monitor systemic humoral immune responses to the implanted cells. At a median follow-up of 3 years, fundus photography revealed no migration of the implant. No unanticipated, severe, implant-related AEs occurred, and the most common anticipated severe AE (severe retinal hemorrhage) was eliminated in the second cohort (9 patients) through improved intraoperative hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or after surgery in all patients as anticipated for a subretinal surgical procedure. Throughout the median 3-year follow-up, results show that implanted eyes were more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 5 letters compared with nonimplanted eyes. This report details the long-term follow-up of patients with GA to receive a scaffold-based stem cell-derived bioengineered RPE implant. Results show that the implant, at a median 3-year follow-up, is safe and well tolerated in patients with advanced dry age-related macular degeneration. The safety profile, along with the early indication of efficacy, warrants further clinical evaluation of this novel approach for the treatment of GA. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

• This review article focuses on the biomechanics of conventional rapid palatal expansion (RPE) and miniscrew-assisted rapid palatal expansion appliances (MARPE). • Three main things play an important role in the type of movements that follow rapid maxillary expansion: 1) Center of resistance and anatomy of maxilla, 2) Appliance system, and 3) Forces, Stress, and Strain. • The nature of forces after expansion is cyclical with force activation and decay occurring after each turn/activation of the expansion appliance. • The stress levels expressed by RPE and MARPE are different which is responsible for the difference in the effects because of RPE and MARPE • Even within MARPE, bone-anchored MARPE design and hybrid MARPE design result in different force systems or stress on the oral structures. Posterior Crossbite is a common condition resulting because of transverse maxillary deficiency. The growth of the craniofacial complex finishes first in the transverse dimension, followed by sagittal and vertical dimensions. Conventional rapid palatal expansion (RPE) appliances are commonly used to correct transverse maxillary deficiency. Although RPE is efficient in correcting posterior crossbite, it results in dental side effects such as buccal tipping of maxillary molars, root resorption, bone dehiscence, and relapse. Mini-implant-assisted RPE has been introduced to increase the skeletal effects of expansion especially in patients with increased maturation and greater interdigitation of midpalatal suture. This article will review the biomechanics of RPE and mini-implant-assisted RPE. Additionally, the different designs of MARPE and the long-term clinical effects of expansion appliances will also be discussed in detail. [ABSTRACT FROM AUTHOR]

Introduction: The confluence of physiological and psychological dynamics is fundamental to athletic performance, particularly in basketball, where physical skill and mental resilience are imperative. While the role of verbal encouragement (VE) as a catalyst for enhancing performance has been explored in various sports disciplines, its specific effects within the basketball have not been adequately examined. Addressing this gap, the current study zeroes in on the influence of coach-delivered VE on the physiological and psychological responses of adolescent basketball players engaged in small-sided games (SSG), providing a focused analysis of how directed encouragement can modulate performance and experience in young athletes. This study aimed to investigate the effects of coach-delivered verbal encouragement on the psychological and physiological responses of adolescent basketball players. Methods: Sixteen male participants (age: 16.93 ± 0.36 years; height: 176.8 ± 0.8 cm; body mass: 73.43 ± 12.57 kg; BMI: 21.70 ± 3.55) were allocated to a Verbal Encouragement Group (VEG, n = 8, mean age: 16.80 ± 0.44) and a Control Group (CG, n = 8, mean age: 17.06 ± 0.26). Each participant engaged in four sessions of small-sided games (SSGs) consisting of four players per side in a 14 x 10 m pitch. Results: The findings revealed significant benefits of coach-delivered verbal encouragement on both the physical and psychophysiological responses of the players (p < 0.05), including increased physical enjoyment, positive mood state, lower heart rate, and higher physical activity intensity level. Discussion: Coaches should incorporate verbal encouragement strategies during SSGs to enhance player performance and optimize both psychological and physiological adaptations. [ABSTRACT FROM AUTHOR]

Vision starts in retinal photoreceptors when specialized proteins (opsins) sense photons via their covalently bonded vitamin A derivative 11cis retinaldehyde (11cis-RAL). The reaction of non-enzymatic aldehydes with amino groups lacks specificity, and the reaction products may trigger cell damage. However, the reduced synthesis of 11cis-RAL results in photoreceptor demise and suggests the need for careful control over 11cis-RAL handling by retinal cells. This perspective focuses on retinoid(s) synthesis, their control in the adult retina, and their role during retina development. It also explores the potential importance of 9cis vitamin A derivatives in regulating retinoid synthesis and their impact on photoreceptor development and survival. Additionally, recent advancements suggesting the pivotal nature of retinoid synthesis regulation for cone cell viability are discussed. [ABSTRACT FROM AUTHOR]

In this study, the role of TiO2 on the physica, and optical properties as well as the γ-ray protection features of a set of six glass samples with the chemical formula (65-X)B2O3–15BaO–5Bi2O3–15ZnO–XTiO2, where X = 0–10 mol% in the step of 2% have been investigated. The density (ρ) increased gradually from 3.70 to 3.93 g/cm3 and the molar volume (Vm) reduced from 27.71 to 26.72 cm3/mol as the TiO2 content increased from 0 to 10 mol%. By the inclusion of TiO2 in the glass networks, some absorption bands in the ultraviolet and visible regions are formed. Values of the indirect optical band gaps (Eg) were 2.550, 2.510, 2.470, 2.370, 2.270, and 2.180 eV for Ti-0.0, Ti-2.0, Ti-4.0, Ti-6.0, Ti-8.0, and Ti-10.0 glasses, respectively. The linear refractive index (n0) calculated values varied from 2.515 to 2.631. The linear-attenuation coefficient ( μ) followed the order: Ti-0.0 < Ti-2.0 < Ti-4.0 < Ti-6.0 < Ti-8.0 < Ti-10.0. The sample coded as Ti-10.0 glass sample (highest content of TiO2) has the lowest half (HVL) and tenth (TVL) value layer. Within the investigated energy range of within the range: 51.590–19.480, 50.676–19.722, 50.696–19.833, 50.271–20.012, 49.860–20.193, and 49.460–20.376 for the prepared samples Ti-0.0, Ti-2.0, Ti-4.0, Ti-6.0, Ti-8.0, and Ti-10.0 glasses, respectively. Results confirmed that the suggested titanium bismo-borate glasses can be used in the optical field and as alternative materials for radiation shielding applications. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise as powerful hRPE cell carriers, but as biodegradability is a requirement, it also poses a challenge due to its limited durability. hRPE cells exhibit several characteristics that putatively respond to the type of membrane carrier, and they can be used as biomarkers to evaluate and further optimize such membranes. Here, we analyze the pigmentation, transepithelial resistance, genome integrity, and maturation markers of hRPE cells plated on commercial polycarbonate (PC) versus in-house electrospun polylactide-based (PLA) membranes, both enabling separate apical/basolateral compartments. Our results show that PLA is superior to PC-based membranes for the cultivation of hRPEs, and the BEST1/RPE65 maturation markers emerge as the best biomarkers for addressing the quality of hRPE cultivated in vitro. The stability of the cultures was observed to be affected by PLA aging, which is an effect that could be partially palliated by the coating of the PLA membranes. [ABSTRACT FROM AUTHOR]

Although studies have indicated that the prior use of video feedback and music listening separately improves physical performance and positive feelings in various sports, to our knowledge, no studies have investigated their combined effect in combat-sports-specific tasks. The aim of this study was to determine the combined effect of listening to preferred music and video feedback on aerobic and anaerobic performance in male kickboxers. In a counterbalanced crossover study design, twenty kickboxers underwent three kicking exercises under one of three conditions: (1) control condition, (2) combined listening to preferred music and video feedback, and (3) video feedback during 10-min of rope warm-up. Kickboxers performed a ten-second kicking test, multiple ten-second kick test, and progressive taekwondo test. The total number of kicks, fatigue index, heart rate, rate of perceived exertion, and feeling scale were measured. The combined music and video feedback condition improved the number of kicks with a better positive feeling scale (F ≥ 7.4, p ≤ 0.002, ηp2 ≥ 0.28) than the video feedback and control conditions in all three kicking exercises, while the video feedback alone led to better kick performances and a better feeling scale than the control condition in the ten-second and multiple ten-second kicking tests (p ≤ 0.016). The combined listening to preferred music and video feedback condition was more effective at enhancing the positive feeling scale and repeated roundhouse kick performance. Future investigations should examine the application of video feedback and listening to music in various kickboxing tasks including punches and kicks. [ABSTRACT FROM AUTHOR]

Background: Monitoring of training load is done to improve physical performance and minimize the incidence of injuries. The study examined the correlation between accumulated training load parameters based on periods with maturity (i.e., maturity offset and peak height velocity -PHV- and wellness variables -e.g., stress and sleep quality-). The second aim was to analyze the multi-linear regression between the above indicators. Methods: Twenty elite young U14 soccer players (M = 13.26 ± 0.52 years, 95% CI [13.02, 13.51]) were evaluated over 26 weeks (early, mid, and end-season) to obtain stress, sleep quality, and measures of workload in the season (accumulated acute workload [AW], accumulated chronic workload [CW], accumulated acute: chronic workload ratio [ACWLR], accumulated training monotony [TM], accumulated training strain [TS]). Results: The analysis revealed a moderate, statistically significant negative correlation between sleep quality and training monotony (r = -0.461, p < 0.05). No significant correlations were observed between other variables (p > 0.05). In the multi-linear regression analysis, maturity, PHV, sleep, and stress collectively accounted for variances of 17% in AW, 17.1% in CW, 11% in ACWLR, 21.3% in TM, and 22.6% in TS. However, individual regression coefficients for these predictors were not statistically significant (p > 0.05), indicating limited predictive power. Conclusion: The study highlights the impact of sleep quality on training monotony, underscoring the importance of managing training load to mitigate the risks of overtraining. The non-significant regression coefficients suggest the complexity of predicting training outcomes based on the assessed variables. These insights emphasize the need for a holistic approach in training load management and athlete wellness monitoring. [ABSTRACT FROM AUTHOR]

Introduction: The increasing prevalence of high-intensity sports activities, notably the burgeoning popularity of CrossFit, underscores the contemporary significance of such physical pursuits. The discernible protective impact of branched-chain amino acids on muscle fatigue and injuries is emerging as a noteworthy area of investigation. Within the realm of sports, integrating BCAA supplementation into dietary practices holds promise for aiding athletes in their recovery, particularly in mitigating Delayed-Onset Muscle Soreness. Methodology: This study adopted an experimental pilot design with repeated measures, employing a controlled and randomized approach through double-blind procedures. The participant engaged in high-intensity activity, specifically the CrossFit Karen® test, which entailed executing 150 wall ball throws (9 kg) to a height of 3 m. The trial incorporated three randomized supplementation conditions: BCAAs in an 8:1:1 ratio or a 2:1:1 ratio or a placebo condition. The participant consumed 15 g daily for 7 days, commencing 72 h prior to the initial blood sample and the first Karen® test. Results: In this study, BCAA supplementation at an 8:1:1 ratio demonstrated a discernible protective effect against muscular damage, as evidenced by creatine kinase values and ratings of perceived exertion. [ABSTRACT FROM AUTHOR]

Basketball clutch time is defined as minutes when the scoring margin is within 5 points with five or fewer minutes remaining in a game. Our aims were to explore the relations and to compare testosterone and cortisol behaviours, vertical jump (CMJ) and perceived exertion (RPE) between clutch time games (CT) and non-clutch time games (N-CT); during a season in an amateur male team (24.02 ± 3.36 years). Data was collected at 22 games considering CT (n = 8) or N-CT (n = 14) depending on the scoring margin with five or fewer minutes. A total of 120 player cases who participated in the last 5 min of each game (CT, n = 48; N-CT, n = 72) were analysed using a mixed linear model for repeated measures to compare the CT and N-CT variations. The main results were Cortisol, CMJ and RPE means turned out to be higher in CT, but relevant differences were only identified for RPE (ES = 0.69). Findings suggested that clutch performance was often viewed through players' subjective parameters. Consequently, we recommend that both players and coaches consider it for CT performance. In addition, we extend current basketball CT indicator knowledge opening future research and applied practice. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a major cause of blindness that affects people over 60. While aging is the prominent factor in AMD, studies have reported a higher prevalence of AMD in women compared to age-matched men. Higher levels of the innate immune response’s effector proteins complement factor B and factor I were also found in females compared to males in intermediate AMD. However, the mechanisms underlying these differences remain elusive. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a key regulator of mitochondrial biogenesis and metabolic pathways. Previously, we showed that Pgc-1α repression and high-fat diet induce drastic AMD-like phenotypes in mice. Our recent data revealed that Pgc-1α repression alone can also induce retinal pigment epithelium (RPE) and retinal dysfunction in mice, and its inhibition in vitro results in lipid droplet accumulation in human RPE. Whether sex is a contributing factor in these phenotypes remains to be elucidated. Using electroretinography, we demonstrate that sex could influence RPE function during aging independent of Pgc-1α in wild-type (WT) mice. We further show that Pgc-1α repression exacerbates RPE and retinal dysfunction in females compared to aged-match male mice. Gene expression analyses revealed that Pgc-1α differentially regulates genes related to antioxidant enzymes and mitochondrial dynamics in males and females. RPE flat mounts immunolabeled with TOMM20 and DRP1 indicated a sex-dependent role for Pgc-1α in regulating mitochondrial fission. Analyses of mitochondrial network morphology suggested sex-dependent effects of Pgc-1α repression on mitochondrial dynamics. Together, our study demonstrates that inhibition of Pgc-1α induces a sex-dependent decline in RPE and retinal function in mice. These observations on the sex-dependent regulation of RPE and retinal function could offer novel insights into targeted therapeutic approaches for age-related RPE and retinal degeneration.

IntroductionEsports or competitive video gaming is a rapidly growing sector and an integral part of today's (youth) culture. Esports athletes are exposed to a variety of burdens, that can potentially impact an athlete's health and performance. Therefore, it is important that esports athletes are aware of (physical) burden and exertion associated with esports. For this purpose, a study was conducted to evaluate the influence of competitive video gaming on the perceived physical exertion and the perceived physical state (PEPS).MethodsThirty-two healthy male esports athletes participated in two competitive video gaming sessions lasting 90–120 min, interrupted by a 10-minute passive sitting break. Repeated measures of perceived physical exertion (Borg Categorial Ratio-10 scale) and perceived physical state were recorded before, during, and after each video game session. Repeated measures ANOVA and Friedman's test were used for statistical analysis.ResultsThe results showed a significant difference in all dimensions of the PEPS (p

Purpose: Endophthalmitis is a severe infection accompanied by inflammation that affects the anterior and posterior parts of the eye. It is typically treated with a combination of antibiotics that cover various microorganisms. However, retinal pigment epithelium (RPE) cells are highly susceptible to damage from intravitreal injection therapy. This study aimed to investigate the impact of clinically relevant concentrations of meropenem (alone or in combination with vancomycin) on the viability and inflammation of RPE cells. Design: In-vitro Study. Methods: RPE cells from passages 5–7 were treated with different concentrations of meropenem (1/4x, x, and 4x; [x = 16 mg/L]), vancomycin (30 mg/L), and meropenem (x) plus vancomycin for 24 h. The morphology assessment and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay were performed to evaluate cytotoxicity due to drug treatment. Real-time PCR was used to measure the relative expression of apoptotic genes (BCL-2 and BAX) and inflammation biomarkers (IL-1b and IL-6). Results: Meropenem (alone or in combination with vancomycin) did not have any significant effect on RPE cell morphology, density, and viability. Gene expression analysis confirmed these results, showing no significant changes in the BCL-2/BAX ratio in drug-treated RPE cells compared to controls. Treatment with meropenem significantly induced the expression of IL-1b at all studied concentrations. Additionally, at concentrations of x and 4x, it also significantly increased the expression of IL-6, which was dose-dependent. However, this effect was not observed with vancomycin alone or in combination with meropenem. Conclusions: The results of this study suggest that meropenem, either alone or in combination with vancomycin, does not induce RPE cytotoxicity. There was an upregulation of IL-1b and IL-6 in meropenem monotherapy, the clinical implication of which should be elucidated in future in-vivo or clinical studies.

Abstract Background The epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells participated in the development of retinal fibrosis. SB431542 is a small molecule inhibitor with inhibitory effects on the ALK4, ALK5 and ALK7. Our study aimed to explore the effect of SB431542 on the EMT of RPE cells and to provide new ideas for the treatment of retinal fibrosis. Methods We performed fundus fluorescein angiography, optical coherence tomography and hematoxylin–eosin staining in vivo to observe the effect of SB431542 on choroidal neovascularization (CNV)-induced retinopathy. The proliferation, migration, cytoskeleton, adhesion, reactive oxygen species (ROS), mitochondrial morphology and membrane potential of RPE cells were observed in vitro through fluorescein diacetate staining, Cell Counting Kit-8 experiment, wound healing assay, phalloidin staining, immunofluorescence, MitoSOX, DCFH-DA, MitoTracker and JC-10 staining. Western blot, reverse transcription quantitative and immunofluorescence were used to detect the expression of EMT–related markers, pERK1/2, pGSK3β and β-catenin. Results SB431542 significantly alleviated retinopathy in the CNV model. The proliferation, migration and adhesion in RPE cells decreased to a certain extent in SB431542 treatment. SB431542 partially normalized the structure of RPE cells. The expression levels of E-cadherin increased, while the expression levels of laminin and N-cadherin decreased with SB431542 treatment. SB431542 reduced the production of total ROS, mitochondrial SOX and recovered the mitochondrial membrane potential to a certain degree. In addition, our study showed that SB431542 downregulated the phosphorylation of ERK1/2, GSK3β and the expression of β-catenin. Conclusion SB431542 improved EMT in RPE cells by maintaining mitochondrial homeostasis via the ERK1/2 and GSK3β/β-catenin pathways. Video Abstract Graphical Abstract SB431542 inhibits EMT in RPE cells under high glucose conditions.

Purpose: To assess the relationship between external and internal load during official women's rugby seven matches. Methods: Six backs (age = 24.2 [3.2] y; height = 161.5 [7.3] cm; body mass = 59.5 [5.0] kg; playing experience = 5.3 [1.5] y) and 8 forwards (age = 22.4 [2.7] y; height = 167.0 [4.8] cm; body mass = 70.6 [5.6] kg; playing experience = 5.0 [1.5] y) belonging to the women's rugby seven Brazilian national team were monitored across 3 international tournaments during the 2019–20 season, with 2 players excluded from the analysis since they did not participate in any investigated match. Total distance (TD), distance during high-intensity running 18.1 to 20.0 km·h−1 and >20 km·h−1 (sprinting), number of accelerations >1.8 m·s−2 (ACC), and of decelerations <1.8 m·s−2 were used as match load volume measures, while their relative values (TD per minute, high-intensity running per minute, sprinting per minute, ACC per minute, and decelerations per minute) were used as external load match intensity measures. Internal load intensity and volume were assessed using the session rating of perceived exertion (sRPE) and its value multiplied by match duration (sRPE-ML), respectively. Spearman correlations and linear mixed models were used to assess the relationships between internal and external load measures. Results: A very large relationship (ρ =.830, P <.001) was found between sRPE-ML and TD, with linear mixed models showing that TD statistically affected sRPE-ML (P <.001). Linear mixed models analysis showed that ACC per minute was also affecting the sRPE-ML (P =.017), while sprinting (P =.007) and ACC per minute (P =.005) were the only 2 measures statistically affecting sRPE. However, weak relationships (trivial to large) were found for these and all other measures. Conclusions: These results highlight that TD is the main external load measure able to anticipate the internal load responses measured via sRPE-ML in elite women's rugby sevens. [ABSTRACT FROM AUTHOR]

In the mammalian retina, a metabolic ecosystem exists in which photoreceptors acquire glucose from the choriocapillaris with the help of the retinal pigment epithelium (RPE). While the photoreceptor cells are primarily glycolytic, exhibiting Warburg-like metabolism, the RPE is reliant on mitochondrial respiration. However, the ways in which mitochondrial metabolism affect RPE cellular functions are not clear. We first used the human RPE cell line, ARPE-19, to examine mitochondrial metabolism in the context of cellular differentiation. We show that nicotinamide induced rapid differentiation of ARPE-19 cells, which was reversed by removal of supplemental nicotinamide. During the nicotinamide-induced differentiation, we observed using quantitative PCR, Western blotting, electron microscopy, and metabolic respiration and tracing assays that (1) mitochondrial gene and protein expression increased, (2) mitochondria became larger with more tightly folded cristae, and (3) mitochondrial metabolism was enhanced. In addition, we show that primary cultures of human fetal RPE cells responded similarly in the presence of nicotinamide. Furthermore, disruption of mitochondrial oxidation of pyruvate attenuated the nicotinamide-induced differentiation of the RPE cells. Together, our results demonstrate a remarkable effect of nicotinamide on RPE metabolism. We also identify mitochondrial respiration as a key contributor to the differentiated state of the RPE and thus to many of the RPE functions that are essential for retinal health and photoreception.

PurposeTo identify key retinal pigment epithelium (RPE) genes linked to the induction of myopia in guinea pigs.MethodsTo induce myopia, two-week-old pigmented guinea pigs (New Zealand strain, n = 5) wore -10 diopter (D) rigid gas-permeable contact lenses (CLs), for one day; fellow eyes were left without CLs and served as controls. Spherical equivalent refractive errors (SE) and axial length (AL) were measured at baseline and one day after initiation of CL wear. RNA sequencing was applied to RPE collected from both treated and fellow (control) eyes after one day of CL-wear to identify related gene expression changes. Additional RPE-RNA samples from treated and fellow eyes were subjected to quantitative real-time PCR (qRT-PCR) analysis for validation purposes.ResultsThe CLs induced myopia. The change from baseline values in SE was significantly different (P = 0.016), whereas there was no significant difference in the change in AL (P = 0.10). RNA sequencing revealed significant interocular differences in the expression in RPE of 13 genes: eight genes were significantly upregulated in treated eyes relative to their fellows, and five genes, including bone morphogenetic protein 2 (Bmp2), were significantly downregulated. The latter result was also confirmed by qRT-PCR. Additional analysis of differentially expressed genes revealed significant enrichment for bone morphogenetic protein (BMP) and TGF-β signaling pathways.ConclusionsThe results of this RPE gene expression study provide further supporting evidence for an important role of BMP2 in eye growth regulation, here from a guinea pig myopia model.

The retinal pigment epithelium-photoreceptor interphase is renewed each day in a stunning display of cellular interdependence. While photoreceptors use photosensitive pigments to convert light into electrical signals, the RPE supports photoreceptors in their function by phagocytizing shed photoreceptor tips, regulating the blood retina barrier, and modulating inflammatory responses, as well as regenerating the 11-cis-retinal chromophore via the classical visual cycle. These processes involve multiple protein complexes, tightly regulated ligand-receptors interactions, and a plethora of lipids and protein-lipids interactions. The role of lipids in maintaining a healthy interplay between the RPE and photoreceptors has not been fully delineated. In recent years, novel technologies have resulted in major advancements in understanding several facets of this interplay, including the involvement of lipids in phagocytosis and phagolysosome function, nutrient recycling, and the metabolic dependence between the two cell types. In this review, we aim to integrate the complex role of lipids in photoreceptor and RPE function, emphasizing the dynamic exchange between the cells as well as discuss how these processes are affected in aging and retinal diseases.

Purpose: To quantify external, internal, and perceived training loads and their relationships in youth basketball players across different playing positions. Methods: Fourteen regional-level youth male players (age: 15.2 [0.3] y) were monitored during team-based training sessions across 10 in-season weeks. The players were monitored with BioHarness-3 devices, to measure external (Impulse Load, in Newtons per second) and internal (summated-heart-rate zones [SHRZ], in arbitrary units [AU]) loads, and with the session rating of perceived exertion (sRPE, in AU) method to quantify perceived training load. Multiple linear mixed models were performed to compare training loads between playing positions (backcourt and frontcourt). Repeated-measures correlations were performed to assess the relationships between the load models, for all players and within playing positions. Results: External load (backcourt: 13,599 [2260] N·s; frontcourt: 14,934 [2173] N·s) and sRPE (backcourt: 345 [132] AU; frontcourt: 505 [158] AU) were higher in the frontcourt (P <.05, effect size: moderate), while SHRZ was similar between positions (backcourt: 239 [45] AU; frontcourt: 247 [43] AU) (P >.05; effect size: trivial). The correlations were as follows: large between the external load and SHRZ (r =.57, P <.001), moderate between SHRZ and sRPE (r =.45, P <.001), and small between the external load and sRPE (r =.26, P =.02). The correlation magnitudes were equivalent for external load–SHRZ (large) and SHRZ–sRPE (moderate) across positions, but different for the external load–sRPE correlation (small in backcourt; moderate in frontcourt). Conclusions: In youth basketball, small–large commonalities were found between the training dose (external load) and players' responses (internal and perceived loads). Practitioners should carefully manage frontcourt players' training loads because they accumulate greater external and perceived loads than backcourt players do. [ABSTRACT FROM AUTHOR]

Purpose: To assess weekly fluctuations in hormonal responses and their relationships with load and well-being during a congested in-season phase in basketball players. Methods: Ten semiprofessional, male basketball players were monitored during 4 congested in-season phase weeks consisting of 3 weekly matches. Salivary hormone variables (testosterone [T], cortisol [C], and T:C ratio) were measured weekly, and external load (PlayerLoad™ and PlayerLoad per minute), internal load session rating of perceived exertion, percentage of maximum heart rate (HR), summated HR zones, and well-being were assessed for each training session and match. Results: Significant (P <.05) moderate to large decreases in T were found in the third and fourth weeks compared with the first week. Nonsignificant moderate to large decreases in C were apparent in the last 2 weeks compared with previous weeks. Summated HR zones and perceived sleep significantly (P <.05) decreased in the fourth week compared with the first week; whereas, percentage of maximum HR significantly (P <.05) decreased in the fourth week compared with the second week. No significant relationships were found between weekly changes in hormonal responses and weekly changes in load and overall wellness. Conclusions: A congested schedule during the in-season negatively impacted the hormonal responses of players, suggesting that T and C measurements may be useful to detect fluctuations in hormone balance in such scenarios. The nonsignificant relationships between weekly changes in hormonal responses and changes in load and well-being indicate that other factors might induce hormonal changes across congested periods in basketball players. [ABSTRACT FROM AUTHOR]

Vogt‒Koyanagi‒Harada (VKH) disease is a severe autoimmune disease. Herein, whole‐exome sequencing (WES) study are performed on 2,573 controls and 229 VKH patients with follow‐up next‐generation sequencing (NGS) in a collection of 2,380 controls and 2,278 VKH patients. A rare c.188T>C (p Val63Ala) variant in the olfactory receptor 11H1 (OR11H1) gene is found to be significantly associated with VKH disease (rs71235604, Pcombined = 7.83 × 10−30, odds ratio = 3.12). Functional study showes that OR11H1‐A63 significantly increased inflammatory factors production and exacerbated barrier function damage. Further studies using RNA‐sequencing find that OR11H1‐A63 markedly increased growth arrest and DNA‐damage‐inducible gamma (GADD45G) expression. Moreover, OR11H1‐A63 activates the MAPK and NF‐κB pathways, and accelerates inflammatory cascades. In addition, inhibiting GADD45G alleviates inflammatory factor secretion, likely due to the regulatory effect of GADD45G on the MAPK and NF‐κB pathways. Collectively, this study suggests that the OR11H1‐A63 missense mutation may increase susceptibility to VKH disease in a GADD45G‐dependent manner. [ABSTRACT FROM AUTHOR]

The green synthesis method used to synthesize Co3O4-NPs has attracted numerous advantages due to its low cost, less time and energy consume, no need of special instruments for experimental and more eco-friendly with environment. In this study, the Co3O4-NPs were synthesized by green synthesis method to overcome the toxicity of chemical synthesis. And Allium tuncelianum plant which is an endemic species in Tunceli was used as a reducing agent and Co(NO3)2.6H2O as a source of cobalt. The synthesized Co3O4-NPs were characterized by using FTIR, XRD, SEM and HR-TEM techniques. The XRD pattern was shown that the Co-NPs were face-centered cubic (fcc) of crystalline nature and the average crystallite size was found nearly 23 nm with a value of COD(R^2): 0.982. The Co3O4-NPs generally had a spherical shape in the SEM images taken at 200 nm. The Co3O4-NPs showed low IC50 value against HeLa cells compare with RPE normal cells. [ABSTRACT FROM AUTHOR]

The rate of perceived effort (RPE) is a subjective scale widely used for defining training loads. However, the subjective nature of the metric might lead to an inaccurate representation of the imposed metabolic/mechanical exercise demands. Therefore, this study aimed to predict the rate of perceived exertions during running using biomechanical parameters extracted from a commercially available running smartwatch. Forty-three recreational runners performed a simulated 5-km race on a track, providing their RPE from a Borg scale (6–20) every 400 m. Running distance, heart rate, foot contact time, cadence, stride length, and vertical oscillation were extracted from a running smartwatch (Garmin 735XT). Machine learning regression models were trained to predict the RPE at every 5 s of the 5-km race using subject-independent (leave-one-out), as well as a subject-dependent regression method. The subject-dependent method was tested using 5%, 10%, or 20% of the runner's data in the training set while using the remaining data for testing. The average root-mean-square error (RMSE) in predicting the RPE using the subject-independent method was 1.8 ± 0.8 RPE points (range 0.6–4.1; relative RMSE ~ 12 ± 6%) across the entire 5-km race. However, the error from subject-dependent models was reduced to 1.00 ± 0.31, 0.66 ± 0.20 and 0.45 ± 0.13 RPE points when using 5%, 10%, and 20% of data for training, respectively (average relative RMSE < 7%). All types of predictions underestimated the maximal RPE in ~ 1 RPE point. These results suggest that the data accessible from commercial smartwatches can be used to predict perceived exertion, opening new venues to improve training workload monitoring. [ABSTRACT FROM AUTHOR]

The T cell marker CD6 regulates both T cells and target cells during inflammatory responses by interacting with its receptors. However, only a few receptors binding to the extracellular domains of CD6 have been identified, and cellular events induced by CD6 engagement with its receptors in target cells remain poorly understood. In this study, we identified CD44 as a novel CD6 receptor by proximity labeling and confirmed the new CD6-CD44 interaction by biochemical and biophysical approaches. CD44 and the other 2 known CD6 receptors, CD166 and CDCP1, were distributed diffusely on resting retinal pigment epithelium (RPE) cells but clustered together to form a receptor complex upon CD6 binding. CD6 stimulation induced dramatic remodeling of the actomyosin cytoskeleton in RPE cells mediated by activation of RhoA, and Rho-associated kinase signaling, resulting in increased myosin II phosphorylation. Such actomyosin activation triggered the disassembly of tight junctions responsible for RPE barrier integrity in a process that required all components of the tripartite CD6 receptor complex. These data provided new insights into the mechanisms by which CD6 mediates T cell–driven disruption of tissue barriers during inflammation. [ABSTRACT FROM AUTHOR]

This study investigated the impact of basketball-induced fatigue on 3-point jump shooting accuracy, the ball's entry angle (EA) into the hoop, shot release time (RT), their relationship with player positions in high-level basketball, and the correlation between cardiorespiratory fitness markers and potential shooting performance changes. Guards (n = 13), forwards (n = 13), and centers (n = 12) underwent physiological assessments. Sequentially, they performed 15 jump shots (PRE), a basketball exercise simulation (BEST) involving 24 × 30 s circuit activities, and a repeated shooting test (POST). The study design was double-blind. The results revealed significant differences (p ≤ 0.05) in RT, EA, and successful shots (SSs) between PRE and POST in each group. The percentage changes from PRE to POST conditions across guards, forwards, and centers were for RT: 25.34% [95%CI: 1.7–48.98], 19.73% [95%CI: −1.9–41.36], 14.95% [95%CI: −5.23–35.13]; for EA: −3.89% [95%CI: −14.82–7.04], −3.13% [95%CI: −12.9–6.64], −3.47% [95%CI: −14.19–7.25]; and for SS: −14.42% [95%CI: −36.5–7.66], −16.76% [95%CI: −40.81–7.29], −19.44% [95%CI: −46.7–7.82], respectively. Post-test differences (p ≤ 0.05) highlighted greater fatigue impact on RT, EA, and SS from guards to centers. Additionally, significant correlations (p ≤ 0.05) were found between the ventilatory threshold, mean HR during BEST, and changes in RT, EA, and SS. This study highlights the substantial impact of basketball-induced fatigue on 3-point shooting parameters across player positions and the interplay with cardiorespiratory factors post-fatigue. Tailored training, considering heart rate, is crucial to optimizing shooting performance. [ABSTRACT FROM AUTHOR]

Retinal pigment epithelium (RPE) cells are important fundamentally for the development and function of the retina. In this regard, the study of the morphological and molecular properties of RPE cells, as well as their regenerative capabilities, is of particular importance for biomedicine. However, these studies are complicated by the fact that, despite the external morphological similarity of RPE cells, the RPE is a population of heterogeneous cells, the molecular genetic properties of which have begun to be revealed by sequencing methods only in recent years. This review carries out an analysis of the data from morphological and molecular genetic studies of the heterogeneity of RPE cells in mammals and humans, which reveals the individual differences in the subpopulations of RPE cells and the possible specificity of their functions. Particular attention is paid to discussing the properties of "stemness," proliferation, and plasticity in the RPE, which may be useful for uncovering the mechanisms of retinal diseases associated with pathologies of the RPE and finding new ways of treating them. [ABSTRACT FROM AUTHOR]

Substantial research has supported using musical stimuli as an ergogenic aid before and during various forms of exercise. Researchers have demonstrated that music shifts attention from associative to dissociative, decreases perceived effort and discomfort, and increases arousal and pleasantness in longer‐duration, low‐to‐moderate‐intensity exercises. Strength training is shorter in duration and higher in intensity than aerobic or muscular endurance training. Limited research has examined the effects of music on strength performance and psychological outcomes. Therefore, the purpose of this study was to investigate the effects of the tempo of self‐selected music on isokinetic knee extension and flexion performance, effort, discomfort, attention, arousal, and pleasantness in resistance‐trained young adults. Thirty resistance‐trained college‐aged adults completed three exercise testing sessions. In a randomized, counterbalanced order, a repeated measures design was used to expose the participants to three conditions (fast music, slow music, and no music). The Biodex isokinetic dynamometer and standardized psychological Likert‐style scales were used to measure concentric maximum effort knee extension and flexion torque at 60°/s and psychological variables, respectively. This study found that music improves knee extension torque but not knee flexion in resistance‐trained young adults. In addition, music or the tempo of music did not influence any psychological outcomes during isokinetic strength testing. Therefore, listening to music is not detrimental to performance or psychological outcomes, but this study provides minimal support for music's use as an ergogenic aid during strengthening exercise. [ABSTRACT FROM AUTHOR]

Purpose: Isometric exercise (IE) and isometric wall squat (IWS) training have been shown to be effective methods of reducing arterial blood pressure. However, most IE interventions require methodologies and equipment that could present a barrier to participation. Therefore, this study aimed to examine the effectiveness of an accessible RPE prescribed IWS intervention. Methods: Thirty normotensive and pre-hypertensive adults were randomly assigned to a control group or one of two 4-week home-based IWS intervention groups: the first group conducted IWS exercise where intensity was prescribed and monitored using RPE (RPE-EX), whilst the other used a previously validated HR prescription method (HR-EX). Resting and ambulatory heart rate (HR) and blood pressure (BP) were measured pre- and post-intervention. Results: Minimum clinically important differences (MCID; − 5 mmHg) in SBP and/or DBP were shown in 100% of intervention participants. Statistically significant reductions were shown in resting seated BP (RPE-EX: SBP: − 9 ± 6, DBP: − 6 ± 4, MAP: − 6 ± 3 mmHg; HR-EX: SBP: − 14 ± 6, DBP: − 6 ± 4, MAP: − 8 ± 4 mmHg), supine BP (RPE-EX: SBP: − 8 (− 5), DBP: − 8 (− 7), MAP: − 8 (− 4) mmHg; HR-EX: SBP: − 5 (− 4), MAP − 5 (− 4) mmHg), and ambulatory SBP (RPE-EX: − 8 ± 6 mmHg; HR-EX: − 10 ± 4 mmHg) following the interventions. There were no statistically significant differences between intervention groups in the magnitude of BP reduction. Conclusion: RPE prescribed IWS exercise can provide an effective and more accessible method for reducing BP at home, providing reductions comparable to the current HR-based prescription method. [ABSTRACT FROM AUTHOR]

This study aimed to (a) quantify weekly fluctuations in hormonal responses (testosterone [T], cortisol [C], and their ratio [T:C]), external (PlayerLoad [PL] and PL·minute21) and internal (session rating of perceived exertion load [sRPE-load], summated heart rate zones [SHRZs], and percentage of maximal heart rate [%HRmax]) load measures, and well-being measured using a self-reported questionnaire and (b) determine the associations between weekly changes in hormonal responses and load measures with weekly changes in well-being during the pre-season phase in basketball players. Twenty-one professional male basketball players (age: 26.2 6 4.9 years) were monitored during a 5-week pre-season phase. Linear mixed models were used to determine weekly differences in each variable and associations between weekly changes in hormonal and load variables with weekly changes in well-being. Findings revealed that T (p < 0.001) and T:C (p50.002) increased toward the end of the pre-season phase. Moreover, higher (p, 0.05) external (PL·minute21) and internal (%HRmax) load intensities were evident during the first 3 weeks of the pre-season, with no significant fluctuations in other load variables. Weekly changes in PL and sRPE-load were negatively associated (p, 0.05) with weekly changes in well-being, albeit weak in magnitudes (R2 5 0.061-0.105). These results highlight that a periodized approach was undertaken across the pre-season predominantly predicated on altering weekly load intensities, which coincided with positive hormonal responses toward the end of the pre-season. In addition, weak relationships were evident between weekly changes in hormonal responses and load measures with well-being, emphasizing that a low commonality may be present between these constructs. [ABSTRACT FROM AUTHOR]

Six specimens of iron (II)-doped borate glasses with the following chemical formula: 75B2O3–15PbO–10BaO3–xFe2O3: x = 0.0–0.5 mol% with an incremental step of 0.1 were produced using the traditional melt quench method. The effects of iron ion doping on mechanical, dielectric properties, and radiation protection effectiveness (RPE) of the prepared samples were investigated. The oxygen-packing density (OPD) and molar volume (OMV) increased as iron (II) content increased in the glasses network. Therefore, the created non-bridging oxygen (NBO) increased. Elastic parameters of the investigated samples enhanced as a function of Fe2O3 content. As the molar percentage of Fe2O3 increased from 0 to 5.0 mol%, Poisson's glasses ratio fluctuates between 0.365 and 0.3700. As the energy of the incoming photon increases, the RPE tends to fall below 100% in low-energy regions. The sample with the code Fe2O3-0.5 exhibits the smallest value (R = 0.156498 cm−1) and the largest molar fraction (Fe2O3 = 0.5 mol%), as well as the maximum molar volume and Vickers hardness. Dielectric spectroscopy of manufactured glasses is investigated at various frequencies ranging from 50 Hz to 5 MHz at room temperature to explore chemical alterations caused by iron doping on dielectric spectroscopy components like the dielectric constant ( ε ′ ) and tangent loss (tan δ). Results showed that the dielectric constant drastically declines with a rise in the frequency domains up to 700 Hz for all glasses doped with varying amounts of iron and appears almost constant at higher frequencies for all glasses. The inclusion of iron increased the amount of (NBO) elements in the inside molecular framework of glass, which significantly increased the dielectric constant. [ABSTRACT FROM AUTHOR]

Background: Pilates Method as been a popular background for almost a century and is now used worldwide as a form of fitness and holistic health because it can be tailored to individual needs and fitness levels. Lucia first adevised mat exercises performed on the floor, adapting them to individual physical and temporal constraints without compromising the wider element. He later labeled a series of specialized devices, including springs and rollers, that provide resistance to develop divergent movement patterns.13 Performing exercise with medium intensity has positive effects on the maternal health.The goal of obstetric care is to provide the right conditionsfor a safe delivery and make it a pleasant experience. Labor pain is an unavoidable component of child birth whose proper management, despite the greatadvances in midwifery, is still one of the major challengesrelated to women's health. Pregnant women should also be clinically evaluated before starting exercise to ensure there is no medical reason to stop exercising. Methods: Patients were randomly divided into two groups of 15 people in each group. In the intervention group, a Pilates exercise program was developed in collaboration with a Pilates trainer. The program was tailored to the susceptibility of pregnant women and was administered twice weekly for 8 weeks. Four tools were used in this study, including a two-part checklist, the Borg Rating of Perceived Exertion (RPE), the Visual Analogue Scale (VAS), and the McKee Childbirth Satisfaction Rating Scale. A two-section checklist was used in this study to collect the required information. Conclusion: According to the results of this study, Pilates exercise during pregnancy is a safe method to reduce the length of the active phase and second stage of labor, reducelabor pain, and increase maternal satisfaction with thechildbirth process. However, Pilates exercise did not significantlyreduce the need to episiotomy and caesarean section. [ABSTRACT FROM AUTHOR]

Activity simulation protocols offer useful applications in research and practice; however, the specificity of such protocols to basketball game-play is currently lacking. Consequently, this study aimed to develop a game-specific basketball activity simulation protocol representative of typical playing durations and assess its reliability and discriminant validity. The simulation protocol was modified from an original version (i.e., Basketball Exercise Simulation Test) to incorporate regular breaks indicative of time-outs, free-throws, and substitutions. Twelve competitive male and female adult basketball players competing in the fourth or fifth Spanish basketball division underwent repeated trials of the simulation protocol (min. 4 to max. 14 days apart) for reliability analyses. In turn, 13 competitive male (fifth division), 9 competitive female (fourth division), and 13 recreational male adult basketball players completed the simulation protocol to assess discriminant validity via comparisons between sexes (competitive players) and playing levels (males). A range of physical, technical, and perceptual-physiological variables were collected during and following the simulation protocol. Several physical and heart rate variables displayed the strongest reliability (intraclass correlation coefficient [ICC] = 0.72–0.96; coefficient of variation [CV] = 1.78–6.75%), with physical decrement, technical, blood lactate concentration, and rating of perceived exertion (RPE) variables having the weakest (ICC = 0.52–0.75; CV = 10.34–30.85%). Regarding discriminant analyses between sexes, males demonstrated significantly greater physical outputs in several variables and lower RPE compared to females (p

IntroductionThe confluence of physiological and psychological dynamics is fundamental to athletic performance, particularly in basketball, where physical skill and mental resilience are imperative. While the role of verbal encouragement (VE) as a catalyst for enhancing performance has been explored in various sports disciplines, its specific effects within the basketball have not been adequately examined. Addressing this gap, the current study zeroes in on the influence of coach-delivered VE on the physiological and psychological responses of adolescent basketball players engaged in small-sided games (SSG), providing a focused analysis of how directed encouragement can modulate performance and experience in young athletes. This study aimed to investigate the effects of coach-delivered verbal encouragement on the psychological and physiological responses of adolescent basketball players.MethodsSixteen male participants (age: 16.93 ± 0.36 years; height: 176.8 ± 0.8 cm; body mass: 73.43 ± 12.57 kg; BMI: 21.70 ± 3.55) were allocated to a Verbal Encouragement Group (VEG, n = 8, mean age: 16.80 ± 0.44) and a Control Group (CG, n = 8, mean age: 17.06 ± 0.26). Each participant engaged in four sessions of small-sided games (SSGs) consisting of four players per side in a 14 × 10 m pitch.ResultsThe findings revealed significant benefits of coach-delivered verbal encouragement on both the physical and psychophysiological responses of the players (p

Abstract Background Although stimulating autophagy caused by UV has been widely demonstrated in skin cells to exert cell protection, it remains unknown the cellular events in UVA-treated retinal pigment epithelial (RPE) cells. Methods Human ARPE-19 cells were used to measure cell viability, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial mass and lysosomal mass by flow cytometry. Mitochondrial oxygen consumption rate (OCR) was recorded using Seahorse XF flux analyzer. Confocal microscopic images were performed to indicate the mitochondrial dynamics, LC3 level, and AMPK translocation after UVA irradiation. Results We confirmed mitochondrial ROS production and DNA damage are two major features caused by UVA. We found the cell death is prevented by autophagy inhibitor 3-methyladenine and gene silencing of ATG5, and UVA induces ROS-dependent LC3II expression, LC3 punctate and TFEB expression, suggesting the autophagic death in the UVA-stressed RPE cells. Although PARP-1 inhibitor olaparib increases DNA damage, ROS production, and cell death, it also blocks AMPK activation caused by UVA. Interestingly we found a dramatic nuclear export of AMPK upon UVA irradiation which is blocked by N-acetylcysteine and olaparib. In addition, UVA exposure gradually decreases lysosomal mass and inhibits cathepsin B activity at late phase due to lysosomal dysfunction. Nevertheless, cathepsin B inhibitor, CA-074Me, reverses the death extent, suggesting the contribution of cathepsin B in the death pathway. When examining the role of EGFR in cellular events caused by UVA, we found that UVA can rapidly transactivate EGFR, and treatment with EGFR TKIs (gefitinib and afatinib) enhances the cell death accompanied by the increased LC3II formation, ROS production, loss of MMP and mass of mitochondria and lysosomes. Although AMPK activation by ROS-PARP-1 mediates autophagic cell death, we surprisingly found that pretreatment of cells with AMPK activators (A769662 and metformin) reverses cell death. Concomitantly, both agents block UVA-induced mitochondrial ROS production, autophagic flux, and mitochondrial fission without changing the inhibition of cathepsin B. Conclusion UVA exposure rapidly induces ROS-PARP-1-AMPK-autophagic flux and late lysosomal dysfunction. Pre-inducing AMPK activation can prevent cellular events caused by UVA and provide a new protective strategy in photo-oxidative stress and photo-retinopathy.

Xue Wang,1– 3 Xiaomei Liu,2 Radouil Tzekov,4 Chaofeng Yu,1 Jiasong Yang,1,5 Yuliang Feng,1 Yajun Wu,1 Yali Xu,1 Shiying Li,6 Wensheng Li1,5,7 1Aier School of Ophthalmology, Central South University, Changsha, People’s Republic of China; 2Suzhou Institute of Biomedical Engineering and Technology, University of Science and Technology of China, Suzhou, People’s Republic of China; 3Department of Ophthalmology, Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Ophthalmology, University of South Florida, Tampa, FL, USA; 5Shanghai Aier Eye Hospital, Shanghai, People’s Republic of China; 6Department of Ophthalmology, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of China; 7Shanghai Aier Eye Insititute, Shanghai, People’s Republic of ChinaCorrespondence: Wensheng Li, Shanghai Aier Eye Hospital, 83 Wuzhong Road, Shanghai, People’s Republic of China, Email drlws@qq.com Shiying Li, Department of Ophthalmology, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of China, Email shiying_li@126.comPurpose: This study aimed to determine the effect and its mechanism of fenofibrate on retinal pigment epithelium (RPE) injury induced by excessive fat in vitro and in vivo.Methods: ARPE-19 cells were co-incubated with palmitic acid (PA) and fenofibric acid (the active form of fenofibrate after metabolism in vivo) and mice fed with high-fat diet (HFD) were supplemented with fenofibrate. The following methods were used: Western blot and immunofluorescent staining to determine expressions of reactive oxygen species (ROS)–associated factors and proinflammatory cytokines; electroretinogram (ERG) c-wave to evaluate RPE function; TUNEL staining to detect the apoptotic cell in RPE tissue. Additionally, ARPE19 cells were treated with PI3K/AKT inhibitor or agonist to investigate the mechanism of fenofibric acid inhibiting PA-induced RPE damage.Results: We found that the application of PA inhibited RPE cell viability in a dose-dependent manner, and increased the levels of NAPDH oxidase 4 (NOX4), 3-nitrotyrosin (3-NT), intracellular adhesion molecule-1(ICAM1), tumor necrosis factor alpha (TNFα) and vascular endothelial growth factor (VEGF) at 400μM. The application of fenofibric acid resulted in the inhibition of NOX4, 3-NT, TNFα, ICAM1 and VEGF expression in ARPE-19 cells treated with PA. Moreover, wortmannin, as a selective inhibitor of PI3K/AKT pathway, abolished the effects of fenofibrate on the oxidative stress and inflammation in ARPE-19 cells. In addition, 740Y-P, a selective agonist of PI3K/AKT pathway, enhanced the protective action of fenofibrate. Meanwhile, in vivo dosing of fenofibrate ameliorated the downregulated amplitudes of ERG c-wave in HFD-fed mice and suppressed the HFD-induced oxidative injury and inflammatory response in RPE tissues.Conclusion: Our results suggested that fenofibrate ameliorated RPE cell damage induced by excessive fat in vitro and in vivo, in part, through activation of the PI3K/AKT signaling pathway.Keywords: fenofibrate, RPE, palmitic acid, high-fat diet, oxidative stress, inflammation

The retinal pigment epithelium (RPE) and choroid are located behind the human retina and have multiple functions in the human visual system. Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies. Here, we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages, revealing regional and age differences within the human RPE and choroid. Cell–cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types. Moreover, the transcription factors and their target genes change during aging. The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level. Moreover, we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging. The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

Abstract Background Increased age is a risk factor for the development and progression of retinal diseases including age-related macular degeneration (AMD). Understanding the changes that occur in the eye due to aging is important in enhancing our understanding of AMD pathogenesis and the development of novel AMD therapies. Microglia, the resident brain and retinal immune cells are associated with both maintaining homeostasis and protection of neurons and loss of microglia homeostasis could be a significant player in age related neurodegeneration. One important characteristic of retinal aging is the migration of microglia from the inner to outer retina where they reside in the subretinal space (SRS) in contact with the retinal pigment epithelial (RPE) cells. The role of aged subretinal microglia is unknown. Here, we depleted microglia in aged C57/BL6 mice fed for 6 weeks with a chow containing PLX5622, a small molecule inhibitor of colony-stimulating factor-1 receptor (Csf1r) required for microglial survival. Results The subretinal P2RY12 + microglia in aged mice displayed a highly amoeboid and activated morphology and were filled with autofluorescence droplets reminiscent of lipofuscin. TEM indicates that subretinal microglia actively phagocytize shed photoreceptor outer segments, one of the main functions of retinal pigmented epithelial cells. PLX5622 treatment depleted up to 90% of the retinal microglia and was associated with significant loss in visual function. Mice on the microglia depletion diet showed reduced contrast sensitivity and significantly lower electroretinogram for the c-wave, a measurement of RPE functionality, compared to age-matched controls. The loss of c-wave coincided with a loss of RPE cells and increased RPE swelling in the absence of microglia. Conclusions We conclude that microglia preserve visual function in aged mice and support RPE cell function, by phagocytosing shed photoreceptor outer segments and lipids, therefore compensating for the known age-related decline of RPE phagocytosis.

Mitochondrial dysfunction is strongly implicated in neurodegenerative diseases including age-related macular degeneration (AMD), which causes irreversible blindness in over 50 million older adults worldwide. A key site of insult in AMD is the retinal pigment epithelium (RPE), a monolayer of postmitotic polarized cells that performs essential functions for photoreceptor health and vision. Recent studies from our group and others have identified several features of mitochondrial dysfunction in AMD including mitochondrial fragmentation and bioenergetic defects. While these studies provide valuable insight at fixed points in time, high-resolution, high-speed live imaging is essential for following mitochondrial injury in real time and identifying disease mechanisms. Here, we demonstrate the advantages of live imaging to investigate RPE mitochondrial dynamics in cell-based and mouse models. We show that mitochondria in the RPE form extensive networks that are destroyed by fixation and discuss important live imaging considerations that can interfere with accurate evaluation of mitochondrial integrity such as RPE differentiation status and acquisition parameters. Our data demonstrate that RPE mitochondria show localized heterogeneities in membrane potential and ATP production that could reflect focal changes in metabolism and oxidative stress. Contacts between the mitochondria and organelles such as the ER and lysosomes mediate calcium flux and mitochondrial fission. Live imaging of mouse RPE flatmounts revealed a striking loss of mitochondrial integrity in albino mouse RPE compared to pigmented mice that could have significant functional consequences for cellular metabolism. Our studies lay a framework to guide experimental design and selection of model systems for evaluating mitochondrial health and function in the RPE.

Purpose: To examine the effect of continuous (CON) and intermittent (INT) running training sessions of different durations and intensities on subsequent performance and calculated training load (TL). Methods: Runners (N = 11) performed a 1500-m time trial as a baseline and after completing 4 different running training sessions. The training sessions were performed in a randomized order and were either maximal for 10 minutes (10CON and 10INT) or submaximal for 25 minutes (25CON and 25INT). An acute performance decrement (APD) was calculated as the percentage change in 1500-m time-trial speed measured after training compared with baseline. The pattern of APD response was compared with that for several TL metrics (bTRIMP, eTRIMP, iTRIMP, running training stress score, and session rating of perceived exertion) for the respective training sessions. Results: Average speed (P <.001, η p 2 =.924) was different for each of the initial training sessions, which all resulted in a significant APD. This APD was similar when compared across the sessions except for a greater APD found after 10INT versus 25CON (P =.02). In contrast, most TL metrics were different and showed the opposite response to APD, being higher for CON versus INT and lower for 10- versus 25-minute sessions (P <.001, η p 2 >.563). Conclusion: An APD was observed consistently after running training sessions, but it was not consistent with most of the calculated TL metrics. The lack of agreement found between APD and TL suggests that current methods for quantifying TL are flawed when used to compare CON and INT running training sessions of different durations and intensities. [ABSTRACT FROM AUTHOR]

Endurance athletes often aim to improve their aerobic metabolism. The aim of this pilot study was to examine if malic acid and L-citrulline supplementation can improve aerobic metabolism and lactate elimination. Nine young (23.9 ± 1.9 years) recreational male athletes participated in this study. Following a standardised breakfast and a body composition analysis (InBody720), 6000 mg of citrulline and 3000 mg of malic acid or a placebo of 300 mL of water were consumed on three separate days in a cross-over design using a double-blind method. Sixty minutes after the supplementation, participants completed a ramp bicycle spiroergometer protocol (35 W/3 min) until reaching a respiratory exchange ratio (RER) of 1.1, followed by a 9 min active recovery. Cadence, heart rate (HR), rate of perceived exertion (RPE), respiratory parameters and lactate levels were registered. The RPExHR value was calculated to accurately characterise exhaustion. During the exercise protocol, citrulline supplementation induced significantly lower RER values at 70-105-140 W compared to malic acid and the placebo, respectively. There was no difference in lactate levels neither during rest nor at RER 1.1. RPExHR rate values were significantly lower after malic acid supplementation compared to placebo at 175 and 210 W. Power at RER 1.1 was higher after malic acid (+4 W) and citrulline (+5 W) supplementation. Although the supplementation failed to decrease lactate levels, lower RER and RPE values may indicate a performance-enhancing benefit.

Monitoring training load, recovery, and wellness in maturation ages is even more relevant than in adulthood, especially during congested schedules. The objective of this study was to quantify and describe the differences in external and internal load, recovery, and perceived wellness in elite under-16 female players during a period of three competitions in seven days based on their participation during matches. An observational design was used to quantify the external load (total distance, high-speed distance, and PlayerLoad) and internal load (differential sRPE), as well as the recovery and wellness of 18 international under-16 players during a development tournament. The external load pattern of the starting players was undulating, with matches showing the highest internal load values compared to training sessions and non-starters. Non-starter players (whether training or matches) showed similar external load and differential sRPE values throughout the tournament (p > 0.05). Starting players experienced higher internal load than non-starters during matches (p < 0.037), without differences between training sessions (p > 0.05). No changes were seen in wellness or recovery (all p-values > 0.05), except for non-starters in Session 3 compared to Session 7 (p = 0.024). Starting players had more weekly total minutes (p = 0.018), differential sRPE (breath: p = 0.002; leg: p = 0.002; cognitive: p = 0.003), total distance (p = 0.003), and PlayerLoad (p = 0.008) than non-starters. Our results indicate differing load patterns between starters and non-starters, which do not affect wellness and recovery differently. Starters accumulate more weekly total load. Coaches can use these findings to guide decisions and load compensations in high competition contexts for young female soccer players.

Mitochondrial malfunction, excessive production of reactive oxygen species (ROS), deficient autophagy/mitophagy, and chronic inflammation are hallmarks of age-related macular degeneration (AMD). Metformin has been shown to activate mitophagy, alleviate inflammation, and lower the odds of developing AMD. Here, we explored the ability of metformin to activate mitophagy and alleviate inflammation in retinal pigment epithelium (RPE) cells. Human ARPE-19 cells were pre-treated with metformin for 1 h prior to exposure to antimycin A (10 µM), which induced mitochondrial damage. Cell viability, ROS production, and inflammatory cytokine production were measured, while autophagy/mitophagy proteins were studied using Western blotting and immunocytochemistry. Metformin pre-treatment reduced the levels of proinflammatory cytokines IL-6 and IL-8 to 42% and 65% compared to ARPE-19 cells exposed to antimycin A alone. Metformin reduced the accumulation of the autophagy substrate SQSTM1/p62 (43.9%) and the levels of LC3 I and II (51.6% and 48.6%, respectively) after antimycin A exposure. Metformin also increased the colocalization of LC3 with TOM20 1.5-fold, suggesting active mitophagy. Antimycin A exposure increased the production of mitochondrial ROS (226%), which was reduced by the metformin pre-treatment (84.5%). Collectively, metformin showed anti-inflammatory and antioxidative potential with mitophagy induction in human RPE cells suffering from mitochondrial damage.

Perceived exertion (RPE, RPEdur) and wellness scores (Hooper) are common methods to assess the training load and readiness in football. However, in professional football, there is a lack of data concerning the application of these tools in microcycles of different durations. Therefore, the purpose of this study was to explore the correlations between (a) RPE, RPEdur, and weekly external load (EXLD) and (b) Hooper and EXLD within microcycles of different durations. Independent of the microcycle’s length, RPE and RPEdur correlated with the EXLD. In MIC5, RPE and RPEdur correlated with the EXLD, except for accelerations > 3 m/s2 (ACh) and distance > 25.5 km/h (SPvh). In MIC6, RPE and RPEdur correlated with the EXLD, except Ach (with RPE). In MIC7 and MIC9, RPE and RPEdur correlated with the EXLD, except RPE with ACh. For Hooper variables, independent of the microcycle duration, SRN and FTG had more correlations in comparison to SLP; the same finding was observed in MIC7 and MIC9, but SRN and SLP in MIC5 and MIC6, respectively, had no correlations. Multiple regression analysis showed that for RPE, the main predictors are total distance (TD), metabolic power distance > 50 w/kg (PWvh), and ACh, which can explain 31% of the variance, but for RPEdur, 58% can be explained by DUR, TD, and PWvh. For SLP, the predictors FTG and SRN can explain a very small percentile of the variance (1%, 4%, and 6%, respectively). The main findings were the multiple correlations between RPE, RPEdur, Hooper, and microcycles of different durations; most of them were found for long durations. This tendency is similar to that described in the literature for microcycles of the same duration. (a) EXLD has a stronger correlation with RPEdur than with RPE, and (b) FTG and SRN are the best predictors of the EXLD during the upcoming training session. It is recommended that fitness coaches use these tools to assess and forecast the training load; thus, they will be able to prepare more effective sessions during microcycles of different durations.

Virtual reality and technology-driven ‘exergaming’ have grown in tandem to expand the possibilities of exercise. However, few studies have investigated these aspects together in the context of treadmill walking. This study examined the effects of immersive virtual reality (IVR) on heart rate (HR) and ratings of perceived exertion (RPE) while walking on a treadmill at three different speeds, only one of which was disclosed to participants. Using a single-blinded, randomized control trial with a crossover research design, sixteen college-aged adults (eight females, mean age of 20.5 ± 1.2 years) were randomly assigned a testing order for six trials of treadmill walking. Three 10 min trials were conducted with IVR and three were conducted without on two separate days; a 3 min break was given in between trials. Borg RPE scores were assessed after each trial, while HR was monitored throughout. The IVR trials produced lower mean RPE scores in comparison to the non-IVR group at 3.5 and 3.7 mph. The IVR trials also yielded a lower mean HR compared to the non-IVR trials at the highest speed of 3.7 mph. These findings suggest that IVR may be able to attenuate RPE scores and HR while walking on a treadmill.

The chromatin-associated protein WDR5 has been widely studied due to its role in histone modification and its potential as a pharmacological target for the treatment of cancer. In humans, the protein with highest sequence homology to WDR5 is encoded by the retrogene WDR5B, which remains unexplored. Here, we used CRISPR-Cas9 genome editing to generate WDR5B knockout and WDR5B-FLAG knock-in cell lines for further characterization. In contrast to WDR5, WDR5B exhibits low expression in pluripotent cells and is upregulated upon neural differentiation. Loss or shRNA depletion of WDR5B impairs cell growth and increases the fraction of non-viable cells in proliferating retinal pigment epithelial (RPE) cultures. CUT&RUN chromatin profiling in RPE and neural progenitors indicates minimal WDR5B enrichment at established WDR5 binding sites. These results suggest that WDR5 and WDR5B exhibit several divergent biological properties despite sharing a high degree of sequence homology.