Iron blocks autophagic flux and induces autophagosomes accumulation in microglia.

Iron is an essential dietary micronutrient for maintaining physiological homeostasis. However, disruption of cerebral iron regulation with the accumulation of iron in different brain structures appears to have a role in the pathogenesis of various neurodegenerative disorders. Studies have reported that autophagy induction could potentially mitigate progression in neurodegenerative diseases with iron deposition, but the relationship between autophagy and iron remains poorly understood. Meanwhile, abnormal autophagy in microglia is closely related to the occurrence of neurodegenerative diseases. Therefore, the effect of iron on microglia autophagy needs to be elaborated. In the present study, we found that iron induces autophagosome accumulation but inhibits its initiation in an Akt-mTOR pathway independent manner. Meanwhile, it caused autophagy flux defects and dysfunction of lysosomes. We also found that iron overload reduced the expression of Rab7, which is an essential protein for the fusion of autophagosomes and lysosomes. These results suggest that iron induces the accumulation of autophagosome in microglia and disrupts the autophagic flux in late stage of autophagy. Therefore, our work provides new insights into the molecular mechanisms of iron neurotoxicity.

NMDA receptor activation induces damage of alveolar type II cells and lung fibrogenesis through ferroptosis.

Ferroptosis, a newly discovered type of regulated cell death, has been implicated in numerous human diseases. Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease with poor prognosis and limited treatment options. Emerging evidence has linked ferroptosis and glutamate-determined cell fate which is considered a new light on the etiology of pulmonary fibrosis. Here, we observed that N-methyl d-aspartate receptor (NMDAR) activation promoted cell damage and iron deposition in MLE-12 cells in a dose-, time-, and receptor-dependent manner. This mediated substantial Ca2+ influx, upregulated the expression levels of nNOS and IRP1, and affected intracellular iron homeostasis by regulating the expression of iron transport-related proteins (i.e., TFR1, DMT1, and FPN). Excessive iron load promoted the continuous accumulation of total intracellular and mitochondrial reactive oxygen species, which ultimately led to ferroptosis. NMDAR inhibition reduced lung injury and pulmonary fibrosis in bleomycin-induced mice. Bleomycin stimulation upregulated the expression of NMDAR1, nNOS, and IRP1 in mouse lung tissues, which ultimately led to iron deposition via regulation of the expression of various iron metabolism-related genes. NMDAR activation initiated the pulmonary fibrosis process by inducing iron deposition in lung tissues and ferroptosis of alveolar type II cells. Our data suggest that NMDAR activation regulates the expression of iron metabolism-related genes by promoting calcium influx, increasing nNOS and IRP1 expression, and increasing iron deposition by affecting cellular iron homeostasis, ultimately leading to mitochondrial damage, mitochondrial dysfunction, and ferroptosis. NMDAR activation-induced ferroptosis of alveolar type II cells might be a key event to the initiation of pulmonary fibrosis.

Effects of Velocity-Based versus Percentage-Based Resistance Training on Explosive Neuromuscular Adaptations and Anaerobic Power in Sport-College Female Basketball Players.

The purpose of this study was to compare the impact of velocity-based resistance training (VBRT) and percentage-based resistance training (PBRT) on anaerobic ability, sprint performance, and jumping ability. Eighteen female basketball players from a Sport College were randomly divided into two groups: VBRT (n = 10) and PBRT (n = 8). The six-week intervention consisted of two sessions per week of free-weight back squats with linear periodization from 65% to 95%1RM. In PBRT, the weights lifted were fixed based on 1RM percentage, while in VBRT, the weights were adjusted based on individualized velocity profiles. The T-30m sprint time, relative power of countermovement jump (RP-CMJ), and Wingate test were evaluated. The Wingate test assessed peak power (PP), mean power (MP), fatigue index (FI), maximal velocity (Vmax), and total work (TW). Results showed that VBRT produced a very likely improvement in RP-CMJ, Vmax, PP, and FI (Hedges' g = 0.55, 0.93, 0.68, 0.53, respectively, p < 0.01). On the other hand, PBRT produced a very likely improvement in MP (Hedges' g = 0.38) and TW (Hedges' g = 0.45). Although VBRT showed likely favorable effects in RP-CMJ, PP, and Vmax compared to PBRT (p < 0.05 for interaction effect), PBRT produced greater improvements in MP and TW (p < 0.05 for interaction effect). In conclusion, PBRT may be more effective in maintaining high-power velocity endurance, while VBRT has a greater impact on explosive power adaptations.

Comparison of Velocity and Percentage-based Training on Maximal Strength: Meta-analysis.

The purpose was to analyze the comparison of velocity-based resistance training and one-repetition maximum (%1RM) percentage-based training in maximal strength improvement by meta-analyzing and to find the reasons for the controversial findings of different studies. Ten studies were included in the systematic review and seven were subjected to meta-analysis. A total of 139 subjects were selected from the included articles after exclusion, including athletes of different specialties (N=93) and non-athletes mainly from fitness groups (N=46). The overall effect size was SMD=0.26 (95%CL 0.03 to 0.49, P=0.03, I²=0). As for the comparison of the analysis of different intervention objects as subgroups, the effect size of athletes as the subgroup was 0.35 (95%CI 0.06 to 0.64, p=0.02, I²=0), indicating that in the RCT with athletes as the intervention target, the effect of VBRT in improving the maximal strength was significantly different from that of PBT. Velocity-based resistance training might be more effective than percentage-based training in maximal strength improvement, in which velocity-based resistance training is more suitable for athletes in season, while percentage-based training is more suitable for the general sports population. More high-quality researches should deal with the effect of other athletic performance with velocity-based resistance training in the future.

The effects of velocity-based versus percentage-based resistance training on athletic performances in sport-collegiate female basketball players.

Introduction: The study compared the effects of 6-week (2 sessions/week) velocity-based resistance training (VBRT) and percentage-based resistance training (PBRT) on athletic performance in Sport-College female basketball players. Methods: Fifteen participants were assigned to the VBRT (n = 8) or PBRT (n = 7) groups. The load in VBRT group were determined through the sessional target velocity and velocity loss monitoring, whereas PBRT group used a fixed-load based on percentage of 1-repetition maximum (1RM). Both groups completed intervention that involved the free weight back squat and bench press using the same relative load (linear periodization from 65% to 95% 1RM). Training loads data was continuously recorded. Measurements at baseline (T0) and post-training (T2) included 1RM, countermovement-jump (CMJ), squat-jump (SJ), eccentric-utilization-ratio (EUR), drop-jump height and reactive-strength-index (DJ, DJ-RSI), plyometric-push-up (PPU), 505 change-of-direction (COD), 10-m、20-m sprint (T-10、T-20), 17 × 15 m drill-lines (17-drill), Hexagon agility, and functional movement screen (FMS). A mid-term (T1) assessment was included to investigate the short-term effects of both methods and the fluctuation of personalized 1RM. Results: No between-group differences were observed at T0 for descriptive variables (p > 0.05). Both groups showed significant improvement in strength gains for back squat and bench press, but VBRT showed likely to very likely favorable improvements in CMJ, SJ, EUR, DJ-RSI, Hexagon and COD among athletic performance. The VBRT showed likely to very likely improvements in 17-drill and DJ, while PBRT showed unclear effects. The lifted weights adjusted by VBRT method were higher than prescribed by PBRT (p < 0.05) for the same subjects. Conclusion: Compared with fixed-load PBRT, VBRT enhanced power and athletic performance despite similar strength gains. VBRT can be regarded as a more functional resistance-training method under linear periodization.