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Background: Proximal spinal muscular atrophy (SMA), a neurodegenerative disorder that causes infant mortality, has no effective treatment. Sodium vanadate has shown potential for the treatment of SMA; however, vanadateinduced toxicity in vivo remains an obstacle for its clinical application. We evaluated the therapeutic potential of sodium vanadate combined with a vanadium detoxification agent, L-ascorbic acid, in a SMA mouse model. Methods: Sodium vanadate (200 µM), L-ascorbic acid (400 µM), or sodium vanadate combined with L-ascorbic acid (combined treatment) were applied to motor neuron-like NSC34 cells and fibroblasts derived from a healthy donor and a type II SMA patient to evaluate the cellular viability and the efficacy of each treatment in vitro. For the in vivo studies, sodium vanadate (20 mg/kg once daily) and L-ascorbic acid (40 mg/kg once daily) alone or in combination were orally administered daily on postnatal days 1 to 30. Motor performance, pathological studies, and the effects of each treatment (vehicle, L-ascorbic acid, sodium vanadate, and combined treatment) were assessed and compared on postnatal days (PNDs) 30 and 90. The Kaplan-Meier method was used to evaluate the survival rate, with P < 0.05 indicating significance. For other studies, one-way analysis of variance (ANOVA) and Student's t test for paired variables were used to measure significant differences (P < 0.05) between values. Results: Combined treatment protected cells against vanadate-induced cell death with decreasing B cell lymphoma 2-associated X protein (Bax) levels. A month of combined treatment in mice with late-onset SMA beginning on postnatal day 1 delayed disease progression, improved motor performance in adulthood, enhanced survival motor neuron (SMN) levels and motor neuron numbers, reduced muscle atrophy, and decreased Bax levels in the spinal cord. Most importantly, combined treatment preserved hepatic and renal function and substantially decreased vanadium accumulation in these organs. Conclusions: Combined treatment beginning at birth and continuing for 1 month conferred protection against neuromuscular damage in mice with milder types of SMA. Further, these mice exhibited enhanced motor performance in adulthood. Therefore, combined treatment could present a feasible treatment option for patients with late-onset SMA. [ABSTRACT FROM AUTHOR]

Receptor tyrosine kinase EphB3 is expressed in cells in the bottom of intestinal crypts near stem cell niches. Loss of Ephb3 has recently been reported to produce invasive colorectal carcinoma in ApcMin/+ mice and EphB-mediated compartmentalization was demonstrated to be a mechanism suppressing colorectal cancer progression; however, it is unknown whether other factors contribute to EphB-mediated tumor suppression. EphA4–ephrin-A and EphB4–ephrin-B2 signaling have been reported to promote mesenchymal-to-epithelial transition (MET). Here, we examine whether EphB3–ephrin-B interaction has a similar effect and investigate its role in tumor suppression. We found in a clinical cohort that EphB3 expression was significantly reduced in advanced Dukes’ stage tumor specimens, so we over-expressed EphB3 in HT-29 cells by stable transfection. EphB3 over-expression inhibited HT-29 growth in monolayer cultures, anchorage-independent growth in soft agar and xenograft growth in nude mice and initiated morphological, behavioral and molecular changes consistent with MET. Specifically, EphB3 over-expression re-organized cytoskeleton (converting spreading cells to a cobble-like epithelial morphology, patterning cortical actin cytoskeleton and polarizing E-cadherin and ZO-1), induced functional changes favoring MET (decreased transwell migration, increased apoptosis and Ca2+-dependent cell–cell adhesion), decreased mesenchymal markers (fibronectin and nuclear β-catenin), increased epithelial markers (ZO-1, E-cadherin and plakoglobin) and inactivated CrkL–Rac1, a known epithelial-to-mesenchymal transition signaling pathway. Additionally, cross talk from Wnt signaling potentiated the restoration of epithelial cell polarity. Noteworthily, the same factors contributing to MET, owing to EphB3 signaling, also facilitated tumor suppression. We conclude that EphB3–ephrin-B interaction promotes MET by re-establishing epithelial cell–cell junctions and such an MET-promoting effect contributes to EphB3-mediated tumor suppression. [ABSTRACT FROM PUBLISHER]

Background: The study aim was to investigate the effect of high intensity circuit training on body composition, muscular performance, and blood parameters in sedentary workers., Methods: A total of 36 middle-aged sedentary female workers were randomly divided into high intensity circuit training (HICT) group, aerobic training (AT) group, and control (CON) group. The exercise training groups performed exercise three times per week for 8 weeks. In HICT, each session was 20-35 min with 2-3 rounds. Rounds were 8 min; the interval between rounds was 4-5 min. In AT, each exercise session comprised 20-35 min of aerobic dance training. Physiological parameters were measured 1 week before and after the interventions. The resulting data were analyzed using two-way mixed design ANOVA, the differences in body composition, muscular performance and blood parameters before and after training were compared., Results: The muscle mass (pre-test: 21.19 ± 2.47 kg; post-test: 21.69 ± 2.46 kg, p < 0.05) and knee extension 60°/s (pre-test: 82.10 ± 22.26 Nm/kg; post-test: 83.47 ± 12.83 Nm/kg, p < 0.05) of HICT group were significantly improved, with knee extension 60°/s significantly higher than that of the CON group (HICT: 83.47 ± 12.83 Nm/kg; CON: 71.09 ± 26.53 Nm/kg). In the AT group, body weight (BW) decreased significantly (Pre-test: 59.37 ± 8.24 kg; Post-test: 58.94 ± 7.98 kg); no significant change was observed in CON group. The groups exhibited no significant change in blood parameters (hs-CRP, TC, and LDL-C) or IGF-1., Conclusions: Sedentary worker's muscle mass and lower-limb muscular performance were effectively improved by performing 8-week HICT with the benefits of short duration, no spatial constraints, and using one's BW, whereas AT caused a significant decrease in BW. However, the AT induced decrease in BW was probably an effect of muscle loss rather than exercise-induced weight loss., Competing Interests: The authors declare that they have no competing interests., (© 2024 Ho et al.)

A discrete lattice model is developed to describe diffusion-mediated polymerization occurring within mesopores, where reaction is enhanced at catalytic sites distributed within the interior of the pores. Diffusive transport of monomers and polymers is one-dimensional, diffusion coefficients for the latter decreasing with polymer length. Kinetic Monte Carlo simulation is utilized to analyze model behavior focusing on a "clogging" regime, where the amount of polymer within the pores grows. We characterize the evolution of the overall and mean length of polymers, the mean number of polymers, as well as the polymer spatial and length distributions.

[reaction: see text] The diphenylamino group is an effective handle for electropolymerization to give electron donor-acceptor conjugated polymers. In addition, interesting electrochromic and photoresponsive behavior of 13 has been investigated.