Effects of blood flow restriction training on bone turnover markers, microstructure, and biomechanics in rats

ObjectiveThe present study aimed to investigate the effects of blood flow restriction training on muscle strength, bone tissue structure material, and biomechanical properties in rats applying various exercise interventions and to analyze the process by identifying the bone turnover markers, it provides a theoretical basis for the application of BFRT in clinical rehabilitation.MethodsA total of 24, 3-month-old male SD (Sprague Dawley) rats were randomly divided into pressurized control group (CON, n=6), low-intensity training group (LIRT, n=6), high-intensity training group (HIRT, n=6), and blood flow restriction training group (LIBFR, n=6) for 8-week ladder-climbing exercises. The pressured control group were given only ischemia treatments and did not undertake any burden. The low-intensity training group was allowed to climb the ladder with 30% of the maximum voluntary carrying capacity (MVCC). The rats in the high-intensity training group were allowed to climb the ladder with 70% MVCC. The blood flow restriction training group climbed the ladder with 30% MVCC while imposing blood flow restriction. Before sampling, the final MVCC was measured using a ladder-climbing protocol with progressively increasing weight loading. The serum, muscle, and bone were removed for sampling. The concentrations of the bone turnover markers PINP, BGP, and CTX in the serum were measured using ELISA. The bone mineral density and microstructure of femur bones were measured using micro-CT. Three-point bending and torsion tests were performed by a universal testing machine to measure the material mechanics and structural mechanics indexes of the femur bone.ResultsThe results of maximum strength test showed that the MVCC in LIRT, HIRT, and LIBFR groups was significantly greater than in the CON group, while the MVCC in the HIRT group was significantly higher than that in the LIRT group (P<0.05). According to the results of the bone turnover marker test, the concentrations of bone formation indexes PINP (amino-terminal extension peptide of type I procollagen) and BGP (bone gla protein) were significantly lower in the CON group than in the HIRT group (P<0.01), while those were significantly higher in the LIRT group compared to the HIRT group (P<0.01). In terms of bone resorption indexes, significant differences were identified only between the HIRT and other groups (P<0.05). The micro-CT examination revealed that the HIRT group had significantly greater bone density index values than the CON and LIRT groups (P<0.05). The results of three-point bending and torsion test by the universal material testing machine showed that the elastic modulus and maximum load indexes of the HIRT group were significantly smaller than those of the LIBFR group (P<0.05). The fracture load indexes in the HIRT group were significantly smaller than in the LIBFR group (P<0.05).Conclusion1. LIRT, HIRT, LIBFR, and CON all have significant differences, and this training helps to improve maximum strength, with HIRT being the most effective. 2. Blood flow restriction training can improve the expression of bone turnover markers, such as PINP and BGP, which promote bone tissue formation. 3. Blood flow restriction training can improve muscle strength and increase the positive development of bone turnover markers, thereby improving bone biomechanical properties such as bone elastic modulus and maximum load

Practical Blind Denoising via Swin-Conv-UNet and Data Synthesis

While recent years have witnessed a dramatic upsurge of exploiting deep neural networks toward solving image denoising, existing methods mostly rely on simple noise assumptions, such as additive white Gaussian noise (AWGN), JPEG compression noise and camera sensor noise, and a general-purpose blind denoising method for real images remains unsolved. In this paper, we attempt to solve this problem from the perspective of network architecture design and training data synthesis. Specifically, for the network architecture design, we propose a swin-conv block to incorporate the local modeling ability of residual convolutional layer and non-local modeling ability of swin transformer block, and then plug it as the main building block into the widely-used image-to-image translation UNet architecture. For the training data synthesis, we design a practical noise degradation model which takes into consideration different kinds of noise (including Gaussian, Poisson, speckle, JPEG compression, and processed camera sensor noises) and resizing, and also involves a random shuffle strategy and a double degradation strategy. Extensive experiments on AGWN removal and real image denoising demonstrate that the new network architecture design achieves state-of-the-art performance and the new degradation model can help to significantly improve the practicability. We believe our work can provide useful insights into current denoising research.Comment: Codes: https://github.com/cszn/SCUNe

The roles of ubiquitination and deubiquitination of NLRP3 inflammasome in inflammation-related diseases: A review

The inflammatory response is a natural immune response that prevents microbial invasion and repairs damaged tissues. However, excessive inflammatory responses can lead to various inflammation-related diseases, posing a significant threat to human health. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a vital mediator in the activation of the inflammatory cascade. Targeting the hyperactivation of the NLRP3 inflammasome may offer potential strategies for the prevention or treatment of inflammation-related diseases. It has been established that the ubiquitination and deubiquitination modifications of the NLRP3 inflammasome can provide protective effects in inflammation-related diseases. These modifications modulate several pathological processes, including excessive inflammatory responses, pyroptosis, abnormal autophagy, proliferation disorders, and oxidative stress damage. Therefore, this review discusses the regulation of NLRP3 inflammasome activation by ubiquitination and deubiquitination modifications, explores the role of these modifications in inflammation-related diseases, and examines the potential underlying mechanisms

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients

IntroductionThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required.MethodsWe have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. ResultsThe aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. DiscussionOur findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

An in vivo study of gene expressions during collateral sprouting accelerated by electrical stimulation in rat dorsal root ganglia

Previous studies have demonstrated that collateral sprouting in sensory neurons is an NGF dependent process, and that the onset of this sprouting can be accelerated by electrical stimulation (depolarization) of nerves, producing a precocious collateral sprouting. However, the mechanism underlying this phenomenon is not clear. -- In the present study, the mechanisms underlying precocious collateral sprouting were studied in adult rats in vivo. Electrical stimulation was performed on the intact cutaneous nerves at 8V, 20 HZ, 1 min. These intact nerves were isolated from the adjacent nerves by dissecting the nearby nerves. The intact dorsal cutaneous nerves were treated under three paradigms: i) electrical stimulation (S); ii) isolation of intact nerves (I); iii) electrical stimulation plus isolation (S+I). After varying periods of time (lh, 4h, 8h, Id, 2d, 4d, 8d, and 14d), the dorsal root ganglia (DRGs) connected with these nerves were dissected and the possible factors related to precocious sprouting were investigated in the DRG neurons using in situ hybridization (ISH), immunocytochemistry (ICC) and Western blot assays. The parameters examined included immediate early genes (IEGs), such as CREB, egr-1, c-fos, c-jun, and Oct-2; NGF receptors (Trk A and p75); and potential members of the NGF – Trk A signal transduction pathways inducing downstream signaling (PI3-kinase, SHC, PLC-y, ERK1). -- The results showed that, among IEGs, CREB mRNA was quickly induced after 1h electrical stimulation, and this increase lasted to 4d. The effects of isolation started at Id, and the combination of isolation plus stimulation resulted in this occurring sooner. At the protein level, the expression of pCREB was only significantiy increased under stimulation at 8h (p<0.05). After 4h, electrical stimulation started to induce the elevation of egr-1 mRNA and this induction lasted until 2d, but the protein level was significant increased only at 8h. Isolation, which would result in increased NGF levels in the skin due to the adjacent cutaneous denervation, did not induce significant changes in Egr-1 protein during the experimental period. Isolation plus stimulation shortened the duration of Egr-1 increase (at 1d) and this increase lasted to 4d. Except for electrical stimulation alone and isolation alone, isolation and stimulation together induced significant increases of Fos in DRGs at 2d and 4d. Stimulation did not have significant effects on Jun protein, but after 8h, isolation plus stimulation, respectively, resulted in significant increases in Jun protein compared with control. Oct-2 was not affected by any of the treatments in these experiments. -- Under the treatments of electrical stimulation and isolation, expression of Trk A receptor mRNA and protein showed different patterns in these experiments. The mRNA level of Trk A did not significantly increase after electrical stimulation; however, isolation alone resulted in a significant increase of TrkA mRNA and this increase reached a peak at 4d. Combined with electrical stimulation, isolation induced a large increase at a very early time point (1h), but this gradually declined at later time points (2d and 4d). -- The protein level of Trk A was only increased at lh and 4h stimulation time points. There was, however, an increase induced by isolation plus stimulation at later time points (4d and 8d). The phosphorylated state of Trk A receptor did not appear to be increased except at the isolation treatment at 1h and longer time points of 4d and 8d. With respect to p75, mRNA levels were altered little by electrical stimulation. Isolation alone induced a peak change at 2d. The combination of electrical stimulation and isolation resulted in increased expression of p75 by 4h, peaking at Id, and then gradually decreasing. -- Among the proteins which propagate NGF signals, PLC-yl was slightly induced by stimulation and isolation at the short time periods (1h, 4h) and the very late time point (8d). PI-3 kinase was increased only at the latest time point (8d) following treatments. SHC and MAP kinase (ERK1) were not obviously affected by any of these treatments. -- The results addressed the hypotheses that, during precocious collateral sprouting, electrical stimulation induces some alterations in IEG expression and elevated Trk A receptor expression and/or activation, and acts in concert with the increased availability of NGF to result in an accelerated terminal sprouting response. This study provided information about the potential mechanisms associated with precocious sprouting at the molecular level

Highly active N, S Co-Doped Ultramicroporous Carbon for High-Performance Supercapacitor Electrodes

N, S-doped ultramicroporous carbons (NSUC-x) with a high nitrogen/sulfur content and a narrow pore-size distribution of around 0.55 nm were firstly prepared using L-cysteine as a nitrogen and sulfur source. The phase, graphitization degree, morphology, specific surface area, pore structure and surface condition of NSUC-x are investigated to analyze the key role in electrochemical performance. Such an ultramicroporous structure and N, S doping not merely provide a high-specific surface area and a suitable pore size, but also induce a good wettability for the fast transport and adsorption of electrolyte ions. Due to the above strategies, the typical NSUC-0.4 exhibits a high gravimetric capacitance of 339 F g−1 at 0.5 A g−1 as well as a capacity retention of 91.6% after 10,000 cycles in a three-electrode system using a 6 M KOH electrolyte. More attractively, a NSUC-0.4-assembled symmetrical supercapacitor delivers an energy output of 7.4 Wh kg−1 at 100 W kg−1 in 6 M KOH as well as a capacity retention of 92.4% after 10,000 cycles, indicating its practical application prospect. Our findings open up new prospects for the design and electrochemical application of N, S-doped ultramicroporous carbons

Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in Cells

The Hippo signaling cascade is frequently dysregulated in a variety of cancers, such as breast cancer (BC), which is one of the most commonly diagnosed malignancies in women. Among BC subtypes, triple-negative BC (TNBC) stands out due to its poor prognosis and high metastatic potential. Despite extensive research aimed at establishing treatment options, existing therapies demonstrate limited efficacy for TNBC. Recently, it has been recognized that targeting the core components of the Hippo pathway (YAP and its paralog TAZ) is a promising strategy for developing anti-cancer treatment. However, no YAP/TAZ inhibitors have been approved by the FDA as anti-TNBC treatments, and only a few compounds have been identified that directly affect YAP and TAZ activity and stability to enhance the prospect of innovative HiBiT biosensors for monitoring of YAP and TAZ in cells. Employing these biosensors, we conducted a small-scale drug screen involving 279 compounds, leading to the identification of several small molecule inhibitors (SMIs) capable of inducing YAP/TAZ degradation in diverse TNBC cell lines. It is worth noting that some drugs may indirectly affect the protein stability following prolonged treatment, and a shorter exposure can be included in the future to identify drug candidates with more direct effects. Nevertheless, our study introduces a novel approach for assessing YAP and TAZ levels, which can have significant implications for developing anti-TNBC targeted therapies

Ti/PbO₂ Electrode Efficiency in Catalytic Chloramphenicol Degradation and Its Effect on Antibiotic Resistance Genes

Livestock farming has led to the rapid accumulation of antibiotic resistance genes in the environment. Chloramphenicol (CAP) was chosen as a model compound to investigate its degradation during electrochemical treatment. Ti/PbO2 electrodes were prepared using electrodeposition. The prepared Ti/PbO2-La electrodes had a denser surface and a more complete PbO2 crystal structure. Ti/PbO2-Co electrodes exhibited improved electrochemical catalytic activity and lifetime in practice. The impact of different conditions on the effectiveness of CAP electrochemical degradation was investigated, and the most favorable conditions were identified (current density: I = 15.0 mA/cm, electrolyte concentration: c = 0.125 mol/L, solution pH = 5). Most importantly, we investigated the effects of the different stages of treatment with CAP solutions on the abundance of resistance genes in natural river substrates (intI1, cmlA, cmle3, and cata2). When CAP was completely degraded (100% TOC removal), no effect on resistance gene abundance was observed in the river substrate; incomplete CAP degradation significantly increased the absolute abundance of resistance genes. This suggests that when treating solutions with antibiotics, they must be completely degraded (100% TOC removal) before discharge into the environment to reduce secondary pollution. This study provides insights into the deep treatment of wastewater containing antibiotics and assesses the environmental impact of the resulting treated wastewater