OR-029 Effects of BCAA Plus Glucose Supplement Timing on Inflammatory Response Indicators after a Resistant Exercise

Objective A single bout of high-intensity exercise (such as resistant exercise) may result in oxidative stress and impaired immunity, for example, excessive-inflammation and compensatory immunosuppression during the recovery period. BCAA supplement has been reported that it can reduce immunosuppression and excessive inflammation after high-intensity resistant exercise. The purpose of this study was conducted to compare the effects of one-time BCAA plus glucose supplement at two different points of time, two hours before exercise and after it immediately, then figure out a better timing for improving human's impaired immune function after resistant exercise. Methods The study was a randomized, controlled, one-blind crossover trial. The entire test lasted two weeks. It recruited 16 non-trained healthy male college students. They were divided into two groups (each group contained 8 people), pre-exercise supplement group (group A) and post-exercise supplement group (group B). All subjects have not had other high-intensity exercises at least 1week before this study. Also, they did not have any exercise-induced injury or physical discomfort. All subjects needed to ingest BCAA plus glucose and placebo supplement in 2 weeks respectively and they consumed them at 2 different timing (group A or B). Because of digestion time of the capsule, subjects of group A consumed supplements 0.5h before exercise, group B need to consume them after exercise immediately. At the test day, subjects were asked not to eat anything 3 hours before their resistant exercise. Besides, subjects' diets were recorded for 2 weeks experience, to make sure if they consumed other excessive essential amino-acid which may influence this study. And the study compared each subject's 2 different results and figured out whether one-time BCAA plus glucose supplement could improve human's impaired immune function after resistant exercise and which timing was better. This exercise was designed to be a circular centrifugal movement which contained 3 different training subjects, including 5 sets of 95%10RM seated leg curl machine training, 3 sets of the maximum Drop-jumps and 2 sets of the maximum strength continuous 20m frog jump. The whole resistant exercise lasted about 1 hour. All subjects went through the same exercise and rest 7 days, then they repeated it in next week. All subjects were taken 8 blood samples in vein in 2 weeks. In other words, there were 4 timing of taking subjects’ blood samples in each test. Samples would be placed on a shaker for 1h at-20℃, before being centrifuged for 10 mins at 3,000 g. The test indicators of this study included serum interleukin-6 (IL-6), serum C-reactive protein (CRP), serum immunoglobulin a (Iga) and DOMS soreness. Among them, the level serum IL-6 was tested using a human interleukin 6 ELISA kit in a double antibody one-step sandwich enzyme-linked immunosorbent assay. The serum C-reactive protein index was tested by a human C-reactive protein (CRP) ELISA kit, which is an experimental method for enzyme-linked immunosorbent assay. Serum Iga was analyzed by collecting peripheral anticoagulation and then using an automated biochemical analyzer. The degree of muscle soreness was evaluated using a visual simulation evaluation method. Participants will be asked to perform and hold a squat (90°knee angle) whilst they rated their perceived muscle soreness on a 200 mm visual analog scale The scale consisted of a line from 0 mm (no pain) to 200mm. Supplement protocol: The pure BCAA supplement contained a ratio of 2:1:1 (leucine, isoleucine, and valine, respectively), a dose of 40 mg per kilogram of body weight and glucose supplement was designed to a dose of 24 mg per kilogram of body weight. The form of BCAA was the capsule, and the glucose supplement was in the powder form; each serving was mixed with 300 ml of water. The placebo was the same dose of oligosaccharides in capsule, and artificial sweetener in 300ml of water to match the taste of glucose supplement. Data analysis was performed using the PC version of SPSS 19.0 software. All indicators were statistically analyzed using repeated measures analysis. If the interaction of supplement x timing was significant, the independent sample t test was performed between the groups, and the paired sample t test or one-way ANOVA was performed in the group. Results In this study, all the data from the two weeks were divided into four groups according to the timing of supplementation and the supplementary category. They were the pre-exercise , placeco  group(called A- group), the post-exercise, placeco group (called B- group), the pre-exercise, BCAA plus glucose group(A+ group), the post-exercise, BCAA plus glucose group(B+ group). The data of A- group and A+ group were compared to determine the effectiveness of BCAA plus glucose supplement on anti-inflammatory response. Also, it’s the same goal to compare the data of B- group and B+ group. Then, through comparison between the the pre-exercise, BCAA plus glucose group and the post-exercise, BCAA plus glucose group, it is determined which supplemental timing IS better for lower resistant exercise-induced inflammatory response. The results showed that serum IL-6 levels were 208.35±11.34 pg/ml in the pre-exercise, BCAA plus glucose group and 273.08±4.76 pg /ml in the pre-exercise, placeco group at 24 h after exercise. There was significantly lower in A+ group(p<0.05); the serum IL-6 level in the post-exercise, BCAA plus glucose group was 169.99±10.85 pg/ml, while the serum IL-6 value of 303.78±8.79 pg/ml in the post-exercise, placeco group. There was a significant decrease in B+ group comparing with the level of B- group (p < 0.05). Besides, the serum IL-6 level in the post-exercise, placeco group was lower than that in the pre-exercise, BCAA plus glucose group, and there was a significant difference at 24 h after exercise (p<0.05). Serum CRP at 24 h after exercise, the serum CRP value of the pre-exercise, BCAA plus glucose group was 4.26 ± 0.29 mg /L ,significantly lower than the data of CRP in pre-exercise, placeco group (4.64 ± 0.35 mg/L,p < 0.05). Similarly, the supplement The serum CRP level of post-exercise, BCAA plus glucose group was 3.75±0.44 mg/L, which was significantly different from it in post-exercise, placeco group (p<0.05). At timing of 48h after exercise, the serum CRP level of the B+ group was 3.92±0.24mg/L, which was significantly lower than the serum CRP value of the B- group after 48h (4.4±0.29 mg/L), and there was a significant difference (p<0.05). ). In addition, at the timing of 24 hour after exercise, the serum CRP level of the post-exercise, BCAA plus glucose group was significantly lower than it in pre-exercise, placeco group, and there was a significant difference (p<0.05). There was no significant difference in the data of exercise–induced immunoglobulin of each group after centrifugation. As a direct indicator of the systemic inflammatory response, serum IL-6 and CRP can significantly reflect the inflammatory response induced by BCAA combined with glucose supplementation at 24 and 48 hours after exercise. And instead of Supplement before exercise, it is better for lowering resistant exercise-induced inflammatory response to supply it after exercise immediately. The degree of delayed onset muscle soreness is considered to be a clear indicator of the local inflammatory response. The Visual Analogue Scale(VAS) of delayed onset muscle soreness (DOMS) was 2.63±1.55 in A+ group at 24 h after exercise, was significantly lower than it (3.31±1.54) in the A- group (p<0.05). And the level of VAS in the B+ group was 1.27±0.72, which was significantly lower than it in the B- group at 24 h after exercise (2.86±1.77, p<0.05). At 48 h after exercise, the DOMS level in the post-exercise, BCAA plus glucose group(1.36±0.85) was significantly lower than the 48-hour DOMS level in the post-exercise, placeco group (4.4±0.29 mg/L). In addition, at the timing of 24 hour after exercise, the VAS of DOMS in the post-exercise, BCAA plus glucose group was significantly lower than it in pre-exercise, placeco group(p<0.05). Conclusions Acute and one-time BCAA plus glucose supplement can reduce the exercise-induced systemic inflammatory response (serum IL-6 and serum CRP) and local inflammatory response (DOMS) 24 h and/or 48 h after a resistant exercise. Besides, compared with a supplementation before a resistant exercise, it’s more effective to supply BCAA plus glucose after the exercise immediately for reducing body’s exercise-induced inflammatory response damage

Cylindrical Three-Dimensional Millimeter-Wave Imaging via Compressive Sensing

Millimeter-wave (MMW) imaging techniques have been used for the detection of concealed weapons and contraband carried by personnel. However, the future application of the new technology may be limited by its large number of antennas. In order to reduce the complexity of the hardware, a novel MMW imaging method based on compressive sensing (CS) is proposed in this paper. The MMW images can be reconstructed from the significantly undersampled backscattered data via the CS approach. Thus the number of antennas and the cost of system can be further reduced than those based on the traditional imaging methods that obey the Nyquist sampling theorem. The effectiveness of the proposed method is validated by numerical simulations as well as by real measured data of objects

Recent advances in the repair of degenerative intervertebral disc for preclinical applications

The intervertebral disc (IVD) is a load-bearing, avascular tissue that cushions pressure and increases flexibility in the spine. Under the influence of obesity, injury, and reduced nutrient supply, it develops pathological changes such as fibular annulus (AF) injury, disc herniation, and inflammation, eventually leading to intervertebral disc degeneration (IDD). Lower back pain (LBP) caused by IDD is a severe chronic disorder that severely affects patients’ quality of life and has a substantial socioeconomic impact. Patients may consider surgical treatment after conservative treatment has failed. However, the broken AF cannot be repaired after surgery, and the incidence of re-protrusion and reoccurring pain is high, possibly leading to a degeneration of the adjacent vertebrae. Therefore, effective treatment strategies must be explored to repair and prevent IDD. This paper systematically reviews recent advances in repairing IVD, describes its advantages and shortcomings, and explores the future direction of repair technology

CKD-TransBTS: Clinical Knowledge-Driven Hybrid Transformer with Modality-Correlated Cross-Attention for Brain Tumor Segmentation

Brain tumor segmentation (BTS) in magnetic resonance image (MRI) is crucial for brain tumor diagnosis, cancer management and research purposes. With the great success of the ten-year BraTS challenges as well as the advances of CNN and Transformer algorithms, a lot of outstanding BTS models have been proposed to tackle the difficulties of BTS in different technical aspects. However, existing studies hardly consider how to fuse the multi-modality images in a reasonable manner. In this paper, we leverage the clinical knowledge of how radiologists diagnose brain tumors from multiple MRI modalities and propose a clinical knowledge-driven brain tumor segmentation model, called CKD-TransBTS. Instead of directly concatenating all the modalities, we re-organize the input modalities by separating them into two groups according to the imaging principle of MRI. A dual-branch hybrid encoder with the proposed modality-correlated cross-attention block (MCCA) is designed to extract the multi-modality image features. The proposed model inherits the strengths from both Transformer and CNN with the local feature representation ability for precise lesion boundaries and long-range feature extraction for 3D volumetric images. To bridge the gap between Transformer and CNN features, we propose a Trans&CNN Feature Calibration block (TCFC) in the decoder. We compare the proposed model with five CNN-based models and six transformer-based models on the BraTS 2021 challenge dataset. Extensive experiments demonstrate that the proposed model achieves state-of-the-art brain tumor segmentation performance compared with all the competitors

Anoikis resistance regulates immune infiltration and drug sensitivity in clear-cell renal cell carcinoma: insights from multi omics, single cell analysis and in vitro experiment

BackgroundAnoikis is a form of programmed cell death essential for preventing cancer metastasis. In some solid cancer, anoikis resistance can facilitate tumor progression. However, this phenomenon is underexplored in clear-cell renal cell carcinoma (ccRCC).MethodsUsing SVM machine learning, we identified core anoikis-related genes (ARGs) from ccRCC patient transcriptomic data. A LASSO Cox regression model stratified patients into risk groups, informing a prognostic model. GSVA and ssGSEA assessed immune infiltration, and single-cell analysis examined ARG expression across immune cells. Quantitative PCR and immunohistochemistry validated ARG expression differences between immune therapy responders and non-responders in ccRCC.ResultsARGs such as CCND1, CDKN3, PLK1, and BID were key in predicting ccRCC outcomes, linking higher risk with increased Treg infiltration and reduced M1 macrophage presence, indicating an immunosuppressive environment facilitated by anoikis resistance. Single-cell insights showed ARG enrichment in Tregs and dendritic cells, affecting immune checkpoints. Immunohistochemical analysis reveals that ARGs protein expression is markedly elevated in ccRCC tissues responsive to immunotherapy.ConclusionThis study establishes a novel anoikis resistance gene signature that predicts survival and immunotherapy response in ccRCC, suggesting that manipulating the immune environment through these ARGs could improve therapeutic strategies and prognostication in ccRCC

AD-linked R47H-TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivation

The hemizygous R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific gene in the brain, increases risk for late-onset Alzheimer’s disease (AD). Using transcriptomic analysis of single nuclei from brain tissues of patients with AD carrying the R47H mutation or the common variant (CV)–TREM2, we found that R47H-associated microglial subpopulations had enhanced inflammatory signatures reminiscent of previously identified disease-associated microglia (DAM) and hyperactivation of AKT, one of the signaling pathways downstream of TREM2. We established a tauopathy mouse model with heterozygous knock-in of the human TREM2 with the R47H mutation or CV and found that R47H induced and exacerbated TAU-mediated spatial memory deficits in female mice. Single-cell transcriptomic analysis of microglia from these mice also revealed transcriptomic changes induced by R47H that had substantial overlaps with R47H microglia in human AD brains, including robust increases in proinflammatory cytokines, activation of AKT signaling, and elevation of a subset of DAM signatures. Pharmacological AKT inhibition with MK-2206 largely reversed the enhanced inflammatory signatures in primary R47H microglia treated with TAU fibrils. In R47H heterozygous tauopathy mice, MK-2206 treatment abolished a tauopathy-dependent microglial subcluster and rescued tauopathy-induced synapse loss. By uncovering disease-enhancing mechanisms of the R47H mutation conserved in human and mouse, our study supports inhibitors of AKT signaling as a microglial modulating strategy to treat AD

Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers’ tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates