Intermittent blood flow restriction with low-load resistance training for older adults with knee osteoarthritis: a randomized, controlled, non-inferiority trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disorder characterized by pain and functional impairment. Blood flow restriction (BFR) with low-load resistance training (LLRT) demonstrates a similar improvement in clinical outcomes to high-load resistance training (HLRT) in treating KOA. It has not been established whether intermittent blood flow restriction (iBFR) with LLRT can lead to clinical outcomes that are comparable to those produced by continuous blood flow restriction (cBFR) with LLRT and HLRT. The aim of the proposed study is to evaluate the efficacy of iBFR with LLRT on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence in KOA patients. METHODS: This is a three-arm, non-inferiority, randomized controlled trial utilizing blinded assessors. Two hundred thirteen participants will be randomly allocated to one of the following three groups: iBFR group-receiving 4 months of LLRT with iBFR, twice weekly (n = 71); cBFR group-receiving 4 months of LLRT with cBFR, twice weekly (n = 71); or HLRT group-receiving 4 months of HLRT without BFR, twice weekly (n = 71). The primary outcome is pain. The secondary outcomes include the WOMAC, muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence. Pain and WOMAC will be measured at the baseline and 4 and 12 months after randomizations. Muscle strength, muscle mass, and physical function will be measured at the baseline and 4 months after randomizations. The perceptions of discomfort and effort will be measured during the first and final sessions. DISCUSSION: BFR with LLRT has a similar improvement in clinical outcomes as HLRT. However, cBFR may cause elevated ratings of perceived exertion and local discomfort, compromising patient tolerability and treatment adherence. If iBFR with LLRT could produce improvement in clinical outcomes analogous to those of HLRT and iBFR with LLRT, it could be considered an alternative approach for treating patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072820. Registered on June 26, 2023.

Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

Home-based exercise program and Health education in patients with patellofemoral pain: a randomized controlled trial.

BACKGROUND: Patellofemoral pain (PFP) is one of the most common disorders of the knee joint. Home-based exercise is an effective intervention to achieve self-management for chronic diseases. This study evaluated the effects of home-based exercise and health education in patients with PFP. METHODS: Patients who had PFP were randomly allocated to an intervention group (IG) or control group (CG). Patients in the IG received a 6-week tailored home-based exercise program with health education via remote support, while patients in the CG group only received health education. Clinical outcomes were compared using the Anterior Knee Pain Scale (AKPS) to measure function and the Visual Analog Scale (VAS) to measure "worst pain" and "pain with daily activity". Muscle strength was measured according to the peak torque of the knee muscles using an isokinetic system. RESULTS: Among a total of 112 participants screened for eligibility, 38 were randomized and analyzed, including 19 participants in the intervention group and 19 participants in the control group. There were no significant differences in baseline characteristics between the groups. At 6-week follow-up, the intervention group showed a greater worst pain reduction (between-group difference, -19.3 [95%CI, -23.2 to -15.5]; P < 0.01) and pain with daily activity (between-group difference, -22.9 [95%CI, -28.3 to -17.4]; P < 0.01) than the control group. Similarly, the intervention group had better improvements in AKPS (between-group difference, 9.0 [95%CI, 4.1 to 13.9]; P < 0.01) and knee extensor strength (between-group difference, 20.1 [95%CI, 14.5 to 25.8]; P < 0.01), compared to the control group. No adverse events were reported. CONCLUSION: Home-based exercise and health education resulted in less pain, better function, and higher knee muscle strength compared with no exercise in patients with PFP. A large randomized controlled trial with long-term follow-up is required to confirm these findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200056224 ( https://www.chictr.org.cn/showproj.aspx?proj=135506 ). Registered on February 1, 2022.

Copper-mediated aerobic trifluoromethyltelluration of boronic acids with [Me4N][TeCF3].

A copper-mediated trifluoromethyltelluration of arylboronic acids with [Me4N][TeCF3] using air as an environmental friendly oxidant is presented. The reaction proceeded smoothly under mild conditions in the presence of Cu(OTf)2 and bipyridine to provide the corresponding trifluoromethyltellurated products in good yields. Vinylboronic acid and arylboronic acid pinacol ester were also suitable substrates in the conversion but the yields are low. This transformation featured simplicity, good functional group tolerance, and a wide range of substrates, allowing for a convenient access to various TeCF3-containing molecules, and represented the first Chan-Lam type trifluoromethyltelluration with the highly reactive [Me4N][TeCF3] salt.

Pan-cancer analysis of LncRNA XIST and its potential mechanisms in human cancers.

Background: X-inactive specific transcript (XIST), it has been found, is abnormal expression in various neoplasms. This work aims to explore its potential molecular mechanisms and prognostic roles in types of malignancies. Methods: This research comprehensively investigated XIST transcription across cancers from Oncomine, TIMER 2.0 and GEPIA2. Correlations of XIST expression with prognosis, miRNAs, interacting protens, immune infiltrates, checkpoint markers, mutations of tumor-associated genes and promoter methylation were also analyzed by public databases. In addition, 98 BRCA samples were collected to investigate XIST expression and evaluate its clinicopathological value. Results: In public databases, compared to normal tissues, XIST was lower in BRCA, CESC, COAD and so on, but increased in KIRC and PRAD. Databases also showed that XIST was a good indicator of prognosis in BRCA, COAD and so on, but a bad one in KIRC, KIRP and so on. From starBase, we found 29 proteins interacting with XIST, and identified 4 miRNAs which might be sponged by XIST in cancers. Furthermore, XIST was linked with immune infiltration, especially T cell CD4+, and was related to over 20 immune checkpoint markers. Moreover, several tumor-associated gene mutations and promoter methylation were negatively related to its expression. In addition, IHC showed that XIST in BRCA was obviously lower in comparison of normal tissues and was negatively related to lymph node invasion and TNM stage. Conclusion: In summary, abnormal expression of XIST influenced prognosis, miRNAs and immune infiltration across cancers, especially BRCA.

Multivariate modular metabolic engineering for enhanced gibberellic acid biosynthesis in Fusarium fujikuroi.

Gibberellic acid (GA3) is one of natural phytohormones, widely used in agriculture and downstream fields. Qualified for the nature productivity, Fusarium fujikuroi was currently employed for the industrial biotransformation from agriculture residues into GA3. Herein, Multivariate modular metabolic engineering (MMME) was assigned to reconstitute the metabolic balance in F. fujikuroi for enhancing GA3 production. Three modules including precursor pool, cluster-specific channel and P450-mediated oxidation in GA3 biosynthetic pathway were defined and optimized separately. The enhancement of both precursor pool and cluster-specific channel pushed metabolic flux transfer into the GA3-specific pathway. Moreover, both introduction of Vitreoscilla hemoglobin and reinforcement of NADPH-dependent cytochrome P450 reductase facilitated oxidation cofactor transfer and subsequently boosted mycelium growth and GA3 biosynthesis. Integration of three modules in the engineered strain accumulated 2.89 g/L GA3 in shake flask via submerged fermentation, presenting a promising modular metabolic engineering model for efficient microbial transformation in agro-industrial application.

Image Recognition of Pediatric Pneumonia Based on Fusion of Texture Features and Depth Features.

Pneumonia is one of the diseases that seriously endangers human health, and it is also the leading cause of death of children under the age of five in China. The most commonly used imaging examination method for radiologists is mainly based on chest X-ray images. Still, imaging errors often result during imaging examinations due to objective factors such as visual fatigue and lack of experience. Therefore, this paper proposes a feature fusion model, FC-VGG, based on the fusion of texture features (local binary pattern LBP and directional gradient histogram HOG) and depth features. The model improves model performance by adding detailed information in texture features to the convolutional neural network while making the model more suitable for clinical use. We input the X-ray image with texture features into the modified VGG16 model, C-VGG, and then add the Add fusion method to C-VGG for feature fusion so that FC-VGG is obtained, so FC-VGG has texture features detailed information and abstract information of deep features. Through experiments, our model has achieved 92.19% accuracy in recognizing children's pneumonia images, 93.44% average precision, 92.19% average recall, and 92.81% average F1 coefficient, and the model performance exceeds existing deep learning models and traditional feature recognition algorithms.

Advances in Stem Cell Therapies for Rotator Cuff Injuries.

Rotator cuff injury is a common upper extremity musculoskeletal disease that may lead to persistent pain and functional impairment. Despite the clinical outcomes of the surgical procedures being satisfactory, the repair of the rotator cuff remains problematic, such as through failure of healing, adhesion formation, and fatty infiltration. Stem cells have high proliferation, strong paracrine action, and multiple differentiation potential, which promote tendon remodeling and fibrocartilage formation and increase biomechanical strength. Additionally, stem cell-derived extracellular vesicles (EVs) can increase collagen synthesis and inhibit inflammation and adhesion formation by carrying regulatory proteins and microRNAs. Therefore, stem cell-based therapy is a promising therapeutic strategy that has great potential for rotator cuff healing. In this review, we summarize the advances of stem cells and stem cell-derived EVs in rotator cuff repair and highlight the underlying mechanism of stem cells and stem cell-derived EVs and biomaterial delivery systems. Future studies need to explore stem cell therapy in combination with cellular factors, gene therapy, and novel biomaterial delivery systems.

Recent advances in metabolic regulation and bioengineering of gibberellic acid biosynthesis in Fusarium fujikuroi.

The plant growth hormone gibberellic acid (GA3), as one of the representative secondary metabolites, is widely used in agriculture, horticulture and brewing industry. GA3 is detected in both plants and several fungi with the ability to stimulate plant growth. Currently, the main mode of industrial production of GA3 is depended on the microbial fermentation via long-period submerged fermentation using Fusarium fujikuroi as the only producing strain, qualified for its natural productivity. However, the demand of large-sale industrialization of GA3 was still restricted by the low productivity. The biosynthetic route of GA3 in F. fujikuroi is now well-defined. Furthermore, the multi-level regulation mechanisms involved in the whole network of GA3 production have also been gradually unveiled by the past two decades based on the identification and characterization of several global regulators and their mutual functions. Combined with the quick development of genetic manipulation techniques, the rational modification of producing strain F. fujikuroi development become practical for higher productivity achievement. Herein, we review the latest advances in the molecular regulation of GA3 biosynthesis in F. fujikuroi and conclude a comprehensive network involving nitrogen depression, global regulator, histone modification and G protein signaling pathway. Correspondingly, the bioengineering strategies covering conventional random mutation, genetic manipulating platform development, metabolic edition and fermentation optimization were also systematically proposed.

Metallic-semiconducting transition and spin polarized-unpolarized transition in a single molecule with a negative Poisson's ratio.

Different from conventional materials, structures with a negative Poisson's ratio (NPR) contract/expand laterally under a longitudinal compressive/tensile strain, usually exhibiting peculiar features. Through first-principles calculations, we investigate the electronic and transport properties of Pd9B16 molecules. Its Poisson's ratio is found to be negative under uniaxial strain along a specific direction. By contacting with Au nanowires, atomic Au chains and atomic C chain electrodes, two kinds of transitions for transmission states could be realized by the modulation of the strain and the contacting site, i.e., metallic-semiconducting transition and spin polarized-unpolarized transition. Further analysis shows that it is the suppression and shifting of density of states, caused by the strain or contacting electrodes, that trigger the transitions. Those findings combine NPR and spintronics at the single-molecule level, which may throw light on the development of nanoelectronic devices.

Discovery and characterization of amentoflavone as a naturally occurring inhibitor against the bile salt hydrolase produced by Lactobacillus salivarius.

Bile salt hydrolases (BSHs), a group of cysteine-hydrolases produced by gut microbes, play a crucial role in the hydrolysis of glycine- or taurine-conjugated bile acids and have been validated as key targets to modulate bile acid metabolism. This study aims to discover one or more efficacious inhibitors against a BSH produced by Lactobacillus salivarius (lsBSH) from natural products and to characterize the mechanism of the newly identified BSH inhibitor(s). Following screening of the inhibition potentials of more than 100 natural compounds against lsBSH, amentoflavone (AMF), a naturally occurring biflavone isolated from various medicinal plants, was discovered to be an efficacious BSH inhibitor (IC50 = 0.34 µM). Further investigation showed that AMF could strongly inhibit the lsBSH-catalyzed hydrolytic reaction in living gut microbes. Inhibition kinetic analyses demonstrated that AMF reversibly inhibited the lsBSH-catalyzed hydrolytic reaction in a mixed-inhibition manner, with an apparent Ki value of 0.65 µM. Fluorescence quenching assays suggested that AMF could quench the fluorescence of lsBSH via a static quenching procedure. Docking simulations suggested that AMF could be fitted into lsBSH at two distinct ligand-binding sites, mainly via hydrophobic interactions and hydrogen bonding, which explained well the mixed inhibition mode of this agent. Animal tests showed that the hydrolytic activities of BSHs in mice feces could be significantly blocked by AMF. In summary, this study reports that AMF is a strong, naturally occurring inhibitor of lsBSH, which offers a promising lead compound to develop novel agents for modulating bile acid metabolism in the host via targeting BSHs.

[Aflatoxins and fungal community distribution during harvesting and processing of Platycladi Semen].

This study aimed to analyze aflatoxins content and fungal community distribution in the harvesting and processing of Platycladi Semen, and explore the key link that affects aflatoxins contamination. The related Platycladi Semen samples of different maturity periods(cone non-rupture period, early rupture, and complete rupture period) and different processing periods(before drying, during 2-d drying, during 7-d drying, before and after seed scale removal, before and after peeling, 1 d after color sorting, and 7 d after color sorting) were collected for identifying the fungal community composition on sample surface by ITS amplicon sequencing. Then the content of aflatoxins B_1, B_2, G_1 and G_2 was determined by HPLC-MS/MS. The results showed that during the harvesting of Platycladi Semen from cone non-rupture to complete rupture, aflatoxins were only detected in the seed scale and seed coat, with aflatoxin G_2 in the seed scale and aflatoxin B_1 in the seed coat. During the drying, with the prolongation of drying time, aflatoxins B_1 and G_2 were detected simultaneously in the seed scale, aflatoxin B_1 in the seed coat, and low-content aflatoxin B_1 in the seed kernel. During subsequent processing, the aflatoxin content in seed kernel during subsequent processing was slighted increased. As demonstrated by fungal detection, Aspergillus flavus was not present during the harvesting of Platycladi Semen, but present during the drying and processing. Its content in the seed coat during the drying process was relatively higher. In short, Platycladi Semen should be harvested as soon as possible after it becomes fully mature. Drying process is the key link of preventing aflatoxin contamination. It is advised to build a sunlight room or adopt similar settings, standardize the operations in other processes, and keep the surrounding environment clean to minimize aflatoxin contamination.

Effect of low-load resistance training with different degrees of blood flow restriction in patients with knee osteoarthritis: study protocol for a randomized trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative disease that causes pain, functional impairment, and reduced quality of life. Resistance training is considered as an effective approach to reduce the risk of muscle weakness in patients with KOA. Blood flow restriction (BFR) with low-load resistance training has better clinical outcomes than low-load resistance training alone. However, the degree of BFR which works more effectively with low-load resistance training has not been determined. The purpose of this study is to evaluate the effectiveness of different degrees of BFR with low-load resistance training in patients with KOA on pain, self-reported function, physical function performance, muscle strength, muscle thickness, and quality of life. METHODS: This is a study protocol for a randomized, controlled trial with blinded participants. One hundred individuals will be indiscriminately assigned into the following groups: two training groups with a BFR at 40% and 80% limb occlusion pressure (LOP), a training group without BFR, and a health education group. The three intervention groups will perform strength training for the quadriceps muscles twice a week for 12 weeks, while the health education group will attend sessions once a week for 12 weeks. The primary outcome is pain. The secondary outcomes include self-reported function, physical function performance, muscle strength of the knee extensors, muscle mass of the quadriceps, quality of life, and adverse events. Intention-to-treat analysis will be conducted for individuals who withdraw during the trial. DISCUSSION: Previous studies have shown that BFR with low-load resistance training is more effective than low-load resistance training alone; however, a high degree of BFR may cause discomfort during training. If a 40% LOP for BFR could produce similar clinical outcomes as an 80% LOP for BFR, resistance training with a low degree of BFR can be chosen for patients with KOA who are unbearable for a high degree of BFR. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000037859 ( http://www.chictr.org.cn/edit.aspx?pid=59956&htm=4 ). Registered on 2 September 2020.

Efficacy and Safety of Blood Flow Restriction Training in Patients With Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of blood flow restriction training (BFRT) in the treatment of patients with knee osteoarthritis (OA). METHOD: Seven electronic databases were searched to identify trials comparing BFRT and conventional resistance training in a population with knee OA. Studies were selected according to the inclusion and exclusion criteria. Standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated to compare outcome measures of the groups. The methodologic quality of selected studies and the quality of evidence were evaluated for included studies. RESULTS: A total of 5 studies were included in this meta-analysis, with very low to moderate risk of bias. The pooled results showed no significant difference between BFRT and conventional resistance training for knee OA, including pain (SMD -0.04 [95% CI -0.31, 0.24], P = 0.79), physical function performance (SMD 0.12 [95% CI -0.55, 0.78], P = 0.73), self-reported function (SMD 0.14 [95% CI -0.24, 0.52], P = 0.48), and adverse events (RR 0.45 [95% CI 0.20, 1.01], P = 0.05). In subgroup analysis, BFRT had a lower incidence of adverse events when compared with high-load resistance training (HLRT). CONCLUSION: Data from pooled studies showed that BFRT may not have greater efficacy for treating patients with knee OA, and it is less likely to have a higher risk of adverse events. However, limited evidence supports the idea that BFRT is likely safer than HLRT. More evidence with high quality is needed in further research on efficacy and safety.