Curcumin regulates autophagy through SIRT3-SOD2-ROS signaling pathway to improve quadriceps femoris muscle atrophy in KOA rat model.

Knee osteoarthritis (KOA) usually leads to quadriceps femoris atrophy, which in turn can further aggravate the progression of KOA. Curcumin (CUR) has anti-inflammatory and antioxidant effects and has been shown to be a protective agent for skeletal muscle. CUR has been shown to have a protective effect on skeletal muscle. However, there are no studies related to whether CUR improves KOA-induced quadriceps femoris muscle atrophy. We established a model of KOA in rats. Rats in the experimental group were fed CUR for 5 weeks. Changes in autophagy levels, reactive oxygen species (ROS) levels, and changes in the expression of the Sirutin3 (SIRT3)-superoxide dismutase 2 (SOD2) pathway were detected in the quadriceps femoris muscle of rats. KOA led to quadriceps femoris muscle atrophy, in which autophagy was induced and ROS levels were increased. CUR increased SIRT3 expression, decreased SOD2 acetylation and ROS levels, inhibited the over-activation of autophagy, thereby alleviating quadriceps femoris muscle atrophy and improving KOA. CUR has a protective effect against quadriceps femoris muscle atrophy, and KOA is alleviated after improvement of quadriceps femoris muscle atrophy, with the possible mechanism being the reduction of ROS-induced autophagy via the SIRT3-SOD2 pathway.

Hirschsprung's disease: m6A methylase VIRMA suppresses cell migration and proliferation by regulating GSK3ß.

BACKGROUND: N6-methyladenosine (m6A) is the most abundant mRNA modification in mammals, participating in various biological processes. VIRMA is a key methyltransferase involved in m6A modification. However, the role of VIRMA in Hirschsprung's disease (HSCR) remains unclear. This study aims to investigate the function of VIRMA in HSCR and identify its corresponding regulatory mechanisms. METHODS: The expression of VIRMA and GSK3ß in colon tissues of HSCR was examined using RT-qPCR, Western blot, and Immunohistochemistry. Immunofluorescence detected localization of VIRMA and GSK3ß. Cell proliferation was measured by CCK8 and EdU assays, and cell migration was evaluated via cell migration and wound healing assays. The stability of GSK3ß mRNA was assessed using the actinomycin D assay and the overall level of m6A in cells was assessed by colorimetric assay. RESULTS: VIRMA was significantly downregulated in narrow-segment colon tissue. Silencing of VIRMA inhibited cell proliferation and migration. VIRMA can inhibit the degradation of GSK3ß mRNA and increase the expression of GSK3ß. GSK3ß was significantly upregulated in narrow-segment colon tissues. Accordingly, our findings showed that GSK3ß mediated the VIRMA-driven cell migration and proliferation. CONCLUSION: VIRMA can inhibit cell migration and proliferation by upregulating the expression of GSK3ß, contributing to the onset of HSCR. IMPACT: The expressions of VIRMA were significantly reduced in HSCR, while GSK3ß expression was increased in HSCR, and can be used as a molecular marker. VIRMA overexpression promoted the proliferation and migration of SH-SY5Y and HEK-293T cells. VIRMA can inhibit the degradation of GSK3ß mRNA and increase the expression of GSK3ß.

Pip5k1c expression in osteocytes regulates bone remodeling in mice.

Research background: The role of osteocytes in maintaining bone mass has been progressively emphasized. Pip5k1c is the most critical isoform among PIP5KIs, which can regulate cytoskeleton, biomembrane, and Ca2+ release of cells and participate in many processes, such as cell adhesion, differentiation, and apoptosis. However, its expression and function in osteocytes are still unclear. Materials and methods: To determine the function of Pip5k1c in osteocytes, the expression of Pip5k1c in osteocytes was deleted by breeding the 10-kb mouse Dmp1-Cre transgenic mice with the Pip5k1cfl/fl mice. Bone histomorphometry, micro-computerized tomography analysis, immunofluorescence staining and western blotting were used to determine the effects of Pip5k1c loss on bone mass. In vitro, we explored the mechanism by siRNA knockdown of Pip5k1c in MLO-Y4 cells. Results: Pip5k1c expression was decreased in osteocytes in senescent and osteoporotic tissues both in humans and mice. Loss of Pip5k1c in osteocytes led to a low bone mass in long bones and spines and impaired biomechanical properties in femur, without changes in calvariae. The loss of Pip5k1c resulted in the reduction of the protein level of type 1 collagen in tibiae and MLO-Y4 cells. Osteocyte Pip5k1c loss reduced the osteoblast and bone formation rate with high expression of sclerostin, impacting the osteoclast activities at the same time. Moreover, Pip5k1c loss in osteocytes reduced expression of focal adhesion proteins and promoted apoptosis. Conclusion: Our studies demonstrate the critical role and mechanism of Pip5k1c in osteocytes in regulating bone remodeling. The translational potential of this article: Osteocyte has been considered to a key role in regulating bone homeostasis. The present study has demonstrated that the significance of Pip5k1c in bone homeostasis by regulating the expression of collagen, sclerostin and focal adhesion expression, which provided a possible therapeutic target against human metabolic bone disease.

The potential mechanisms underlying the modulating effect of perirenal adipose tissue on hypertension: Physical compression, paracrine, and neurogenic regulation.

Hypertension, a prevalent global cardiovascular disease, affects approximately 45.4 % of adults worldwide. Despite advances in therapy, hypertension continues to pose a significant health risk due to inadequate management. It has been established that excessive adiposity contributes majorly to hypertension, accounting for 65 to 75 % of primary cases. Fat depots can be categorised into subcutaneous and visceral adipose tissue based on anatomical and physiological characteristics. The metabolic impact and the risk of hypertension are determined more significantly by visceral fat. Perirenal adipose tissue (PRAT), a viscera enveloping the kidney, is known for its superior vascularisation and abundant innervation. Although traditionally deemed as a mechanical support tissue, recent studies have indicated its contributing potential to hypertension. Hypertensive patients tend to have increased PRAT thickness compared to those without, and there is a positive correlation between PRAT thickness and elevated systolic blood pressure. This review encapsulates the anatomical characteristics and biogenesis of PRAT. We provide an overview of the potential mechanisms where PRAT may modulate blood pressure, including physical compression, paracrine effects, and neurogenic regulation. PRAT has become a promising target for hypertension management, and continuous effort is required to further explore the underlying mechanisms.

Effects of foot reflexology massage on pregnant women: a systematic review and meta-analysis of randomized controlled studies.

To explore the effects of foot reflexology massage on anxiety, pain, duration of labor, labor satisfaction, blood pressure, pulse rate and respiratory rate in pregnant women. We systematically searched eight databases for randomized controlled studies on the effects of foot reflexology massage on pregnant women. The inclusion criteria were as follow: participants were pregnant woman; the intervention is foot reflexology or foot massage; the control intervention is placebo, usual care, or no intervention; outcome indicators included pain, anxiety, birth satisfaction, duration of labor, blood pressure, pulse, and respiration; and study type was randomized controlled study. Studies that did not meet the above requirements were excluded. We assessed the quality of the included studies using the Physiotherapy Evidence Database scale, the risk of bias using the Risk of Bias 2.0 tool, and the level of evidence for the outcomes using the Grading of Recommendations Assessment Development and Evaluation. We used Review Manager 5.3 for data analysis and generated funnel plots to assess publication bias. In addition, sensitivity analysis was used to test the stability of the results. A total of 13 randomized controlled studies with 1189 participants were included in this study. Compared to the control group, foot reflexology massage reduced anxiety and pain in pregnant women, shortened the three stages of labor, and increased birth satisfaction. In addition, it also reduced the pulse rate and respiratory rate of pregnant women, but not for blood pressure. Foot reflexology massage can significantly reduce anxiety and pain, shorten the duration of labor, increase birth satisfaction, and stabilize vital signs in pregnant women. It is a safe and non-invasive form of complementary therapy.PROSPERO registered number: CRD42022359641. URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359641 .

Cytisine: State of the art in pharmacological activities and pharmacokinetics.

Cytisine is a naturally occurring bioactive compound, an alkaloid mainly isolated from legume plants. In recent years, various biological activities of cytisine have been explored, showing certain effects in smoking cessation, reducing drinking behavior, anti-tumor, cardiovascular protection, blood sugar regulation, neuroprotection, osteoporosis prevention and treatment, etc. At the same time, cytisine has the advantages of high efficiency, safety, and low cost, has broad development prospects, and is a drug of great application value. However, a summary of cytisine's biological activities is currently lacking. Therefore, this paper summarizes the pharmacological action, mechanism, and pharmacokinetics of cytisine by referring to numerous databases, and analyzes the new and core targets of cytisine with the help of computer simulation technology, to provide reference for doctors.

Effects of rapeseed oil on body composition and glucolipid metabolism in people with obesity and overweight: a systematic review and meta-analysis.

To investigate the effects of rapeseed oil on body composition, blood glucose and lipid metabolism in people with overweight and obesity compared to other cooking oils. We searched eight databases for randomized controlled studies (including randomized crossover trials). The risk of bias for the included studies was assessed using the Cochrane Risk of Bias 2.0 tool. The Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria were used to evaluate the quality of the outcomes. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. Sensitivity analysis was used to check the stability of the pooled results. Statistical analysis was carried out using Review Manager 5.3 software. As a result, fifteen randomized controlled studies (including six parallel studies and nine crossover studies) were included in this study. Compared to other edible oils, rapeseed oil significantly reduced low density lipoprotein cholesterol (LDL-C) (MD = -0.14 mmol/L, 95% CI: -0.21, -0.08, I2 = 0%, P < 0.0001), apolipoprotein B (ApoB) (MD = -0.03 g/L, 95% CI: -0.05, -0.01, I2 = 0%, P = 0.0003), ApoB/ApoA1 (MD = -0.02, 95% CI: -0.04, -0.00, I2 = 0%, P = 0.02) and insulin (MD = -12.45 pmol/L, 95% CI: -19.61, -5.29, I2 = 37%, P = 0.0007) levels, and increased fasting glucose (MD = 0.16 mmol/L, 95% CI: 0.05, 0.27, I2 = 27%, P = 0.003) levels. However, the differences in body weight and body composition between rapeseed oil and control oils were not significant. In a word, rapeseed oil is effective in reducing LDL-C, ApoB and ApoB/ApoA1 levels in people with overweight and obesity, which is helpful in preventing and reducing the risk of atherosclerosis. PROSPERO registration number: CRD42022333436.

The Effects and Mechanisms of pH and Dissolved Oxygen Conditions on the Release of Arsenic at the Sediment-Water Interface in Taihu Lake.

The pH and dissolved oxygen (DO) conditions are important environmental factors that control the migration of arsenic (As) at the sediment-water interface. This study investigates the distribution differences of reactive iron, manganese, and arsenic at the sediment-water interface under anaerobic and aerobic conditions at different pH levels. The strong buffering capacity of sediment to water pH results in a shift towards neutral pH values in the overlying water under different initial pH conditions. The level of DO becomes a key factor in the release of As from sediment, with lower DO environments exhibiting higher release quantities and rates of As compared to high DO environments. Under low DO conditions, the combined effects of ion exchange and anaerobic reduction lead to the most significant release of As, particularly under pH 9.5 conditions. The formation of amorphous ferrous sulfide compounds under low DO conditions is a significant factor contributing to increased arsenic concentration in the interstitial water. Therefore, the re-migration of endogenous arsenic in shallow lake sediments should consider the combined effects of multiple driving forces.

[Construction of a 10rolGLP-1-expressing glucose-lowing Saccharomyces cerevisiae by CRISPR/Cas9 technique].

To develop a novel glucose-lowering biomedicine with potential benefits in the treatment of type 2 diabetes, we used the 10rolGLP-1 gene previously constructed in our laboratory and the CRISPR/Cas9 genome editing technique to create an engineered Saccharomyces cerevisiae strain. The gRNA expression vector pYES2-gRNA, the donor vector pNK1-L-PGK-10rolGLP-1-R and the Cas9 expression vector pGADT7-Cas9 were constructed and co-transformed into S. cerevisiae INVSc1 strain, with the PGK-10rolGLP-1 expressing unit specifically knocked in through homologous recombination. Finally, an S. cerevisiae strain highly expressing the 10rolGLP-1 with glucose-lowering activity was obtained. SDS-PAGE and Western blotting results confirmed that two recombinant strains of S. cerevisiae stably expressed the 10rolGLP-1 and exhibited the desired glucose-lowering property when orally administered to mice. Hypoglycemic experiment results showed that the recombinant hypoglycemic S. cerevisiae strain offered a highly hypoglycemic effect on the diabetic mouse model, and the blood glucose decline was adagio, which can avoid the dangerous consequences caused by rapid decline in blood glucose. Moreover, the body weight and other symptoms such as polyuria also improved significantly, indicating that the orally hypoglycemic S. cerevisiae strain that we constructed may develop into an effective, safe, economic, practical and ideal functional food for type 2 diabetes mellitus treatment.

Healable Ionic Conductors with Extremely Low-Hysteresis and High Mechanical Strength Enabled by Hydrophobic Domain-Locked Reversible Interactions.

Extremely low hysteresis, high mechanical strength, superior toughness, and excellent healability are essential for stretchable ionic conductors to enhance their reliability and meet for cutting-edge applications. However, the fabrication of stretchable ionic conductors with such mutually exclusive properties remains challenging. Herein, extremely low-hysteresis and healable ionic conductors with a tensile strength of ≈8.9 MPa and toughness of ≈23.2 MJ m-3 are fabricated through the complexation of 4-carboxybenzaldehyde (CBA) grafted poly(vinyl alcohol) (PVA) (denoted as PVA-CBA) and poly (allylamine hydrochloride) (PAH) followed by acidification and ion-loading steps. The acidification step generates the PVA-CBA/PAH ionic conductors with in situ formed dynamic hydrophobic domains that lock and stabilize noncovalent interactions. This significantly minimizes the energy dissipation of the ionic conductors during cyclic mechanical loading (≤200% strain), resulting in ionic conductors with extremely low hysteresis (≈5%). The fractured ionic conductors can be healed at 60 °C to restore their original properties. Because of the extremely low hysteresis, the PVA-CBA/PAH ionic conductors show a highly stable and reproducible electrical response over 5000 uninterrupted loading-unloading cycles at a strain of 200%. The ionic conductor based sensors exhibit a high sensitivity to a wide range of strains (1-500%).

Deep learning assisted diagnosis system: improving the diagnostic accuracy of distal radius fractures.

Objectives: To explore an intelligent detection technology based on deep learning algorithms to assist the clinical diagnosis of distal radius fractures (DRFs), and further compare it with human performance to verify the feasibility of this method. Methods: A total of 3,240 patients (fracture: n = 1,620, normal: n = 1,620) were included in this study, with a total of 3,276 wrist joint anteroposterior (AP) X-ray films (1,639 fractured, 1,637 normal) and 3,260 wrist joint lateral X-ray films (1,623 fractured, 1,637 normal). We divided the patients into training set, validation set and test set in a ratio of 7:1.5:1.5. The deep learning models were developed using the data from the training and validation sets, and then their effectiveness were evaluated using the data from the test set. Evaluate the diagnostic performance of deep learning models using receiver operating characteristic (ROC) curves and area under the curve (AUC), accuracy, sensitivity, and specificity, and compare them with medical professionals. Results: The deep learning ensemble model had excellent accuracy (97.03%), sensitivity (95.70%), and specificity (98.37%) in detecting DRFs. Among them, the accuracy of the AP view was 97.75%, the sensitivity 97.13%, and the specificity 98.37%; the accuracy of the lateral view was 96.32%, the sensitivity 94.26%, and the specificity 98.37%. When the wrist joint is counted, the accuracy was 97.55%, the sensitivity 98.36%, and the specificity 96.73%. In terms of these variables, the performance of the ensemble model is superior to that of both the orthopedic attending physician group and the radiology attending physician group. Conclusion: This deep learning ensemble model has excellent performance in detecting DRFs on plain X-ray films. Using this artificial intelligence model as a second expert to assist clinical diagnosis is expected to improve the accuracy of diagnosing DRFs and enhance clinical work efficiency.

Effects of Web-Based Mindfulness-Based Interventions on Anxiety, Depression, and Stress Among Frontline Health Care Workers During the COVID-19 Pandemic: Systematic Review and Meta-Analysis.

BACKGROUND: Since 2019, the COVID-19 outbreak has spread around the world, and health care workers, as frontline workers, have faced tremendous psychological stress. OBJECTIVE: The purpose of this study is to explore whether web-based mindfulness-based interventions continue to have a positive impact on anxiety, depression, and stress among health care workers during the COVID-19 pandemic. METHODS: The inclusion criteria were as follows: (1) participants were frontline health care workers during the COVID-19 pandemic; (2) the experimental group was a web-based mindfulness-based intervention; (3) the control group used either general psychological intervention or no intervention; (4) outcome indicators included scales to assess anxiety, depression, and stress; and (5) the study type was a randomized controlled study. Studies that did not meet the above requirements were excluded. We searched 9 databases, including Web of Science, Embase, PubMed, Cochrane Library, Scopus, ScienceDirect, SinoMed, China National Knowledge Infrastructure (CNKI), and Wanfang Database, for randomized controlled studies on the effects of web-based mindfulness-based interventions on common mental disorder symptoms among health care workers from January 1, 2020, to October 20, 2022. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database scale. The Cochrane risk of bias tool was used to assess the risk of bias. Subgroup analysis was used to look for sources of heterogeneity and to explore whether the results were the same for subgroups under different conditions. Sensitivity analysis was used to verify the stability of the pooled results. RESULTS: A total of 10 randomized controlled studies with 1311 participants were included. The results showed that web-based mindfulness-based interventions were effective in reducing the symptoms of anxiety (standard mean difference [SMD]=-0.63, 95% CI -0.96 to -0.31, P<.001, I2=87%), depression (SMD=-0.52, 95% CI -0.77 to -0.26, P<.001, I2=75%), and stress (SMD=-0.20, 95% CI -0.35 to -0.05, P=.01, I2=58%) among health care workers during the COVID-19 pandemic, but with wide CIs and high heterogeneity. CONCLUSIONS: Web-based mindfulness-based interventions may be effective in reducing the symptoms of anxiety, depression, and stress among frontline health care workers during the COVID-19 pandemic. However, this effect is relatively mild and needs to be further explored by better studies in the future. TRIAL REGISTRATION: PROSPERO CRD42022343727; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=343727.

Pneumonia, lymphocytes and C-reactive protein are valuable tests for predicting surgical intervention in necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is one of the important causes of neonatal death, and proper timing of operation is of critical significance. This study aimed to explore the high-risk factors for NEC requiring surgical intervention and to provide a reference for its clinical diagnosis and treatment. Methods: Clinical and radiological evidence of NEC neonates admitted to Zhujiang Hospital of Southern Medical University and Zhongshan Boai Hospital from January 2010 to October 2022 were retrospectively analyzed. Patients were divided into surgical group and conservative group according to whether they underwent surgery or not. Univariate analysis of the clinical data of the two groups was conducted, and multivariate logistic regression analysis was then performed for statistically significant results in the univariate analysis. Results: 267 infants were included in this study, of which 90 patients underwent surgical intervention for NEC and 177 conservation treatment. The univariate analysis showed that the gestational age, pneumonia, leukocytes, lymphocytes, erythrocytes, platelets, C-reactive protein, and blood glucose were statistically significant in the surgical group compared to the conservative group (All P < 0.05). Furthermore, the results of multivariate logistic regression analysis showed that compared to the conservative group, patients in the surgical group had a higher proportion of pneumonia (OR = 2.098; 95% CI: 1.030-4.272; P = 0.041), lower lymphocyte values (OR = 0.749; 95% CI: 0.588-0.954; P = 0.019), and higher C-reactive protein values (OR = 1.009; 95% CI: 1.003-1.016; P = 0.004). Conclusions: Pneumonia, decreased lymphocytes, and elevated C-reactive protein are potential high-risk factors for neonates with NEC requiring surgical intervention and may have potential clinical implications for predicting surgical risk.

Deep learning system assisted detection and localization of lumbar spondylolisthesis.

Objective: Explore a new deep learning (DL) object detection algorithm for clinical auxiliary diagnosis of lumbar spondylolisthesis and compare it with doctors' evaluation to verify the effectiveness and feasibility of the DL algorithm in the diagnosis of lumbar spondylolisthesis. Methods: Lumbar lateral radiographs of 1,596 patients with lumbar spondylolisthesis from three medical institutions were collected, and senior orthopedic surgeons and radiologists jointly diagnosed and marked them to establish a database. These radiographs were randomly divided into a training set (n = 1,117), a validation set (n = 240), and a test set (n = 239) in a ratio of 0.7 : 0.15: 0.15. We trained two DL models for automatic detection of spondylolisthesis and evaluated their diagnostic performance by PR curves, areas under the curve, precision, recall, F1-score. Then we chose the model with better performance and compared its results with professionals' evaluation. Results: A total of 1,780 annotations were marked for training (1,242), validation (263), and test (275). The Faster Region-based Convolutional Neural Network (R-CNN) showed better precision (0.935), recall (0.935), and F1-score (0.935) in the detection of spondylolisthesis, which outperformed the doctor group with precision (0.927), recall (0.892), f1-score (0.910). In addition, with the assistance of the DL model, the precision of the doctor group increased by 4.8%, the recall by 8.2%, the F1-score by 6.4%, and the average diagnosis time per plain X-ray was shortened by 7.139 s. Conclusion: The DL detection algorithm is an effective method for clinical diagnosis of lumbar spondylolisthesis. It can be used as an assistant expert to improve the accuracy of lumbar spondylolisthesis diagnosis and reduce the clinical workloads.

Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1.

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.

Do dietary supplements prevent loss of muscle mass and strength during muscle disuse? A systematic review and meta-analysis of randomized controlled trials.

Objective: We performed a systematic review and meta-analysis of existing randomized controlled trials (RCTs) to assess whether dietary supplements can prevent loss of muscle mass and strength during muscle disuse. Methods: We searched the following databases: PubMed, Embase, Cochrane, Scopus, Web of Science, and CINAHL for RCTs assessing the effect of dietary supplements on disuse muscular atrophy without language and time restrictions. Muscle strength and leg lean mass were used as the primary outcome indicators. Muscle cross-sectional area (CSA), muscle fiber type distribution, peak aerobic capacity and muscle volume were used as secondary outcome indicators. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. Heterogeneity was tested using the I2 statistic index. Mean and standard deviation of outcome indicators were extracted from the intervention and control groups to calculate effect sizes and 95% confidence intervals, with the significance level set at P < 0.05. Results: Twenty RCTs were included with a total of 339 subjects. The results showed that dietary supplements had no effect on muscle strength, CSA, muscle fiber type distribution, peak aerobic capacity or muscle volume. But dietary supplements have a protective effect on the lean mass of the legs. Conclusion: Dietary supplements can improve lean leg mass, but did not show a tendency to have an effect on muscle strength, CSA, muscle fiber type distribution, peak aerobic capacity or muscle volume during muscle disuse. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42022370230.

Characterization of beta subunit variants of recombinant human chorionic gonadotrophin.

Human chorionic gonadotropin (hCG), an endogenous glycoprotein hormone, has been widely used for the treatment of infertility and corpus luteum defect in women. The biological specificity of hCG is essentially determined by its beta (ß-) subunit, whereas the alpha (α-) subunit is a common subunit shared among the gonadotropin family. In development of a therapeutic recombinant hCG, the purity analysis showed that the beta (ß-) subunit has two variants, ß1 and ß2. Structural characterization using a combination of analytical techniques has demonstrated that ß1-subunit is derived from non-glycosylation at Asn 13, whereas ß2-subunit is a normal species with complete N-glycosylation at both Asn 13 and Asn 30. In vivo Bioactivity evaluation of the r-hCG fractions with various ratios of ß1-and ß2-subunits showed that incomplete glycosylation at Asn 13 potentially reduced the biological activity of r-hCG to promote uterus growth. Although hCG has a long history of medicinal use, this is the first report to identify the structural difference of hCG ß-subunit variants, as well as to preliminary establish the structure-activity relationship of this variation. The obtained results also suggest the importance of variant characterization and necessary quality control of product variants during the development of recombinant protein therapeutics.

Effect of focused power ultrasound-mediated perirenal fat modification on primary hypertension: protocol of a multicenter, randomized, double-blinded, sham-controlled study.

BACKGROUND: Perirenal fat plays a key role in sustaining pathological high blood pressure. We aim to investigate the efficacy of intervention for perirenal fat mediated by focused power ultrasound (FPU) on primary hypertension. METHODS: A multicenter, randomized, sham-controlled, double-blinded trial will be implemented in 200 participants with mild to moderate hypertension. All enrolled participants will be randomly allocated to perirenal fat modification (PFM) intervention using FPU or sham-procedure at a ratio of 1:1 and will be followed up at 24 h, 14 days, 30 days, and 90 days after the intervention. The primary endpoint is changes in office systolic blood pressure (SBP) at 30 days compared with baseline. The secondary endpoints include the changes in office SBP from baseline to 90 days, changes in 24-h mean SBP from baseline to 30 days and 90 days, and changes in heart rate from baseline to 30 days. Safety endpoint is defined as any severe adverse events related to the intervention. DISCUSSION: The present study is the first to use noninvasive FPU to intervene in perirenal fat to achieve the goal of reducing blood pressure for patients with essential hypertension. Our study is expected to provide a new treatment strategy to control high blood pressure. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05049096. Registered on September 7, 2021. PROTOCOL VERSION: Version 1.3.1, data 23 August 2021. SPONSOR: Prof. Xiangqing Kong is the principal investigator of this trial.

Cu-Catalyzed Decarboxylative Annulation of N-Phenylglycines with Maleimides: Synthesis of 1H-Pyrrolo[3,4-c]quinoline-1,3(2H)-diones.

A novel protocol for the construction of functionalized 1H-pyrrolo[3,4-c]quinoline-1,3(2H)-diones (PQLs, 3) from N-phenylglycines and maleimides was developed. The cascade reaction was enabled by heating a mixture of the two substrates in the presence of di-tert-butyl peroxide (DTBP) as an oxidant and anhydrous CuBr as a catalyst in chlorobenzene. Consequently, a diverse series of PQLs 3 were synthesized in moderate-to-good yields (43-73%). The synthesis of the PQLs was enabled via a one-pot cascade reaction that proceeded through subsequent oxidative decarboxylation, 1,2-addition, intramolecular cyclization, tautomerization, and aromatization reactions. This protocol can be used for the synthesis of functionalized PQLs via a one-pot oxidative decarboxylation annulation reaction rather than through a series of multistep reactions, making it suitable for both combinatorial and parallel syntheses of PQLs.