Evaluating the efficacy and safety of Alzheimer's disease drugs: A meta-analysis and systematic review.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial. OBJECTIVE: The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis. METHODS: We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results. RESULTS: All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs. CONCLUSION: ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.

Deep learning-assisted diagnosis of benign and malignant parotid tumors based on ultrasound: a retrospective study.

BACKGROUND: To develop a deep learning(DL) model utilizing ultrasound images, and evaluate its efficacy in distinguishing between benign and malignant parotid tumors (PTs), as well as its practicality in assisting clinicians with accurate diagnosis. METHODS: A total of 2211 ultrasound images of 980 pathologically confirmed PTs (Training set: n = 721; Validation set: n = 82; Internal-test set: n = 89; External-test set: n = 88) from 907 patients were retrospectively included in this study. The optimal model was selected and the diagnostic performance evaluation is conducted by utilizing the area under curve (AUC) of the receiver-operating characteristic(ROC) based on five different DL networks constructed at varying depths. Furthermore, a comparison of different seniority radiologists was made in the presence of the optimal auxiliary diagnosis model. Additionally, the diagnostic confusion matrix of the optimal model was calculated, and an analysis and summary of misjudged cases' characteristics were conducted. RESULTS: The Resnet18 demonstrated superior diagnostic performance, with an AUC value of 0.947, accuracy of 88.5%, sensitivity of 78.2%, and specificity of 92.7% in internal-test set, and with an AUC value of 0.925, accuracy of 89.8%, sensitivity of 83.3%, and specificity of 90.6% in external-test set. The PTs were subjectively assessed twice by six radiologists, both with and without the assisted of the model. With the assisted of the model, both junior and senior radiologists demonstrated enhanced diagnostic performance. In the internal-test set, there was an increase in AUC values by 0.062 and 0.082 for junior radiologists respectively, while senior radiologists experienced an improvement of 0.066 and 0.106 in their respective AUC values. CONCLUSIONS: The DL model based on ultrasound images demonstrates exceptional capability in distinguishing between benign and malignant PTs, thereby assisting radiologists of varying expertise levels to achieve heightened diagnostic performance, and serve as a noninvasive imaging adjunct diagnostic method for clinical purposes.

Mechanism and ecological environmental risk assessment of peroxymonosulfate for the treatment of heavy metals in soil.

Oxidation technologies based on peroxymonosulfate (PMS) have been effectively used for the remediation of soil organic pollutants due to their high efficiency. However, the effects of advanced PMS-based oxidation technologies on other soil pollutants, such as heavy metals, remain unknown. In this study, changes in the form of heavy metals in soil after using PMS and the risk of pollution to the ecological environment were investigated. Furthermore, two risk assessment methods, the mung bean germination toxicity test and groundwater leaching soil column test, were employed to evaluate the soil before and after PMS treatment. The results showed that PMS has a strong ability to degrade complex compounds, enabling the transformation of heavy metals, such as Cd, Pb, and Zn, from stable to active states in the soil. The risk assessments showed that PMS treatment activated heavy metals in the soil, which delayed the growth of plants, increased heavy metal content in plant tissues and the risk of groundwater pollution. These findings provide a new perspective for understanding the effects of PMS on soil, thus facilitating the sustained and reliable development of future research in the field of advanced oxidation applied to soil treatment.

Faecal Microbiota Transplantation Alleviates Ferroptosis after Ischaemic Stroke.

Ischaemic stroke can induce changes in the abundance of gut microbiota constituents, and the outcome of stroke may also be influenced by the gut microbiota. This study aimed to determine whether gut microbiota transplantation could rescue changes in the gut microbiota and reduce ferroptosis after stroke in rats. Male Sprague-Dawley rats (6 weeks of age) were subjected to ischaemic stroke by middle cerebral artery occlusion (MCAO). Fecal samples were collected for 16S ribosomal RNA (rRNA) sequencing to analyze the effects of FMT on the gut microbiota. Neurological deficits were evaluated using the Longa score. triphenyl tetrazolium chloride (TTC) staining was performed in the brain, and kits were used to measure malondialdehyde (MDA), iron, and glutathione (GSH) levels in the ipsilateral brain of rats. Western blotting was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and the transferrin receptor 2 (TFR2) in the ipsilateral brain of rats. Stroke induced significant changes in the gut microbiota, and FMT ameliorated these changes. TTC staining results showed that FMT reduced cerebral infarct volume. In addition, FMT diminished MDA and iron levels and elevated GSH levels in the ipsilateral brain. Western blot analysis showed that FMT increased GPX4 and SLC7A11 protein expression and decreased TFR2 protein expression in the ipsilateral brain after stroke. FMT can reverse gut microbiota dysbiosis, reduce cerebellar infarct volume, and decrease ferroptosis after stroke.

Deep learning to assist composition classification and thyroid solid nodule diagnosis: a multicenter diagnostic study.

OBJECTIVES: This study aimed to propose a deep learning (DL)-based framework for identifying the composition of thyroid nodules and assessing their malignancy risk. METHODS: We conducted a retrospective multicenter study using ultrasound images from four hospitals. Convolutional neural network (CNN) models were constructed to classify ultrasound images of thyroid nodules into solid and non-solid, as well as benign and malignant. A total of 11,201 images of 6784 nodules were used for training, validation, and testing. The area under the receiver-operating characteristic curve (AUC) was employed as the primary evaluation index. RESULTS: The models had AUCs higher than 0.91 in the benign and malignant grading of solid thyroid nodules, with the Inception-ResNet AUC being the highest at 0.94. In the test set, the best algorithm for identifying benign and malignant thyroid nodules had a sensitivity of 0.88, and a specificity of 0.86. In the human vs. DL test set, the best algorithm had a sensitivity of 0.93, and a specificity of 0.86. The Inception-ResNet model performed better than the senior physicians (p < 0.001). The sensitivity and specificity of the optimal model based on the external test set were 0.90 and 0.75, respectively. CONCLUSIONS: This research demonstrates that CNNs can assist thyroid nodule diagnosis and reduce the rate of unnecessary fine-needle aspiration (FNA). CLINICAL RELEVANCE STATEMENT: High-resolution ultrasound has led to increased detection of thyroid nodules. This results in unnecessary fine-needle aspiration and anxiety for patients whose nodules are benign. Deep learning can solve these problems to some extent. KEY POINTS: • Thyroid solid nodules have a high probability of malignancy. • Our models can improve the differentiation between benign and malignant solid thyroid nodules. • The differential performance of one model was superior to that of senior radiologists. Applying this could reduce the rate of unnecessary fine-needle aspiration of solid thyroid nodules.

Cost-effectiveness of active surveillance versus early surgery for thyroid micropapillary carcinoma based on diagnostic and treatment norms in China.

Objectives: In this study, we compared the cost-effectiveness comparison of the active surveillance (AS) and early surgery (ES) approaches for papillary thyroid microcarcinoma (PTMC) from the perspective of the Chinese healthcare system. Methods: We performed a cost-effectiveness analysis using a Markov model of PTMC we developed to evaluate the incremental cost-effectiveness ratio of AS and ES. Our reference case was of a 40-year-old woman diagnosed with unifocal (<10 mm) PTMC. Relevant data were extracted after an extensive literature review, and the cost incurred in each state was determined using China Medicare data on payments for ES and AS. The willingness-to-pay threshold was set at ¥242,928/quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to account for any uncertainty in the model's variables. Additional subgroup analyses were performed to determine whether AS was cost-effective when different initial monitoring ages were used. Results: ES exhibited an effectiveness of 5.2 QALYs, whereas AS showed an effectiveness of 25.8 QALYs. Furthermore, the incremental cost-effectiveness ratio for ES versus AS was ¥1,009/QALY. The findings of all sensitivity analyses were robust. Compared with ES, AS was found to be the cost-effective strategy at initial monitoring ages of 20 and 60 years, with an incremental cost-effectiveness ratio of ¥3,431/QALY and -¥1,316/QALY at 20 and 60 years, respectively. AS was a more cost-effective strategy in patients with PTMC aged more than 60. Conclusions: With respect to the norms of the Chinese healthcare system, AS was more cost-effective for PTMC over lifetime surveillance than ES. Furthermore, it was cost-effective even when the initial monitoring ages were different. In addition, if AS is incorporated into the management plan for PTMC in China at the earliest possible stage, a predicted savings of ¥10 × 108/year could be enabled for every 50,000 cases of PTMC, which indicates a good economic return for future management programs. The identification of such nuances can help physicians and patients determine the best and most individualized long-term management strategy for low-risk PTMC.

Combined conventional ultrasonography with clinicopathological features to predict axillary status after neoadjuvant therapy for breast cancer: A case-control study.

OBJECTIVES: This study aimed to evaluate the value of a model combining conventional ultrasonography and clinicopathologic features for predicting axillary status after neoadjuvant therapy in breast cancer. METHODS: This retrospective study included 329 patients with lymph node-positive who underwent neoadjuvant systemic treatment (NST) from June 2019 to March 2022. Ultrasound and clinicopathological characteristics of breast lesions and axillary lymph nodes were analyzed before and after NST. The diagnostic efficacy of ultrasound, clinicopathological characteristics, and combined model were evaluated using multivariate logistic regression and receiver operator characteristic curve (ROC) analyses. RESULTS: The area under ROC (AUC) for the ability of the combined model to predict the axillary pathological complete response (pCR) after NST was 0.882, that diagnostic effectiveness was significantly better than that of the clinicopathological model (AUC of 0.807) and the ultrasound feature model (AUC of 0.795). In addition, eight features were screened as independent predictors of axillary pCR, including clinical N stage, ERBB2 status, Ki-67, and after NST the maximum diameter reduction rate and margins of breast lesions, the short diameter, cortical thickness, and fatty hilum of lymph nodes. CONCLUSIONS: The combined model constructed from ultrasound and clinicopathological features for predicting axillary pCR has favorable diagnostic results, which allowed more accurate identification of BC patients who had received axillary pCR after NST. ADVANCES IN KNOWLEDGE: A combined model incorporated ultrasound and clinicopathological characteristics of breast lesions and axillary lymph nodes demonstrated favorable performance in evaluating axillary pCR preoperatively and non-invasively.

Nucleocapsid protein residues 35, 36, and 113 are critical sites in up-regulating the Interleukin-8 production via C/EBPα pathway by highly pathogenic porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious and pathogenic agent that causes considerable economic damage in the swine industry. It regulates the inflammatory response, triggers inflammation-induced tissue damage, suppresses the innate immune response, and leads to persistent infection. Interleukin-8 (IL-8), a pro-inflammatory chemokine, plays a crucial role in inflammatory response during numerous bacteria and virus infections. However, the underlying mechanisms of IL-8 regulation during PRRSV infection are not well understood. In this study, we demonstrate that PRRSV-infected PAMs and Marc-145 cells release higher levels of IL-8. We screened the nucleocapsid protein, non-structural protein (nsp) 9, and nsp11 of PRRSV to enhance IL-8 promoter activity via the C/EBPα pathway. Furthermore, we identified that the amino acids Q35A, S36A, R113A, and I115A of the nucleocapsid protein play a crucial role in the induction of IL-8. Through reverse genetics, we generated two mutant viruses (rQ35-2A and rR113A), which showed lower induction of IL-8 in PAMs during infection. This finding uncovers a previously unrecognized role of the PRRSV nucleocapsid protein in modulating IL-8 production and provides insight into an additional mechanism by which PRRSV modulates immune responses and inflammation.

Ultrasound and clinicopathological characteristics-based model for prediction of pathologic response to neoadjuvant chemotherapy in HER2-positive breast cancer: a case-control study.

BACKGROUND: The objective of this study was to develop a model combining ultrasound (US) and clinicopathological characteristics to predict the pathologic response to neoadjuvant chemotherapy (NACT) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. MATERIALS AND METHODS: This is a retrospective study that included 248 patients with HER2-positive breast cancer who underwent NACT from March 2018 to March 2022. US and clinicopathological characteristics were collected from all patients in this study, and characteristics obtained using univariate analysis at p < 0.1 were subjected to multivariate analysis and then the conventional US and clinicopathological characteristics independently associated with pathologic complete response (pCR) from the analysis were used to develop US models, clinicopathological models, and their combined models by the area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, and specificity to assess their predictive efficacy. RESULTS: The combined model had an AUC of 0.808, a sensitivity of 88.72%, a specificity of 60.87%, and an accuracy of 75.81% in predicting pCR of HER2-positive breast cancer after NACT, which was significantly better than the clinicopathological model (AUC = 0.656) and the US model (AUC = 0.769). In addition, six characteristics were screened as independent predictors, namely the Clinical T stage, Clinical N stage, PR status, posterior acoustic, margin, and calcification. CONCLUSION: The conventional US combined with clinicopathological characteristics to construct a combined model has a good diagnostic effect in predicting pCR in HER2-positive breast cancer and is expected to be a useful tool to assist clinicians in effectively determining the efficacy of NACT in HER2-positive breast cancer patients.

Value of Artificial Intelligence in Improving the Accuracy of Diagnosing TI-RADS Category 4 Nodules.

OBJECTIVE: Considerable heterogeneity is observed in the malignancy rates of thyroid nodules classified as category 4 according to the Thyroid Imaging Reporting and Data System (TI-RADS). This study was aimed at comparing the diagnostic performance of artificial intelligence algorithms and radiologists with different experience levels in distinguishing benign and malignant TI-RADS 4 (TR4) nodules. METHODS: Between January 2019 and September 2022, 1117 TR4 nodules with well-defined pathological findings were collected for this retrospective study. An independent external data set of 125 TR4 nodules was incorporated for testing purposes. Traditional feature-based machine learning (ML) models, deep convolutional neural networks (DCNN) models and a fusion model that integrated the prediction outcomes from all models were used to classify benign and malignant TR4 nodules. A fivefold cross-validation approach was employed, and the diagnostic performance of each model and radiologists was compared. RESULTS: In the external test data set, the area under the receiver operating characteristic curve (AUROC) of the three DCNN-based secondary transfer learning models-InceptionV3, DenseNet121 and ResNet50-were 0.852, 0.837 and 0.856, respectively. These values were higher than those of the three traditional ML models-logistic regression, multilayer perceptron and random forest-at 0.782, 0.790, and 0.767, respectively, and higher than that of an experienced radiologist (0.815). The fusion diagnostic model we developed, with an AUROC of 0.880, was found to outperform the experienced radiologist in diagnosing TR4 nodules. CONCLUSION: The integration of artificial intelligence algorithms into medical imaging studies could improve the accuracy of identifying high-risk TR4 nodules pre-operatively and have significant clinical application potential.

Relationship between inflammatory-related cytokines with aortic dissection.

Aortic dissection, characterized by severe intramural hematoma formation and acute endometrial rupture, is caused by excessive bleeding within the aortic wall or a severe tear within the intimal layer of the aorta, which subsequently promotes the separation or dissection in the layers of the aortic wall. Epidemiological surveys showed that aortic dissection was most observed among those patients from 55 to 80 years of age, with a prevalence of approximately 40 cases per 100,000 individuals per year, posing serious risks to future health and leading to high mortality. Other risk factors of aortic dissection progression contained dyslipidemia, hypertension, and genetic disorders, such as Marfan syndrome. Currently, emerging evidence indicates the pathological progression of aortic dissection is significantly complicated, which is correlated with the aberrant infiltration of pro-inflammatory cells into the aortic wall, subsequently facilitating the apoptosis of vascular smooth muscle cells (VSMCs) and inducing the aberrant expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interferon (IF). Other pro-inflammatory-related cytokines, including the colony-stimulating factor (CSF), chemotactic factor, and growth factor (GF), played an essential function in facilitating aortic dissection. Multiple studies focused on the important relationship between pro-inflammatory cytokines and aortic dissection, which could deepen the understanding of aortic dissection and further guide the therapeutic strategies in clinical practice. The present review elucidated pro-inflammatory cytokines' functions in modulating the risk of aortic dissection are summarized. Moreover, the emerging evidence that aimed to elucidate the potential mechanisms wherebyvarious pro-inflammatory cytokines affected the pathological development of aortic dissection was also listed.

Cholesteric liquid crystal biosensor platform with image analysis for rapid detection of COVID-19.

Rapid and low-cost diagnosis of coronavirus disease 2019 (COVID-19) is essential to identify infected subjects, particularly asymptomatic cases, primarily to arrest the spread of the disease through local transmission. Antibody-based chromatographic serological tests, as an alternative to the RT-PCR technique, offer only limited help due to high false positives. We propose to exploit our cholesteric liquid crystal biosensor platform for one-step, wash-free, rapid detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus directly with minimal sample pre-processing. As mentioned above, cholesteric liquid crystals are an effective and innovative approach to healthcare as a rapid test for the diagnosis of COVID-19 and other diseases.

Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83.

Porcine reproductive and respiratory syndrome virus (PRRSV), the most economically important infectious disease of pigs, elicits poor innate and adaptive immune responses. Soluble CD83 (sCD83), a secretion from various immune cell populations, especially MoDCs, is involved in negatively regulating the immune response. We speculate sCD83 may be a critical factor in the process of PRRSV-coordinated macrophage polarization. In this study, we found that PAMs co-cultured with PRRSV-infected MoDCs inhibited the M1 macrophage while enhancing the M2 macrophage. This was accompanied by a decrease in the pro-inflammatory cytokine TNF-α and iNOS and an increase in the anti-inflammatory cytokine IL-10 and Arg1. Meanwhile, sCD83 incubation causes the same specific effects lead to a switch in macrophage from M1 to M2. Neutralization of sCD83 removes the inhibitory effects of PRRSV on PAMs. Using reverse genetics, we generated recombinant PRRSVs with mutations in N protein, nsp1α, and nsp10 (knockout sCD83-concerned key amino acid site). Four mutant viruses lost the suppression of M1 macrophage markers, in contrast to the restriction of the upregulation of M2 macrophage markers. These findings suggest that PRRSV modulates the switch of macrophage polarization from M1 to M2 by upregulating the MoDC-induced secretion of CD83, providing new insights into the mechanism by which PRRSV regulates host immunity.

Performance-enhanced fiber optic humidity sensors based on SiO2/porous PMMA coatings.

Employing functional and structured thin films on fiber optic sensors has tremendously improved capabilities in humidity sensing applications. In this paper, we demonstrate fabrication of a fiber optic evanescent wave humidity sensor based on S i O 2/porous polymethyl methacrylate (PMMA) thin films. With the exposure to moisture, S i O 2/porous PMMA thin films absorb water molecules. The refractive index and absorption coefficient of thin films change with ambient humidity, resulting in modulation of the light intensity transmitted in fiber. A good linearity is determined between the logarithm of output light intensity and relative humidity (RH). An optimal average sensitivity of 188.3 lux/%RH is achieved with an increase of 11.7 fold in the RH range of 5% to 95%. The response and recovery times are 8 s and 23 s, respectively. Furthermore, the sensor exhibits low hysteresis, and excellent stability and repeatability.

Novel Spinal Cord Stimulation Waveforms for Treating Back and Leg Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Spinal cord stimulation (SCS) has been suggested as a treatment option to improve the quality-adjusted life years of individuals with low back pain. However, previous reviews have some methodologic limitations. This review aims to evaluate the effectiveness of novel SCS waveforms on pain outcomes in patients with low back pain (LBP) compared with traditional SCS or placebo comparator. MATERIALS AND METHODS: Nine electronic data bases, ongoing trials, gray literature, and targeted journals were searched from inception to December 27, 2021. The Cochrane risk of bias and Grading of Recommendation, Assessment, Development, and Evaluations were used to appraise individual and overall evidence. Subjects aged ≥ 18 years with or without previous surgeries and having LBP for at least three months were included. The primary outcome was pain intensity including back or leg pain scores at postintervention. Secondary outcomes comprised decrease in back, leg, and overall pain, and health-related quality of life. RESULTS: A total of 11 randomized controlled trials (RCTs) involving 955 participants across four countries were included. Our meta-analysis revealed that novel SCS waveform was superior to traditional SCS or placebo comparator for treating leg pain (Z = -2.12, p = 0.03) with a small effect size (Hedges' g = -0.18, 95% CI: -0.34 to -0.01). Back-pain intensity (g = -0.22, 95% CI: -0.47 to 0.02) and health-related quality of life (g = -0.12, 95% CI: -0.43 to 0.18) were similar between the novel SCS waveform group and the traditional SCS or placebo comparator groups. The meta-regression did not identify any effect of the covariates on back-pain intensity. CONCLUSIONS: With low certainty of evidence, this finding provides a rationale for considering the novel SCS waveform as complements to the usual therapeutic plan. Future trials should adopt well-designed RCTs with larger sample size and follow-up assessment.

Novel Insights into the Important Role of Leptin in Modulating the Pathological Development of Fibrotic-related Diseases.

Leptin, as one of the most important cytokines within the circulation, has been confirmed to play a vital role in the hypothalamus of the central nervous system (CNS), which could modulate energy homeostasis by suppressing food intake. Furthermore, leptin could also influence cell metabolism by acting directly on the leptin receptor, which is a relatively small peptide and is mainly produced and released by fat tissue in mammals. On the other hand, the excessive extracellular matrix (ECM) could induce damage in normal tissues or organ structures, which might further induce fibrotic development in multiple tissues or organs, including the liver, heart, and kidneys. Notably, the sustainable development of fibrosis promotes the structural lesion and functional decline of different organs, which subsequently threatens human health and poses serious risks to human life. Emerging evidence has shown that leptin plays an important role in the fibrotic progression within multiple tissues and organs in mammals and has an alleviating effect on fibrosis. Concerning this notion, it has been proposed that leptin could be identified as a vital therapeutic strategy for fibrotic progression in clinical practice. Consequently, this review summarized the potential mechanisms of leptin in modulating fibrotic development in diverse tissues and organs to provide a theoretical basis for treating fibrotic-related diseases. In addition, the potential mechanisms whereby leptin affects the development of fibrosis were also summarized in the current review.

MiR-424-5p targets HSP90AA1 to facilitate proliferation and restrain differentiation in skeletal muscle development.

MiR-424-5p was found to be a potential regulator in the proliferation, migration, and invasion of various cancer cells. However, the effects and functional mechanism of miR-424-5p in the process of myogenesis are still unclear. Previously, using microRNA (miRNA) sequencing and expression analysis, we discovered that miR-424-5p was expressed differentially in the different skeletal muscle growth periods of Xuhuai goats. We hypothesized that miR-424-5p might play an important role in skeletal muscle myogenesis. Then, we found that the proliferation ability of the mouse myoblast cell (C2C12 myoblast cell line) was significantly augmented, whereas the C2C12 differentiation was repressed after increasing the expression of miR-424-5p. Mechanistically, HSP90AA1 presented a close interrelation with miR-424-5p, which was predicted as a target gene in the progression of skeletal muscle myogenesis, using transcriptome sequencing, dual luciferase reporter gene detection, and qRT-PCR. The silencing of HSP90AA1 obviously increased C2C12 proliferation and diminished differentiation, which is consistent with the ability of miR-424-5p in C2C12. Altogether, our findings indicated the role of miR-424-5p as a novel potential regulator via HSP90AA1 during muscle myogenesis progression.

Apolipoprotein A1 Inhibits Adipogenesis Progression of Human Adipose-Derived Mesenchymal Stem Cells.

BACKGROUND: According to the reports, the most vital characteristic of obesity is an aberrant accumulation of triglycerides (TG) in the adipocyte. On the other hand, circulating concentrations of apolipoprotein A1 (apoA1) have been demonstrated to be strongly correlated with the prevalence and the pathological development of obesity. Nevertheless, the underlying mechanisms whereby apoA1 modulates the pathogenesis of obesity is still not fully elucidated. METHODS: Adipose-derived mesenchymal stem cells (AMSCs, isolated from the hospitalized patients were combined with 15 µg/ml recombined human apoA1 protein. The effects of apoA1 on modulating the intracellular levels of TG and the expression contents of adipogenic related cytokines were also analyzed. Furthermore, whether apoA1 modulated the adipogenesis progression via sortilin was also explored in the current research. RESULTS: During the adipogenesis progression, apoA1 could significantly lower the quantity of intracellular lipid droplets (LDs). Meanwhile, apoA1 could decrease the intracellular levels of TG and down-regulate the expression contents of several vital adipogenic related cytokines, such as CCAAT enhancer-binding proteins α/ß (C/EBPα/ß), fatty acid synthetase (FAS), and fatty acid-binding protein 4 (FABP4). Moreover, the inhibitory effect of apoA1 was further verified to be induced through upregulating the SORT1 gene expression which subsequently increased sortilin protein. Consistent with these findings, silencing the SORT1 gene expression could induce the loss-of-function (LOF) of apoA1 in modulating the adipogenesis progression of AMSCs. CONCLUSION: In conclusion, apoA1 could suppress the adipogenesis progression of human AMSCs through, at least partly, up-regulating the SORT1 gene expression which subsequently increases the sortilin protein content. Thereby, the present research sheds light on a novel pathogenic mechanism by which apoA1 regulates adipogenesis progression and proposes that apoA1 embraces the function to treat obesity in clinical practice.

The effect of wearable-delivered sleep interventions on sleep outcomes among adults: A systematic review and meta-analysis of randomized controlled trials.

The aims of the review were to (i) evaluate the effectiveness of wearable-delivered sleep interventions on sleep outcomes among adults, and (ii) explore the effect of factors affecting total sleep time. Eight databases were searched to identify relevant studies in English from inception until December 23, 2021. The Cochrane Risk of Bias tool version 2.0 and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria were used to assess the risk of bias and certainty of the evidence, respectively. Twenty randomized controlled trials (RCTs) were included, involving 1608 adults across nine countries. Wearable-delivered sleep interventions elicited significant improvement of 1.96 events/h for the oxygen desaturation index and 3.13 events/h for the respiratory distress index. Meta-analyses found that wearable-delivered sleep interventions significantly decreased sleep disturbance (Hedges' g [g] = -0.37, 95% confidence interval [CI]: -0.59, -0.15) and sleep-related impairment (g = -1.06, 95% CI: -1.99, -0.13) versus the comparators. The wearable-delivered sleep interventions may complement usual care to improve sleep outcomes. More rigorous RCTs with a long-term assessment in a wide range of populations are warranted.

Peptide GL13K releasing hydrogel functionalized micro/nanostructured titanium enhances its osteogenic and antibacterial activity.

Bacterial infection and the subsequent lack of osseointegration are two of the main problems encountered during the early stage of implantation. To resolve these issues, in this study, the micro/nanostructure on titanium surface was fabricated by dual-acid treatment and anodic oxidation, and then GelMA hydrogel loaded with GL13K was coated onto the micro/nanostructured titanium. The surface properties of different titanium substrates were characterized by scanning electron microscopy, atomic force microscope, water contact angle measurement, and in vitro release of GL13K. The results demonstrated that peptide GL13K releasing hydrogel was successfully modified onto the micro/nanostructured titanium and GL13K displayed an effective controlled release. In vitro cell experiments including cytoskeleton observation, cell viability, phosphatase activity, mineralization and the expression of osteogenic related genes proved that the peptide GL13K releasing hydrogel modified micro/nanostructured titanium had good biocompatibility, promoted osteoblast differentiation. In vitro antibacterial experiments showed that it also can prevent the growth of gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria by the release of GL13K. This study demonstrates titanium surface modification that allows for the development of anti-bacterial titanium implants.