Serum SERCA2a levels in heart failure patients are associated with adverse events after discharge.

Calcium homeostasis imbalance is one of the important pathological mechanisms in heart failure. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), a calcium ATPase on the sarcoplasmic reticulum in cardiac myocytes, is a myocardial systolic-diastolic Ca2 + homeostasis regulating enzyme that is not only involved in cardiac diastole but also indirectly affects cardiac myocyte contraction. SERCA2a expression was found to be decreased in myocardial tissue in heart failure, however, there are few reports on serum SERCA2a expression in patients with heart failure, and this study was designed to investigate whether serum SERCA2a levels are associated with the occurrence of adverse events after discharge in patients hospitalized with heart failure. Patients with heart failure hospitalized in the cardiovascular department of the Second Affiliated Hospital of Guangdong Medical University, China, from July 2018 to July 2019 were included in this study, and serum SERCA2a concentrations were measured; each enrolled patient was followed up by telephone after 6 months (6 ±â€…1 months) for general post-discharge patient status. The correlation between serum SERCA2a levels and the occurrence of adverse events (death or readmission due to heart failure) after hospital discharge was assessed using multiple analysis and trend analysis. Seventy-one patients with heart failure were finally included in this study, of whom 38 (53.5%) were men and 33 (46.5%) were women (All were postmenopausal women). Multiple analysis revealed no correlation between serum SERCA2a levels and the occurrence of adverse events in the total study population and in male patients, but serum SERCA2a levels were associated with the occurrence of adverse outcome events after hospital discharge in female patients (OR = 1.02, P = .047). Further analysis using a trend analysis yielded a 4.0% increase in the risk of adverse outcomes after hospital discharge for each unit increase in SERCA2a in female patients (OR = 1.04; P = .02), while no significant difference was seen in men. This study suggests that serum SERCA2a levels at admission are associated with the occurrence of post-discharge adverse events in postmenopausal female patients hospitalized with heart failure.

Credit risk assessment of small and micro enterprise based on machine learning.

Small and micro enterprises are pivotal in national economic and social development. To foster their growth, managing their credit risks scientifically is crucial. This study starts by examining the credit information of these enterprises. We use imbalanced sample processing algorithms to ensure a balanced representation of minority-class samples. Then, a machine learning classifier is employed to identify key factors contributing to these enterprises' low credibility. Based on these factors, an XGBoost scoring card model is developed. The study reveals: firstly, the integration of the SMOTE algorithm with the XGBoost model exhibits certain performance advantages in handling imbalanced datasets; secondly, trustworthy financial information remains at the heart of crucial risk determinants; thirdly, the XGBoost scoring card model based on significant features effectively enhances the accuracy of credit risk assessment. These insights provide both theoretical references and practical tools for enhancing the robustness of small and micro enterprises, facilitating early warnings on credit risks, and refining financing efficiency.

Insight into roles of carbon anodes for removal of refractory organic contaminants in electro-peroxone system: Mechanism, performance and stability.

Electro-peroxone (EP) is a novel technique for the removal of refractory organic contaminants (ROCs), while the role of anode in this system is neglected. In this work, the EP system with graphite felt anode (EP-GF) and activated carbon fiber anode (EP-ACF) was developed to enhance ibuprofen (IBP) removal. The results showed that 91.2% and 98.6% of IBP was removed within 20 min in EP-GF and EP-ACF, respectively. Hydroxy radical (O⋅H) was identified as the dominant reactive species, contributing 80.9% and 54.0% of IBP removal in EP-ACF and EP-GF systems, respectively. The roles of adsorption in EP-ACF and direct electron transfer in EP-GF cannot be ignored. Due to the differences in mechanism, EP-GF and EP-ACF systems were suitable for the removal of O⋅H-resistant ROCs (e.g., oxalic acid and pyruvic acid) and non-O⋅H-resistant ROCs (e.g., IBP and nitrobenzene), respectively. Both systems had excellent stability relying on the introduction of oxygen functional groups on the anode, and their electrolysis energy consumption was significantly lower than that of EP-Pt system. The three degradation pathways of IBP were proposed, and the toxicity of intermediates were evaluated. In general, carbon anodes have a good application prospect in the removal of ROCs in EP systems.

Predicting voxel-level dose distributions of single-isocenter volumetric modulated arc therapy treatment plan for multiple brain metastases.

Purpose: Brain metastasis is a common, life-threatening neurological problem for patients with cancer. Single-isocenter volumetric modulated arc therapy (VMAT) has been popularly used due to its highly conformal dose and short treatment time. Accurate prediction of its dose distribution can provide a general standard for evaluating the quality of treatment plan. In this study, a deep learning model is applied to the dose prediction of a single-isocenter VMAT treatment plan for radiotherapy of multiple brain metastases. Method: A U-net with residual networks (U-ResNet) is employed for the task of dose prediction. The deep learning model is first trained from a database consisting of hundreds of historical treatment plans. The 3D dose distribution is then predicted with the input of the CT image and contours of regions of interest (ROIs). A total of 150 single-isocenter VMAT plans for multiple brain metastases are used for training and testing. The model performance is evaluated based on mean absolute error (MAE) and mean absolute differences of multiple dosimetric indexes (DIs), including (D max and D mean) for OARs, (D 98, D 95, D 50, and D 2) for PTVs, homogeneity index, and conformity index. The similarity between the predicted and clinically approved plan dose distribution is also evaluated. Result: For 20 tested patients, the largest and smallest MAEs are 3.3% ± 3.6% and 1.3% ± 1.5%, respectively. The mean MAE for the 20 tested patients is 2.2% ± 0.7%. The mean absolute differences of D 98, D 95, D 50, and D2 for PTV60, PTV52, PTV50, and PTV40 are less than 2.5%, 3.0%, 2.0%, and 3.0%, respectively. The prediction accuracy of OARs for D max and D mean is within 3.2% and 1.2%, respectively. The average DSC ranges from 0.86 to 1 for all tested patients. Conclusion: U-ResNet is viable to produce accurate dose distribution that is comparable to those of the clinically approved treatment plans. The predicted results can be used to improve current treatment planning design, plan quality, efficiency, etc.

A highly accurate and semi-automated method for quantifying spherical microplastics based on digital slide scanners and image processing.

Microplastics (MPs), the emerging pollutants appeared in water environment, have grabbed significant attention from researchers. The quantitative method of spherical MPs is the premise and key for the study of MPs in laboratory researches. However, the manual counting is time-consuming, and the existing semi-automated analysis lacked of robustness. In this study, a highly accurate quantification method for spherical MPs, called VS120-MC was proposed. VS120-MC consisted of the digital slide scanner VS120 and the MPs image processing software, MPs-Counter. The full-area scanning photography was employed to fundamentally avoid the error caused by random or partition sampling modes. To accomplish high-performance batch recognition, the Weak-Circle Elimination Algorithm (WEA) and the Variable Coefficient Threshold (VCT) was developed. Finally, lower than 0.6% recognition error rate of simulated images with different aggregated indices was achieved by MPs-Counter with fast processing speed (about 2 s/image). The smallest size for VS120-MC to detect was 1 µm. And the applicability of VS120-MC in real water body was investigated. The measured value of 1 µm spherical MPs in ultra-pure water and two kinds of polluted water after digestion showed a good linear relationship with the Manual measurements (R2 = 0.982,0.987 and 0.978, respectively). For 10 µm spherical MPs, R2 reached 0.988 for ultra-pure water and 0.984 for both of the polluted water. MPs-Counter also showed robustness when using the same set of parameters processing the images with different conditions. Overall, VS120-MC eliminated the error caused by traditional photography and realized an accurate, efficient, stable image processing tool, providing a reliable alternative for the quantification of spherical MPs.

Glycyrrhizin regulates antioxidation through Nrf2 signaling pathway in rat temporomandibular joint osteoarthritis.

BACKGROUND: Regulation of redox homeostasis could reduce osteoarthritis severity and limit disease progression, while glycyrrhizin (GL) shows great antioxidant and anti-inflammatory capacity. OBJECTIVE: The aim of this study was to investigate the role of GL on oxidative stress and the potential regulatory mechanism in rat temporomandibular joint (TMJ) chondrocytes under oxidative stress, and investigate the effect of GL in the rat temporomandibular joint osteoarthritis (TMJOA) model. METHODS: Rat TMJ chondrocytes were cultured in oxidative stress with different doses of GL. The effect of glycyrrhizin on the nuclear factor-erythroid 2-related factor 2 (Nrf2) in oxidative stress was evaluated by western blot and immunofluorescence staining. A rat model of TMJOA was treated with GL. Micro-computed tomography, histological and immunohistochemical analysis were used to assess the pathological change of TMJOA. RESULTS: The expression of superoxide dismutase 1 (SOD1), heme oxygenase-1 (HO-1), and peroxiredoxin 6 (PRDX6) were decreased, and intracellular Nrf2 signaling pathway was activated in chondrocytes in oxidative stress. GL upregulates the expression of antioxidants, especially PRDX6, as well as increases Nrf2 expression and nuclear translocation in rat condylar chondrocytes. Administration of GL attenuates condylar bone destruction, cartilage degeneration, and synovitis in rats TMJOA. Meanwhile, GL alleviated oxidative stress and enhanced the antioxidant capacity of TMJOA cartilage. CONCLUSION: This study suggested that GL alleviates rat TMJOA by regulating oxidative stress in condylar cartilage.

Preliminary study of cine-MRI compression in MR-guided radiotherapy.

Background: Cine-magnetic resonance imaging (MRI) is currently used in real-time tumor tracking during magnetic resonance (MR)-guided radiotherapy. As a type of MRI specified for motion tracking, a few minutes' acquisition results in thousands of 2-dimensional (2D) images. For MR-guided radiotherapy consisting of multiple treatment fractions, the large number of cine-MRI images would be disproportionate to the tight clinical data storage available. To alleviate this issue, the feasibility of compression of cine-MRI via video encoders was investigated in this study. Methods: The cine-MRI images were first sorted into 3 sequences according to their plane orientations. Then, each sequence was reordered according to their acquisition times [time-based (TB)] or content similarities [similarity-based (SB)]. As a result, 3 sequences were obtained for 3 plan orientations. Next, the obtained sequences were processed by a video encoder and the corresponding 3 video files were achieved. We employed 3 popular video encoders: Motion JPEG (M-JPEG), Advanced Video Coding (AVC), and High Efficiency Video Coding (HEVC). The performances of the sequence reordering methods and video encoders were evaluated based on a total of 150 image sets. Results: The mean correlation quantities for SB sequences were higher than those for TB sequences by 3% (sagittal), 2% (coronal), and 1% (transverse), respectively. The average compression ratio (CR) yielded by the SB sequences was higher than that achieved by the TB sequences. Comparing with M-JPEG, the CRs obtained by AVC and HEVC were increased by 58% and 62% (sagittal), 16% and 23% (coronal), and 48% and 56% (transverse), respectively. Among the 3 video encoders, the highest CRs and restoration accuracy were achieved by HEVC. Conclusions: HEVC with inter-frame coding is more effective in reducing the redundant information in consecutive images. It is feasible to implement the video encoder for high-performance cine-MRI compression.

Quality assurance in a phase III, multicenter, randomized trial of POstmastectomy radioThErapy in Node posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a planning benchmark case.

PURPOSE: To report the planning benchmark case results of the POTENTIAL trial-a multicenter, randomized, phase 3 trial-to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer. METHODS: All participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission. RESULTS: The plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. In the first and final submission, the mean values of PTVim V100% were 79.9% vs. 92.7%; the mean values of heart Dmean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively. CONCLUSION: The major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials.

Association between the triglyceride-glucose index and calcified aortic stenosis in elderly patients: a cross-sectional study.

Insulin resistance (IR) is associated with a variety of cardiovascular diseases, but there are few studies on the correlation between IR and calcified aortic stenosis (CAS). In this study, the triglyceride-glucose (TyG) index, which reflects IR, was used to investigate the correlation between IR and CAS. The study included 183 elderly patients who were diagnosed with CAS by transthoracic echocardiography. The patients were matched 1:1 according to age and sex, and elderly patients who were hospitalized during the same period and underwent transthoracic echocardiography without aortic stenosis were included as the control group. The relationship between the TyG index and CAS was analyzed by a multivariable logistic regression model, curve fitting and trend test. Multivariate logistic regression analysis showed that the TyG index as a continuous variable was negatively associated with CAS (P < 0.001); trend tests and curve fitting further supported this association. Our study showed that the TyG index was negatively associated with CAS in elderly patients, which may be related to the impairment of insulin receptors and signaling pathways in IR.

Pyroptosis of chondrocytes activated by synovial inflammation accelerates TMJ osteoarthritis cartilage degeneration via ROS/NLRP3 signaling.

OBJECTIVES: Synovial inflammation and chondrocyte death have been widely acknowledged as key contributors to the pathological progression of temporomandibular joint osteoarthritis (TMJ-OA), a degenerative joint disease currently lacking definitive treatments. This study aims to understand the regulatory role of chondrocyte pyroptosis in condylar cartilage degradation during TMJ-OA. METHODS: The levels of cytokines, cartilage degeneration markers, and pyroptotic biomarkers in the synovium and synovial fluid of temporomandibular disorders (TMD) patients were examined. The synovitis, cartilage degradation, and chondrocyte pyroptosis in wild-type and alpha-kinase 1 (ALPK1)-deficient TMJ-OA mice were then compared following monosodium iodoacetate (MIA) induction. Subsequently, we investigated the downstream mechanisms of cytokines- or macrophage supernatants-induced metabolic disorders and pyroptosis in chondrocytes using primary TMJ chondrocytes and ATDC5 chondrocyte cultures. RESULTS: We found a positive correlation between pyroptotic biomarkers and cartilage degradation mediators and cytokines in the synovial fluid of TMD patients. MIA-induced TMJ-OA mice demonstrated significant synovitis, cartilage degradation, and chondrocyte pyroptosis, which were mitigated in ALPK1-deficient TMJ-OA mice, inflammation-restrained mice. Ex-vivo study revealed the contribution of reactive oxygen species (ROS) to inflammation-irritated macrophage supernatants-induced pyroptosis and metabolic disorders in chondrocytes. Targeting NOD-like receptor protein 3 (NLRP3) alleviated cytokines- or ROS-induced pyroptosis and metabolic disorders in chondrocytes by inhibiting caspase-1 activation and interleukin-1ß (IL-1ß) secretion. CONCLUSION: Our findings offer novel insight into the role of synovial inflammation-induced chondrocyte pyroptosis in promoting cartilage degradation during TMJ-OA via the ROS and NLRP3 signaling pathway.

Improving accelerated 3D imaging in MRI-guided radiotherapy for prostate cancer using a deep learning method.

PURPOSE: This study was to improve image quality for high-speed MR imaging using a deep learning method for online adaptive radiotherapy in prostate cancer. We then evaluated its benefits on image registration. METHODS: Sixty pairs of 1.5 T MR images acquired with an MR-linac were enrolled. The data included low-speed, high-quality (LSHQ), and high-speed low-quality (HSLQ) MR images. We proposed a CycleGAN, which is based on the data augmentation technique, to learn the mapping between the HSLQ and LSHQ images and then generate synthetic LSHQ (synLSHQ) images from the HSLQ images. Five-fold cross-validation was employed to test the CycleGAN model. The normalized mean absolute error (nMAE), peak signal-to-noise ratio (PSNR), structural similarity index measurement (SSIM), and edge keeping index (EKI) were calculated to determine image quality. The Jacobian determinant value (JDV), Dice similarity coefficient (DSC), and mean distance to agreement (MDA) were used to analyze deformable registration. RESULTS: Compared with the LSHQ, the proposed synLSHQ achieved comparable image quality and reduced imaging time by ~ 66%. Compared with the HSLQ, the synLSHQ had better image quality with improvement of 57%, 3.4%, 26.9%, and 3.6% for nMAE, SSIM, PSNR, and EKI, respectively. Furthermore, the synLSHQ enhanced registration accuracy with a superior mean JDV (6%) and preferable DSC and MDA values compared with HSLQ. CONCLUSION: The proposed method can generate high-quality images from high-speed scanning sequences. As a result, it shows potential to shorten the scan time while ensuring the accuracy of radiotherapy.

Combining autoencoder with clustering analysis for anomaly detection in radiotherapy plans.

Background: To develop an unsupervised anomaly detection method to identify suspicious error-prone treatment plans in radiotherapy. Methods: A total of 577 treatment plans of breast cancer patients were used in this study. They were labeled as either normal or abnormal plans by experienced clinicians. Multiple features of each plan were extracted and selected by the learning algorithms. The training set consisted of feature samples from 400 normal plans and the testing set consisted of feature samples from 158 normal plans and 19 abnormal plans. Using the k-means clustering algorithm in the training stage, 4 normal plan clusters were formed. The distance between the samples in the testing set and the cluster centers were then determined. To evaluate the effect of dimensionality reduction (DR) on detection accuracy, principal component analysis (PCA) and autoencoder (AE) methods were compared. Results: The sensitivity of the anomaly detection model based on PCA and AE methods were 84.2% (16/19) and 94.7% (18/19), respectively. The specificity of the anomaly detection model based on PCA and AE methods were 64.6% (102/158) and 69.0% (109/158), respectively. The areas under the receiver operating characteristic (ROC) curve (AUCs) based on PCA and AE methods were 0.81 and 0.90, respectively. Conclusions: The unsupervised learning method was effective for detecting anomalies from the feature samples. Accuracy could be improved with the introduction of AE-based DR technique. The combination of AE and k-means clustering methods provides an automated way to identify abnormal plans among clinical treatment plans in radiotherapy.

A method for adjusting MLC leaf positions outside a reference region for VMAT plans in a commercial treatment planning system.

Multileaf collimators (MLC) leaf positions in a volumetric modulated arc therapy (VMAT) plan is determined from inverse treatment planning process. On the isocenter plane, leaf projections should not be set too far out of projected PTV boundary. In this study we developed an automatic method of adjusting leaf positions outside a reference region of interest (ROI) for VMAT plans generated in Pinnacle treatment planning system (TPS). The proposed method consisted of a Pinnacle script and a Python program. It checked each MLC leaf position for all control points in a VMAT arc relative to a reference ROI created by adding a small margin to PTV. For leaves opened outside the reference ROI, the method adjusted their positions to reduce dose to normal tissue while maintaining PTV coverage and satisfying leaf position constraints. The deliverability and dose accuracy of the method was verified by applying it to 15 VMAT plans which were delivered in five different linacs in our department. Dosimetric improvement of the proposed method was analyzed for another group of 16 randomly selected VMAT plans. The average gamma passing rate using a 3%/3 mm criteria for the verification group of VMAT plans was 98.3% and all passing rates were above our internal passing threshold. Dosimetric improvement was observed for the evaluation group of VMAT plans. The method can improve normal tissue protection for VMAT plans. It can be safely applied in routine clinic work.

Anomaly detection in radiotherapy plans using deep autoencoder networks.

Purpose: Treatment plans are used for patients under radiotherapy in clinics. Before execution, these plans are checked for safety and quality by human experts. A few of them were identified with flaws and needed further improvement. To automate this checking process, an unsupervised learning method based on an autoencoder was proposed. Methods: First, features were extracted from the treatment plan by human experts. Then, these features were assembled and used for model learning. After network optimization, a reconstruction error between the predicted and target signals was obtained. Finally, the questionable plans were identified based on the value of the reconstruction error. A large value of the reconstruction error indicates a longer distance from the standard distribution of normal plans. A total of 576 treatment plans for breast cancer patients were used for the test. Among them, 19 were questionable plans identified by human experts. To evaluate the performance of the autoencoder, it was compared with four baseline detection algorithms, namely, local outlier factor (LOF), hierarchical density-based spatial clustering of applications with noise (HDBSCAN), one-class support vector machine (OC-SVM), and principal component analysis (PCA). Results: The results showed that the autoencoder achieved the best performance than the other four baseline algorithms. The AUC value of the autoencoder was 0.9985, while the second one was 0.9535 (LOF). While maintaining 100% recall, the average accuracy and precision of the results by the autoencoder were 0.9658 and 0.5143, respectively. While maintaining 100% recall, the average accuracy and precision of the results by LOF were 0.8090 and 0.1472, respectively. Conclusion: The autoencoder can effectively identify questionable plans from a large group of normal plans. There is no need to label the data and prepare the training data for model learning. The autoencoder provides an effective way to carry out an automatic plan checking in radiotherapy.

Sirtuin 3 regulation: a target to alleviate ß-hydroxybutyric acid-induced mitochondrial dysfunction in bovine granulosa cells.

BACKGROUND: During the transition period, the insufficient dry matter intake and a sharply increased in energy consumption to produce large quantities of milk, high yielding cows would enter a negative energy balance (NEB) that causes an increase in ketone bodies (KBs) and decrease in reproduction efficiency. The excess concentrations of circulating KBs, represented by ß-hydroxybutyric acid (BHBA), could lead to oxidative damage, which potentially cause injury to follicular granulosa cells (fGCs) and delayed follicular development. Sirtuin 3 (Sirt3) regulates mitochondria reactive oxygen species (mitoROS) homeostasis in a beneficial manner; however, the molecular mechanisms underlying its involvement in the BHBA-induced injury of fGCs is poorly understood. The aim of this study was to explore the protection effects and underlying mechanisms of Sirt3 against BHBA overload-induced damage of fGCs. RESULTS: Our findings demonstrated that 2.4 mmol/L of BHBA stress increased the levels of mitoROS in bovine fGCs. Further investigations identified the subsequent mitochondrial dysfunction, including an increased abnormal rate of mitochondrial architecture, mitochondrial permeability transition pore (MPTP) opening, reductions in mitochondrial membrane potential (MMP) and Ca2+ release; these dysfunctions then triggered the caspase cascade reaction of apoptosis in fGCs. Notably, the overexpression of Sirt3 prior to treatment enhanced mitochondrial autophagy by increasing the expression levels of Beclin-1, thus preventing BHBA-induced mitochondrial oxidative stress and mitochondrial dysfunction in fGCs. Furthermore, our data suggested that the AMPK-mTOR-Beclin-1 pathway may be involved in the protective mechanism of Sirt3 against cellular injury triggered by BHBA stimulation. CONCLUSIONS: These findings indicate that Sirt3 protects fGCs from BHBA-triggered injury by enhancing autophagy, attenuating oxidative stress and mitochondrial damage. This study provides new strategies to mitigate the fGCs injury caused by excessive BHBA stress in dairy cows with ketosis.

Controllable 3D Flower-Like Ag-CF Electrodes as Flexible Marine Electric Field Sensors with High Stability.

Construction of three-dimensional (3D) flower-like nanostructures with controlled morphologies has emerged as an attractive tool by scientists in the marine electric field sensor research field due to their peculiar structural features. Herein, novel 3D flower-like Ag-CF capacitive composite electrodes have been created by an eco-friendly water-bath strategy via AgNO3 as a sliver source and subsequently compounded with carbon fibers (CFs) pretreated by thermal oxidation. A series of electrode samples with various morphologies obtained by modulating different reaction times and temperatures bring about the dominant formation mechanism of these nanostructures and the influence behavior on the CF electrode in detail. Especially, the 3D flower-like Ag-CF electrode shows a large surface area acquired under the conditions of 80 °C and 15 min, which can provide more electroactive sites in electrochemical analysis and exhibit a maximum areal specific capacitance of 619.75 mF·cm-2 at a scanning speed of 10 mV·s-1. This is mainly due to the synergistic behavior of the unique 3D flower-like morphology and the large specific surface area of CFs. Furthermore, a cylinder-shaped Ag-CF sensor is designed, which delivers a superior potential difference of 33.08 µV, a potential difference drift of 18.62 µV/24 h for 30 days, and a self-noise of 0.92 nV/rt (Hz)@1 Hz. In this work, the intriguing synthesis strategy can be a promising facile approach to manufacture the controllable 3D flower-like Ag-CF electrode for electric field sensor applications.

Transglutaminase 2 inhibitors attenuate osteoarthritic degeneration of TMJ-osteoarthritis by suppressing NF-κB activation.

BACKGROUND: The temporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive cartilage degradation, subchondral bone erosion, and chronic pain, leading to articular damage and chewing dysfunction. Studies have shown that interleukin-1ß (IL-1ß) plays a critical role in the development of TMJ-OA. Transglutaminase 2 (TG2) has been identified as a marker of chondrocyte hypertrophy and IL-1ß was able to increase TG2 expression in chondrocytes. Therefore, the aim of this study was to explore the ability of TG2 inhibitors to suppress TMJ-OA progression. METHODS: Firstly, toluidine blue staining, cell counting kit-8 assay, immunocytofluorescent staining and western blot were used to investigate the anti-inflammatory effects of TG2 inhibitors in IL-1ß-stimulated murine chondrocytes and the underlying mechanisms. Afterwards, micro-CT analysis, histological staining, immunohistochemical and immunohistofluorescent staining were used to evaluate the therapeutic efficacy of TG2 inhibitors in monosodium iodoacetate (MIA)-induced TMJ-OA in rats. RESULTS: TG2 inhibitors suppressed the IL-1ß-induced upregulation of COX-2, iNOS, MMP-13, and MMP-3 and reversed the IL-1ß-induced proteoglycan loss in chondrocytes through inhibiting NF-κB activation. Consistently, the MIA-induced upregulation of MMP-13 and MMP-3, and loss of structural integrity of the articular cartilage and subchondral bone were markedly reversed by TG2 inhibitors via inhibiting NF-κB activation. CONCLUSIONS: TG2 inhibitors demonstrated a potent therapeutic efficacy on cartilage and subchondral bone structures of TMJ-OA by reducing inflammation and cartilage degradation through suppressing NF-κB activation.

The variants in PTPRB, TRAF3IP3, and DISC1 genes were associated with Graves' disease in the Chinese population.

Previously, a case series study was conducted on our part in which 5 patients with Graves' disease (GD) were collected from a 3-generation family to screen for susceptibility genes responsible for GD. The single nucleotide variants of Microtubule-associated protein 7 domain containing 2 c. 452C > T, p. Ala151Val, Solute carrier family 1 member 7 c. 1204C > T, p. Arg402Cys, tumor necrosis factor receptor-associated factor 3 interacting protein 3 (TRAF3IP3) c. 209A > T, p. Asn70Ile, protein tyrosine phosphatase receptor type B (PTPRB) c. 3472A > G, p. Ser1158Gly, Phosphoinositide-3-kinase regulatory subunit 3 c. 121C > T, p. Pro41Ser, disrupted in schizophrenia 1 (DISC1), c. 1591G > C p. Gly531Arg were associated with the familial GD. We then further confirmed these variants and investigated whether other mutations render susceptibility to GD. The case-control study collected patients with sporadic GD or no GD family history. A snapshot program was used for genotyping the selected SNPs in 235 GD patients (GD group 1) and 284 healthy patients (control group). Furthermore, another 184 GD patients were recruited (GD group 2) to sequence the specified exons of these genes. The sequenced data was compared with Chinese Millionome Database (CMDB). Several variants of PTPRB, phosphoinositide-3-kinase regulatory subunit 3, TRAF3IP3, and DISC1 were found in GD group 2 but not in CMDB. Moreover, the allele frequency of SNP rs2076150 (TRAF3IP3) and rs2492367 DISC1 in GD group 2 was significantly higher than that of in CMDB (all P < .05). When the control group or CMDB was set as a reference group, a significantly higher frequency in alter allele C of SNP rs186466118 PTPRB was observed in GD group 1 and GD group (constituted by GD group 1 and GD group 2). Equally importantly, there was a correlation between the allele C of SNP rs186466118 and the increased risk of GD susceptibility (all P < .05). PTPRB, TRAF3IP3, and DISC1 may be susceptibility genes for GD, and more variants of PTPRB, TRAF3IP3, and DISC1 were found in GD patients.

Identification of spermatogenesis-related lncRNA in Holstein bull testis after sexual maturity based on transcriptome analysis.

Under the large-scale breeding model, the performance of the Holstein bull is directly related to the economic efficiency of the whole dairy farm and is the key factor affecting the genetic quality of the herd. Although the number of reported studies on the association of long noncoding RNAs (lncRNAs) with male reproduction is increasing, there is a lack of research on how lncRNAs regulate Holstein bull testicular development and spermatogenesis. To explore the molecular mechanisms between lncRNAs and spermatogenesis, three 8-week-old Holstein bull (young bull, YB) testes and three 80-week-old Holstein bull (adult bull, AB) testes from the same herd were randomly chosen, and transcriptome analysis was performed to find associations between spermatogenesis and transcriptome profiles. About 16,956 differentially expressed lncRNAs (DELs) and 7970 differentially expressed mRNAs (DEMs) were identified, and 3642 significantly relationship pairs were screened out based on co-expression analysis. Further Hub analysis obtained 6 lncRNAs, and 71 mRNAs regulated by them were enriched subsequently. Functional analysis results of differentially expressed Hub LncRNA-mRNA pairs showed that more positive cell cycle checkpoints, spindle assembly and the sister chromatids separation in AB testes indicated higher production rates of sperm in AB as compared to YB. This study reveals physiological changes and further broaden our understanding of lncRNA regulation of spermatogenesis in the fully mature testis according to the transcriptome profiles.

Uncovering Novel Features of the Pc Locus in Horn Development from Gene-Edited Holstein Cattle by RNA-Sequencing Analysis.

The Polled Celtic (Pc) mutation locus is a genetically simple single mutation that is the best choice for breeding polled cattle using gene editing. However, the mechanism of the Pc locus for regulating horn development is unclear, so we used gene editing, somatic cell nuclear transfer and embryo transfer to obtain polled Holstein fetal bovine (gestation time 90 days) with a homozygous Pc insertion (gene-edited Holstein fetal bovine, EH) and the wild-type 90 days Holstein fetal bovine (WH) as controls. The hematoxylin-eosin (HE) staining results showed that, compared to the WH, the EH horn buds had no white keratinized projections or vacuolated keratinocytes and no thick nerve bundles under the dermal tissue. Furthermore, DNA sequencing results showed that the Pc locus was homozygously inserted into the fetal bovine genome. A total of 791 differentially expressed genes were identified by transcriptome sequencing analysis. Enrichment analysis and protein interaction analysis results of differentially expressed genes showed that abundant gene changes after Pc insertion were associated with the adhesion molecule regulation, actin expression, cytoskeletal deformation and keratin expression and keratinization. It was also noted that the results contained several genes that had been reported to be associated with the development of horn traits, such as RXFP2 and TWIST1. This study identified these changes for the first time and summarized them. The results suggested that the Pc mutant locus may inhibit neural crest cell EMT generation and keratin expression, leading to failures in neural crest cell migration and keratinization of the horn bud tissue, regulating the production of the polled phenotype.