RGS19 activates the MYH9/ß-catenin/c-Myc positive feedback loop in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide, and the identification of novel treatment targets and prognostic biomarkers is urgently needed because of its unsatisfactory prognosis. Regulator of G-protein signaling 19 (RGS19) is a multifunctional protein that regulates the progression of various cancers. However, the specific function of RGS19 in HCC remains unclear. The expression of RGS19 was determined in clinical HCC samples. Functional and molecular biology experiments involving RGS19 were performed to explore the potential mechanisms of RGS19 in HCC. The results showed that the expression of RGS19 is upregulated in HCC tissues and is significantly associated with poor prognosis in HCC patients. RGS19 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, RGS19, via its RGS domain, stabilizes the MYH9 protein by directly inhibiting the interaction of MYH9 with STUB1, which has been identified as an E3 ligase of MYH9. Moreover, RGS19 activates ß-catenin/c-Myc signaling via MYH9, and RGS19 is also a transcriptional target gene of c-Myc. A positive feedback loop formed by RGS19, MYH9, and the ß-catenin/c-Myc axis was found in HCC. In conclusion, our research revealed that competition between RGS19 and STUB1 is a critical mechanism of MYH9 regulation and that the RGS19/MYH9/ß-catenin/c-Myc feedback loop may represent a promising strategy for HCC therapy.

Unsaturation effects on lipid transmembrane asymmetry.

Within cell plasma membranes, unsaturated lipids are asymmetrically distributed over the inner and outer leaflets, offering an attractive local structural feature. However, the mechanism to keep lipid transmembrane asymmetry and the closely related transmembrane movement (flip-flop) for unsaturated lipids remain poorly understood. Here, we applied sum frequency generation vibrational spectroscopy to investigate this lipid transmembrane asymmetry upon mimicking the cell membrane homeostatic processes. On the one hand, unsaturated lipids were found to hinder the flip-flop process and preserve lipid transmembrane asymmetry in model cell membranes, owing to the steric hindrance caused by their bent tails. On the other hand, local unsaturated lipids in the mixed unsaturated/saturated lipid bilayer were conducive to the formation of the local asymmetry. Therefore, lipid unsaturation can be recognized as an intrinsic key factor to form and maintain lipid transmembrane asymmetry in cell membranes.

The effect of a Schema-based method on correcting persistent errors in mental arithmetic: an experimental study.

Introduction: Arithmetic calculation is a fundamental skill for mathematical learning and daily life. However, elementary school students often make errors in practice. Methods: Grounded in the schema theory and the memory retrieval theory of mental arithmetic, this study employs a controlled experiment to investigate the effect of a schema-based method in correcting persistent errors in mental arithmetic, specifically in the context of simple addition operations. The experimental group utilizes a schema-based method to help participants rectify incorrect answers in memory retrieval, while the control group did not receive this treatment. Results: The results showed that significant differences emerged between the experimental and control groups in both the post-test performance and the reduction of persistent error count, indicating that the experimental group had rectified incorrect answers in memory; and persistent errors in simple addition were indeed caused by interference from incorrect answers during memory retrieval; and the schema-based method proves to be effective. Discussion: The findings of this study contribute to enhancing practical mental arithmetic instruction, assisting students in correcting relevant errors, and improving their mental arithmetic abilities. Not only does it offer directive guidance for teaching practices, but it also provides an enlightening reference for promoting innovative teaching methods.

The Role of Traditional Chinese Medicines in the Treatment of Osteoporosis.

Osteoporosis (OP) represents a substantial public health issue and is associated with increasing rates of morbidity and mortality. It is characterized by reduced bone mineral density, deterioration of bone tissue quality, disruption of the microarchitecture of bones, and compromised bone strength. These changes may be attributed to the following factors: intercellular communication between osteoblasts and osteoclasts; imbalanced bone remodeling; imbalances between osteogenesis and adipogenesis; imbalances in hormonal regulation; angiogenesis; chronic inflammation; oxidative stress; and intestinal microbiota imbalances. Treating a single aspect of the disease is insufficient to address its multifaceted nature. In recent decades, traditional Chinese medicine (TCM) has shown great potential in the treatment of OP, and the therapeutic effects of Chinese patent drugs and Chinese medicinal herbs have been scientifically proven. TCMs, which contain multiple components, can target the diverse pathogeneses of OP through a multitargeted approach. Herbs such as XLGB, JTG, GSB, Yinyanghuo, Gusuibu, Buguzhi, and Nvzhenzi are among the TCMs that can be used to treat OP and have demonstrated promising effects in this context. They exert their therapeutic effects by targeting various pathways involved in bone metabolism. These TCMs balance the activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells), and they exhibit anti-inflammatory, immunomodulatory, anti-oxidative, and estrogen-like functions. These multifaceted mechanisms underlie the efficacy of these herbs in the management and treatment of OP. Herein, we examine the efficacy of various Chinese herbs and Chinese patent drugs in treating OP by reviewing previous clinical trials and basic experiments, and we examine the potential mechanism of these therapies to provide evidence regarding the use of TCM for treating OP.

A comprehensive analysis of m6A/m7G/m5C/m1A-related gene expression and immune infiltration in liver ischemia-reperfusion injury by integrating bioinformatics and machine learning algorithms.

BACKGROUND: Liver ischemia-reperfusion injury (LIRI) is closely associated with immune infiltration, which commonly occurs after liver surgery, especially liver transplantation. Therefore, it is crucial to identify the genes responsible for LIRI and develop effective therapeutic strategies that target immune response. Methylation modifications in mRNA play various crucial roles in different diseases. This study aimed to identify potential methylation-related markers in patients with LIRI and evaluate the corresponding immune infiltration. METHODS: Two Gene Expression Omnibus datasets containing human liver transplantation data (GSE12720 and GSE151648) were downloaded for integrated analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted to investigate the functional enrichment of differentially expressed genes (DEGs). Differentially expressed methylation-related genes (DEMRGs) were identified by overlapping DEG sets and 65 genes related to N6-methyladenosine (m6A), 7-methylguanine (m7G), 5-methylcytosine (m5C), and N1-methyladenosine (m1A). To evaluate the relationship between DEMRGs, a protein-protein interaction (PPI) network was utilized. The core DEMRGs were screened using three machine learning algorithms: least absolute shrinkage and selection operator, random forest, and support vector machine-recursive feature elimination. After verifying the diagnostic efficacy using the receiver operating characteristic curve, we validated the expression of the core DEMRGs in clinical samples and performed relative cell biology experiments. Additionally, the immune status of LIRI was comprehensively assessed using the single sample gene set enrichment analysis algorithm. The upstream microRNA and transcription factors of the core DEMRGs were also predicted. RESULTS: In total, 2165 upregulated and 3191 downregulated DEGs were identified, mainly enriched in LIRI-related pathways. The intersection of DEGs and methylation-related genes yielded 28 DEMRGs, showing high interaction in the PPI network. Additionally, the core DEMRGs YTHDC1, METTL3, WTAP, and NUDT3 demonstrated satisfactory diagnostic efficacy and significant differential expression and corresponding function based on cell biology experiments. Furthermore, immune infiltration analyses indicated that several immune cells correlated with all core DEMRGs in the LIRI process to varying extents. CONCLUSIONS: We identified core DEMRGs (YTHDC1, METTL3, WTAP, and NUDT3) associated with immune infiltration in LIRI through bioinformatics and validated them experimentally. This study may provide potential methylation-related gene targets for LIRI immunotherapy.

lncTIMP3 promotes osteogenic differentiation of bone marrow mesenchymal stem cells via miR-214/Smad4 axis to relieve postmenopausal osteoporosis.

BACKGROUND: Promoting the balance between bone formation and bone resorption is the main therapeutic goal for postmenopausal osteoporosis (PMOP), and bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation plays an important regulatory role in this process. Recently, several long non-coding RNAs (lncRNAs) have been reported to play an important regulatory role in the occurrence and development of OP and participates in a variety of physiological and pathological processes. However, the role of lncRNA tissue inhibitor of metalloproteinases 3 (lncTIMP3) remains to be investigated. METHODS: The characteristics of BMSCs isolated from the PMOP rat model were verified by flow cytometry assay, alkaline phosphatase (ALP), alizarin red and Oil Red O staining assays. Micro-CT and HE staining assays were performed to examine histological changes of the vertebral trabeculae of the rats. RT-qPCR and western blotting assays were carried out to measure the RNA and protein expression levels. The subcellular location of lncTIMP3 was analyzed by FISH assay. The targeting relationships were verified by luciferase reporter assay and RNA pull-down assay. RESULTS: The trabecular spacing was increased in the PMOP rats, while ALP activity and the expression levels of Runx2, Col1a1 and Ocn were all markedly decreased. Among the RNA sequencing results of the clinical samples, lncTIMP3 was the most downregulated differentially expressed lncRNA, also its level was significantly reduced in the OVX rats. Knockdown of lncTIMP3 inhibited osteogenesis of BMSCs, whereas overexpression of lncTIMP3 exhibited the reverse results. Subsequently, lncTIMP3 was confirmed to be located in the cytoplasm of BMSCs, implying its potential as a competing endogenous RNA for miRNAs. Finally, the negative targeting correlations of miR-214 between lncTIMP3 and Smad4 were elucidated in vitro. CONCLUSION: lncTIMP3 may delay the progress of PMOP by promoting the activity of BMSC, the level of osteogenic differentiation marker gene and the formation of calcium nodules by acting on the miR-214/Smad4 axis. This finding may offer valuable insights into the possible management of PMOP.

Effects of bisphenol A and tauroursodeoxycholic acid on maturation of porcine oocytes and parthenogenetic development of embryos.

Prolonged exposure of bisphenol A (BPA) has adverse effects on in vitro maturation (IVM) of oocytes, but treatment with tauroursodeoxycholic acid (TUDCA) can improve the IVM and development of embryos. The purpose of this study was to investigate the effects of BPA and both BPA and TUDCA on IVM and parthenogenetic development of embryos. The results showed that BPA treatment adverse effects on the cumulus expansion index, survival rate, polar body rate, mitochondrial distribution of the oocytes after maturation culture, and that it also decreased the cleavage rate and blastocyst rate of embryos after parthenogenetic develpoment. In addition, BPA treatment upregulated expression of genes related to endoplasmic reticulum stress and apoptosis and increased the intracellular reactive oxygen species (ROS) level, while it decreased expression of genes related to cumulus expansion. However, the supplementation of TUDCA relieved these adverse effects of BPA except polar body rate, blastocyst rate, and expression of BCL2 and PTGS1. In conclusion, the supplementation of TUDCA can partly attenuate the negative effects of BPA on IVM and parthenogenetic development of embryos, possibly by modification of the expression of genes related to endoplasmic reticulum stress, apoptosis and cumulus expansion, intracellular ROS level, and mitochondrial distribution.

Adults Ischium Age Estimation Based on Deep Learning and 3D CT Reconstruction.

OBJECTIVES: To develop a deep learning model for automated age estimation based on 3D CT reconstructed images of Han population in western China, and evaluate its feasibility and reliability. METHODS: The retrospective pelvic CT imaging data of 1 200 samples (600 males and 600 females) aged 20.0 to 80.0 years in western China were collected and reconstructed into 3D virtual bone models. The images of the ischial tuberosity feature region were extracted to create sex-specific and left/right site-specific sample libraries. Using the ResNet34 model, 500 samples of different sexes were randomly selected as training and verification set, the remaining samples were used as testing set. Initialization and transfer learning were used to train images that distinguish sex and left/right site. Mean absolute error (MAE) and root mean square error (RMSE) were used as primary indicators to evaluate the model. RESULTS: Prediction results varied between sexes, with bilateral models outperformed left/right unilateral ones, and transfer learning models showed superior performance over initial models. In the prediction results of bilateral transfer learning models, the male MAE was 7.74 years and RMSE was 9.73 years, the female MAE was 6.27 years and RMSE was 7.82 years, and the mixed sexes MAE was 6.64 years and RMSE was 8.43 years. CONCLUSIONS: The skeletal age estimation model, utilizing ischial tuberosity images of Han population in western China and employing the ResNet34 combined with transfer learning, can effectively estimate adult ischium age.

Structural identification of single boron-doped graphdiynes by computational XPS and NEXAFS spectroscopy.

Boron-doped graphdiyne (B-GDY) material exhibits an excellent performance in electrocatalysis, ion transport, and energy storage. However, accurately identifying the structures of B-GDY in experiments remains a challenge, hindering further selection of suitable structures with the most ideal performance for various practical applications. In the present work, we employed density functional theory (DFT) to simulate the X-ray photoelectron spectra (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectra of pristine graphdiyne (GDY) and six representative single boron-doped graphdiynes at the B and C K-edges to establish the structure-spectroscopy relationship. A notable disparity in the C 1s ionization potentials (IPs) between substituted and adsorbed structures is observed upon doping with a boron atom. By analyzing the C and B 1s NEXAFS spectra on energy positions, spectral widths, spectral intensities, and different spectral profiles, we found that the six single boron-doped graphdiyne configurations can be sensitively identified. Moreover, this study provides a reliable theoretical reference for distinguishing different single boron-doped graphdiyne structures, enabling accurate selection of B-GDY structures for diverse practical applications.

ANP alleviates motion sickness potentially through regulating endolymph volume in the inner ear increased by AVP.

INTRODUCTION: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aims to investigate the anti-motion sickness action and inner ear-related mechanisms of ANP. METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. RESULTS: Both rotational stimulus and intraperitoneal AVP injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour, and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in-vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. CONCLUSION: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

NUP43 promotes PD-L1/nPD-L1/PD-L1 feedback loop via TM4SF1/JAK/STAT3 pathway in colorectal cancer progression and metastatsis.

Programmed cell death-ligand 1 (PD-L1) has a significant role in tumor progression and metastasis, facilitating tumor cell evasion from immune surveillance. PD-L1 can be detected in the tumor cell nucleus and exert an oncogenic effect by nuclear translocation. Colorectal cancer (CRC) progression and liver metastasis (CCLM) are among the most lethal diseases worldwide, but the mechanism of PD-L1 nuclear translocation in CRC and CCLM remains to be fully understood. In this study, using CRISPR-Cas9-based genome-wide screening combined with RNA-seq, we found that the oncogenic factor NUP43 impacted the process of PD-L1 nuclear translocation by regulating the expression level of the PD-L1 chaperone protein IPO5. Subsequent investigation revealed that this process could stimulate the expression of tumor-promoting factor TM4SF1 and further activate the JAK/STAT3 signaling pathway, which ultimately enhanced the transcription of PD-L1, thus establishing a PD-L1-nPD-L1-PD-L1 feedback loop that ultimately promoted CRC progression and CCLM. In conclusion, our study reveals a novel role for nPD-L1 in CRC, identifies the PD-L1-nPD-L1-PD-L1 feedback loop in CRC, and provides a therapeutic strategy for CRC patients.

A Brillouin microscopy analysis of the crystalline lenses of Chinese adults with myopia.

To evaluate lenticular biomechanical and geometric parameters in Chinese adults with myopia and identify relevant factors using Brillouin microscopy (BM) and Pentacam. The biomechanical and geometric properties of the ocular lenses of Chinese adults with myopia were quantified using BM. Anterior segment images were acquired using a Pentacam. Correlated factors including age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), white-to-white ratio (WTW), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were analyzed. We studied 65 eyes from 65 participants (mean age, 25.23 ± 6.12 years). Width of Top Plateau (WTP), Width of Bottom Plateau (WBP), Slope of Anterior Cortex (SAC), Slope of Posterior Cortex (SPC), and Height of Plateau (Height) metrics obtained using BM showed mean values of 2.597 ± 0.393 mm, 4.310 ± 0.535 mm, 1.344 ± 0.549 GPa/mm, -1.343 ± 0.480 GPa/mm, and 3.373 ± 0.048 GPa, respectively. No significant correlation was found between these parameters and sex, SE, IOP, CCT, ACA, or Height. Interestingly, WBP (r = 0.467, P < 0.001), SAC (r = 0.412, P = 0.001), and SPC (r = -0.280, P = 0.024) were significantly associated with age, and an age-related increase of WBP (slope of 35.36 ± 10.08 µm per year) was identified. Both ACD and ACV showed significant correlations with SAC (r = 0.329 and 0.380, P = 0.008 and 0.002, respectively), but not with SPC. BM provided a novel perspective on lenticular biomechanical and geometric properties in Chinese adults with myopia, which correlated with age, AL, WTW, ACD, and ACV.

Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

Triple-task mutual consistency for semi-supervised 3D medical image segmentation.

Semi-supervised deep learning algorithm is an effective means of medical image segmentation. Among these methods, multi-task learning with consistency regularization has achieved outstanding results. However, most of the existing methods usually simply embed the Signed Distance Map (SDM) task into the network, which underestimates the potential ability of SDM in edge awareness and leads to excessive dependence between tasks. In this work, we propose a novel triple-task mutual consistency (TTMC) framework to enhance shape and edge awareness capabilities, and overcome the task dependence problem underestimated in previous work. Specifically, we innovatively construct the Signed Attention Map (SAM), a novel fusion image with attention mechanism, and use it as an auxiliary task for segmentation to enhance the edge awareness ability. Then we implement a triple-task deep network, which jointly predicts the voxel-wise classification map, the Signed Distance Map and the Signed Attention Map. In our proposed framework, an optimized differentiable transformation layer associates SDM with voxel-wise classification map and SAM prediction, while task-level consistency regularization utilizes unlabeled data in an unsupervised manner. Evaluated on the public Left Atrium dataset and NIH Pancreas dataset, our proposed framework achieves significant performance gains by effectively utilizing unlabeled data, outperforming recent state-of-the-art semi-supervised segmentation methods. Code is available at https://github.com/Saocent/TTMC.

Additional suture augmentation to anterior cruciate ligament reconstruction with hamstring autografts bring no benefits to clinical results, graft maturation and graft-bone interface healing.

BACKGROUND: From the perspective of graft protection and early rehabilitation during the maturation and remodeling phases of graft healing, suture augmentation (SA) for anterior cruciate ligament reconstruction (ACLR) has attracted more and more attention. STUDY DESIGN: Retrospective study. PURPOSE: To determine whether the additional SA affects clinical results, graft maturation and graft-bone interface healing during two years follow-up after ACLR. METHODS: 20 ACLRs with additional SA (ACLR-SA group) and 20 ACLRs without additional SA (ACLR group) were performed between January 2020 and December 2021 by the same surgeon and were retrospectively analyzed. Pre- and postoperative International Knee Documentation Committee (IKDC) scores, Lysholm scores, graft failure and reoperation were evaluated. The signal/noise quotient (SNQ) of autografts and the signal intensity of graft-bone interface were analyzed. All 40 patients in ACLR-SA group and ACLR group completed 2-years follow-up. RESULTS: There was no patient in the two cohorts experienced graft failure and reoperation. The postoperative IKDC and Lysholm scores have been significantly improved compared with preoperative scored in both ACLR-SA group and ACLR group, however, there was no significant difference between two groups. The SNQ of proximal graft of ACLR-SA group (14.78 ± 8.62 vs. 8.1 ± 5.5, p = 0.041) was significantly greater while the grades of graft-bone interface healing of posterior tibial was significantly lower than that of ACLR group at 1-year postoperatively (p = 0.03), respectively. There were no significant differences between the two groups of the SNQ of proximal, distal medial graft segments, and the graft-bone interface healing grades of anterior femoral, posterior femoral, anterior tibial and posterior tibial at other time points (p>0.05). CONCLUSIONS: The additional SA in ACLR had no effect on IKDC scores, Lysholm scores, graft maturation and graft-bone interface healing at 2-year postoperatively. Our research does not support the routine use of SA in ACLR.

General Hyperspectral Image Super-Resolution via Meta-Transfer Learning.

Recent advances in deep learning-based methods have led to significant progress in the hyperspectral super-resolution (SR). However, the scarcity and the high dimension of data have hindered further development since deep models require sufficient data to learn stable patterns. Moreover, the huge domain differences between hyperspectral image (HSI) datasets pose a significant challenge in generalizability. To address these problems, we present a general hyperspectral SR framework via meta-transfer learning (MTL). We randomly sample various spectral ranges for SR tasks during MTL, allowing the model to accumulate diverse task experiences. Additionally, we implement a task schedule to gradually expand the number of bands, bridging the significant domain differences between datasets. By leveraging multiple datasets, we are able to achieve better performance and greater generalizability, making it applicable under various circumstances. Meanwhile, as a general framework, our scheme can be applied to existing methods to obtain performance improvements. In addition, we design an advanced network architecture based on the multifusion features to further improve the performance. Experiments demonstrate that our method not only achieves superior performance in both qualitative and quantitative terms but also can adapt robustly to a new and difficult sample, where few epochs can yield quite considerable results.

[Medical emergency support for the snowboarding project during the Beijing Winter Olympics].

OBJECTIVE: To analyze and summarize the medical security situation of the snowmobile, sled, and steel frame snowmobile tracks at the National Sliding Centre, and to provide experience for future event hosting and medical security work for mass ice and snow sports. METHODS: Retrospective analysis of injuries and treatment of athletes participating in the International Training Week and World Cup for Ski, Sled, and Steel Frame Ski from October to November 2021(hereinafter referred to as "International Training Week"), as well as the Ski, Sled, and Steel Frame Ski events at the Beijing Winter Olympics in February 2022 (hereinafter referred to as the "Beijing Winter Olympics"). We referred to and drew on the "Medical Security Standards for Winter Snow Sports" to develop specific classification standards for analyzing injured areas, types of injuries, and accident locations. RESULTS: A total of 743 athletes participated in the International Training Week and the Beijing Winter Olympics. During the competition, there were 58 incidents of overturning, prying, and collision, of which 28 (28 athletes) were injured, accounting for 48.3% of the total accidents and 3.8% of the total number of athletes. Among them, there were 9 males (32.1%) and 19 females (67.9%), with an average age of (26.3 ± 4.7) years. Among the 28 injured athletes, 20 cases (71.4%) received on-site treatment for Class Ⅰ injuries, while 8 cases (28.6%) had more severe injuries, including Class Ⅱ injuries (7 cases) and Class Ⅲ injuries (1 case), which were referred to designated hospitals for further treatment. Among the 28 injured athletes, 3 cases (10.7%) experienced multiple injuries, including 2 cases of 2 injuries and 1 case of 3 injuries. The most common injuries were in the ankle and toes (10/32, 31.3%). Out of 28 injured athletes, one (3.6%) experienced two types of injuries simultaneously, with joint and/or ligament injuries being the most common (11/29, 37.9%). The most accident prone point on the track was the ninth curve (18/58, 31.0%). CONCLUSION: Through the analysis and summary of medical security work, it can provide better experience and reference for the future development of snowmobile, sled, and steel frame snowmobile sports in China, making the National Snowy and Ski Center truly a sustainable Olympic heritage.

Composite Hydrogel Containing Collagen-Modified Polylactic Acid-Hydroxylactic Acid Copolymer Microspheres Loaded with Tetramethylpyrazine Promotes Articular Cartilage Repair.

Articular cartilage defects pose a significant challenge due to the limited self-healing ability of cartilage. However, traditional techniques face limitations including autologous chondrocyte expansion issues. This study aims to investigate the effects of the polylactic acid-glycolic acid (PLGA) and collagen-surface modified polylactic acid-glycolic acid (CPLGA) microspheres loaded with tetramethylpyrazine (TMP) on two cell types and the regeneration potential of articular cartilage. CPLGA microspheres are prepared by Steglich reaction and characterized. They evaluated the effect of TMP-loaded microspheres on HUVECs (Human Umbilical Vein Endothelial Cells) and examined the compatibility of blank microspheres with BMSCs (Bone marrow mesenchymal stromal cells) and their potential to promote cartilage differentiation. Subcutaneous implant immune tests and cartilage defect treatment are conducted to assess biocompatibility and cartilage repair potential. The results highlight the efficacy of CPLGA microspheres in promoting tissue regeneration, attributed to improved hydrophilicity and collagen-induced mitigation of degradation. Under hypoxic conditions, both CPLGA and PLGA TMP-loaded microspheres exhibit inhibitory effects on HUVEC proliferation, migration, and angiogenesis. Notably, CPLGA microspheres show enhanced compatibility with BMSCs, facilitating chondrogenic differentiation. Moreover, the CPLGA microsphere-composite hydrogel exhibits potential for cartilage repair by modulating angiogenesis and promoting BMSC differentiation.

Physical breakdown of CH4 hydrate under stress: a molecular dynamics simulation study.

As a solid energy source, CH4 hydrate will inevitably break down physically as the result of geological movement or exploitation. Here, the molecular dynamics method was employed to simulate the uniaxial-deformation behavior of structure I (sI type) CH4 hydrate under stress. The stress increases regardless of whether the hydrate is stretched or squeezed, and other physical parameters also changed, such as hydrate cage numbers, order parameters, and the number of water molecules. A noticeable difference is observed between the two systems. Upon stretching, the stress immediately recovers to 0 GPa once the hydrate is completely stretched apart. During the squeeze process, the stress is ultimately not zero since solid and liquid are always in contact. When the hydrate is stretched apart, about 5% of water molecules change from solid to liquid, about 7.8% of CH4 molecules lose their shelter and become free due to the disintegration of water cages. While in the squeezing process, large cages (51262) are crushed more easily than small cages (512); in the end, about 93.5% of large cages and 73% of small cages are crushed, and approximately 87.5% CH4 is released from the cages. In mining CH4 hydrates, caution must be exercised, as if the hydrates break as a result of stress, a large release of CH4 may pose a security risk.

p-Smad3 differentially regulates the cytological behavior of osteoclasts before and after osteoblasts maturation.

BACKGROUND: A series of previous investigations have revealed that p-Smad3 plays a facilitative role in the differentiation and maturation of osteoblasts, while also regulating the expression of certain intercellular communication factors. However, the effects of p-Smad3 in osteoblasts before and after maturation on the proliferation, migration, differentiation, apoptosis and other cellular behaviors of osteoclasts have not been reported. METHODS: MC3T3-E1 cells were cultured in osteogenic induction medium for varying durations, After that, the corresponding conditioned medium was collected and the osteoclast lineage cells were treated. To elucidate the regulatory role of p-Smad3 within osteoblasts, we applied the activator TGF-ß1 and inhibitor SIS3 to immature and mature osteoblasts and collected corresponding conditioned media for osteoclast intervention. RESULTS: We observed an elevation of p-Smad3 and Smad3 during the early stage of osteoblast differentiation, followed by a decline in the later stage. we discovered that as osteoblasts mature, their conditioned media inhibit osteoclasts differentiation and the osteoclast-coupled osteogenic effect. However, it promotes apoptosis in osteoclasts and the angiogenesis coupled with osteoclasts. p-Smad3 in immature osteoblasts, through paracrine effects, promotes the migration, differentiation, and osteoclast-coupled osteogenic effects of osteoclast lineage cells. For mature osteoblasts, p-Smad3 facilitates osteoclast apoptosis and the angiogenesis coupled with osteoclasts. CONCLUSIONS: As pre-osteoblasts undergo maturation, p-Smad3 mediated a paracrine effect that transitions osteoclast cellular behaviors from inducing differentiation and stimulating bone formation to promoting apoptosis and coupling angiogenesis.