Panoramic heat map for spatial distribution of necrotic lesions.

Aims: In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method. Methods: We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis. Results: The results showed that the LLDS has high inter-rater reliability. As illustrated by the heat map, the distribution of Japanese Investigation Committee (JIC) classification type C necrotic lesions exhibited clustering characteristics, with the lesions being concentrated in the northern and eastern regions, forming a hot zone (90% probability) centred on the N4-N6E2, N3-N6E units of outer ring blocks. Statistical results showed that the distribution difference between type C2 and type C1 was most significant in the E1 and E2 units and, combined with the heat map, indicated that the spatial distribution differences at N3-N6E1 and N1-N3E2 units are crucial in understanding type C1 and C2 necrotic lesions. Conclusion: The LLDS can be used to accurately measure the spatial location of necrotic lesions and display their distribution characteristics.

Relationship between preoperative hemoglobin levels and length of stay in elderly patients with hip fractures: A retrospective cohort study.

Globally, hip fractures in elderly individuals are a prevalent and serious issue. Patients typically have a longer length of stay (LOS), which increases the risk of complications and increases hospitalization costs. Hemoglobin (Hb) is a routine blood test that is associated with disease prognosis. This study aimed to investigate the relationship between preoperative Hb and LOS in elderly hip fracture patients and to determine a reliable transfusion threshold. The clinical data of hip fracture patients (aged ≥ 60 years) admitted to the Department of Orthopaedics, Shenzhen Second People's Hospital, between January 2012 and December 2021 were retrospectively analyzed. Multiple linear regression analysis was used to assess the linear relationship between preoperative Hb and LOS. Smooth curve fitting was performed to investigate potential nonlinear relationships. In the case of discovering nonlinear relationships, a weighted two-piecewise linear regression model was built, and the inflection points were determined using a recursive algorithm. Subgroup analyses were conducted based on age and gender. A total of 1444 patients with an average age of (77.54 ±â€…8.73) years were enrolled. After adjusting for covariates, a nonlinear relationship was found between preoperative Hb and LOS. The two-piecewise linear regression model revealed an inflection point of 10 g/dL. On the left of the inflection point (Hb < 10 g/dL), the LOS was reduced by 0.735 days for every 1 g/dL increase in Hb (ß = -0.735, 95% confidence interval: -1.346 to -0.124, P = .019). On the right side of the inflection point (Hb > 10 g/dL), the relationship was not statistically significant (ß = 0.001, 95% confidence interval: -0.293 to 0.296, P = .992). In elderly hip fracture patients, there is a nonlinear association between preoperative Hb and LOS. However, when Hb levels were <10 g/dL, there was a negative correlation with the LOS. No correlation was observed when Hb levels were >10 g/dL. These findings underscore the importance of timely intervention to manage Hb levels in elderly patients with hip fractures, potentially reducing hospitalization durations and associated complications.

Recent advances of m6A methylation in skeletal system disease.

Skeletal system disease (SSD) is defined as a class of chronic disorders of skeletal system with poor prognosis and causes heavy economic burden. m6A, methylation at the N6 position of adenosine in RNA, is a reversible and dynamic modification in posttranscriptional mRNA. Evidences suggest that m6A modifications play a crucial role in regulating biological processes of all kinds of diseases, such as malignancy. Recently studies have revealed that as the most abundant epigentic modification, m6A is involved in the progression of SSD. However, the function of m6A modification in SSD is not fully illustrated. Therefore, make clear the relationship between m6A modification and SSD pathogenesis might provide novel sights for prevention and targeted treatment of SSD. This article will summarize the recent advances of m6A regulation in the biological processes of SSD, including osteoporosis, osteosarcoma, rheumatoid arthritis and osteoarthritis, and discuss the potential clinical value, research challenge and future prospect of m6A modification in SSD.

The role of AMPK in macrophage metabolism, function and polarisation.

AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays a key role in regulating cellular energy homeostasis and multiple aspects of cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming of macrophages, but also counter-regulates the inflammatory function of macrophages and promotes their polarisation toward the anti-inflammatory phenotype. AMPK is located at the intersection of macrophage metabolism and inflammation. The metabolic characteristics of macrophages are closely related to immune-related diseases, infectious diseases, cancer progression and immunotherapy. This review discusses the structure of AMPK and its role in the metabolism, function and polarisation of macrophages. In addition, it summarises the important role of the AMPK pathway and AMPK activators in the development of macrophage-related diseases.

Xanthohumol alleviates palmitate-induced inflammation and prevents osteoarthritis progression by attenuating mitochondria dysfunction/NLRP3 inflammasome axis.

Osteoarthritis (OA) is a prevalent chronic degenerative joint disease worldwide. Obesity has been linked to OA, and increased free fatty acid levels (e.g., palmitate) contribute to inflammatory responses and cartilage degradation. Xanthohumol (Xn), a bioactive prenylated chalcone, was shown to exhibit antioxidative, anti-inflammatory, and anti-obesity capacities in multiple diseases. However, a clear description of the preventive effects of Xn on obesity-associated OA is unavailable. This study aimed to assess the chondroprotective function of Xn on obesity-related OA. The in vitro levels of inflammatory and ECM matrix markers in human chondrocytes were assessed after the chondrocytes were treated with PA and Xn. Additionally, in vivo cartilage degeneration was assessed following oral administration of HFD and Xn. This study found that Xn treatment completely reduces the inflammation and extracellular matrix degradation caused by PA. The proposed mechanism involves AMPK signaling pathway activation by Xn, which increases mitochondrial biogenesis, attenuates mitochondrial dysfunction, and inhibits NLRP3 inflammasome and the NF-κB signaling pathway induced by PA. In summary, this study highlights that Xn could decrease inflammation reactions and the degradation of the cartilage matrix induced by PA by inhibiting the NLRP3 inflammasome and attenuating mitochondria dysfunction in human chondrocytes.

Mechanical upside of PAO mainstream fixations: co-simulation based on early postoperative gait characteristics of DDH patients.

Purpose: To investigate the early postoperative gait characteristics of patients who underwent periacetabular osteotomy (PAO) and predict the biomechanical performance of two commonly used PAO fixation methods: iliac screw (IS) and transverse screw (TS). Methods: A total of 12 patients with unilateral developmental dysplasia of the hip (DDH) (mean age 27.81 ± 4.64 years, 42% male) that were scheduled to undergo PAO surgery were included in this study. Their preoperative CT images and pre- and postoperative gait data were used to create subject-specific musculoskeletal models and complete the inverse dynamics analysis (IDA). Two patients with typical gait characteristics were selected using clustering analysis, and their IDA data were incorporated into finite element (FE) models of IS and TS fixations. Failure simulation was performed by applying iterative steps with increasing gait load to predict yield load. Stress results and yield loads were calculated for each FE model at different phases of the gait cycle. Results: Postoperative gait showed improvement compared to preoperative gait but remained inferior to that of healthy individuals. Postoperative gait was characterized by a lower hip range of motion, lower peri-ilium muscle forces, particularly in the abductors, and a sharper initial peak and flatter second peak of hip joint reaction force (HRF). Finite element analysis (FEA) showed a trend of increasing stress during the second-fourth phases of the gait cycle, with lower stress levels in other phases. At high-stress gait phases, the mean stress of maximum p¯100 differed significantly between IS and TS (p < 0.05) and between coupled and uncoupled muscle forces (p < 0.05). Failure analysis predicted a slightly larger yield load for TS configurations (6.21*BW) than that for IS (6.16*BW), but both were well above the gait load. Coupled and uncoupled groups showed similar results, but uncoupled groups had lower yield loads (5.9*BW). Conclusion: PAO early postoperative gait shows a normalized trend, but abnormalities persist. IS and TS are both capable of resisting mechanical strain failure, with no significant mechanical advantage found for transverse screw fixation during PAO early postoperative gait. Additionally, it is important to note that the TS may have a higher risk of cyclic fatigue failure due to the localized greater stress concentration. Furthermore, the most medial screw is crucial for pelvic stability.

RNA binding proteins in extracellular vesicles and their potential value for cancer diagnosis and treatment (Review).

Extracellular vesicles (EVs) are spherical bilayer membrane vesicles released by cells into extracellular spaces and body fluids, including plasma and synovial fluid. EV cargo comprises various biomolecules, such as proteins, DNA, mRNAs, non­coding RNAs, lipids and metabolites. By delivering these bioactive molecules to recipient cells, EVs mediate intercellular communications and play a critical role in maintaining cellular homeostasis and promoting pathological progression. Of note, cells can selectively sort these bioactive molecules (particularly RNAs) into EVs for secretion, as well as regulate cell­cell communications. RNA­binding proteins (RBPs) are a large class of proteins capable of binding to RNA molecules and function in regulating RNA metabolism. There is increasing evidence to indicate that RBPs can be delivered to receipt cells to influence their cell biology and play a significant role in the sorting of coding and non­coding RNAs in EVs. The present review summarized the current knowledge on EV­associated RBPs, their functions in tumorigenesis and RBP­related exosome engineering. It is hoped that the present review may provide novel insight into RBPs and targeted cancer treatment.

Fndc5/irisin deficiency leads to dysbiosis of gut microbiota contributing to the depressive-like behaviors in mice.

BACKGROUND: Depression is one of the most common mental diseases and the leading cause of disability worldwide. A dysfunctional gut microbiota-brain axis is one of the main pathological bases of depression. Irisin, an exercise-related myokine, reduces depression-like behaviors and may guide the relief of depressive symptoms by exercise. However, its underlying mechanism remains unclear. METHODS: Fibronectin type III domain containing 5 (Fndc5)/Irisin was knocked out in male wide-type C57BL/6N mice using CRISPR-cas9. The depression and anxiety symptoms were examined in irisin knockout and control mice with or without chronic unpredictable mild stress by sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Fecal microbiota was assessed by 16S rRNA sequencing and microbiota-related metabolites using liquid chromatography with tandem mass spectrometry. Differential metabolites were analyzed with the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: The knockout mice showed anxiety- and depression-like behaviors and altered diversity and richness of gut microbiota. At the phylum level, these mice had decreased Firmicutes and increased Bacteroidota populations, while at the genus level, they exhibited a low relative abundance of Lactobacillus and Bifidobacterium. Moreover, knocking out of Irisin gene in these mice significantly reduced N-desmethyl-mifepristone (RU 42633) and elevated (-)-stercobilin levels. The KEGG results showed that the microbiota-related metabolites affected by irisin mainly clustered into arginine and proline metabolism and affected the mechanistic target of rapamycin kinase (mTOR) signaling pathway. CONCLUSION: Our findings show that Fndc5/irisin deficiency causes depression in mice by inducing dysbiosis of gut microbiota and changes in microbiota-related metabolites.

Recent advances of exosomal circRNAs in cancer and their potential clinical applications.

Circular RNA (circRNA) is a type of non-coding RNA that forms a covalently closed, uninterrupted loop. The expression of circRNA differs among cell types and tissues, and various circRNAs are aberrantly expressed in a variety of diseases, including cancer. Aberrantly expressed circRNAs contribute to disease progression by acting as microRNA sponges, functional protein sponges, or novel templates for protein translation. Recent studies have shown that circRNAs are enriched in exosomes. Exosomes are spherical bilayer vesicles released by cells into extracellular spaces that mediate intercellular communication by delivering cargoes. These cargoes include metabolites, proteins, lipids, and RNA molecules. Exosome-mediated cell-cell or cell-microenvironment communications influence the progression of carcinogenesis by regulating cell proliferation, angiogenesis, metastasis as well as immune escape. In this review, we summarize the current knowledge about exosomal circRNAs in cancers and discuss their specific functions in tumorigenesis. Additionally, we discuss the potential value of exosomal circRNAs as diagnostic biomarkers and the potential applications of exosomal circRNA-based cancer therapy.

Extracellular vesicles in tumorigenesis, metastasis, chemotherapy resistance and intercellular communication in osteosarcoma.

HIGHLIGHTS: Extracellular vehicles play crucial function in osteosarcoma tumorigenesis.Extracellular vehicles mediated the intercellular communication of osteosarcoma cells with other types cells in tumor microenvironment.Extracellular vehicles have potential utility in osteosarcoma diagnosis and treatment.

Superior Selective CO2 Adsorption and Separation over N2 and CH4 of Porous Carbon Nitride Nanosheets: Insights from GCMC and DFT Simulations.

Development of high-performance materials for the capture and separation of CO2 from the gas mixture is significant to alleviate carbon emission and mitigate the greenhouse effect. In this work, a novel structure of C9N7 slit was developed to explore its CO2 adsorption capacity and selectivity using Grand Canonical Monte Carlo (GCMC) and Density Functional Theory (DFT) calculations. Among varying slit widths, C9N7 with the slit width of 0.7 nm exhibited remarkable CO2 uptake with superior CO2/N2 and CO2/CH4 selectivity. At 1 bar and 298 K, a maximum CO2 adsorption capacity can be obtained as high as 7.06 mmol/g, and the selectivity of CO2/N2 and CO2/CH4 was 41.43 and 18.67, respectively. In the presence of H2O, the CO2 uptake of C9N7 slit decreased slightly as the water content increased, showing better water tolerance. Furthermore, the underlying mechanism of highly selective CO2 adsorption and separation on the C9N7 surface was revealed. The closer the adsorption distance, the stronger the interaction energy between the gas molecule and the C9N7 surface. The strong interaction between the C9N7 nanosheet and the CO2 molecule contributes to its impressive CO2 uptake and selectivity performance, suggesting that the C9N7 slit could be a promising candidate for CO2 capture and separation.

Circular RNAs in chemotherapy resistance of lung cancer and their potential therapeutic application.

Lung cancer is one of the high malignancy-related incidence and mortality worldwide, accounting for about 13% of total cancer diagnoses. Currently, the use of anti-cancer agents is still the main therapeutic method for lung cancer. However, cancer cells will gradually show resistance to these drugs with the progress of treatment. And the molecular mechanisms underlying chemotherapy agents resistance remain unclear. circRNAs are newly identified noncoding RNAs molecules with covalently closed circular structures. Previous studies have shown that circRNAs are associated with tumorigenesis and progression of various cancers, including lung cancer. Recently, growing reports have suggested that circRNAs could contribute to drug resistance of lung cancer cell through different mechanisms. Therefore, in this review, we summarized the functions and underlying mechanisms of circRNAs in regulating chemoresistance of lung cancer and discussed their potential applications for diagnosis, prognosis, and treatment of lung cancer.

Molecular basis and therapeutic potential of myostatin on bone formation and metabolism in orthopedic disease.

Myostatin, a member of the transforming growth factor-ß (TGF-ß) superfamily, is a key autocrine/paracrine inhibitor of skeletal muscle growth. Recently, researchers have postulated that myostatin is a negative regulator of bone formation and metabolism. Reportedly, myostatin is highly expressed in the fracture area, affecting the endochondral ossification process during the early stages of fracture healing. Furthermore, myostatin is highly expressed in the synovium of patients with rheumatoid arthritis (RA) and is an effective therapeutic target for interfering with osteoclast formation and joint destruction in RA. Thus, myostatin is a potent anti-osteogenic factor and a direct modulator of osteoclast differentiation. Evaluation of the molecular pathway revealed that myostatin can activate SMAD and mitogen-activated protein kinase signaling pathways, inhibiting the Wnt/ß-catenin pathway to synergistically regulate muscle and bone growth and metabolism. In summary, inhibition of myostatin or the myostatin signaling pathway has therapeutic potential in the treatment of orthopedic diseases. This review focused on the effects of myostatin on bone formation and metabolism and discussed the potential therapeutic effects of inhibiting myostatin and its pathways in related orthopedic diseases.

Soil copper concentration map in mining area generated from AHSI remote sensing imagery.

Hyperspectral remote sensing has the advantages to predict and map soil heavy metal concentration over conventional monitoring methods and multispectral remote sensing. In quantitative applications of hyperspectral remote sensing imagery, the contribution of hyperspectral bands is different, and abnormal prediction values resulted from incorrectly classified bare soil images are a major problem. In this study, a variable weighting method was proposed to weight the hyperspectral bands, and a probability threshold was used to improve the classification to mitigate the problem of abnormal prediction values. The variable weighting was conducted by using the absorption depths obtained by continuum removal. Soil samples were collected from a mining area in southwestern China. Hyperspectral remote sensing imagery was acquired by the Advanced Hyperspectral Imager (AHSI) abroad on Geofen-5 (GF-5) satellite. Genetic algorithm and partial least squares regression (PLSR) were adopted to calibrate prediction models. In prediction of soil copper (Cu) concentration, root mean square error (RMSE) and coefficient of determination (R2) were 21.59 mg kg-1 and 0.60 for the prediction using raw reflectance spectra, and the values were improved to 18.33 mg kg-1 and 0.71 by using the weighted reflectance spectra. The developed prediction model was applied to the AHSI imagery to predict Cu concentration in bare soil areas. In prediction of Cu concentration using the AHSI imagery, negative prediction values were eliminated by using the bare soil image extracted by the improved classification. Based on the prediction, soil Cu concentration map was generated by kriging spatial interpolation. The result indicates that the proposed variable weighting method is effective and the problem of abnormal prediction values could be mitigated by using improved bare soil images. Further analysis indicates that some indices with proper thresholds also could be used to get improved bare soil images.

Caffeic acid phenethyl ester attenuates osteoarthritis progression by activating NRF2/HO­1 and inhibiting the NF­κB signaling pathway.

Osteoarthritis (OA) is the most common degenerative disease affecting the joints, and inflammation appears to play a critical role in the initiation and progression of OA. Caffeic acid phenethyl ester (CAPE), a natural flavonoid compound, has anti­inflammatory and antioxidant functions. However, its anti­inflammatory effects on OA and the underlying mechanisms of action of CAPE in the treatment of OA remain elusive. Therefore, the present study investigated the anti­inflammatory effects of CAPE on IL­1ß­stimulated chondrocytes in vitro and surgically induced rat models of OA in vivo. In vitro, CAPE reduced the expression of inducible nitric oxide synthase and cyclooxygenase­2 in IL­1ß­stimulated chondrocytes, as well as the extracellular secretion of nitric oxide and prostaglandin E2 in the cell culture supernatants. In addition, CAPE attenuated the degradation of extracellular matrix by increasing the expression of aggrecan and collagen II, and decreasing the expression of MMP3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motif­5. Furthermore, CAPE attenuated NF­κB signaling and activated the nuclear factor erythroid 2­related factor 2/heme oxygenase­1 signaling pathway in IL­1ß­stimulated chondrocytes. In vivo, CAPE protected cartilage from destruction and delayed the progression of OA in rats. Taken together, the findings of the present study indicated that CAPE may be a potential therapeutic agent for the prevention or treatment of OA.

The role of lincRNA-p21 in regulating the biology of cancer cells.

Long non-coding RNAs (lncRNAs) are a type of multifunctional endogenous RNA transcript. The dysregulation of lncRNAs is considered to play a role in the initiation and progression of cancer. One such lncRNA, long intergenic non-coding RNA-p21 (lincRNA-p21), was identified in 2010 as a regulator in the p53 pathway and is gradually being identified to play crucial roles in diverse cellular processes. In this review, we have summarised the diverse regulatory functions of lincRNA-p21. For example, lincRNA-p21 has been reported to function as a protein decoy, act as a competitive endogenous RNA, regulate the transcription, regulate the translation processes and exist in the secreted exosomes. Furthermore, we highlight the emerging roles of lincRNA-p21 in cancer cell regulation. Various types of cancers, including colorectal carcinoma, hepatocellular carcinoma and non-small cell lung carcinoma, aberrantly express lincRNA-p21. However, the current understanding of the roles of lincRNA-p21 in cancer remains limited. Therefore, considering its potential as a valuable therapeutic target or biomarker for cancer, more research should be conducted to understand the role of lincRNA-p21 in cancer and other diseases.

RNA binding proteins in osteoarthritis.

Osteoarthritis (OA) is a common chronic degenerative joint disease worldwide. The pathological features of OA are the erosion of articular cartilage, subchondral bone sclerosis, synovitis, and metabolic disorder. Its progression is characterized by aberrant expression of genes involved in inflammation, proliferation, and metabolism of chondrocytes. Effective therapeutic strategies are limited, as mechanisms underlying OA pathophysiology remain unclear. Significant research efforts are ongoing to elucidate the complex molecular mechanisms underlying OA focused on gene transcription. However, posttranscriptional alterations also play significant function in inflammation and metabolic changes related diseases. RNA binding proteins (RBPs) have been recognized as important regulators in posttranscriptional regulation. RBPs regulate RNA subcellular localization, stability, and translational efficiency by binding to their target mRNAs, thereby controlling their protein expression. However, their role in OA is less clear. Identifying RBPs in OA is of great importance to better understand OA pathophysiology and to figure out potential targets for OA treatment. Hence, in this manuscript, we summarize the recent knowledge on the role of dysregulated RBPs in OA and hope it will provide new insight for OA study and targeted treatment.

ADAR1 Prevents R-loop Accumulation-Driven ATR Pathway Activation in Ovarian Cancer.

Adenosine (A)-to-inosine (I) RNA editing is the most prevalent RNA editing mechanism, in which adenosine deaminase acting on RNA 1 (ADAR1) is a major adenosine deaminase. Increasing evidence suggests that editing dysregulation of ADAR1 plays an important role in human tumorigenesis, while the underlying mechanism remains elusive. Here, we demonstrated that ADAR1 was highly expressed in ovarian cancer tissues and negatively correlated with progression free survival of ovarian cancer patients. Importantly, silence of ADAR1 repressed ovarian cancer cell growth and colony formation in vitro and inhibited ovarian cancer cell tumorigenesis in vivo. Further cell cycle and transcriptome profile analysis revealed that silence of ADAR1 in ovarian cancer cells induced cell cycle arrest at G1/G0 stage. Mechanistically, loss of ADAR1 caused R-loop abnormal accumulation, thereby contributing to single stand DNA break and ATR pathway activation. Additionally, ADAR1 interacted with DHX9 to regulate R-loop complex formation, and A-to-I editing of nascent RNA repressed R-loop formation during co-transcriptional process. Together, our results identify a novel ADAR1/R-loop/ATR axis critical for ovarian cancer progression and a potential target for ovarian cancer therapy.

ResDNet: Efficient Dense Multi-Scale Representations With Residual Learning for High-Level Vision Tasks.

Deep feature fusion plays a significant role in the strong learning ability of convolutional neural networks (CNNs) for computer vision tasks. Recently, works continually demonstrate the advantages of efficient aggregation strategy and some of them refer to multiscale representations. In this article, we describe a novel network architecture for high-level computer vision tasks where densely connected feature fusion provides multiscale representations for the residual network. We term our method the ResDNet which is a simple and efficient backbone made up of sequential ResDNet modules containing the variants of dense blocks named sliding dense blocks (SDBs). Compared with DenseNet, ResDNet enhances the feature fusion and reduces the redundancy by shallower densely connected architectures. Experimental results on three classification benchmarks including CIFAR-10, CIFAR-100, and ImageNet demonstrate the effectiveness of ResDNet. ResDNet always outperforms DenseNet using much less computation on CIFAR-100. On ImageNet, ResDNet-B-129 achieves 1.94% and 0.89% top-1 accuracy improvement over ResNet-50 and DenseNet-201 with similar complexity. Besides, ResDNet with more than 1000 layers achieves remarkable accuracy on CIFAR compared with other state-of-the-art results. Based on MMdetection implementation of RetinaNet, ResDNet-B-129 improves mAP from 36.3 to 39.5 compared with ResNet-50 on COCO dataset.