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[Display omitted] • The reconstruction exploits the low rank constraint and the parallel computing technique. • The proposed approach uses a sliding window algorithm to improve the reconstruction process. • The proposed method outperforms the typical low rank methods in time performance. • The proposed algorithm is suitable for small computing platforms. Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most promising analytical chemistry techniques, although it takes a long time to acquire data. Non-uniform sampling (NUS) is an effective way to reduce the sampling time, but faithful reconstruction methods are needed. The low rank Hankel matrix (LRHM) approach uses the low rank constraint to obtain high-quality spectra from NUS signals, but the reconstruction has a considerable time overhead. In this work, we propose a sliding window based low rank Hankel matrix approach to speed up the spectra reconstruction from NUS signals. Using the sliding window to construct a matrix can effectively reduce the size of the Hankel matrix for faster reconstructions. To further decrease the reconstruction time, parallel computation is applied in the proposed approach. The experiments on both synthetic data and realistic data demonstrate that the reconstruction speed of the proposed method is the fastest among compared methods without sacrificing the quality of spectra. [ABSTRACT FROM AUTHOR]

In this article, C/SiC ceramic matrix composites (CMC) were polished by femtosecond laser. The effects of different laser incidence angles on the machined surface were studied in detail, and the process parameters were optimized. The results have indicated that different laser incident angles influence the machined surface of CMC. With the increase of laser incident angle, the defects and oxidation degree decrease significantly, the carbon (C) content gradually decreases, silica (Si) content gradually increases, and oxygen (O) content is almost unchanged. Under an incident angle of 70°, the surface carbon fiber along the axial direction was neatly cut, and the bump structure was eliminated. The laser's incident angle greatly influences the corrugated structure of the carbon fiber section. The response surface method establishes the quadratic response model of four parameters and surface roughness. The small-scale optimization method predicted the optimal expected value as follows: single pulse energy is 71.53 μJ, defocus amount is −0.13 mm, incident angle is 20.61°, Y-axis spot overlap rate 77.50%, and the optimal surface roughness (Ra) is predicted as 1.03 μm. The experimental results show that the average surface roughness of 0.92 μm is within the 95% confidence interval mean (95% CI Mean), indicating that the experimental results are reliable. It is 51.98% lower than the original surface roughness value of 1.92 μm. The optimal surface roughness value is 0.71 μm, 63.02% lower than the original surface roughness value. [ABSTRACT FROM AUTHOR]

Background: Risperidone, an atypical antipsychotic, impedes serotonin and dopamine receptor systems. Meanwhile, tumor necrosis factor-α (TNF-α) is known to participate in regulating osteoblast functions. Consequently, the current study aimed to investigate whether the influences of Risperidone on osteoblast functions are associated with TNF-α and special AT-rich sequence-binding protein (SATB2). Methods: Firstly, we searched the DGIdb, MEM and GeneCards databases to identify the critical factors involved in the effects of Risperidone on osteoblasts, as well as their interactions. Afterwards, osteoblast cell line MC3T3-E1 was transduced with lentivirus carrying si-TNF-α, si-SATB2 or both and subsequently treated with Risperidone. Various abilities including differentiation, autophagy and apoptosis of osteoblasts were examined after different treatments. Finally, animal experiments were performed with Risperidone alone or together with lentivirus to verify the function of Risperidone in vivo and the mechanism. Results: It was found that Risperidone might promote TNF-α expression, thereby inhibiting the expression of SATB2 to affect the autophagy and apoptosis in osteoblasts. Furthermore, as shown by our experimental findings, Risperidone treatment inhibited the differentiation and autophagy, and promoted the apoptosis of osteoblasts, as evidenced by elevated levels of OPG, p62, cleaved PARP1, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9, and reduced levels of LC3 II/I, Beclin1, collagen I, and RANKL. In addition, Risperidone was also found to elevate the expression of TNF-α to down-regulate SATB2, thereby inhibiting the differentiation and autophagy and enhancing the apoptosis of osteoblasts in vitro and in vivo. Conclusions: Collectively, our findings indicated that Risperidone affects the differentiation of osteoblasts by inhibiting autophagy and enhancing apoptosis via TNF-α-mediated down-regulation of SATB2. [ABSTRACT FROM AUTHOR]

Objective. To investigate the differences in uric acid (UA), interleukin-6 (IL-6), and free prostatic-specific antigen (fPSA)/total prostatic-specific antigen (tPSA) (F/T) between patients with and without prostate cancer (PCa) in order to discover the value of the three indicators in improving PCa diagnostic accuracy. Methods. Patients with pathologically diagnosed PCa (PCa group, n = 25), patients with other benign prostate diseases (benign group, n = 25), and men who underwent normal physical examination (control group, n = 25) at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between October 2020 and January 2021 were included. The serum UA, IL-6, and F/T levels of participants in the three groups were measured, and the measured data were statistically analyzed. Results. There were statistically significant differences in IL-6 and F/T among the three groups (all P < 0.05), but there were no statistically significant differences in UA (P > 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) for the three indicators was, respectively, as follows: PCa group-benign group 0.5416, 0.6776, and 0.6832; PCa group-control group 0.5432, 0.9536, and 0.9887; and benign group-control group 0.5000, 0.8784, and 0.9456. Logistic regression analysis indicated that IL-6 and F/T were independent predictors of PCa, with AUCs of 0.6776 and 0.6832, respectively, and a combined accuracy of 72.0%. Conclusion. These results suggest that IL-6 and F/T have a good detection effect for PCa screening. Compared with the detection of F/T alone, the combined detection of IL-6 and F/T can improve the diagnosis rate of PCa to a certain extent, providing effective guidance for the clinical diagnosis and treatment of patients. The value of UA needs to be further studied, and its feasibility in the diagnosis of PCa needs to be further explored. [ABSTRACT FROM AUTHOR]

• This study found that adipose-derived stem cell exosomes can promote M2 polarization of macrophages through the transmission of LncRNA DLEU2. • The aim of this study was to explore the molecular mechanism of adipose-derived stem cell exosomes in sepsis-induced lung injury. • Through high-throughput sequencing, this study found that LncRNA DLEU2 is enriched in exosomes of sepsis lung tissue. • This study confirmed that ADSC-Exos can promote M2 polarization of macrophages and alleviate inflammation and apoptosis of lung injury cells. This study investigates the molecular mechanisms by which extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSCs) promote M2 polarization of macrophages and thus reduce lung injury caused by sepsis. High-throughput sequencing was used to identify differentially expressed genes related to long non-coding RNA (lncRNA) in ADSC-derived EVs (ADSC-EVs) in sepsis lung tissue. Weighted gene co-expression network analysis (WGCNA) was employed to predict the downstream target genes of the lncRNA DLEU2. The RNAInter database predicted miRNAs that interact with DLEU2 and LXN. Functional and pathway enrichment analyses were performed using GO and KEGG analysis. A mouse model of sepsis was established, and treatment with a placebo or ADSC-EVs was administered, followed by RT-qPCR analysis. ADSC-EVs were isolated and identified. In vitro cell experiments were conducted using the mouse lung epithelial cell line MLE-12, mouse macrophage cell line RAW264.7, and mouse lung epithelial cell line (LEPC). ADSC-EVs were co-cultured with RAW264.7 and MLE-12/LEPC cells to study the regulatory mechanism of the lncRNA DLEU2. Cell viability, proliferation, and apoptosis of lung injury cells were assessed using CCK-8, EdU, and flow cytometry. ELISA was used to measure the levels of inflammatory cytokines in the sepsis mouse model, flow cytometry was performed to determine the number of M1 and M2 macrophages, lung tissue pathology was evaluated by H&E staining, and immunohistochemistry was conducted to examine the expression of proliferation- and apoptosis-related proteins. High-throughput sequencing and bioinformatics analysis revealed enrichment of the lncRNA DLEU2 in ADSC-EVs in sepsis lung tissue. Animal and in vitro cell experiments showed increased expression of the lncRNA DLEU2 in sepsis lung tissue after treatment with ADSC-EVs. Furthermore, ADSC-EVs were found to transfer the lncRNA DLEU2 to macrophages, promoting M2 polarization, reducing inflammation response in lung injury cells, and enhancing their viability, proliferation, and apoptosis inhibition. Further functional experiments indicated that lncRNA DLEU2 promotes M2 polarization of macrophages by regulating miR-106a-5p/LXN, thereby enhancing the viability and proliferation of lung injury cells and inhibiting apoptosis. Overexpression of miR-106a-5p could reverse the biological effects of ADSC-EVs-DLEU2 on MLE-12 and LEPC in vitro cell models. Lastly, in vivo animal experiments confirmed that ADSC-EVs-DLEU2 promotes high expression of LXN by inhibiting the expression of miR-106a-5p, further facilitating M2 macrophage polarization and reducing lung edema, thus alleviating sepsis-induced lung injury. lncRNA DLEU2 in ADSC-EVs may promote M2 polarization of macrophages and enhance the viability and proliferation of lung injury cells while inhibiting inflammation and apoptosis reactions, thus ameliorating sepsis-induced lung injury in a mechanism involving the regulation of the miR-106a-5p/LXN axis. [ABSTRACT FROM AUTHOR]

• The structure of proposed network is designed via a view of iterative reconstruction. • Better performance in artifacts removal and detail preservation. • More robustness to the samplings than the state-of-the-art methods. Magnetic resonance imaging has been widely applied in clinical diagnosis. However, it is limited by its long data acquisition time. Although the imaging can be accelerated by sparse sampling and parallel imaging, achieving promising reconstructed images with a fast computation speed remains a challenge. Recently, deep learning methods have attracted a lot of attention for encouraging reconstruction results, but they are lack of proper interpretability for neural networks. In this work, in order to enable high-quality image reconstruction for the parallel magnetic resonance imaging, we design the network structure from the perspective of sparse iterative reconstruction and enhance it with the residual structure. Experimental results on a public knee dataset indicate that, as compared with the state-of-the-art deep learning-based and optimization-based methods, the proposed network achieves lower error in reconstruction and is more robust under different samplings. [ABSTRACT FROM AUTHOR]

• A hybrid model with validated numerical model, DNN and meta -heuristic algorithms is developed. • Solar receivers are applied in diverse application scenarios. • Multi-objective optimizations are studied to ensure the safe and optimal performance of receivers. • Maximum heliostat scale is found for solar receivers due to material limitations. • The proposed method effectively reduces the maximum receiver tube wall temperature. Efficient and secure operation of solar receivers is key to the development of concentrated solar power (CSP). Its precise and quick optimization is essential for receiver to achieve optimum thermal performance and safety across diverse application scenarios. In this study, we propose a hybrid model based on numerical simulation and deep learning to achieve this target. The hybrid model accounting for conduction, convection and radiation shows a small relative error (<2%) in over 96 % cases. We apply the model to two different application scenarios considering multiple performance objectives simultaneously and demonstrate that it can identify optimal structure parameters and heliostat scale for each inlet flow rate of the receiver. In combination with gas turbines, maximum efficiencies of 48.9 %, 53.2 %, and 56.8 % are achieved for flow rates of 0.5, 0.75, and 1 kg/s, respectively. When integrated into heating systems, the receiver achieves a maximum thermal efficiency of 89.8 % with a heliostat field scale of 5.76 MW. Furthermore, for the operation optimization, the proposed aiming strategy results in a 76 ℃ reduction in maximum tube wall temperature compared to the conventional aiming strategy. Our approach not only provides an advanced solution for rapid cavity receiver design and operation optimization but also has the potential for extension to other structures. [ABSTRACT FROM AUTHOR]

• miR-214 is highly expressed in mice with viral myocarditis (VMC) induced by CVB3 infection. • miR-214 targets and inhibits p53, promoting the activity of cardiac fibroblasts (CFs). • miR-214 targets and inhibits PTEN, activating the PI3K/Akt signaling pathway to promote the growth of CFs. • miR-214 promotes myocardial fibrosis and cardiac mesenchymal transition in VMC mice by regulating p53 and the PTEN-PI3K-Akt signaling pathway. • This study provides a new theoretical basis for exploring the role of miRNA in myocardial fibrosis and cardiac interstitial transformation. This study aimed to investigate the role of miR-214 in the bidirectional regulation of p53 and PTEN and its influence on myocardial fibrosis and cardiac mesenchymal transformation in mice with viral myocarditis (VMC). The study established a VMC model in BALB/c mice by injecting them with the CVB3 virus intraperitoneally. Techniques such as ELISA, H&E staining, Masson staining, immunohistochemical staining, RT-qPCR, western blot, and dual-luciferase reporter gene assay were used to detect the expression levels of relevant factors in tissues and cells. Isolation and culture of cardiac fibroblasts (CFs) were also conducted. The study found that miR-214 bidirectional regulation of p53 and PTEN promotes myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. The expression levels of collagen-related peptides, inflammatory-related factors, miR-214, mesenchymal transformation-related factors, and fibrosis-related factors were significantly increased, while the expression levels of p53, PTEN, and epithelial/endothelial cell phenotype marker factors were significantly decreased. Downregulation of miR-214 or upregulation of p53 and PTEN expression inhibited inflammatory cell and fibroblast infiltration in VMC mouse myocardial tissue. It reduced the proliferation ability while increasing the apoptosis of cardiac fibroblasts. miR-214 plays a significant role in the bidirectional inhibition of p53 and PTEN, which leads to myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. Downregulation of miR-214 or upregulation of p53 and PTEN expression may provide potential therapeutic targets for treating VMC-induced cardiac fibrosis and mesenchymal transformation. [ABSTRACT FROM AUTHOR]

[Display omitted] • A network structure of bias field estimation and uniform image reconstruction was designed to compensate for the intensity loss; • The proposed BFCNet improves the image uniformity by 8.3% and 10.1%, the segmentation accuracy by 4.1% and 6.8% on white and grey matter in T2-weighted brain images; • The proposed BFCNet outperforms the state-of-the-art traditional methods and deep learning methods on estimating bias field and preserving image structure; • The proposed BFCNet is robust to different levels of bias field and noise. Bias field is one of the main artifacts that degrade the quality of magnetic resonance images. It introduces intensity inhomogeneity and affects image analysis such as segmentation. In this work, we proposed a deep learning approach to jointly estimate bias field and reconstruct uniform image. By modeling the quality degradation process as the product of a spatially varying field and a uniform image, the network was trained on 800 images with true bias fields from 12 healthy subjects. A network structure of bias field estimation and uniform image reconstruction was designed to compensate for the intensity loss. To further evaluate the benefit of bias field correction, a quantitative analysis was made on image segmentation. Experimental results show that the proposed BFCNet improves the image uniformity by 8.3% and 10.1%, the segmentation accuracy by 4.1% and 6.8% on white and grey matter in T2-weighted brain images. Moreover, BFCNet outperforms the state-of-the-art traditional methods and deep learning methods on estimating bias field and preserving image structure, and BFCNet is robust to different levels of bias field and noise. [ABSTRACT FROM AUTHOR]

[Display omitted] • The high strength steel was treated by nanosecond laser shock peening. • The laser treatment enhanced the surface microhardness and induce compressive residual stress. • The laser shock peening can improve the corrosion resistance and fatigue life of high strength steel. Laser shock peening is a surface treatment technology inducing high-pressure shock waves on metallic materials and structures. In this study, the life cycle performance improvement in high-strength steel by nanosecond laser shock peening is investigated. It is found that microstructures formed by laser shock peening lead to higher microhardness, corrosion resistance, and fatigue life, which are significantly beneficial for preventing life cycle failure of mega-scale engineering structures in critical environments. The residual stress is also measured on the surface of samples, which shows that the compressive residual stress can be found in the treated area. [ABSTRACT FROM AUTHOR]

Objective: Several studies show that the inflammatory component in atherosclerosis may contribute to increased risk for cardiovascular disease (CVD). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-stimulatory cytokine of presumed importance for CVD and the metabolic syndrome. Methods and results: In this case–control study, 1179 surviving myocardial infarction (MI) cases and 1528 healthy controls were genotyped for three IL-6 promoter SNPs, and serum concentrations of IL-6 and C-reactive protein (CRP) were measured. In men, MI risk assessed as odds ratios (OR) was higher with increasing IL-6 levels, with the highest compared to the lowest IL-6 quartiles giving an OR of 2.7 [95% CI 1.7–4.4]. The ORs were independent from the effects of elevated CRP which were associated with modest MI risks (OR=1.6 [95% CI 1.0–2.5]). Also, synergistic interactions between high IL-6 levels and hypercholesterolaemia further increased MI risk estimates. The −174C allele was associated with lower serum-insulin levels among male controls but did not significantly influence MI risk or IL-6 levels. Conclusions: Elevated IL-6 levels are important risk markers for MI in men, the risk being further enhanced through synergistic interaction with hypercholesterolaemia. The data provide no clear evidence that polymorphisms in the IL-6 promotor region play a significant role in the pathogenesis of MI, and it remains to be further evaluated whether or not the −174C allele is of relevance for insulin resistance. [Copyright &y& Elsevier]

Background: Diabetes and cardiovascular diseases represent significant global health challenges, leading to organ dysfunction and increased mortality rates. Managing these conditions is complex, especially in the elderly population. The study addresses this pressing issue by exploring the application of the Chronic Illness Trajectory Framework (CITF), aiming to improve self-care and quality of life in elderly patients with diabetes and cardiovascular diseases., Methods: A total of 127 patients with diabetes mellitus and cardiovascular diseases admitted to the hospital were enrolled between January 2020 and January 2022. According to the implementation of CITF management mode, they were divided into a control group (62 cases, non-implementation) and an observation group (65 cases, implementation). The control group was given routine intervention, while the observation group was given CITF-based target management mode for 3 months. The changes in blood glucose, blood lipid, negative emotions, self-efficacy, self-management, compliance, and quality of life before and after intervention in both groups were observed. This study was approved by the Ethics Committee of Zhujiang Hospital., Results: After intervention, levels of fasting plasma glucose (FPG), 2h plasma glucose (2hPG), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), scores of self-rating depression scale (SDS), self-rating anxiety scale (SAS) and Diabetes Specific Quality of Life Scale (DSQL) were decreased (P < .05), while scores of General Self-Efficacy Scale (GSES) and Scale of the Diabetes Self-Care Activities Chinese version (SDSCA), and compliance rate were increased in both groups (P < .05). The levels of FPG, 2hPG, HbA1c, TC, TG, and LDL-C, scores of SDS, SAS, and DSQL in the observation group were lower than those in the control group (P < .001), and scores of GSES and SDSCA, and compliance rate were higher than those in the control group (P < .001). These results highlight the positive role of comprehensive intervention in improving the physical and mental health of patients with diabetes and provide strong support for the application of comprehensive intervention strategies in diabetes management., Conclusion: CITF-based target management mode can alleviate negative emotions in patients with diabetes mellitus and cardiovascular diseases, improve self-management, self-efficacy, and compliance, effectively control blood glucose and lipids, and improve quality of life. The study conclusions highlight the importance of CITF management models in improving the management of patients with diabetes and cardiovascular disease. This comprehensive intervention helps reduce negative emotions, improve self-management and compliance, effectively control blood sugar and blood lipids, and improve quality of life. These results have important clinical implications and provide strong support for better care of patients with chronic diseases.

The prevalence of plastics in the oceans has significantly intensified microplastic pollution, contributing to broader marine secondary pollution issues. This paper examines how plastic structure affects the aging characteristics of plastics and the release of metal ions, to better understand this secondary source of marine pollution. This study simulate the photoaging of plastics in natural environments, focusing on aliphatic and aromatic polymers. The results showed that the photodegradation degree was higher for aliphatic than aromatic polymers. All polymers contained thirteen detectable metals, with their release increasing over time due to photoaging, The release dynamics of these metal ions correlated more strongly with the level of polymer degradation rather than with the polymer structure itself, adhering to a second-order kinetic model driven by surface and intraparticle diffusion processes. The results will help control and treat marine plastic pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Lung adenocarcinoma (LUAD), a global leading cause of cancer deaths, remains inadequately addressed by current protein biomarkers. Our study focuses on developing a protein-based risk signature for improved prognosis of LUAD., Methods: We employed the least absolute shrinkage and selection operator (LASSO)-COX algorithm on The Cancer Genome Atlas database to construct a prognostic model incorporating six proteins (CD49B, UQCRC2, SMAD1, FOXM1, CD38, and KAP1). The model's performance was assessed using principal component, Kaplan-Meier (KM), and receiver operating characteristic (ROC) analysis, indicating strong predictive capability. The model stratifies LUAD patients into distinct risk groups, with further analysis revealing its potential as an independent prognostic factor. Additionally, we developed a predictive nomogram integrating clinicopathologic factors, aimed at assisting clinicians in survival prediction. Gene set enrichment analysis (GSEA) and examination of the tumor immune microenvironment were conducted, highlighting metabolic pathways in high-risk genes and immune-related pathways in low-risk genes, indicating varied immunotherapy sensitivity. Validation through immunohistochemistry from the Human Protein Atlas (HPA) database and immunofluorescence staining of clinical samples was performed, particularly focusing on CD38 expression., Results: Our six-protein model (CD49B, UQCRC2, SMAD1, FOXM1, CD38, KAP1) effectively categorized LUAD patients into high and low-risk groups, confirmed by principal component, KM, and ROC analyses. The model showed high predictive accuracy, with distinct survival differences between risk groups. Notably, CD38, traditionally seen as protective, was paradoxically associated with poor prognosis in LUAD, a finding supported by immunohistochemistry and immunofluorescence data. GSEA revealed that high-risk genes are enriched in metabolic pathways, while low-risk genes align with immune-related pathways, suggesting better immunotherapy response in the latter group., Conclusions: This study presented a novel prognostic protein model for LUAD, highlighting the CD38 expression paradox and enhancing our understanding of protein roles in lung cancer progression. It offered new clinical tools for prognosis prediction and provided assistance for future lung cancer pathogenesis research., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1940/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Background: This study aims to construct a three-dimensional model of skin dermis utilizing continuous tissue sections, with the primary objective of obtaining anatomical structure data for normal human dermal tissues. Methods: Normal skin tissue specimens were acquired, paraffin-embedded, and subjected to HE staining. Panoramic images of skin sections were captured using a microscope. Tissue section images were aligned using the SIFT and StackReg image alignment methods, with analysis conducted using the OpenCV module. Mimics17 software facilitated the reconstruction of the skin dermal 3D model, enabling the calculation of dermal porosity and the void diameter. Results: Panoramic skin slices exhibited high-resolution differentiation of dermal fibers and cellular structures. Both SIFT and StackReg image alignment methods yielded similar results, although the SIFT method demonstrated greater robustness. Successful reconstruction of the three-dimensional dermal structure was achieved. Quantitative analysis revealed a dermal porosity of 18.96 ± 4.41% and an average pore diameter of 219.29 ± 34.27 μm. Interestingly, the porosity of the dermis exhibited a gradual increase from the papillary layer to the fourth layer, followed by a transient decrease and then a gradual increase. The distribution of the mean pore diameter mirrored the pattern observed in porosity distribution. Conclusion: Utilizing the continuous skin tissue slice reconstruction technique, this study successfully reconstructed a high-precision three-dimensional tissue structure of the skin. The quantitative analysis of dermal tissue porosity and average pore diameter provides a standardized dataset for the development of biomimetic tissue-engineered skin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhang and Huang.)

The target of this study is to gain a deeper understanding of the micro-dissolution process of cellulose in alkaline aqueous solutions and to develop a novel method for extracting cellulose nanofibrils (CNFs). Herein, the dissolution process of cellulose in alkaline aqueous solutions will be controlled by varying the temperature, and the undissolved cellulose will be analyzed to reveal the microscopic dissolution process of cellulose, and a novel process for extracting cellulose nanofibrils (CNFs) will be developed based on the findings. The crystalline structure of cellulose was gradually disrupted as the dissolution progressed, and the crystal form of cellulose changed gradually from cellulose I to cellulose II during the dissolution process, while all undissolved cellulose crystals remained as cellulose I. Cellulose, after its structure is disrupted during the dissolution process, will inevitably decompose into CNFs, and the microscopic dissolution process of cellulose follows a "top-down" dissolution sequence. The CNFs extraction method developed in this study can extract CNFs with high yield (>60 %) in a stable manner, as well as narrow particle size distribution, high crystallinity (>77 %), and good thermal stability. This study enhances the comprehension of the dissolution process of cellulose and paves a possible way for industrialization of CNFs production., Competing Interests: Declaration of competing interest We would like to submit the enclosed manuscript entitled “Microscopic dissolution process of cellulose in alkaline aqueous solvents and its application in CNFs extraction - investigating temperature as a variable”, which we wish to be considered for publication in Carbohydrate Polymers. No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. The work was original research that has not been published previously, and not under consideration for publication elsewhere. I have not submitted my manuscript to a preprint server before submitting it to Carbohydrate Polymers., (Copyright © 2023. Published by Elsevier Ltd.)

Aerobic glycolysis is a hallmark property of cancer metabolism. Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate into phosphoenolpyruvate. In mammals, enolases exist in three isoforms, encoded by the genes ENO1 , ENO2 , and ENO3 . The altered expression of enolases is a common occurrence in various types of cancer. Although most published studies on enolases have predominantly focused on the role of ENO1 in cancer, ENO2 and ENO3 have recently emerged as crucial regulatory molecules in cancer development. Significant progress has been made in understanding their multifaceted roles in oncogenesis. In this comprehensive review, we provide an overview of the structure, subcellular localization, diagnostic and prognostic significance, biological functions, and molecular mechanisms of ENO2 and ENO3 in cancer progression. The importance of enolase in cancer development makes it a novel therapeutic target for clinical applications. Furthermore, we discuss anticancer agents designed to target enolases and summarize their anticancer efficacy in both in vitro and in vivo studies., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

The nonuniform sampling (NUS) is a powerful approach to enable fast acquisition but requires sophisticated reconstruction algorithms. Faithful reconstruction from partially sampled exponentials is highly expected in general signal processing and many applications. Deep learning (DL) has shown astonishing potential in this field, but many existing problems, such as lack of robustness and explainability, greatly limit its applications. In this work, by combining the merits of the sparse model-based optimization method and data-driven DL, we propose a DL architecture for spectra reconstruction from undersampled data, called MoDern. It follows the iterative reconstruction in solving a sparse model to build the neural network, and we elaborately design a learnable soft-thresholding to adaptively eliminate the spectrum artifacts introduced by undersampling. Extensive results on both synthetic and biological data show that MoDern enables more robust, high-fidelity, and ultrafast reconstruction than the state-of-the-art methods. Remarkably, MoDern has a small number of network parameters and is trained on solely synthetic data while generalizing well to biological data in various scenarios. Furthermore, we extend it to an open-access and easy-to-use cloud computing platform (XCloud-MoDern), contributing a promising strategy for further development of biological applications.

Exponential function is a basic form of temporal signals, and how to fast acquire this signal is one of the fundamental problems and frontiers in signal processing. To achieve this goal, partial data may be acquired but result in severe artifacts in its spectrum, which is the Fourier transform of exponentials. Thus, reliable spectrum reconstruction is highly expected in the fast data acquisition in many applications, such as chemistry, biology, and medical imaging. In this work, we propose a deep learning method whose neural network structure is designed by imitating the iterative process in the model-based state-of-the-art exponentials' reconstruction method with the low-rank Hankel matrix factorization. With the experiments on synthetic data and realistic biological magnetic resonance signals, we demonstrate that the new method yields much lower reconstruction errors and preserves the low-intensity signals much better than compared methods.

Introduction: The porcine reproductive and respiratory syndrome virus (PRRSV) continues to pose a significant threat to the global swine industry, attributed largely to its immunosuppressive properties and the chronic nature of its infection. The absence of effective vaccines and therapeutics amplifies the urgency to deepen our comprehension of PRRSV's intricate pathogenic mechanisms. Previous transcriptomic studies, although informative, are partially constrained by their predominant reliance on in vitro models or lack of long-term infections. Moreover, the role of circular RNAs (circRNAs) during PRRSV invasion is yet to be elucidated., Methods: In this study, we employed an in vivo approach, exposing piglets to a PRRSV challenge over varied durations of 3, 7, or 21 days. Subsequently, porcine alveolar macrophages were isolated for a comprehensive transcriptomic investigation, examining the expression patterns of mRNAs, miRNAs, circRNAs, and long non-coding RNAs (lncRNAs)., Results: Differentially expressed RNAs from all four categories were identified, underscoring the dynamic interplay among these RNA species during PRRSV infection. Functional enrichment analyses indicate that these differentially expressed RNAs, as well as their target genes, play a pivotal role in immune related pathways. For the first time, we integrated circRNAs into the lncRNA-miRNA-mRNA relationship, constructing a competitive endogenous RNA (ceRNA) network. Our findings highlight the immune-related genes, CTLA4 and SAMHD1, as well as their associated miRNAs, lncRNAs, and circRNAs, suggesting potential therapeutic targets for PRRS. Importantly, we corroborated the expression patterns of selected RNAs through RT-qPCR, ensuring consistency with our transcriptomic sequencing data., Discussion: This study sheds lights on the intricate RNA interplay during PRRSV infection and provides a solid foundation for future therapeutic strategizing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peng, Xia, Wei, Zeng, Zou, Hu, Xu, Huang, Geng, Hu, Cao and Zhang.)

Porcine epidemic diarrhea virus (PEDV) has led to significant economic losses in the global porcine industry since the emergence of variant strains in 2010. The high mutability of coronaviruses endows PEDV with the ability to evade the host immune response, which impairs the effectiveness of vaccines. In our previous study, we generated a highly cell-passaged PEDV strain, CT-P120, which showed promise as a live attenuated vaccine candidate by providing satisfactory protection against variant PEDV infection in piglets. However, the mechanism by which the attenuated CT-P120 adapts to cells during passage, resulting in increased replication efficiency, remains unclear. To address this question, we conducted a comparative transcriptomic analysis of Vero E6 cells infected with either the original parental strain (CT-P10) or the cell-attenuated strain (CT-P120) of PEDV at 6, 12, and 24 h post-infection. Compared to CT-P10, CT-P120 infection resulted in a significant decrease in the number of differentially expressed genes (DEGs) at each time point. Functional enrichment analysis of genes revealed the activation of various innate immune-related pathways by CT-P10, notably attenuated during CT-P120 infection. To validate these results, we selected eight genes (TRAF3, IRF3, IFNL1, ISG15, NFKB1, MAP2K3, IL1A, and CCL2) involved in antiviral processes and confirmed their mRNA expression patterns using RT-qPCR, in line with the transcriptomic data. Subsequent protein-level analysis of selected genes via Western blotting and enzyme-linked immunosorbent assay corroborated these results, reinforcing the robustness of our findings. Collectively, our research elucidates the strategies underpinning PEDV attenuation and immune evasion, providing invaluable insights for the development of effective PEDV vaccines.

Lung cancer (LC) is a common cancer with high incidence and mortality rates. In recent years, ginsenoside Rg3 (Rg3), a traditional medicine, is widely used for the treatment of LC. Herein, we concentrate on assessing the effect of Rg3 on LC cell migration and invasion. The effects of Rg3 (0, 25, 50, and 100 μg/ml) on the viability, migration, invasion, angiogenesis, and expressions of epithelial-mesenchymal transition (EMT)-related proteins, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) of LC cell lines were evaluated by cell counting kit-8 (CCK-8), scratch, transwell, tube formation, and western blot assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess transfection efficiency. COX2 overexpression plasmid and short hairpin RNA for VEGF (shVEGF) were applied to evaluate whether the effect of Rg3 is related to COX2 and VEGF through rescue assay. In this study, Rg3 significantly dose-dependently suppressed the viability, migration, invasion, angiogenesis, and protein expressions of N-cadherin, vimentin, COX2, and VEGF in H1299 and A549 cells, while promoting the expression of E-cadherin protein. COX2 overexpression markedly reversed the effects of Rg3 on the viability, migration, invasion, angiogenesis, and EMT-related protein expression levels in LC cells; however, such effects of COX2 overexpression were offset by VEGF knockdown. In sum, Rg3 alleviates the migration, invasion, and angiogenesis of LC cells by inhibiting the expressions of COX2 and VEGF., (© 2023 John Wiley & Sons Ltd.)

Seawater intrusion in the Minjiang River estuary has gravely endangered the water security of the surrounding area in recent years. Previous studies mainly focused on exploring the mechanism of intrusion, but failed to provide a scheme for suppressing seawater intrusion. The three most relevant determinants to chlorine level, which represented the strength of seawater intrusion, were determined using Pearson correlation analysis as being the daily average discharge, daily maximum tidal range, and daily minimum tidal level. Considering the lower requirement of sample data and the ability to handle high-dimensional data, the random forest algorithm was used to construct a seawater intrusion suppression model and was combined with a genetic algorithm. The critical river discharge for suppressing estuary seawater intrusion determined using this model. The critical river discharge was found to gradually increase with the maximum tidal range, which in three different tide scenarios was 487 m 3 /s, 493 m 3 /s, and 531 m 3 /s. The practicable seawater intrusion suppression scheme was built up with three phases to make it easier to regulate upstream reservoirs. In the scheme, the initial reading of river discharge was 490 m 3 /s, and it rose to 650 m 3 /s over six days, from four days before the high tide's arrival to two days following it, and before falling down to 490 m 3 /s at the end. Verified with the 16 seawater intrusion events in the five dry years, this scheme could eliminate 75% of the seawater intrusion risk and effectively reduce the chlorine level for the remaining 25% of events.

High-quality postoperative rehabilitation is the focus of most patients currently, and hypertrophic scar (HS) greatly reduces the patient's quality of life due to the symptom of severe itching. Traditional HS therapies are associated with limitations, such as poor drug delivery efficiency for topical administration and severe pain for intralesional injection. In this study, we developed a personalized microneedle patch system for minimally invasive and effective treatment of HSs. The microneedle patches were personalized designed and fabricated with 3D printing in order to adapt to individual HS. The optimized microneedle patches were composed of dissolving gelatin and starch and loaded with losartan. Losartan, as a drug class of angiotensin II receptor blockers (ARBs), can effectively inhibit the proliferation and migration of hypertrophic scar fibroblasts (HSFs) and downregulate the gene expression related to scar formation in HSFs. The dissolving microneedle patches exhibited strong mechanical strength, effectively penetrated the stratum corneum of HSs and increased the losartan delivery into HSs upon dissolution of gelatin and starch. Together, the losartan-loaded microneedle patches effectively inhibited the formation of HSs in rabbit ears with reduced scar elevation index (SEI), and decreased fibrosis and collagen deposition in HSs. This personalized microneedle patch system increases the drug delivery efficiency into HSs with minimal invasion, and opens a new window for personalized management and treatment of skin diseases.

Background: The clinical TNM staging system does not differ between the 7 th and 8 th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed., Methods: Data were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy., Results: This retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively., Conclusion: We developed a more practical and prognosis-relevant staging system than that of the 8 th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Liu, Chen, Huang, Zeng, Wei, Zhang, Zhou, Chen, Wu and Guo.)

To address the problems of uneven distribution and low coverage of wireless sensor network (WSN) nodes in random deployment, a node coverage optimization strategy with an improved COOT bird algorithm (COOTCLCO) is proposed. Firstly, the chaotic tent map is used to initialize the population, increase the diversity of the population, and lay the foundation for the global search for the optimal solutions. Secondly, the Lévy flight strategy is used to perturb the individual positions to improve the search range of the population. Thirdly, Cauchy mutation and an opposition-based learning strategy are fused to perturb the optimal solutions to generate new solutions and enhance the ability of the algorithm to jump out of the local optimum. Finally, the COOTCLCO algorithm is applied to WSN coverage optimization problems. Simulation results show that COOTCLCO has a faster convergence speed and better search accuracy than several other typical algorithms on 23 benchmark test functions; meanwhile, the coverage rate of the COOTCLCO algorithm is increased by 9.654%, 13.888%, 6.188%, 5.39%, 1.31%, and 2.012% compared to particle swarm optimization (PSO), butterfly optimization algorithm (BOA), seagull optimization algorithm (SOA), whale optimization algorithm (WOA), Harris hawks optimization (HHO), and bald eagle search (BES), respectively. This means that in terms of coverage optimization effect, COOTCLCO can obtain a higher coverage rate compared to these algorithms. The experimental results demonstrate that COOTCLCO can effectively improve the coverage rate of sensor nodes and improve the distribution of nodes in WSN coverage optimization problems.

Background: In this study, we investigated the relationship between serum lactate dehydrogenase (LDH) level and disease progression and prognosis of patients with COVID-19. Methods: We retrospectively reviewed the information of 1,751 patients with COVID-19 from Leishenshan Hospital in Wuhan, China. Univariate and multivariate Cox regression analyses as well as Logistics regression analyses, and Kaplan-Meier curves were used to determine the association between LDH levels and the prognosis of COVID-19 patients. Results: LDH was an independent risk factor for in-hospital death no matter it was taken as classified variable and continuous variable (all P = 0.001) but not for severe or critical illness status. The Kaplan-Meier curves for LDH level showed that an elevated level of LDH was associated with in-hospital death. Conclusions: In patients with COVID-19, the increased LDH level is associated with a higher risk of negative clinical prognosis and higher mortality. This will provide a reference for clinicians and researchers to understand, diagnose, and treat patients with COVID-19. Further prospective studies with larger sample sizes are needed to verify these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Guo, Chen, Wu, Zhang, Liu, Li, Li, Xiong, Wu, Li, Luo, Yuan and Wu.)

Decellularized meniscal extracellular matrix (ECM) material holds great potential for meniscus repair and regeneration. Particularly, injectable ECM hydrogel is highly desirable for the minimally invasive treatment of irregularly shaped defects. Although regional-specific variations of the meniscus are well documented, no ECM hydrogel has been reported to simulate zonally specific microenvironments of the native meniscus. To fill the gap, different (outer, middle, and inner) zones of porcine menisci were separately decellularized. Then the regionally decellularized meniscal ECMs were solubilized by pepsin digestion, neutralized, and then form injectable hydrogels. The hydrogels were characterized in gelation behaviors and mechanical properties and seeded with bovine fibrochondrocytes to evaluate the regionally biochemical effects on the cell-matrix interactions. Our results showed that the decellularized inner meniscal ECM (IM) contained the greatest glycosaminoglycan (GAG) content and the least collagen content compared with the decellularized outer meniscal ECM (OM) and middle meniscal ECM (MM). The IM hydrogel showed lower compressive strength than the OM hydrogel. When encapsulated with fibrochondrocytes, the IM hydrogel accumulated more GAG, contracted to a greater extent and reached higher compressive strength than that of the OM hydrogel at 28 days. Our findings demonstrate that the regionally specific meniscal ECMs present biochemical variation and show various effects on the cell behaviors, thus providing information on how meniscal ECM hydrogels may be utilized to reconstruct the microenvironments of the native meniscus., (© 2021 IOP Publishing Ltd.)

Background: Coronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients., Methods: Patient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality., Results: Logistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19., Conclusion: Elevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Hu, Li, Xia, Gong, Li, Wu, Yi, Huang, Wu, Guo and Wu.)

Aims: To explore the role of the Sphingosine 1-Phosphate (S1P)/Receptor2 (S1PR2) pathway in thrombin-induced hyperpermeability (TIP) and to test whether bivalirudin can reverse TIP via the S1P-S1PRs pathway. Methods and Results: Using western blot, we demonstrated that Human umbilical vein endothelial cells (HUVECs) that were cultured with 2 U/ml thrombin showed significantly increased S1PR2 expression while S1PR1and three kept unchanged. Such increment was attenuated by JTE-013 pretreatment and by presence of bivalirudin. Exposure of 2 U/ml of thrombin brought a higher level of S1P both intracellularly and extracellularly within the HUVECs by using ELISA detecting. Thrombin induced S1P and S1PR2 increment was restored by usage of PF543 and bivalirudin. Bivalirudin alone did not influenced the level of S1P and S1PR1,2, and S1PR3 compare to control group. As a surrogate of cytoskeleton morphology, phalloidin staining and immunofluorescence imaging were used. Blurry cell edges and intercellular vacuoles or spaces were observed along thrombin-exposed HUVECs. Presence of JTE-013 and bivalirudin attenuated such thrombin-induced permeability morphological change and presence of heparin failed to show the protective effect. Transwell chamber assay and probe assay were used to measure and compare endothelial permeability in vitro . An increased TIP was observed in HUVECs cultured with thrombin, and coculture with bivalirudin, but not heparin, alleviated this increase. JTE-013 treatment yielded to similar TIP alleviating effect. In vivo , an Evans blue assay was used to test subcutaneous and organ microvascular permeability after the treatment of saline only, thrombin + saline, thrombin + bivalirudin, thrombin + heparin or thrombin + JTE-013. Increased subcutaneous and organ tissue permeability after thrombin treatment was observed in thrombin + saline and thrombin + heparin groups while treatment of bivalirudin and JTE-013 absent this effect. Conclusion: S1P/S1PR2 mediates TIP by impairing vascular endothelial barrier function. Unlike heparin, bivalirudin effectively blocked TIP by inhibiting the thrombin-induced S1P increment and S1PR2 expression, suggesting the novel endothelial protective effect of bivalirudin under pathological procoagulant circumstance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ye, Zhang, Huang, Li, Cao, Dai, Huang, Tian, Li and Han.)

Medullary thyroid carcinoma (MTC) is a rare and lethal cancer. There are currently controversies regarding its staging. This study aimed to verify the significance of the patient's age in the prognosis of MTC and propose its addition to the current staging system. Data on cancer-specific survival (CSS) from the Surveillance, Epidemiology, and End Results database between 2010 and 2015 were used. X-Tile, nomograms, Cox proportional hazards regression analysis, Kaplan-Meier curves, and log-rank tests were used to evaluate mortality rates to create a new staging system. A total of 849 patients were included. Patients were divided into three categories based on their ages at diagnosis: ≤41 years, n = 224 (26.4%); 42-71 years, n = 516 (60.8%); and ≥72 years, n = 109 (12.8%). Independent factors for survival in the multivariate analysis included age (42-71 years, hazard ratio [HR], 2.81, 95% confidence interval [CI], 1.07-7.42; ≥72 years, HR, 8.71, 95% CI, 2.88-26.34), T stage (T2, HR, 3.60, 95% CI, 1.31-9.88), and M stage (M1, HR, 8.43, 95% CI, 4.40-16.16), with P<0.05. The Harrell's concordance index for tumor node metastasis (TNM) nomogram and TNM-age nomogram was 0.904 and 0.908, respectively. The areas under the curve (AUCs) for a 3-year CSS were 0.88 and 0.873, respectively. The corresponding AUCs for a 5-year CSS were 0.892 and 0.888, respectively. A new TNM-age staging system based on cancer-specific mortality rate analysis is proposed. This system provides a more accurate risk stratification and ensures more rational treatment measures for patients with stage IV MTC., Competing Interests: None., (AJTR Copyright © 2021.)

Abstract: It has been reported that some male breast cancer patients may refuse the recommended surgery, but the incidence rate in the United States is not clear. The purpose of this study was to identify the incidence, trends, risk factors, and eventual survival outcomes associated with the rejection of such cancer-directed surgery.We collected data on 5860 patients with male breast cancer (MBC) from the Surveillance, Epidemiology, and End Results database, including 50 patients refusing surgery as recommended. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to identify the effects of refusing surgery on cancer-specific survival (CSS) and overall survival (OS). The association between acceptance or rejection of surgery and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age, race, clinical characteristics, and radiation.Of the 5860 patients identified, 50 (0.9%) refused surgery. Old age (≥65: hazard ratio [HR]: 3.056, 95% confidence interval [CI]: 1.738-5.374, P < .0001), higher AJCC stage (III: HR: 3.283, 95% CI: 2.134-5.050, P < .0001, IV: HR: 14.237, 95% CI: 8.367-24.226, P < .0001), progesterone receptor status (negative: HR: 1.633, 95% CI: 1.007-2.648, P = .047) were considered risk factors. Compared with the surgery group, the refusal group was associated with a poorer prognosis in both OS and CSS (χ2 = 94.81, P < .001, χ2 = 140.4, P < .001). Moreover, significant differences were also observed in OS and CSS among 1:3 matched groups (P = .0002, P < .001).Compared with the patients undergoing surgery, the patients who refused the cancer-directed surgery had poor prognosis in the total survival period, particularly in stage II and III. The survival benefit for undergoing surgery remained even after adjustment, which indicates the importance of surgical treatment before an advanced stage for male breast cancer patients., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Six months since the outbreak of coronavirus disease (COVID-19), the pandemic continues to grow worldwide, although the outbreak in Wuhan, the worst-hit area, has been controlled. Thus, based on the clinical experience in Wuhan, we hypothesized that there is a relationship between the patient's CO 2 levels and prognosis. Methods: COVID-19 patients' information was retrospectively collected from medical records at the Leishenshan Hospital, Wuhan. Logistic and Cox regression analyses were conducted to determine the correlation between decreased CO 2 levels and disease severity or mortality risk. The Kaplan-Meier curve analysis was coupled with the log-rank test to understand COVID-19 progression in patients with decreased CO 2 levels. Curve fitting was used to confirm the correlation between computed tomography scores and CO 2 levels. Results: Cox regression analysis showed that the mortality risk of COVID-19 patients correlated with decreased CO 2 levels. The adjusted hazard ratios for decreased CO 2 levels in COVID-19 patients were 8.710 [95% confidence interval (CI): 2.773-27.365, P < 0.001], and 4.754 (95% CI: 1.380-16.370, P = 0.013). The adjusted odds ratio was 0.950 (95% CI: 0.431-2.094, P = 0.900). The Kaplan-Meier survival curves demonstrated that patients with decreased CO 2 levels had a higher risk of mortality. Conclusions: Decreased CO 2 levels increased the mortality risk of COVID-19 patients, which might be caused by hyperventilation during mechanical ventilation. This finding provides important insights for clinical treatment recommendations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hu, Li, Gao, Wang, Li, Chen, Huang, Huang, Li, Long, Liu, Guo and Wu.)

Background: We aimed to investigate clinical symptoms and epidemiologic features of emergency surgery patients infected with the 2019 novel coronavirus disease (COVID-19). More than 5 million people worldwide have been diagnosed with COVID-19 since December 2019 to the time of this publication. Thousands of emergency operations have been carried out since December 2019. To date, however, no literature has focused on the clinical symptoms of emergency surgery patients with COVID-19 pneumonia., Methods: We conducted a retrospective cohort study of 164 emergency surgery patients with or without COVID-19 pneumonia in Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1, 2020, to January 20, 2020. For this report, the final date of follow-up was February 5, 2020. The associated clinical, laboratory, epidemiologic, demographic, radiologic, and outcome data were collected and analyzed., Results: Of the 164 emergency surgery patients, the median age was 41 years (interquartile range, 29-89), and 136 (82.9%) were women. The associated main clinical symptom included fever (93 [56.7%])，dry cough (56 [34.2%]), fatigue (86 [52.4%]), nausea (78 [47.6%]), and dizziness (77 [47%]). Of 54 emergency surgery patients infected with COVID-19, the median age was 46 years (interquartile range: 25-89), and 45 (83.3%) were women. The pathologic clinical symptoms investigated included fever (54 [100%]), fatigue (48 [88.9%]), nausea (52 [96.3%]), dizziness (46 [85.2%]), and dry cough (44 [81.5%]). The lymphopenia (0.37 × 10 9 /L [interquartile range: 0.23-0.65]) and increased C-reactive protein (24.7 × 10 9 /L [interquartile range: 13.57-38]) were observed. The preoperative fever and postoperative fever in emergency surgery patients with or without COVID-19 pneumonia were analyzed in this study. Of 54 emergency surgery patients with COVID-19, 15 (27.8%) showed preoperative fever, 54 (100%) had postoperative fever. Of 110 emergency surgery patients without COVID-19, 5 (4.5%) had preoperative fever, 31 (28.2%) patients had postoperative fever. In emergency surgery patients with COVID-19, the fever lasted more than 7 days, markedly exceeded the length of time non-COVID-19 patients experienced fever (approximately 3 days). Furthermore, 43 health care workers were exposed to emergency surgery patients with COVID-19 pneumonia and were infected with COVID-19 pneumonia., Conclusion: In our study, the clinical symptoms of emergency surgery patients infected with COVID-19 displayed marked differences from those reporting common COVID-19 pneumonia. In addition, the health care workers were suspected to have been exposed to a great risk when caring for emergency surgery patients with COVID-19 pneumonia. Management guidelines of emergency surgery patients are described in in this report., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: In this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer., Materials and Methods: Cox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate., Results: A total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4-2.3, p < 0.001; HR = 1.9, 95% CI: 1.6-2.3, p < 0.001; HR = 1.4, 95% CI: 1.0-1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2-1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3-1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9-1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects., Conclusion: Patients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Medullary thyroid carcinoma (MTC) has been separated into its own chapter in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. However, controversies still exist for the staging of MTC. This study aimed to identify prognostic differences among patients with MTC to define a more accurate staging system., Methods: Data on cancer-specific survival from the Surveillance, Epidemiology, and End Results database between 2010 and 2014 were used for this study. Kaplan-Meier (K-M) curves, Cox proportional hazards regression analysis, and mortality per 1000-person-years were used to evaluate the mortality rate to create the new staging system., Results: A total of 960 cases were included in this analysis. The mortality rates of 24 different groups, which were classified using T stage (T1-4), N stage (N0-1b), and M stage (M0-1) were assessed using K-M curves. Cox proportional hazards regression analysis and mortality per 1000-person-years were used to classify patients, as stage I (T1-3N0-1aM0, 654, 68.34%), stage II (T1-3N1bM0, 181, 18.91%), stage III (T4N0-1bM0, 58, 6.06%), and stage IV (T1-4N0-1bM1, 64, 6.69%). The hazard ratios of stages II, III, and IV, using stage I as a reference, were 5.281 (95% confidence interval [CI], 1.236-22.562), 20.603 (95% CI, 4.400-96.467), and 55.717 (95% CI, 14.307-216.988), respectively. The mortality rates per 1000-person-years of stages I, II, III, and IV were 2.036 (95% CI, 0.657-6.312), 14.867 (95% CI, 6.679-33.092), 98.287 (95% CI, 54.432-177.478), and 224.199 (95% CI, 146.180-343.860), respectively., Conclusions: Compared with the current AJCC tumor-node-metastasis (TNM) staging system for MTC, this new proposed TNM staging system, which is based on cancer-specific mortality rate analysis, provides more accurate risk stratification and can ensure more rational treatment measures., Competing Interests: None., (AJTR Copyright © 2020.)

Prostate cancer (PCa) is the most prevalent cancer in U.S. men and many other countries. Although primary PCa can be controlled with surgery or radiation, treatment options of preventing metastatic PCa are still limited. To develop a new treatment of eradicating metastatic PCa, we have created an injectable cancer trap that can actively recruit cancer cells in bloodstream. The cancer trap is composed of hyaluronic acid microparticles that have good cell and tissue compatibility and can extend the release of chemokines to 4 days in vitro. We find that erythropoietin (EPO) and stromal derived factor-1α can attract PCa in vitro. Animal results show that EPO-releasing cancer trap attracted large number of circulating PCa and significantly reduced cancer spreading to other organs compared with controls. These results support that cancer trap may serve as a unique device to sequester circulating PCa cells and subsequently reduce distant metastasis.

Cartilage injury affects millions of people throughout the world, and at this time there is no cure. While transplantation of stem cells has shown some success in the treatment of injured cartilage, such treatment is limited by limited cell sources and safety concerns. To overcome these drawbacks, a microscaffolds system was developed capable of targeting, reducing the inflammatory response and recruiting endogenous progenitor cells to cartilage-defect. Erythropoietin (EPO)-loaded-hyaluronic acid (HA) microscaffolds (HA + EPO) were fabricated and characterized. HA-microscaffolds showed good cell-compatibility and could target chondrocytes via CD44 receptors. HA + EPO was designed to slowly release EPO while recruiting progenitor cells. Finally, the ability of HA + EPO to repair cartilage-defects was assessed using a rabbit model of full-thickness cartilage-defect. Our results showed that the intra-articular administration of EPO, HA, and EPO + HA reduced the number of inflammatory cells inside the synovial-fluid, while EPO + HA had the greatest anti-inflammatory effects. Furthermore, among all groups, EPO + HA achieved the greatest progenitor cell recruitment and subsequent chondrogenesis. The results of this work support that, by targeting and localizing the release of growth-factors, HA + EPO can reduce inflammatory responses and promote progenitor cells responses. This new platform represents an alternative treatment to stem-cell transplantation for the treatment of cartilage injury., Competing Interests: None., (© 2020 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Background: Lung cancer brain metastases are very common and one of the common causes of treatment failure. We aimed to examine the clinical use of chemical exchange saturation transfer (CEST) technology in the evaluation of brain metastases for lung cancer diagnosis and prognosis., Methods: We included26 cases of lung cancer brain metastases, 15 cases of gliomas, and 20 cases with normal tests. The magnetization transfer ratio (MTR;3.5 ppm) image from the GRE-EPI-CEST sequence was analyzed using the ASSET technique and APT technology. The MTR values were measured in the lesion-parenchymal, edema, and non-focus regions, and the MTR image was compared with the conventional MRI. ANOVA and t-test were used for statistical analysis., Results: The lesion-parenchymal, edema, and non-focus areas in the metastatic-tumor-group were red-yellow, yellow-green, and green-blue, and the MTR values were 3.29 ± 1.14%,1.28 ± 0.36%,and 1.26 ± 0.31%, respectively. However, in the glioma-group, the corresponding areas were red, red-yellow, and green-blue, and the MTR values were 6.29 ± 1.58%, 2.87 ± 0.65%, and 1.03 ± 0.30%, respectively. The MTR values of the corresponding areas in the normal-group were 1.07 ± 0.22%,1.04 ± 0.23%, and 1.06 ± 0.24%, respectively. Traditional MR images are in black-white contrast and no metabolic information is displayed. The MTRvalues of the three regions were significantly different among the three groups. The values were also significantly different between the parenchymal and edema areas in the metastatic-tumor-group. There were significant differences in the MTR values between the non-lesion and edema regions, but there was no significant difference between the edema and non-focus areas. In the glioma-group, there were significant differences in the MTR values between the parenchymal and edema areas, between the parenchymal and non-focus areas, and between the edema and non-focus areas., Conclusions: CEST reflects the protein metabolism; therefore, early diagnosis of brain metastases and assessment of the prognosis can be achieved using molecular imaging.

Ischemic osteonecrosis (IO) is caused by disruption of the blood supply to bone. It is a debilitating condition with pathological healing characterized by excessive bone resorption and delayed osteogenesis. Although the majority of research has focused on the role of osteoblasts and osteoclasts in the disease progression, we hypothesize that innate immune cells, macrophages and neutrophils, play a significant role. With the recent development of real-time imaging probes for neutrophils and macrophages, the purpose of this study was to investigate the kinetic immune cell response in a mouse model of IO. Our results show that induction of IO leads to a significant accumulation of activated neutrophils and macrophages at the affected tissue by 48 h after surgery. Additionally, the accumulation of these immune cells remained elevated in comparison to sham controls for up to 6 weeks, indicative of chronic inflammation. Immunohistochemistry confirmed the immune cell infiltration into the necrotic bone marrow and the increased presence of TNFα-positive cells, demonstrating, for the first time, a direct response of these cells to ischemia induced necrotic bone. These new findings support a hypothesis that IO is an osteoimmunologic condition where innate immune cells play a significant role in the chronic inflammation., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)