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Abstract Hepatocellular cancer (HCC) remained a life-threatening carcinoma. Agents for HCC imaging and therapy were expected to possess different intratumoral retention time. To construct an agent with different intratumoral retention time when applied for tumor imaging or therapy remained great values. A lasialoglycoprotein receptor (ASGPR) targeted lactobionic acid derivative (LABO) was constructed for fluorescent imaging and photodynamic therapy of HCC. 18F labeled LABO (18F-LABO) was developed for PET imaging of HCC. LABO and 18F-LABO showed similar molecular structure. LABO exhibited characteristic of viscosity and concentration-induced intratumoral in-situ self-assembly to expand the intratumoral retention. LABO was non-fluorescent at free stage, but emitted NIR fluorescence and generated irradiation-induced ROS after self-assembly for fluorescent imaging and photodynamic therapy. ASGPR specificity of LABO and 18F-LABO was confirmed using HepG2 cell. Biodistribution and fluorescent imaging confirmed the different tumor retention time of LABO and 18F-LABO when used for photodynamic therapy and PET imaging. PET imaging and photodynamic therapy were performed on HepG2 tumor bearing mice, which revealed that 18F-LABO/LABO could specifically accumulated in the HepG2 tumor for tumor location/inhibition. LABO/18F-LABO with excellent HCC specificity but different intratumoral behaviors showed great values for the PET/NIR imaging and photodynamic therapy for HCC. Graphical Abstract

Summary: Homoharringtonine (HHT), an alkaloid isolated from Cephalotaxus, is an effective anti-leukemia agent and exhibits inhibitory effects in various solid tumors. However, the impacts of HHT treatment on thyroid cancer (TC) remain unclear. Our findings demonstrated that HHT exhibited remarkable anti-TC activity that involved inhibiting cell proliferation, invasion, and migration, as well as inducing apoptosis. Proteomics analysis revealed that the expression of the tissue inhibitor of metalloproteinase 1 (TIMP1) was downregulated in TC cells after HHT treatment. TIMP1 overexpression promoted TC progression and partially reversed the anti-TC effects of HHT, while TIMP1 downregulation inhibited TC progression and enhanced the anti-TC effects of HHT. Furthermore, TIMP1 re-expression attenuated the enhancement of anti-TC effects of HHT induced by TIMP1 knockdown. Mechanistically, HHT exerted anti-TC effects by downregulating TIMP1 expression and then inactivating the FAK/PI3K/AKT signaling pathway. Taken together, our study demonstrated that HHT could inhibit TC progression by inhibiting the TIMP1/FAK/PI3K/AKT signaling pathway.

PurposeEndothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy.MethodsWe recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients.ResultsWe analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p

Background: The BRAFV600E mutation is a valuable indicator for thyroid cancer diagnosis. This study aimed to develop a deep convolutional neural network (DCNN) model based on ultrasound images to predict the BRAFV600E mutation status of thyroid nodules. Methods: The ultrasound images were obtained from four hospitals between January 2017 and January 2022. We trained and validated the DCNN model based on the primary set from center 1 (979 images, 528 patients). The DCNN network consists of Conv block, Downsample block, Gaussian error linear unit, Global Average Polling, and Full Connected. The predictive performance of this model was evaluated by using areas under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity in four independent test sets from center 1 to center 4 (531 images, 282 patients). Heatmaps were used to visualize the most predictive regions of each image. Specimens obtained through fine‐needle aspiration or surgery were used to detect the BRAFV600E mutation. Results: The DCNN model achieved encouraging predictive performance by fivefold cross‐validation (AUC 0.95) in the primary set. This performance was further confirmed in the independent internal test set (AUC 0.93) and three independent external test sets (AUC 0.84–0.88). The deep learning score revealed significant differences between BRAFV600E‐mutant and BRAFV600E‐wild‐type groups (all test sets p < .001). The heatmaps visualized the most predictive region located inside or alongside the thyroid nodules. Conclusion: A DCNN model with encouraging predictive performance was developed based on ultrasound images to predict the BRAFV600E mutation status of thyroid nodules.

Objective. Antithyroglobulin antibodies (TgAbs) could be used as a surrogate tumor marker of TgAb-positive-differentiated thyroid carcinoma. This study aims to determine whether the change in TgAb levels over time could be used as a predictor of responses to therapy in pediatric papillary thyroid carcinoma (PTC) patients. Methods. We retrospectively analyzed the records of 48 pediatric PTC patients with TgAb levels ≥50 IU/ml 6 months after initial 131I treatment. Suppressed thyroglobulin (Tg) levels 6 months after initial 131I treatment were used to divide the patients into positive Tg (P-Tg, Tg ≥ 0.2 ng/ml) and negative Tg (N-Tg, Tg

ObjectiveThe objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up.MethodsA retrospective review of medical records identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019.ResultsIn total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent prognostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively).ConclusionsWDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.

Inflammation is crucial to tumorigenesis and progression of many cancers. Inflammatory molecules in tumor microenvironment exert pro- or anti-tumor effects. Among them, interleukin, mainly produced by CD3+ and CD4+ T lymphocytes, is a class of small molecule proteins which play an important role in intercellular communication. Numerous studies have confirmed that interleukins are closely related to thyroid cancer. Interleukins regulate the proliferation and migration of thyroid cancer cells and they have prospects in discriminating benign and malignant thyroid diseases, predicting the risk of tumorigenesis, evaluating the prognosis and monitoring the recurrence of thyroid cancer. Besides, the effective application of interleukins in treatment of thyroid cancer has been confirmed by some cell and animal researches. The present review will introduce the potential mechanisms of interleukins in thyroid cancer and focus on the applications of interleukins in clinical practice of thyroid cancer, which will help update understanding of the progress of interleukins researches in thyroid cancer.

Radioiodine treatment is a fundamental therapy for patients with papillary thyroid cancer (PTC). Sodium/iodide symporter (NIS)-mediated iodine uptake is a prerequisite for the efficacy of radioiodine therapy. Interleukin-6 (IL-6) is a pro-tumor cytokine, but its regulation of NIS expression in PTC has not been elucidated. In this study, we found that IL-6 enhanced the proliferation ability of PTC cells. Moreover, the negative association between IL-6 and NIS expression in thyroid cancer tissues was demonstrated. IL-6 downregulated thyroid-specific genes such as NIS, thyroid peroxidase, and thyroidstimulating hormone receptor and thyroid-specific transcription factors including thyroid transcription factor-1 (TTF-1) and paired box protein-8 (PAX-8). The inhibitory effects of IL-6 on NIS expression were alleviated by mitogen-activated protein kinase and Janus kinase inhibitors. Depletion of c-Jun or STAT3 also rescued IL-6-induced NIS downregulation, with STAT3 depletion exerting a stronger effect. TTF-1 protein expression was also restored by depleting c-Jun or STAT3. STAT3 depletion, but not c-Jun depletion, alleviated the inhibitory effect of IL-6 on PAX-8 expression. Moreover, the downregulation of NIS by IL-6 was rescued by overexpressing TTF-1 and PAX-8. Tocilizumab, an IL-6 receptor blocker, did not have any cytostatic activity in PTC cells, and it also failed to induce redifferentiation in vitro. However, we found that the drug blocked the inhibitory effect of IL-6 on NIS expression. In summary, IL-6 inhibits NIS transcription in PTC cells by activating mitogen-activated protein kinase and Janus kinase signaling. [ABSTRACT FROM AUTHOR]

This study aimed to address the issue of the low solubility in the model drug probenecid (PRO) and its impact on bioavailability. Two salts of probenecid (PRO), 4-aminopyridine (4AMP), and 4-dimethylaminopyridine (4DAP) were synthesized and characterized by PXRD, DSC, TGA, FTIR, and SEM. The crystal structures of the two salts were determined by SCXRD, demonstrating that the two salts exhibited different hydrogen bond networks, stacking modes, and molecular conformations of PRO. The solubility of PRO and its salts in a phosphate-buffered solution (pH = 6.8) at 37 °C was determined, the results showed that the solubility of PRO salts increased to 142.83 and 7.75 times of the raw drug, respectively. Accelerated stability experiments (40 °C, 75% RH) showed that the salts had good phase stability over 8 weeks. Subsequently, Hirshfeld surface (HS), atom in molecules (AIM), and independent gradient model (IGM) were employed for the assessment of intermolecular interactions. The analyses of salt-forming sites and principles were conducted using molecular electrostatic potential surfaces (MEPs) and pKa rules. The lattice energy (EL) and hydration-free energy (EHF) of PRO and its salts were calculated, and the relationships between these parameters and melting points and the solubility changes were analyzed.

Photosensitive resins (PSR) were exposed to challenging operational conditions in different technological domains. It is desirable to enhance the mechanical durability of PSR for its usage in real-world applications. We use TiO2 to improve the mechanical strength and durability of PSR and comprehend nanoparticles' impact on PSR's durability. Herein, we compare the mechanical properties of photosensitive resins (PSR) and TiO2-based polymer nanocomposites (T@PNCs) with varying nanoparticle sizes [1 μm and 20 nm]. Firstly, the ultrasonic dual mixing (UDM) technique is employed, which involves the simultaneous use of ultrasonic mixing and stirring to produce nanocomposites of T@PNCs slurry. Before printing, the initial designs were created using solidworks software, and 3D-Printing was performed using a 3D Moon Ray Printer. Rod and flat specimens were printed, and their structural and mechanical strength were analyzed. The experimental results suggest that larger nanoparticles, measuring 1 μm, decrease the mechanical durability of T@PNCs. However, reducing the size of nanoparticles in polymer nanocomposites (PNCs) to 20 nm increases mechanical resilience, leading to improved flexural and tensile strength. Our experimental results demonstrate that the nanoparticles' size strongly influences PSR's mechanical properties.

Context: Pregnancy-related hormones may stimulate thyroid cancer growth, but whether pregnancy affects the prognoses of patients with lung metastases from differentiated thyroid cancer (DTC-LM) after surgery and radioiodine therapy is unclear.Objective: To assess the impact of pregnancy on DTC-LM through the comparison of prognoses between female patients with DTC-LM who did and did not become pregnant after surgery and radioiodine therapy.Methods: We retrospectively analyzed the records of 124 female patients aged 16 to 35 years who underwent surgery and radioiodine therapy for DTC-LM. These patients were divided into pregnancy group (n = 37) and nonpregnancy group (n = 87) according to whether they became pregnant after surgery and radioiodine therapy, regardless of whether they had a pregnant history before treatment.Results: The 5- and 10-year progression-free survival rates were 94.52% and 63.22% in pregnancy group versus 89.82% and 58.13% in nonpregnancy group. The 5- and 10-year cumulative overall survival rates of pregnancy group were 97.30% and 85.77% versus 93.50% and 81.95% in nonpregnancy group (all P > 0.05). The median time of follow-up in the pregnancy and nonpregnancy groups was 82 months (25-136 months) and 68 months (13-133 months), respectively. Non-radioiodine-avid LM and primary tumors needing repeated resection were independent predictors of poor progression-free survival for patients in pregnancy group.Conclusion: Pregnancy does not affect the prognoses of patients with DTC-LM after surgery and radioiodine therapy. Non-radioiodine-avid LM and repeated primary tumor surgeries are independent risk factors for poor prognoses of pregnant patients. [ABSTRACT FROM AUTHOR]

Predicting the health status of lithium-ion batteries is crucial for ensuring safety. The prediction process typically requires inputting multiple time series, which exhibit temporal dependencies. Existing methods for health status prediction fail to uncover both coarse-grained and fine-grained temporal dependencies between these series. Coarse-grained analysis often overlooks minor fluctuations in the data, while fine-grained analysis can be overly complex and prone to overfitting, negatively impacting the accuracy of battery health predictions. To address these issues, this study developed a Hybrid-grained Evolving Aware Graph (HEAG) model for enhanced prediction of lithium-ion battery health. In this approach, the Fine-grained Dependency Graph (FDG) helps us model the dependencies between different sequences at individual time points, and the Coarse-grained Dependency Graph (CDG) is used for capturing the patterns and magnitudes of changes across time series. The effectiveness of the proposed method was evaluated using two datasets. Experimental results demonstrate that our approach outperforms all baseline methods, and the efficacy of each component within the HEAG model is validated through the ablation study.

As a common vegetable variety, asparagus is rich in B vitamins, vitamin A, and trace elements such as folate, selenium, iron, manganese, and zinc. With the increasing market demand, China has become the world’s largest cultivated area for asparagus production and product exportation. However, traditional asparagus grading mostly relies on manual visual judgment and needs a lot of manpower input to carry out the classification operation, which cannot meet the needs of large-scale production. To address the high labor cost and labor-intensive production process resulting from the large amount of manpower input and low accuracy of existing asparagus grading devices, this study proposed an improved asparagus grading system and method based on TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution) objective evaluation and SVM (support vector machine) prediction. The key structure of classification device was analyzed first, the key components were designed, and the structural parameters were determined by theoretical calculation. Through analysis of the factors affecting asparagus quality, three key attributes were determined: length, diameter, and bruises, which were used as reference attributes to conduct experimental analysis. Then, the graded control groups were set up, combining the TOPSIS principle with weighting, and a score for each asparagus sample was determined. These scores were compared with those of a graded control group to derive the grade of each asparagus, and these subsets of the dataset were used as the training set and the test set, excluding the error caused by the subjectivity of the manual judgment. Based on a comparison of the accuracies of different machine learning models, the support vector machine (SVM) was determined to be the most accurate, and four SVM methods were used to evaluate the test set: linear SVM, quadratic SVM, cubic SVM, and medium Gaussian SVM. The test results showed that the grading device was feasible for asparagus. The bruises had a large influence on asparagus quality. The training accuracy of the medium Gaussian SVM method was high (96%), whereas its test accuracy was low (86.67%). The training accuracies and test accuracy of the quadratic and cubic SVM methods were 93.34%. The quadratic SVM and cubic SVM were demonstrated to have better generalization ability than the medium Gaussian SVM method for predicting unknown grades of asparagus and meeting the operational requirements of the asparagus grading.

Recrystallization of polyoxymethylene (POM) in solvent is an effective post-treatment method for manufacturing a better POM product. Herein, the crystallization process of POM in methanol was investigated with the use of a series of equipment. The results reveal that POM crystallization in methanol yields two kinds of particle morphologies, including small particles with lamellar structures branching and growing in all directions and large particles resulting from melt agglomeration. The mechanism of POM crystallization in methanol with two distinct pathways was proposed, in which solution cooling crystallization of POM at higher temperature yields small particles while melt crystallization yields large particles. Furthermore, both non-isothermal and isothermal crystallization kinetics of POM were determined. The Avrami equation was employed to derive the crystallization rate constant via data fitting. The activation energy of crystallization was then obtained using the Arrhenius formula. The kinetics suggest that recrystallization of POM in methanol may dissolve and remove substances hindering raw material crystallization, achieving a faster crystallization rate for products.

The geoacoustic and physical properties of the bottom, as well as spatial distribution, are crucial factors in analyzing the underwater acoustic field structure and establishing a geoacoustic model. Acoustic inversion has been widely used as an economical and effective method to obtain multi-parameters of the bottom. Compared with traditional inversion methods based on acoustic propagation models, acoustic backscattering models are more suitable for multi-parameter inversion, because they contain more bottom information. In this study, a Bayesian inversion method based on an acoustic backscattering model is proposed to obtain bottom multi-parameters, including geoacoustic parameters (the sound speed and loss parameter), partial physical parameters of the sediment, and statistical parameters of the seafloor roughness and sediment heterogeneity. The bottom was viewed as a kind of fluid medium. A high-frequency backscattering model based on fluid theory was adopted as the forward model to fit the scattering strength between the model prediction and the measured data. The Bayesian inversion method was used to obtain the posterior probability density (PPD) of the inversion parameters. Parameter estimation, uncertainty, and correlation were acquired by calculating the maximum a posterior (MAP), the mean values, the one-dimensional marginal distributions of the PPD, and the covariance matrix. Finally, the high-frequency bottom backscattering strength from the Quinault Range site was employed for inversion tests. The estimated values and uncertainties of various bottom parameters are presented and compared with the directly measured bottom parameters. The comparison results demonstrate that the method proposed herein can be used to estimate the sediment/water sound speed ratio, the sediment/water density ratio, and the spectral exponent of the roughness spectrum effectively and reliably.

ObjectiveThe purpose of this study was to investigate the association between serum polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).MethodsWe performed a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. The weighted multiple linear regression model was utilized to determine the association between serum PUFAs and BMD. Further smoothed curve fitting and threshold effect analysis were conducted. Finally, we performed a subgroup analysis.ResultsIn total, 1979 participants aged 20-59 years were enrolled. After adjusting for all covariates, we found that serum docosapentaenoic acid (DPA) was positively associated with head BMD (β = 0.0015, 95% Cl: 0.0004, 0.0026, P = 0.008296) and lumbar spine BMD (β = 0.0005, 95% Cl: 0.0000, 0.0010, P = 0.036093), and serum eicosadienoic acid (EDA) was negatively associated with thoracic spine BMD (β = -0.0008, 95% Cl: -0.0016, -0.0000, P = 0.045355). Smoothed curve fitting revealed a nonlinear positive association between serum DPA and lumbar spine BMD. Threshold effect analysis indicated that the threshold of serum DPA was 81.4 µmol/L. Subgroup analysis revealed a positive correlation between serum DPA and head BMD in the subgroup aged 50-59 years (β = 0.0025, 95% Cl: 0.0002, 0.0049, P = 0.035249) and females (β = 0.0026, 95% Cl: 0.0008, 0.0044, P = 0.005005). There was a positive relationship between serum DPA and lumbar spine BMD in females (β = 0.0008, 95% Cl: 0.0001, 0.0015, P = 0.017900) and a negative association between serum EDA and thoracic spine BMD in the subgroup aged 30-39 years (β = -0.0016, 95% Cl: -0.0031, -0.0001, P = 0.041331), males (β = -0.0012, 95% Cl: -0.0023, -0.0001, P = 0.039364) and other races (β = -0.0021, 95% Cl: -0.0037, -0.0006, P = 0.008059).ConclusionThis study demonstrated a linear positive relationship between serum DPA and head BMD, a nonlinear positive association between serum DPA and lumbar spine BMD, and a linear negative correlation between serum EDA and thoracic spine BMD in US adults.

Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES.

For blood pumps with a rotating vane-structure, hemolysis values are estimated using a stress-based power-law model. It has been reported that this method does not consider the red blood cell (RBC) membrane’s shear resistance, leading to inaccurate estimation of the hemolysis value. The focus of this study was to propose a novel hemolysis model which can more accurately predict the hemolysis value when designing the axial flow blood pump. The movement behavior of a single RBC in the shear flow field was simulated at the mesoscale. The critical value of shear stress for physiological injury of RBCs was determined. According to the critical value, the equivalent treatment of RBC aging was studied. A novel hemolysis model was established considering the RBC’s aging and the hemolysis’ initial value. The model’s validity was verified under the experimental conditions of shear stress loading and the conditions of the shear flow field of the blood pump. The results showed that compared with other hemolysis models for estimating the hemolysis value of blood pumps, the novel hemolysis model proposed in this paper could effectively reduce the estimation error of the hemolysis value and provide a reference for the optimal design of rotary vane blood pumps.

Abstract The objective of this study was to evaluate the accuracy, reliability, and time requirements of two methods for measuring thoracolumbar kyphosis: a conventional method using a picture archiving and communication system (PACS) and this new method using the integrated inclinometer of a smartphone. The thoracolumbar kyphotic angles of one hundred consecutive patients were measured by a PACS and this novel smartphone method. The measured angles were analysed by multiple statistical methods, and the two measurement tools were compared in terms of accuracy, reliability, and time requirements. The mean result of thoracolumbar kyphosis measured by the PACS was 21.43 ± 12.96°, and the mean value measured by the smartphone was 21.03 ± 13.01°. A Bland–Altman plot for these two methods showed a mean difference of 0.4°, with the limits of agreement being -2.4° and 3.2°. One-way ANOVA showed no significant difference (F = 0.080, P = 0.999) among measurements by different observers and different methods. The intraclass correlation coefficients (ICCs) of the mean values of four repeated measurements of thoracolumbar kyphosis between these two methods were 0.997 (0.995–0.998), revealing that the two methods were highly correlated. The ICC results showed that the concordance between these two methods was very good for all measurements of thoracolumbar kyphosis, and the inter- and intra-observer reliability of the novel smartphone method were very good. The PACS method (36.95 ± 0.98 s) took significantly longer than the smartphone method (17.68 ± 0.97 s) when compared by an independent-samples t test (P = 0.000). This new method using the integrated inclinometer of a smartphone has satisfactory validity and reliability compared to the PACS method. Additionally, the new method took significantly less time than the PACS method. Measuring with a smartphone is more convenient than using a PACS, which is always rooted in a full-sized computer. In summary, this new method using the integrated inclinometer of a smartphone is rapid, convenient, accurate and reliable when measuring thoracolumbar kyphosis in osteoporotic vertebral compression fracture (OVCF) patients.

BackgroundAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood.MethodsWe developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman’s rank correlation coefficient test.ResultsCoinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated.ConclusionCoinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota.

BackgroundPrevious studies have shown that the Unilateral Biportal Endoscopy is an effective and safety surgery for sufficient decompression of degenerative lumbar spinal stenosis. However, data are lacking in terms of its benefits when compared with conventional open lumbar discectomy (OLD), especially in patients with severe degenerative lumbar spinal stenosis (DLSS).AimTo compare the clini cal outcomes of two types decompressive surgery: unilateral biportal endoscopy-unilateral laminectomy bilateral decompression (UBE-ULBD) and conventional open lumbar discectomy (OLD) in severe degenerative lumbar spinal stenosis (DLSS).MethodsWe retrospectively analyzed patients who underwent UBE-ULBD (n = 50, operated at 50 levels; UBE-ULBD group) and conventional open lumbar discectomy (n = 59, operated at 47 levels; OLD group) between February 2019 and July 2021. All patients were diagnosed with severe stenosis based on the Schizas classification (Grade C or D) on MRI. We compared radiographic and clinical outcome scores [including the visual analog scale (VAS), Oswestry Disability Index (ODI), and Zurich Claudication Questionnaire (ZCQ)] between the 2 groups at 1 year of follow-up. The radiographic evaluation included the cross-sectional area (CSA) of the thecal sac and paraspinal muscles on MRI. Fasting blood was drawn before and 1 and 7 days after the operation to detect creatine kinase (CK). Surgical data perioperative complications were also investigated.ResultsThe baseline demographic data of the 2 groups were comparable, including VAS, ODI and ZCQ scores, the cross-sectional area of the thecal sac and paraspinal muscles and creatine kinase levels. The dural sac CSA significantly increased post -operatively in both groups, which confirmed they benefited from comparable decompressive effects. The operative duration in the OLD group was less than the UBE-ULBD group (43.9 ± 5.6 min vs. 74.2 ± 9.3 min, p < 0.05). The OLD group was associated with more estimated blood loss than the UBE-ULBD group (111.2 ± 25.0 ml vs. 41.5 ± 22.2 ml, P < 0.05). The length of hospital stay (HS) was significantly longer in the OLD group than in the UBE-ULBD group (6.8 ± 1.6 vs. 4.0 ± 1.4 days, P < 0.05). The VAS, ODI, and ZCQ scores improved in both groups after the operation. Serum creatine kinase values in the UBE-ULBD group were significantly lower than in the OLD group at 1 day after surgery (108. 1 ± 11.9 vs. 347.0 ± 19.5 U/L, P < 0.05). The degree of paraspinal muscle atrophy in the UBE-ULBD group was significantly lower than in the OLD group at 1 year (4.50 ± 0.60 vs. 11.42 ± 0.87, P < 0.05).ConclusionsUBE-ULBD and conventional OLD demonstrate comparable short-term clinical outcomes in treating severe DLSS. However, UBE-ULBD surgery was associated with a shorter hospital stay, less EBL and paravertebral muscle injury than OLD surgery.

Abstract Background In recent years, numerous investigations have been conducted to determine the clinical significance and critical functions of vascular endothelial growth factor (VEGF) in various malignant cancers. The purpose of this meta-analysis was to comprehensively evaluate the prognostic and clinicopathological value of VEGF in patients with osteosarcoma. Methods We performed a systematic literature retrieval of available databases. Odds ratios (ORs) or standard mean difference (SMD) for clinicopathological parameters, hazard ratios (HRs) for overall survival and disease-free survival were calculated to assess the correlation between VEGF expression and prognosis in patients with osteosarcoma. Results A total of 22 studies with 1144 patients were included in our study. Pooled analyses showed that VEGF overexpression predicted worse overall survival (HR, 2.42; 95% CI, 1.87–3.11, p

BackgroundWith the arrival of the era of the aging population, the amount of joint arthroplasty surgery keeps rising, and the articles related to the application of tranexamic acid (TXA) in joint arthroplasty (we called the application of tranexamic acid in joint arthroplasty as TIA in this study) also show a blowout growth. Therefore, we conducted a bibliometric analysis of TIA-related publications to identify the main research trends and hot spots in this field in the last 20 years.MethodsIn this study, publications in the field of TIA from January 1, 2002 to December 31, 2021 were searched in the Web of Science Core Collection (WoSCC). A total of 1,013 publications were evaluated for specific characteristics with Microsoft Excel software, CiteSpace, VOSviewer, and Online Analysis Platform of Literature Metrology (http://bibliometric.com/).ResultsA total of 1,013 TIA-related articles were included in this study, and the number of articles in this field has increased yearly over the past 20 years. The USA and China dominated in the field of TIA. The Sichuan University published the most TIA-related articles among all the institutions. Of all the authors, Professor Pei was the most productive author with 64 articles. The lack of international cooperation was a significant problem in this field during the past 20 years. Furthermore, the results of the co-citation analysis and citation bursts analysis revealed that the safety and effectiveness of TIA and the optimal use strategy were the main trends and hotspots for the current and future.ConclusionThis bibliometric study reviewed the evolution trend of TIA research, and identified the countries, institutions, authors and journals that have made significant contributions to this field in the past 20 years, as well as the limitations and deficiencies in this field. In addition, this study revealed that the effectiveness and safety of TIA and the optimal use strategy was the current or future research trend and hotspot in this field.

Malignant tumor is a disease caused by the imbalance of cell growth and proliferation mechanism, which seriously threatens human health and life safety. However, side effects and drug resistance are the key factors that limit the efficacy of anti-tumor drugs. Therefore, it is urgent and necessary to explore and unearth natural, safe and effective chemosensitizers in tumor researches. Curcumin is the main active ingredient in Curcuma, which has anti-inflammatory, anti-inflammatory and anti-oxidation effects, and has inhibitory effects on a variety of cancers. Bibliometric analysis is a scientific and quantitative method to assess the published articles, which can help researchers to find the development trends and the research hotspots of a specific research field, providing the development of future research for researchers. This study searched the Web Science Core Collection (woscc) for publications related to curcumin and tumors from January 1, 2001 to December 31, 2021. The specific characteristics of 1707 publications were analyzed by using Microsoft Excel software, CiteSpace, Vosviewer and online analysis platform of literature metrology. China had the largest number of published articles, with 579 publications. Aggarwal BB’s articles total citations and average citations were the most. PLoS One had the largest number of publications, with 32 publications. The current research focuses on “nanoparticles”, “delivery”, “micells” and “doxorubicin”. At present, nano based drug delivery system to improve the bioavailability of curcumin and thus to treat tumors will be the focus of future research.

Osteosarcoma (OS) is one of the most common types of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is supposed to develop new drugs with low toxicity and low side effects. As a Chinese traditional medicine, Neferine(C38H44N2O6) has inhibitory effects in various tumors. In the present study, we investigated the effects of Nef on OS cells in vitro and in vivo. We found that Nef inhibited cell proliferation, reduced migration, decreased invasion, and induced cell cycle arrest of OS cells. Notably, we demonstrated that Nef had no obvious effect on proliferation and apoptosis of normal cells. Besides, Nef repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that Nef increased the phosphorylation level of P38 and JNK and suppressed Wnt/β-Catenin signaling pathway. In summary, our research validates that Nef may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38/JNK and suppressing Wnt/β-Catenin signaling pathway.

The regulation of solid-state emission based on cocrystal engineering is an emerging strategy for developing next-generation luminescent materials. Here, three luminescent cocrystals (AA-DITFB, AA-TFTPA and AA-TCNB) of 9-anthraldehyde (9-AA) are reported, which exhibit a broad range of green-to-red emission. Tuning the photophysical properties of 9-AA via cocrystals is based on different mechanisms. Compared with single-component crystals, the difference in the emission properties of AA-DITFB and AA-TFTPA originates from the π–π interaction between chromophores. As for AA-TCNB, its prominent red-shifted emission is the result of the charge-transfer interaction, which is confirmed by infrared spectroscopy, “hole-electron” analysis and charge-transfer spectroscopy. This work not only reveals the relationship between molecular structure and fluorescent properties, but also proposes a strategy to develop multicolor luminescent systems with tunable efficiency and lifetime.

Thermosalient (TS) crystals have gained considerable attention due to their potential applications in various fields, including in actuators, sensors, energy harvesting, and artificial muscles. Herein, co-crystallization was employed to construct TS crystals by forming a twisted angle between aromatic rings. Two multicomponent trimethoprim (TMP) TS cocrystals, TMP-25HBA and TMP-OA, were obtained. Differential scanning calorimetry (DSC) and variable-temperature powder X-ray diffraction (VT-PXRD) revealed that TMP-OA undergoes a solid-to-solid phase transition, while TMP-25HBA does not exhibit any phase transition. To the best of our knowledge, TMP-25HBA is the first multicomponent TS crystal without phase transition. The TS effect of both crystals is a result of the unit cell’s anisotropic expansion.

Suppose that $f(z)$ is a meromorphic function with hyper order $\sigma_{2}(f)

Ferroptosis, as a form of programmed cell death independent of apoptosis, has been demonstrated that plays a major role in tumorigenesis and cancer treatment. A comprehensive analysis of ferroptosis-related genes (FRGs) may lead to a novel choice for the treatment of Ewing sarcoma (ES). Here, 148 differentially expressed FRGs (DEFRGs) were identified between normal and ES tissue. And the GO and KEGG analyses of DEFRGs indicated that these genes were enriched in cancer and immune-related signaling pathways. Then, the GSE17679 cohort was randomly divided into train and test cohorts. Based on the train cohort, AURKA, RGS4, and RIPK1 were identified as key genes through the univariate Cox regression analysis, the random survival forest algorithm, and the multivariate Cox regression analysis and utilized to establish a prognostic FRG signature. The validation results demonstrated that the gene signature has not only excellent prediction performance and generalization ability but is also good at predicting the response of immunotherapy and chemotherapy. Subsequent analysis indicated that all 3 key genes play key roles in tumor immunity and prognosis of ES. Of these, AURKA was highly associated with EWSR1, which was verified by a single-cell dataset (GSE130019). Therefore, the 3 genes may be potential therapeutic targets for ES. At the end of this study, we also constructed an accurate nomogram that helps clinicians to assess the survival time of ES patients. In conclusion, our study constructed an excellent gene signature, which is helpful in improving the prognosis of ES patients.

Vascular dementia (VD) is the second most common dementia syndrome worldwide, and effective treatments are lacking. Gastrodia elata Blume (GEB) has been used in traditional Chinese herbal medicine for centuries to treat cognitive impairment, ischemic stroke, epilepsy, and dizziness. Gastrodin (p-hydroxymethylphenyl-b-D-glucopyranoside, Gas) and Gastrodigenin (p-hydroxybenzyl alcohol, HBA) are the main bioactive components of GEB. This study explored the effects of Gas and HBA on cognitive dysfunction in VD and their possible molecular mechanisms. The VD model was established by bilateral common carotid artery ligation (2-vessel occlusion, 2-VO) combined with an intraperitoneal injection of sodium nitroprusside solution. One week after modeling, Gas (25 and 50 mg/kg, i.g.) and HBA (25 and 50 mg/kg, i.g.) were administered orally for four weeks, and the efficacy was evaluated. A Morris water maze test and passive avoidance test were used to observe their cognitive function, and H&E staining and Nissl staining were used to observe the neuronal morphological changes; the expressions of Aβ1-42 and p-tau396 were detected by immunohistochemistry, and the changes in energy metabolism in the brain tissue of VD rats were analyzed by targeted quantitative metabolomics. Finally, a Hippocampus XF analyzer measured mitochondrial respiration in H2O2-treated HT-22 cells. Our study showed that Gas and HBA attenuated learning memory dysfunction and neuronal damage and reduced the accumulation of Aβ1-42, P-Tau396, and P-Tau217 proteins in the brain tissue. Furthermore, Gas and HBA improved energy metabolism disorders in rats, involving metabolic pathways such as glycolysis, tricarboxylic acid cycle, and the pentose phosphate pathway, and reducing oxidative damage-induced cellular mitochondrial dysfunction. The above results indicated that Gas and HBA may exert neuroprotective effects on VD by regulating energy metabolism and mitochondrial function.

A gradient preconditioning approach based on transmitted wave energy for least-squares reverse time migration (LSRTM) is proposed in this study. The gradient is preconditioned by using the energy of “approximate transmission wavefield,” which is calculated based on the non-reflecting acoustic equation. The proposed method can effectively avoid a huge amount of calculation and storage required by the Hessian matrix or approximated Hessian matrix and can overcome the influence of reflected waves, multiples, and other wavefields on the gradient in gradient preconditioning based on seismic wave energy (GPSWE). The numerical experiments, compared with that using GPSWE, show that LSRTM using the gradient preconditioning based on transmitted wave energy (GPTWE) can significantly improve the imaging accuracy of deep target and accelerate the convergence rate without trivial increased calculation.

Reverse time migration (RTM) is an ideal seismic imaging method for complex structures. However, in conventional RTM based on rectangular mesh discretization, the medium interfaces are usually distorted. Besides, reflected waves generated by the two-way wave equation can cause artifacts during imaging. To overcome these problems, a high-order finite-difference (FD) scheme and stability condition for the pseudo-space-domain first-order velocity-stress acoustic wave equation were derived, and based on the staggered-grid FD scheme, the RTM of the pseudo-space-domain acoustic wave equation was implemented. Model experiments showed that the proposed RTM of the pseudo-space-domain acoustic wave equation could systematically avoid the interface distortion problem when the velocity interfaces were considered to compute the pseudo-space-domain intervals. Moreover, this method could effectively suppress the false scattering of dipping interfaces and reflections during wavefield extrapolation, thereby reducing migration artifacts on the profile and significantly improving the quality of migration imaging.

Reverse time migration (RTM) is based on the two-way wave equation, so its imaging results obtained by conventional zero-lag cross-correlation imaging conditions contain a lot of low-wavenumber noises. So far, the wavefield decomposition method based on the Poynting vector has been developed to suppress these noises; however, this method also has some problems, such as unstable calculation of the Poynting vector, low accuracy of wavefield decomposition, and poor effect of large-angle migration artifacts suppression. This article introduces the optical flow vector method to RTM to realize high-precision wavefield decomposition for both the source and receiver wavefields and obtains four directions of wavefields: up-, down-, left-, and right-going. Then, the cross-correlation imaging sections of one-way propagation components of forward- and back-propagated wavefields are optimized and stacked. On this basis, the reflection angle of each imaging point is calculated based on the optical flow vector, and an attenuation factor related to the reflection angle is introduced as the weight to generate the optimal stack images. The tests of theoretical model and field marine seismic data illustrate that compared with the conventional RTM with wavefield decomposition based on the Poynting vector, the angle-weighted RTM with wavefield decomposition based on the optical flow vector proposed in this article can achieve wavefield decomposition for both the source and receiver wavefields and calculate the reflection angle of each imaging point more accurately and stably. Moreover, the proposed method adopts angle weighting processing, which can further eliminate large-angle migration artifacts and effectively improve the imaging accuracy of RTM.