Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis.

Osteoarthritis (OA), known as one of the most common types of aseptic inflammation of the musculoskeletal system, is characterized by chronic pain and whole-joint lesions. With cellular and molecular changes including senescence, inflammatory alterations, and subsequent cartilage defects, OA eventually leads to a series of adverse outcomes such as pain and disability. CRISPR-Cas-related technology has been proposed and explored as a gene therapy, offering potential gene-editing tools that are in the spotlight. Considering the genetic and multigene regulatory mechanisms of OA, we systematically review current studies on CRISPR-Cas technology for improving OA in terms of senescence, inflammation, and cartilage damage and summarize various strategies for delivering CRISPR products, hoping to provide a new perspective for the treatment of OA by taking advantage of CRISPR technology.

Exploring the Application of Graphene Oxide-Based Nanomaterials in the Repair of Osteoporotic Fractures.

Osteoporotic fractures are induced by osteoporosis, which may lead to the degradation of bone tissues and microstructures and impair their healing ability. Conventional internal fixation therapies are ineffective in the treatment of osteoporotic fractures. Hence, developing tissue engineering materials is crucial for repairing osteoporotic fractures. It has been demonstrated that nanomaterials, particularly graphene oxide (GO), possess unique advantages in tissue engineering due to their excellent biocompatibility, mechanical properties, and osteoinductive abilities. Based on that, GO-nanocomposites have garnered significant attention and hold promising prospects for bone repair applications. This paper provides a comprehensive insight into the properties of GO, preparation methods for nanocomposites, advantages of these materials, and relevant mechanisms for osteoporotic fracture applications.

Global research trends in CRISPR-related technologies associated with extracellular vesicles from 2015 to 2022: a bibliometric, dynamic, and visualized study.

PURPOSE: This study aims to explore the emerging trends, dynamic development, and research hotspots of clustered regularly interspaced short palindromic repeats (CRISPR) technology associated with extracellular vesicles during the past 7 years and demonstrate them by visualization. METHODS: A total of 219 records related to CRISPR technology associated with extracellular vesicles from 2015 to 2022 in the Web of Science Core Collection (WoSCC) database were collected. R language, VOSviewer, CiteSpace, and GraphpadPrism software packages were used to analyze the history of this research, the general characteristics of the literature, and keywords. Finally, the hotspots and latest trends in CRISPR technology associated with extracellular vesicles are predicted. RESULTS: A total of 219 articles were collected for this study. The production of publications about CRISPR technology associated with extracellular vesicles has increased annually. Researchers from China, the USA, and Germany made the most important contributions to this trend, while RLUK Research Libraries UK offers the largest amount of literature in this field. Shenzhen University, Nanjing Medicine University, and Peking University exhibited the closest cooperation. Additionally, active topics burst during different periods, as identified according to 317 keywords belonging to 39 disciplines. Keywords were clustered into seven research subareas, namely exosome, nanovesicles, DNA, gene editing, gene therapy, cancer therapy, and endometrial stromal cells. The alluvial map of keywords reveals that the most enduring concepts are gene therapy, nanovesicles, etc., while the emerging keywords are genome, protein delivery, plasma, etc. CONCLUSIONS: We reviewed 219 previous publications and conducted the first bibliometric study of CRISPR technology related to extracellular vesicles from 2015 to 2022. This comprehensive summary constructed a knowledge map and demonstrates the trends in this area. The current trends and potential hotpots for this topic are also identified, which will be a great help for researchers in the future.

Correction: Plasma extracellular vesicle phenotyping for the differentiation of early-stage lung cancer and benign lung diseases.

Correction for 'Plasma extracellular vesicle phenotyping for the differentiation of early-stage lung cancer and benign lung diseases' by Liwen Yuan et al., Nanoscale Horiz., 2023, 8, 746-758, https://doi.org/10.1039/d2nh00570k.

Plasma extracellular vesicle phenotyping for the differentiation of early-stage lung cancer and benign lung diseases.

The development of a minimally invasive technique for early-stage lung cancer detection is crucial to reducing mortality. Phenotyping of tumor-associated extracellular vesicles (EVs) has the potential for early-stage lung cancer detection, yet remains challenging due to the lack of sensitive, integrated techniques that can accurately detect rare tumor-associated EV populations in blood. Here, we integrated gold core-silver shell nanoparticles and nanoscopic mixing in a microfluidic assay for sensitive phenotypic analysis of EVs directly in plasma without EV pre-isolation. The assay enabled multiplex detection of lung cancer-associated markers PTX3 and THBS1 and canonical EV marker CD63 by surface-enhanced Raman spectroscopy, providing a squared correlation coefficient of 0.97 in the range of 103-107 EVs mL-1 and a limit of detection of 19 EVs mL-1. Significantly, our machine learning-based nanostrategy provided 92.3% sensitivity and 100% specificity in differentiating early-stage lung cancer from benign lung diseases, superior to the CT scan-based lung cancer diagnosis (92.3% sensitivity and 71.4% specificity). Overall, our integrated nanostrategy achieved an AUC value of 0.978 in differentiating between early-stage lung cancer patients (n = 28) and controls consisting of patients with benign lung diseases (n = 23) and healthy controls (n = 26), which showed remarkable diagnostic performance and great clinical potential for detecting the early occurrence of lung cancer.

The value of CT-based radiomics in early assessment of chemotherapeutic effect in patients with advanced lung adenocarcinoma: a preliminary study.

BACKGROUND: Computed tomography (CT) is the preferred method for evaluating the therapeutic effect of lung cancer. Radiomics parameters can provide a lot of supplementary information for clinical diagnosis and treatment. PURPOSE: To investigate the value of radiomics features of CT imaging to predict and evaluate the early efficacy of chemotherapy in patients with advanced lung adenocarcinoma. MATERIAL AND METHODS: A total of 101 patients with advanced lung adenocarcinoma were enrolled. Patients were classified into a response group and non-response group according to RECIST 1.1 standard. All patients underwent chest CT examination before and after two cycles of chemotherapy. A total of 293 radiomics features were calculated. The features between response group and non-response group were compared before and after chemotherapy. The diagnostic efficacy was evaluated using the receiver operating characteristic curve. RESULTS: The six pre-chemotherapy radiomics features were selected, with area under the curve (AUC), sensitivity, and specificity at 0.720, 68.3%, and 69.0% in the training group and 0.573, 50.0%, and 76.9% in the test group, respectively. The eleven post-chemotherapy radiomics features were selected, with AUC, sensitivity, specificity at 0.789, 75.6%, and 75.9% in the training group and 0.718, 61.1%, and 76.9% in the test group, respectively. The prognostic value of △f8, △f16, %f8, and %f16 were higher than the other features with AUCs of 0.787, 0.837, 0.763, and 0.877, respectively. CONCLUSION: Radiomics is expected to provide more valuable information for evaluating the chemotherapy efficacy of lung adenocarcinoma.

Moisture content monitoring in withering leaves during black tea processing based on electronic eye and near infrared spectroscopy.

Monitoring the moisture content of withering leaves in black tea manufacturing remains a difficult task because the external and internal information of withering leaves cannot be simultaneously obtained. In this study, the spectral data and the color/texture information of withering leaves were obtained using near infrared spectroscopy (NIRS) and electronic eye (E-eye), respectively, and then fused to predict the moisture content. Subsequently, the low- and middle-level fusion strategy combined with support vector regression (SVR) was applied to detect the moisture level of withering leaves. In the middle-level fusion strategy, the principal component analysis (PCA) and random frog (RF) were employed to compress the variables and select effective information, respectively. The middle-level-RF (cutoff line = 0.8) displayed the best performance because this model used fewer variables and still achieved a satisfactory result, with 0.9883 and 5.5596 for the correlation coefficient of the prediction set (Rp) and relative percent deviation (RPD), respectively. Hence, our study demonstrated that the proposed data fusion strategy could accurately predict the moisture content during the withering process.

The post-translational modification of Fascin: impact on cell biology and its associations with inhibiting tumor metastasis.

The post-translational modifications (PTMs), which are crucial in the regulation of protein functions, have great potential as biomarkers of cancer status. Fascin (Fascin actin-bundling protein 1, FSCN1), a key protein in the formation of filopodia that is structurally based on actin filaments (F-actin), is significantly associated with tumor invasion and metastasis. Studies have revealed various regulatory mechanisms of human Fascin, including PTMs. Although a number of Fascin PTM sites have been identified, their exact functions and clinical significance are much less explored. This review explores studies on the functions of Fascin and briefly discusses the regulatory mechanisms of Fascin. Next, to review the role of Fascin PTMs in cell biology and their associations with metastatic disease, we discuss the advances in the characterization of Fascin PTMs, including phosphorylation, ubiquitination, sumoylation, and acetylation, and the main regulatory mechanisms are discussed. Fascin PTMs may be potential targets for therapy for metastatic disease.

Optimization of Process Parameters for Fabricating Polylactic Acid Filaments Using Design of Experiments Approach.

The amount of wasted polylactic acid (PLA) is increasing because 3D printing services are an increasingly popular offering in many fields. The PLA is widely employed in the fused deposition modeling (FDM) since it is an environmentally friendly polymer. However, failed prototypes or physical models can generate substantial waste. In this study, the feasibility of recycling PLA waste plastic and re-extruded it into new PLA filaments was investigated. An automatic PLA filament extruder was first developed for fabricating new PLA filaments. This paper also discusses the process, challenges, and benefits of recycling PLA waste plastic in an effort to fabricate new PLA filaments more sustainable. It was found that it was possible to fabricate PLA filament using recycled PLA waste plastic. The production cost is only 60% of the commercially available PLA filament. The tensile strength of the developed PLA filament is approximately 1.1 times that of the commercially available PLA filament. The design of experiments approach was employed to investigate the optimal process parameters for fabricating PLA filaments. The most important control factor affecting the diameter of PLA filament is the barrel temperature, followed by recycled material addition ratio, extrusion speed, and cooling distance. The optimal process parameters for fabricating PLA filament with a diameter of 1.7 mm include the barrel temperature of 184 °C, extrusion speed of 490 mm/min, cooling distance of 57.5 mm, and recycled material addition ratio of 40%.

Pretreatment MR-based radiomics nomogram as potential imaging biomarker for individualized assessment of perineural invasion status in rectal cancer.

PURPOSE: To investigate whether pretreatment magnetic resonance (MR)-based radiomics nomogram can individualize prediction of perineural invasion (PNI) status in rectal cancer (RC). MATERIAL AND METHODS: A total of 122 RC patients with pathologically confirmed were classified as training cohort (n = 87) and test cohort (n = 35). 180 radiomics features were extracted from all lesions based on oblique axial T2WI TSE images. The dimensionality reduction and feature selection in training cohort were realized by the maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) regression model. A predictive model combining radiomics features and clinical risk factors (pathological N stage, pathological LVI status) was established by multivariate logistic regression analysis. The performance of the model was assessed based on its receiver operating characteristic (ROC) curve, nomogram, and calibration. RESULTS: The developed radiomics nomogram that integrated the radiomics signature and clinical risk factors could provide discrimination in the training and test cohorts. The accuracy and the area under the curve (AUC) for assessing PNI status were 0.82, 0.86, respectively, in the training cohort, while they were 0.71 and 0.85 in the test cohort. The goodness-of-fit of the nomogram was evaluated using the Hosmer-Lemeshow test (p = 0.52 in training cohort and p = 0.24 in test cohort). Decision curve analysis (DCA) showed that the radiomics nomogram was clinically useful. CONCLUSION: The developed radiomics nomogram might be helpful in the individualized assessment PNI status in patients with RC. This stratification of RC patients according to their PNI status may provide the basis for individualized adjuvant therapy, especially for stage II patients.

Diffusion kurtosis imaging and tumour microstructure for monitoring response to radiotherapy in human nasopharyngeal carcinoma xenografts.

OBJECTIVE: To investigate the correlations and feasibility of diffusion kurtosis imaging (DKI) parameters and tumour histopathology after radiotherapy in human nasopharyngeal carcinoma (NPC) xenografts on nude mice. MATERIALS AND METHODS: Seventy-two nude mice were used for the construction of CNE-1 (radio-insensitive) and CNE-2 (radio-sensitive) NPC xenograft models, followed by fraction irradiation at different doses of X-ray. The nude mice were randomly divided into six groups in each cell line models according to the dose of X-ray they have received and with six mice in each group. DKI scan was performed after radiation. DKI parameters, tumour histopathology and AQP-1 biomarkers were detected. One-way ANOVA and Pearson's correlation analysis were used in statistical analysis. RESULTS: In CNE-1 and CNE-2 NPC xenografts, D values were increased (P < 0.01 and P < 0.001), while K values (P < 0.01 and P < 0.001) and tumour size (P < 0.001 and P < 0.001) were reduced during fraction irradiation. Additionally, cell density (CD) and AQP-1 expressions were decreased, and necrosis ratio (NR) was increased in CNE-2 xenografts after fraction irradiation (P < 0.001). The changes in D values were negatively correlated with tumour size (r = -0.856, P < 0.001), CD (r = -0.918, P < 0.001), AQP-1 mRNA (r = -0.856, P < 0.001) and protein (r = -0.381, P = 0.022) expressions while positively correlated with NR (r = 0.908, P < 0.001) in CNE-2 xenografts. The changes in K values were positively correlated with tumour size (r = 0.964, P < 0.001), CD (r = 0.888, P < 0.001), AQP-1 mRNA (r = 0.955, P < 0.001) and protein (r = 0.330, P = 0.049) expression levels while negatively correlated with NR (r = -0.930, P < 0.001). However, in CNE-1 xenografts, there were no correlation between DKI parameters and the expression of AQP-1. CONCLUSION: Changes in D and K parameters after fractional irradiation are closely related with NPC cellular and pathological characteristics, especially size reduction and necrosis induction. These parameters exhibit potential abilities of monitoring the response to fractional irradiation in radio-sensitive NPC xenografts.

Pretreatment MR-Based Radiomics Signature as Potential Imaging Biomarker for Assessing the Expression of Topoisomerase II alpha (TOPO-IIα) in Rectal Cancer.

BACKGROUND: Rectal cancer (RC) is one of the most common cancers throughout the world. Chemotherapy or neoadjuvant chemotherapy play an important role in the treatment of advanced RC. Whether to add topoisomerase inhibitor to individualized chemotherapy is a puzzling question for clinicians. PURPOSE: To investigate whether pretreatment MR-based radiomics signature can assess the expression of topoisomerase II alpha (TOPO-IIα) in RC. STUDY TYPE: Retrospective. POPULATION: In all, 122 patients with RC. Field Strength/Sequence: Pretreatment 3.0T; T2 WI turbo spin echo (TSE) sequence. ASSESSMENT: A training group (n = 85) and a test group (n = 37) with pathologically confirmed RC. Patients underwent TOPO-IIα expression. A total of 180 radiomics features were extracted from oblique axial T2 WI TSE images of the entire primary tumor. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce the dimension of the data and select the features. STATISTICAL TESTS: The assessment models were established by multivariable logistic regression analysis. The performance of the model was assessed by the receiver operating characteristic (ROC) curve, nomogram, and calibration. RESULTS: The radiomics signature, which consisted of 10 selected optimal features, was significantly associated with TOPO-IIα expression (P < 0.01 for both training and test groups). The area under the curve (AUC), the sensitivity, and the specificity for assessing TOPO-IIα expression, were 0.859, 0.872, and 0.739, respectively, in the training group, while they were 0.762, 0.941, and 0.600 in the test group. The nomogram model of the radiomics signature (Rad-score) had good calibration. Calibration curves were plotted to assess the calibration of the radiomics nomogram that was accompanied with the Hosmer-Lemeshow test (P = 0.52). DATA CONCLUSION: The proposed pretreatment MR-based radiomics signature was associated with TOPO-IIα expression. A radiomics nomogram might be helpful in the individualized assessment of TOPO-IIα expression in patients with RC. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1881-1889.

Quantitative Imaging of Gd Nanoparticles in Mice Using Benchtop Cone-Beam X-ray Fluorescence Computed Tomography System.

Nanoparticles (NPs) are currently under intensive research for their application in tumor diagnosis and therapy. X-ray fluorescence computed tomography (XFCT) is considered a promising non-invasive imaging technique to obtain the bio-distribution of nanoparticles which include high-Z elements (e.g., gadolinium (Gd) or gold (Au)). In the present work, a set of experiments with quantitative imaging of GdNPs in mice were performed using our benchtop XFCT device. GdNPs solution which consists of 20 mg/mL NaGdF4 was injected into a nude mouse and two tumor-bearing mice. Each mouse was then irradiated by a cone-beam X-ray source produced by a conventional X-ray tube and a linear-array photon counting detector with a single pinhole collimator was placed on one side of the beamline to record the intensity and spatial information of the X-ray fluorescent photons. The maximum likelihood iterative algorithm with scatter correction and attenuation correction method was applied for quantitative reconstruction of the XFCT images. The results show that the distribution of GdNPs in each target slice (containing liver, kidney or tumor) was well reconstructed and the concentration of GdNPs deposited in each organ was quantitatively estimated, which indicates that this benchtop XFCT system provides convenient tools for obtaining accurate concentration distribution of NPs injected into animals and has potential for imaging of nanoparticles in vivo.

Photo-rewritable flexible LCD using indium zinc oxide/polycarbonate substrates.

This work presents a photo-rewritable transmissive flexible-LCD based on the alignment effect of the photo-induced adsorption of azo dye on flexible indium zinc oxide/polycarbonate (IZO/PC) substrates. Images can be displayed without applying an external field and rewritten by changing the direction of the writing laser beam while the cell temperature is controlled. By using IZO/PC substrates, the writing and erasing processes can be achieved within 1 min with a high contrast.