Differential diagnostic value of radiomics models in benign versus malignant vertebral compression fractures: A systematic review and meta-analysis.

PURPOSE: Early diagnosis of benign and malignant vertebral compression fractures by analyzing imaging data is crucial to guide treatment and assess prognosis, and the development of radiomics made it an alternative option to biopsy examination. This systematic review and meta-analysis was conducted with the purpose of quantifying the diagnostic efficacy of radiomics models in distinguishing between benign and malignant vertebral compression fractures. METHODS: Searching on PubMed, Embase, Web of Science and Cochrane Library was conducted to identify eligible studies published before September 23, 2023. After evaluating for methodological quality and risk of bias using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), we selected studies providing confusion matrix results to be included in random-effects meta-analysis. RESULTS: A total of sixteen articles, involving 1,519 vertebrae with pathological-diagnosed tumor infiltration, were included in our meta-analysis. The combined sensitivity and specificity of the top-performing models were 0.92 (95 % CI: 0.87-0.96) and 0.93 (95 % CI: 0.88-0.96), respectively. Their AUC was 0.97 (95 % CI: 0.96-0.99). By contrast, radiologists' combined sensitivity was 0.90 (95 %CI: 0.75-0.97) and specificity was 0.92 (95 %CI: 0.67-0.98). The AUC was 0.96 (95 %CI: 0.94-0.97). Subsequent subgroup analysis and sensitivity test suggested that part of the heterogeneity might be explained by differences in imaging modality, segmentation, deep learning and cross-validation. CONCLUSION: We found remarkable diagnosis potential in correctly distinguishing vertebral compression fractures in complex clinical contexts. However, the published radiomics models still have a great heterogeneity, and more large-scale clinical trials are essential to validate their generalizability.

Remarkable Toughening of Plastic with Monodispersed Nano-CaCO3: From Theoretical Predictions to Experimental Validation.

The structure-property relationship of poly(vinyl chloride) (PVC)/CaCO3 nanocomposites is investigated by all-atom molecular dynamics (MD) simulations. MD simulation results indicate that the dispersity of nanofillers, interfacial bonding, and chain mobility are imperative factors to improve the mechanical performance of nanocomposites, especially toughness. The tensile behavior and dissipated work of the PVC/CaCO3 model demonstrate that 12 wt % CaCO3 modified with oleate anion and dodecylbenzenesulfonate can impart high toughness to PVC due to its good dispersion, favorable interface interaction, and weak migration of PVC chains. Under the guidance of MD simulation, we experimentally prepared a transparent PVC/CaCO3 nanocomposite with good mechanical properties by in situ polymerization of monodispersed CaCO3 in vinyl chloride monomers. Interestingly, experimental tests indicate that the optimum toughness of a nanocomposite (a 368% increase in the elongation at break and 204% improvement of the impact strength) can be indeed realized by adding 12 wt % CaCO3 modified with oleic acid and dodecylbenzenesulfonic acid, which is remarkably consistent with the MD simulation prediction. In short, this work provides a proof-of-concept of using MD simulation to guide the experimental synthesis of PVC/CaCO3 nanocomposites, which can be considered as an example to develop other functional nanocomposites.

De novo assembly and characterization of the transcriptome of Morchella esculenta growth with selenium supplementation.

Although Morchella esculenta (L.) Pers. is an edible and nutritious mushroom with significant selenium (Se)-enriched potential, its biological response to selenium stimuli remains unclear. This study explored the effect of selenium on mushroom growth and the global gene expression profiles of M. esculenta. While 5 µg mL-1selenite treatment slightly promoted mycelia growth and mushroom yield, 10 µg mL-1significantly inhibited growth. Based on comparative transcriptome analysis, samples treated with 5 µg mL-1 and 10 µg mL-1 of Se contained 16,061 (452 upregulated and 15,609 downregulated) and 14,155 differentially expressed genes (DEGs; 800 upregulated and 13,355 downregulated), respectively. Moreover, DEGs were mainly enriched in the cell cycle, meiosis, aminoacyl-tRNA biosynthesis, spliceosome, protein processing in endoplasmic reticulum pathway, and mRNA surveillance pathway in both selenium-treated groups. Among these, MFS substrate transporter and aspartate aminotransferase genes potentially involved in Se metabolism and those linked to redox homeostasis were significantly upregulated, while genes involved in isoflavone biosynthesis and flavonoid metabolism were significantly downregulated. Gene expression levels increased alongside selenite treatment concentration, suggesting that high Se concentrations promoted M. esculenta detoxification. These results can be used to thoroughly explain the potential detoxification and Se enrichment processes in M. esculenta and edible fungi.

NEK2 promotes the development of ovarian endometriosis and impairs decidualization by phosphorylating FOXO1.

Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial decidualization lead to impaired endometrial receptivity and embryo implantation, thus affecting early pregnancy and women's desire to have children. However, the mechanisms underlying the development of endometriosis and its associated defective decidualization are unclear. We find that NEK2 expression is increased in the ectopic and eutopic endometrium of patients with endometriosis. Meanwhile, NEK2 interacts with FOXO1 and phosphorylates FOXO1 at Ser184, inhibiting the stability of the FOXO1 protein. Importantly, NEK2-mediated phosphorylation of FOXO1 at Ser184 promotes cell proliferation, migration, invasion and impairs decidualization. Furthermore, INH1, an inhibitor of NEK2, inhibits the growth of ectopic lesions in mouse models of endometriosis and promotes endometrial decidualization in mouse models of artificially induced decidualization. Taken together, these findings indicate that NEK2 regulates the development of endometriosis and associated disorders of decidualization through the phosphorylation of FOXO1, providing a new therapeutic target for its treatment.

POI-associated EIF4ENIF1 mutations exhibit impaired translation regulation abilities.

Various genetic variants have been found to be associated with the clinical onset of premature ovarian insufficiency (POI). However, when measured in vitro, the functional influence of the variants can be difficult to determine. By whole-exome sequencing (WES) of 93 patients with sporadic POI, we found a missense variant c.623G > A;p.R208H in the EIF4ENIF1 gene. In silico prediction of the variant using different algorithms suggested it might be a damaging variant. We compared the property of EIF4ENIF1 R208H and Q842P, a POI-related mutant that we reported previously, with wildtype (WT) protein using 293FT cells in vitro. Surprisingly, a change in subcellular distribution and granule forming ability (Q842P) and nuclear import capacity (R208H) was not observed, despite domain prediction evidences. Since EIF4ENIF1 was reported to inhibit translation, we employed T&T-seq, a translation-transcription dual-omics sequencing method, to profile gene expression upon overexpression of EIF4ENIF1 WT and mutants. EIF4ENIF1 WT overexpression group exhibited significantly (P < 0.0001) lower translation efficiency (TE) than empty vector or GFP overexpression control group. Surprisingly, EIF4ENIF1 Q842P overexpression failed to repress global translation, showing an overall TE significantly higher than WT group. Overexpression R208H significantly (P < 0.0001) lowered the overall TE, whereas exhibiting a reduced translation inhibitory effect on high-TE genes (TE > 2 in GFP control group). Several fertility-associated genes, such as AMH in Q842P group and SERPINE1 and THBS1 in R208H group, was translationally up-regulated in mutant groups versus WT control, suggesting a potential mechanism of mutated EIF4ENIF1 causing POI via impaired translation repression. It is further proposed that T&T-seq can be a sensitive evaluation tool for the measurement of functional alteration by variants in many other translational regulator genes, not only EIF4ENIF1, helping to eliminate misinterpretation of clinical significance of genetic variants.

AURKA Enhances the Glycolysis and Development of Ovarian Endometriosis Through ERß.

Ovarian endometriosis (EMs) is a benign, estrogen-dependent gynecological disorder. Estrogen receptor beta (ERß), a nuclear receptor for estradiol, plays an important role in the development of ovarian EMs. Here, we investigated the biological significance of aurora kinase A (AURKA) in ovarian EMs and the mechanism by which it regulates ERß. We used immunohistochemical assays to verify that AURKA and ERß were highly expressed in ectopic endometrial tissues. Cell proliferation and colony formation assays were used to demonstrate that AURKA promoted the proliferation of EMs cells. Wound-healing assay, Transwell migration assay, and Matrigel invasion assay further showed that AURKA enhanced the ability of EMs cells to migrate and invade. In addition, AURKA was shown to stimulate glycolysis in EMs cells by measuring the concentration of glucose and lactate in the cell supernatants. Moreover, the AURKA inhibitor alisertib was found to inhibit the progression of ovarian EMs and glycolysis in a mouse model of EMs by measuring ectopic tissues as well as by testing the peritoneal fluid of mice. Furthermore, coimmunoprecipitation assay showed that AURKA interacted with ERß. The rescue experiments confirmed that AURKA regulated the development and glycolysis of ovarian EMs in an ERß-dependent manner. AURKA contributed to the development of ovarian EMs by upregulating of ERß. AURKA may represent a new target for the treatment of ovarian EMs.

STING/TBK1 Regulates Inflammation in Macrophages and Titanium Particles-Induced Osteolysis.

Inflammatory response in macrophages on account of prostheses-derived wear particles is the leading cause of artificial joint failure. However, the mechanism by which wear particles initiate macrophage inflammation has not been fully elucidated. Previous research studies have identified TANK-binding kinase 1 (TBK1) and stimulator of interferon genes (STING) as potential factors in inflammation and autoimmune diseases. Here, we found that both TBK1 and STING were increased in synovium from aseptic loosening (AL) patients and were activated in titanium particles (TiPs)-stimulated macrophages. Lentivirus-mediated knockdown of TBK or STING significantly inhibited the inflammatory effects of macrophages, while overexpression of TBK or STING exerted opposite results. In concrete, STING/TBK1 promoted the activation of NF-κB and IRF3 pathways and macrophage M1 polarization. For further validation, a mice cranial osteolysis model was constructed for in vivo assays, and we found that STING-overexpressed lentivirus injection exacerbated osteolysis and inflammation, which was counteracted by TBK1-knockdown injection. In conclusion, STING/TBK1 enhanced TiP-induced macrophage inflammation and osteolysis via orchestrating the activation of NF-κB and IRF3 pathways and M1 polarization, which suggested STING/TBK1 as potential therapeutic targets for preventing AL of prostheses.

Extraction of tree crown parameters of high-density pure Cunninghamia lanceolata plantations by combining the U-Net model and watershed algorithm.

As one of the important timber species in China, Cunninghamia lanceolata is widely distributed in southern China. The information of tree individuals and crown plays an important role in accurately monitoring forest resources. Therefore, it is particularly significant to accurately grasp such information of individual C. lanceolata tree. For high-canopy closed forest stands, the key to correctly extract such information is whether the crowns of mutual occlusion and adhesion can be accurately segmented. Taking the Fujian Jiangle State-owned Forest Farm as the research area and using the UAV image as the data source, we developed a method to extract crown information of individual tree based on deep learning method and watershed algorithm. Firstly, the deep learning neural network model U-Net was used to segment the coverage area of the canopy of C. lanceolata, and then the traditional image segmentation algorithm was used to segment the individual tree to obtain the number and crown information of individual tree. Under the condition of maintaining the same training set, validation set and test set, the extraction results of the canopy coverage area by the U-Net model and traditional machine learning methods [random forest (RF) and support vector machine (SVM)] were compared. Then, two individual tree segmentation results were compared, one using the marker-controlled watershed algorithm, and the other using the combination of the U-Net model and marker-controlled watershed algorithm. The results showed that the segmentation accuracy (SA), precision, IoU (intersection over union) and F1-score (harmonic mean of precision and recall) of the U-Net model were higher than those of RF and SVM. Compared with RF, the value of those four indicators increased by 4.6%, 14.9%, 7.6% and 0.05, respectively. Compared with SVM, the four indicators increased by 3.3%, 8.5%, 8.1% and 0.05, respectively. In terms of extracting the number of trees, the overall accuracy (OA) of the U-Net model combined with the marker-controlled watershed algorithm was 3.7% higher than that of the marker-controlled watershed algorithm, with the mean absolute error (MAE) being decreased by 3.1%. In terms of extracting crown area and crown width of individual tree, R2 increased by 0.11 and 0.09, mean squared error decreased by 8.49 m2 and 4.27 m, and MAE decreased by 2.93 m2 and 1.72 m, respectively. The combination of deep learning U-Net model and watershed algorithm could overcome the challenges in accurately extracting the number of trees and the crown information of individual tree of high-density pure C. lanceolata plantations. It was an efficient and low-cost method of extracting tree crown parameters, which could provide a basis for developing intelligent forest resource monitoring.

Microanalysis Characterization and Immunomodulatory Effect for Selenium-Enriched Polysaccharide from Morchella esculenta (L.) Pers.

Morchella esculenta (L.) Pers., referred to as Morel, is a medicinal and edible homologous fungus, which contains many bioactive substances. In Morel, polysaccharides are the most abundant and have various bioactivities. In the present work, two novel polysaccharides, Se-MPS and MPS, were prepared and purified from selenium-enriched (Se-enriched) and common Morel mycelia, respectively, and their structural and immunomodulatory properties were evaluated. The results show that Se-enriched treatment significantly changed the polysaccharides' chemical composition, molecular weight, and sugar chain configuration. In addition, the Se-enriched treatment also improved the polysaccharides' fragmentation and thermal stability. Importantly, Se-enriched Morel polysaccharide (Se-MPS) could significantly enhance phagocytosis of RAW 264.7 macrophage cells and, remarkably, activate their immune response via activating the TLR4-TRAF6-MAPKs-NF-κB cascade signaling pathway, finally exerting an immunomodulatory function. Based on these findings, selenium-enriched Morel polysaccharide appears to have more potential for development and utilization in functional foods or medicines than ordinary Morel polysaccharide.

Genetically Modified Mesenchymal Stromal Cells in Cartilage Regeneration.

Articular cartilage injury is common in various conditions, including osteoarthritis, rheumatic diseases, and trauma. Current treatments for cartilage injury fail to completely regenerate the damaged cartilage. Mesenchymal stromal cells (MSCs) have emerged as potential candidates for cartilage regeneration. However, MSCs exhibit hypertrophic differentiation, and their chondrogenic ability is reduced in an inflammatory environment. In recent years, genetic modification has been proposed for optimizing MSC-based therapies, some of which are expected to enter clinical trials. This review summarizes recent research findings and developments in genetic engineering strategies to enhance stem cell-based therapy for cartilage regeneration. We also discuss the mechanisms of biofunctions of MSCs in cartilage regeneration and outline the efficacy and safety of the different genetic modification strategies, including viral and nonviral delivery transduction. Finally, we highlight the major challenges and prospects for clinical translation of genetically modified MSCs.

PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis.

Endometriosis is a common gynecological disorder characterized by the presence of the endometrial glands and the stroma outside the uterine cavity. The disease affects reproductive function and quality of life in women of reproductive age. Endometriosis is similar to tumors in some characteristics, such as glycolysis. PIM2 can promote the development of tumors, but the mechanism of PIM2 in endometriosis is still unclear. Therefore, our goal is to study the mechanism of PIM2 in endometriosis. Through immunohistochemistry, we found PIM2, HK2, PKM2, SMH (smooth muscle myosin heavy chain), Desmin, and α-SMA (α-smooth muscle actin) were strongly expressed in the ovarian endometriosis. In endometriotic cells, PIM2 enhanced glycolysis and fibrosis via upregulating the expression of PKM2. Moreover, the PIM2 inhibitor SMI-4a inhibited the development of endometriosis. And we established a PIM2 knockout mouse model of endometriosis to demonstrate the role of PIM2 in vivo. In summary, our study indicates that PIM2 promotes the development of endometriosis. PIM2 may serve as a promising therapeutic target for endometriosis.

Extraction, Physicochemical Properties, Functional Activities and Applications of Inulin Polysaccharide: a Review.

Inulin is a naturally soluble dietary fiber that is widely distributed and primarily derived from plants. As a reserve biopolysaccharide in plants, inulin is considered an indigestible carbohydrate of fructan because of its unique ß-(2,1)-glycosidic bond structure. Numerous recent animal and human experimental studies have shown that functional inulin possesses multiple bioactivities, including immunomodulatory, antioxidant, antitumor, hepatoprotective, hypoglycemic, and gastrointestinal protective activities. Due to its increasing popularity, people tend to consume foods containing inulin. Moreover, inulin holds promise as a bioactive compound for use in the development of various food products. Therefore, this paper provides a detailed review of the extraction method, physicochemical properties, functional activity, and application development of inulin polysaccharides, to provide a theoretical foundation for further advancements in the fields of preparation and application of functional foods.

Synergistic antibacterial and biofilm eradication activity of quaternary-ammonium compound with copper ion.

Antibiotics overuse and misuse increase the emergence of multidrug-resistant bacterial strains, which often leads to the failure of conventional antibiotic therapies. Even worse, the tendency of bacteria to form biofilms further increases the therapeutic difficulty, because the extracellular matrix prevents the penetration of antibiotics and triggers bacterial tolerance. Therefore, developing novel antibacterial agents or therapeutic strategies with diverse antibacterial mechanisms and destruction of bacteria biofilm is a promising way to combat bacterial infections. In the present study, the combination of quaternary ammonium compound poly(diallyl dimethyl ammonium chloride) (PDDA) with Cu2+ was screened out to fight common pathogenic Staphylococcus aureus (S. aureus) through multi-mechanisms. This combination appeared strong synergistic antibacterial activity, and the fractional inhibitory concentration index was as low as 0.032. The synergistic antibacterial mechanism involved the destruction of the membrane function, generation of intracellular reactive oxygen, and promotion more Cu2+ into the cytoplasm. Further, the combination of PDDA and Cu2+ reduced the extracellular polysaccharide matrix, meanwhile killing the bacteria embedded in the biofilm. The biocompatibility study in vitro revealed this combination exhibited low cytotoxicity and hemolysis ratio even at 8 times of minimum bactericidal concentration. This work provides a novel antibacterial agents combination with higher efficiency to fight planktonic and biofilm conditions of S. aureus.

PBAT/PLA humic acid biodegradable film applied on solar greenhouse tomato plants increased lycopene and decreased total acid contents.

This work aims to resolve residual film pollution in farmlands and improve tomato quality. The mechanical properties and degradation of PBAT/PLA lignin (MZS) and PBAT/PLA humic acid (FZS) composite biodegradable film were analyzed, and its effect on soil temperature and humidity, soil microorganisms, soil physical and chemical properties, tomato yield, and quality was studied. Polyethylene film (PE) was used as a control. The results demonstrate a higher degradation degree of FZS film than of MZS film. The degradation degree of FZS and MZS films reached level 2 and level 1, respectively, after 131 days of film covering. The weight loss rate of FZS and MZS films reached 52.74 % and 57.82 %, respectively, when buried for 160 days. Compared to the coverings of PE and MZS films, FZS film could significantly increase the soil's electric conductivity and organic matter content (p < 0.05). The relative abundance of soil fungi Chaetomium also increased. The yield, soluble solids, vitamin C (Vc), soluble sugar, and lycopene of tomato plants covered with FZS film significantly increased by 6.74 %, 8.75 %, 15.41 %, 8.30 %, and 27.27 % compared to plants covered with PE film, and the total acid and hardness significantly decreased by 24.95 % and 8.46 %, respectively (p < 0.05). Using 10 µm PBAT/PLA humic acid biodegradable film for tomato cultivation in autumn and winter increased the lycopene and decreased the total acid content by changing the soil's physical and chemical characteristics and increasing the content of Chaetomium soil.

Comparison of chimeric antigen receptor-T cell-mediated cytotoxicity assays with suspension tumor cells using plate-based image cytometry method.

In the recent decade, chimeric antigen receptor (CAR)-T cell therapy has revolutionized strategies for cancer treatments due to its highly effective clinical efficacy and response for B cell malignancies. The success of CAR-T cell therapy has stimulated the increase in the research and development of various CAR constructs to target different tumor types. Therefore, a robust and efficient in vitro potency assay is needed to quickly identify potential CAR gene design from a library of construct candidates. Image cytometry methodologies have been utilized for various CAR-T cell-mediated cytotoxicity assay using different fluorescent labeling methods, mainly due to their ease-of-use, ability to capture cell images for verification, and higher throughput performance. In this work, we employed the Celigo Image Cytometer to evaluate and compare two CAR-T cell-mediated cytotoxicity assays using GFP-expressing or fluorescent dye-labeled myeloma and plasmacytoma cells. The GFP-based method demonstrated higher sensitivity in detecting CAR-T cell-mediated cytotoxicity when compared to the CMFDA/DAPI viability method. We have established the criteria and considerations for the selection of cytotoxicity assays that are fit-for-purpose to ensure the results produced are meaningful for the specific testing conditions.

Catalase and interleukin-6 serum elevation in a prediction of treatment-resistance in male schizophrenia patients.

BACKGROUND: Oxidative stress (OS) and neuroinflammatory pathways play an important role in the pathophysiology of schizophrenia. The present study investigated the relationship between OS, inflammatory cytokines, and clinical features in male patients with treatment-resistant schizophrenia (TRS). METHOD: We measured plasma OS parameters, including manganese-superoxide dismutase (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD), total-SOD (T-SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px); and serum inflammatory cytokines, including interleukin (IL)- 1α, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN)-γ, from 80 male patients with chronic schizophrenia (31 had TRS and 49 had chronic stable schizophrenia (CSS)), and 42 healthy controls. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, plasma Mn-SOD, CuZn-SOD, T-SOD, GSH-Px, and MDA levels were significantly lower, while CAT and serum IL-6 levels were higher in both TRS and CSS male patients (all P < 0.05). Significant differences in the activities of CAT (F = 6.068, P = 0.016) and IL-6 levels (F = 6.876, P = 0.011) were observed between TRS and CSS male patients after analysis of covariance. Moreover, a significant positive correlation was found between IL-6 levels and PANSS general psychopathology subscores (r = 0.485, P = 0.006) and between CAT activity and PANSS total scores (r = 0.409, P = 0.022) in TRS male patients. CAT and IL-6 levels were predictors for TRS. Additionally, in chronic schizophrenia patients, a significant positive correlation was observed between IL-6 and GSH-Px (r = 0.292, P = 0.012), and the interaction effect of IL-6 and GSH-Px was positively associated with PANSS general psychopathology scores (r = 0.287, P = 0.014). CONCLUSION: This preliminary study indicated that variations in OS and inflammatory cytokines may be involved in psychopathology for patients with chronic schizophrenia, especially in male patients with TRS.

CHIP induces ubiquitination and degradation of HMGB1 to regulate glycolysis in ovarian endometriosis.

Ovarian endometriosis is a common gynecological condition that can cause infertility in women of childbearing age. However, the pathogenesis is still unknown. We demonstrate that the carboxyl terminus of Hsc70-interacting protein (CHIP) is a negative regulator in the development of endometriosis and reduces HMGB1 expression in endometriotic cells. Meanwhile, CHIP interacts with HMGB1 and promotes its ubiquitinated degradation, thereby inhibiting aerobic glycolysis and the progression of endometriosis. Furthermore, the CHIP agonist YL-109 effectively suppresses the growth of ectopic endometrium in endometriosis mouse model, which could be a potential therapeutic approach for endometriosis. In conclusion, our data suggest that CHIP may inhibit the development of endometriosis by suppressing the HMGB1-related glycolysis.

Ovarian tumorB1-mediated heat shock transcription factor 1 deubiquitination is critical for glycolysis and development of endometriosis.

Endometriosis is a common chronic condition characterized by abnormal growth of the endometrium outside the uterus. Heat shock transcription factor 1 (HSF1) is a significant regulator of the proteotoxic stress response and plays an essential role in developing endometriosis. However, the mechanisms regulating HSF1 protein stability in endometriosis remain unclear. Here, we demonstrate that OTUB1 interacts with HSF1 and promotes HSF1 protein stability through deubiquitination. In addition, OTUB1 enhances glycolysis and epithelial-mesenchymal transition of endometriosis cells, leading to promote proliferation, migration, and invasion of endometriosis cells. The progression of endometriosis is inhibited in an OTUB1-knockout mouse model. In summary, OTUB1 promotes the development of endometriosis by up-regulating HSF1. OTUB1/HSF1 axis may become a new therapeutic target for endometriosis.