A Novel Perspective on Enhancing Photocatalytic Performance through the Synergistic Effect of Nd Single Atoms and Heterostructures.

There are few reports on lanthanide single atom modified catalysts, as the role of the 4f levels in photocatalysis is difficult to explain clearly. Here, the synergistic effect of 4f levels of Nd and heterostructures is studied by combining steady-state, transient, and ultrafast spectral analysis techniques with DFT theoretical calculations based on the construction of Nd single atom modified black phosphorus/g-C3N4 (BP/CN) heterojunctions. As expected, the generation rates of CO and CH4 of the optimized heterostructure are 7.44 and 6.85 times higher than those of CN, and 8.43 and 9.65 times higher than those of BP, respectively. The Nd single atoms can not only cause surface reconstruction and regulate the active sites of BP, but also accelerate charge separation and transfer, further suppressing the recombination of electron-hole pairs. The electrons can transfer from g-C3N4:Nd to BP:Nd, with a transfer time of ≈11.4 ps, while the radiation recombination time of electron-hole pairs of g-C3N4 is ≈26.13 µs, indicating that the construction of heterojunctions promotes charge transfer. The 2P1/2/2G9/2/4G7/2/2H11/2/4F7/2→4I9/2 emissions from Nd3+ can also be absorbed by heterostructures, which improves the utilization of light. The energy change of the key rate measurement step CO2 *→COOH* decreases through Nd single atom modification.

MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs.

Chronic liver disease mediated by the activation of hepatic stellate cells (HSCs) leads to liver fibrosis. The signal adaptor MyD88 of Toll-like receptor (TLR) signaling is involved during the progression of liver fibrosis. However, the specific role of MyD88 in myeloid cells in liver fibrosis has not been thoroughly investigated. In this study, we used a carbon tetrachloride (CCl4)-induced mouse fibrosis model in which MyD88 was selectively depleted in myeloid cells. MyD88 deficiency in myeloid cells attenuated liver fibrosis in mice and decreased inflammatory cell infiltration. Furthermore, deficiency of MyD88 in macrophages inhibits the secretion of CXC motif chemokine 2 (CXCL2), which restrains the activation of HSCs characterized by NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation. Moreover, targeting CXCL2 by CXCR2 inhibitors attenuated the activation of HSCs and reduced liver fibrosis. Thus, MyD88 may represent a potential candidate target for the prevention and treatment of liver fibrosis.

Epigenomic profiling of DNA methylation for hepatocellular carcinoma diagnosis and prognosis prediction.

BACKGROUND AND AIM: DNA hypermethylation has emerged as a novel molecular biomarker for the diagnosis and prognosis prediction of many cancers. We aimed to identify clinically useful biomarkers regulated by DNA methylation in hepatocellular carcinoma (HCC). METHODS: Genome-wide methylation analysis in HCCs and paired noncancerous tissues was performed using an Illumina Infinium HumanMethylation 450K BeadChip array. Methylation-specific polymerase chain reaction and pyrosequencing were used to validate the methylation status of selected genes in 100 paired HCCs and noncancerous samples. RESULTS: A total of 97 027 (20.0%) out of 485 577 CpG sites significantly were differed between HCC and noncancerous tissues. Among all the significant CpG sites, 48.8% are hypermethylated and 51.2% are hypomethylated in HCCs. Multiple signaling pathways (AMP-activated protein kinase, estrogen, and adipocytokine) involved in gene methylation were identified in HCC. FES was selected for further analysis based on its high level of methylation confirmed by polymerase chain reaction and pyrosequencing. The result showed that FES hypermethylation was correlated with tumor size (0.001), serum alpha fetoprotein (0.023), and tumor differentiation (0.006). FES protein was significantly downregulated in 51/100 (51%) HCCs, and 94.12% (48/51) of them were due to promoter hypermethylation. Both FES hypermethylation and protein downregulation were associated with the progression-free survival and overall survival of HCC patients. Overexpressed and knockdown of FES confirmed its inhibitory effect on the proliferation and migration of HCC cells. CONCLUSIONS: We identified many new differentially methylated CpGs in HCCs and demonstrate that FES functions as a tumor suppressor gene in HCC and its methylation status could be used as an indicator for prognosis of HCC.

Serum microRNA-195 is down-regulated in breast cancer: a potential marker for the diagnosis of breast cancer.

MicroRNA-195 (miR-195) is a tumor suppressor that plays an important role in tumorigenesis. There are few studies on miR-195 expression in breast cancer patients and the results have been inconsistent; therefore, this study examined miR-195 expression in the serum of BC patients. Samples from 102 normal subjects and 210 subjects with BC who had detailed clinical follow-up information available were selected. An internal reference (miR-16) and serum miR-195 were amplified and quantitatively detected by SYBR green-based real-time RT-PCR. We analyzed the differences in miR-195 levels between BC and healthy cases and the relationships between the miR-195 level and TNM stage and other clinicopathological parameters. In addition, changes in miR-195 levels were examined for 21 BC cases using paired samples before and after neoadjuvant chemotherapy. miR-195 was downregulated in BC compared with control samples (P = 0.000, Mann-Whitney U test). The sensitivity and specificity of miR-195 in the diagnosis of BC were 69.0 and 89.2 %, respectively; whereas, the sensitivities of carcinoembryonic antigen (CEA) and carbohydrate antigen 153 (CA153) were only 15.08 and 21.1 %, respectively. Remarkably, serum miR-195 had higher sensitivity, 73.97 % (108/146), as a tumor marker in the diagnosis of early stage BC [ductal carcinoma in situ, tumor-node-metastasis (TNM) I, II] compared with the conventional tumor markers CA153 and CEA (12.41 and 7.59 %). Moreover, compared with CEA and CA153, miR-195 had a higher sensitivity for detecting the response to neoadjuvant chemotherapy and significantly increased, more than twofold, after neoadjuvant chemotherapy (P = 0.025, paired t test) in 52.381 % (11/21) of BC cases. However, there were no significant relationships between miR-195 expression and other clinicopathological parameters (TNM stage/pathotype/ER/PR/lymph node status). Our data indicate serum miR-195 is a promising tumor marker for BC diagnosis and general screening, especially for early stage BC. The high sensitivity of miR-195 to neoadjuvant chemotherapy may lay the foundation for future studies on the use of miRNA-based methods for monitoring BC treatment and therapy.

Global attention based GNN with Bayesian collaborative learning for glomerular lesion recognition.

BACKGROUND: Glomerular lesions reflect the onset and progression of renal disease. Pathological diagnoses are widely regarded as the definitive method for recognizing these lesions, as the deviations in histopathological structures closely correlate with impairments in renal function. METHODS: Deep learning plays a crucial role in streamlining the laborious, challenging, and subjective task of recognizing glomerular lesions by pathologists. However, the current methods treat pathology images as data in regular Euclidean space, limiting their ability to efficiently represent the complex local features and global connections. In response to this challenge, this paper proposes a graph neural network (GNN) that utilizes global attention pooling (GAP) to more effectively extract high-level semantic features from glomerular images. The model incorporates Bayesian collaborative learning (BCL), enhancing node feature fine-tuning and fusion during training. In addition, this paper adds a soft classification head to mitigate the semantic ambiguity associated with a purely hard classification. RESULTS: This paper conducted extensive experiments on four glomerular datasets, comprising a total of 491 whole slide images (WSIs) and 9030 images. The results demonstrate that the proposed model achieves impressive F1 scores of 81.37%, 90.12%, 87.72%, and 98.68% on four private datasets for glomerular lesion recognition. These scores surpass the performance of the other models used for comparison. Furthermore, this paper employed a publicly available BReAst Carcinoma Subtyping (BRACS) dataset with an 85.61% F1 score to further prove the superiority of the proposed model. CONCLUSION: The proposed model not only facilitates precise recognition of glomerular lesions but also serves as a potent tool for diagnosing kidney diseases effectively. Furthermore, the framework and training methodology of the GNN can be adeptly applied to address various pathology image classification challenges.

UV-stimulated riboflavin exerts immunosuppressive effects in BALB/c mice and human PBMCs.

Riboflavin (RF) as a photosensitizer has been used in corneal surgery and the inactivation of blood products. However, the effect of RF on immune cells after ultraviolet (UV) light stimulation has not been investigated. This study pioneered a novel application method of RF. Firstly, UV-stimulated RF was co-cultured with human peripheral blood mononuclear cells in vitro, and the apoptosis rate of lymphocyte subsets, cell proliferation inhibition rate and concentrations of IL-1ß, IL-6, IL-10, TNF-α were assessed. UV-stimulated RF was then administered intravenously to mice via the tail vein for a consecutive period of 5 days. The levels of immunoglobulin (IgG, IgM, IgA), complement (C3, C4) and cytokines (IFN-γ, IL-4, IL17, TGF-ß) were detected by ELISA. Flow cytometry was employed to analyze the populations of CD3+T, CD4+T, CD8+T and CD4+T/CD8+T cells in spleen lymphocytes of mice. The data showed that UV-stimulated RF can effectively induce apoptosis in lymphocytes, and different lymphocyte subtypes exhibited varying degrees of treatment tolerance. Additionally, the proliferative capacity of lymphocytes was suppressed, while their cytokine secretion capability was augmented. The animal experiments demonstrated that UV-stimulated RF led to a significant reduction observed in serum immunoglobulin and complement levels, accompanied by an elevation in IFN-γ, IL-17 and TGF-ß levels, as well as a decline in IL-4 level. In summary, the results of both in vitro and in vivo experiments have demonstrated that UV-stimulated RF, exhibits the ability to partially inhibit immune function. This novel approach utilizing RF may offer innovative perspectives for diseases requiring immunosuppressive treatment.

The nasal microbiota is a potential diagnostic biomarker for sepsis in critical care units.

This study aimed to characterize the composition of intestinal and nasal microbiota in septic patients and identify potential microbial biomarkers for diagnosis. A total of 157 subjects, including 89 with sepsis, were enrolled from the affiliated hospital. Nasal swabs and fecal specimens were collected from septic and non-septic patients in the intensive care unit (ICU) and Department of Respiratory and Critical Care Medicine. DNA was extracted, and the V4 region of the 16S rRNA gene was amplified and sequenced using Illumina technology. Bioinformatics analysis, statistical processing, and machine learning techniques were employed to differentiate between septic and non-septic patients. The nasal microbiota of septic patients exhibited significantly lower community richness (P = 0.002) and distinct compositions (P = 0.001) compared to non-septic patients. Corynebacterium, Staphylococcus, Acinetobacter, and Pseudomonas were identified as enriched genera in the nasal microbiota of septic patients. The constructed machine learning model achieved an area under the curve (AUC) of 89.08, indicating its efficacy in differentiating septic and non-septic patients. Importantly, model validation demonstrated the effectiveness of the nasal microecological diagnosis prediction model with an AUC of 84.79, while the gut microecological diagnosis prediction model had poor predictive performance (AUC = 49.24). The nasal microbiota of ICU patients effectively distinguishes sepsis from non-septic cases and outperforms the gut microbiota. These findings have implications for the development of diagnostic strategies and advancements in critical care medicine.IMPORTANCEThe important clinical significance of this study is that it compared the intestinal and nasal microbiota of sepsis with non-sepsis patients and determined that the nasal microbiota is more effective than the intestinal microbiota in distinguishing patients with sepsis from those without sepsis, based on the difference in the lines of nasal specimens collected.

A nomogram based on hematological markers to predict radiosensitivity in patients with esophageal squamous cell carcinoma.

This study aimed to determine the predictive value of pretreatment levels of hematological markers on the radiosensitivity of patients with esophageal squamous cell carcinoma (ESCC). The specific hematological markers assessed included total lymphocyte count (TLC), neutrophil count, platelet count, monocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR). A total of 353 ESCC patients who received radiotherapy (RT) alone or concurrent RT between 2015 and 2019 were reviewed. Pretreatment levels of hematological markers (NLR, PLR, LMR, and TLC) were used to assess the radiosensitivity of individual patients. Receiver operating characteristics curves were used to determine optimal cutoff values. Multivariate logistic models with radiosensitivity were established with meaningful results used for univariate analyses. Finally, a nomogram was developed and validated from the calibration curve and concordance index. One month after RT, 121 (34.3%) cases were shown to have low levels of radiosensitivity based on hematological markers. Univariate analyses showed that NLR, PLR, LMR, and TLC were associated with high levels of radiosensitivity (all markers, P < .05). Due to the collinearity between NLR, PLR, and LMR, these markers were separately evaluated by multivariate analysis. Multivariate analysis showed that high pretreatment NLP and PLR were independently associated with high radiosensitivity. In contrast, high pretreatment LMR and TLC were independent biomarkers associated with lower radiosensitivity. The concordance index of the nomogram was 0.737, and the calibration curves predicted by the nomogram were highly consistent with the observed experimental findings. Pretreatment hematologic markers (NLR, PLR, LMR, and TLC) can be used to predict the radiosensitivity of patients with ESCC accurately.

Determining factors affecting the user's intention to disclose privacy in online health communities: a dual-calculus model.

Background: As a new type of medical service application for doctor-patient interaction, online health communities (OHCs) have alleviated the imbalance between the supply and demand of medical resources in different regions and the problems of "difficult and expensive access to medical care", but also raised the concern of patients about the risk of disclosure of their health privacy information. Methods: In this study, a dual-calculus model was developed to explore users' motivation and decision-making mechanism in disclosing privacy information in OHCs by combining risk calculus and privacy calculus theories. Results: In OHCs, users' trust in physicians and applications is a prerequisite for their willingness to disclose health information. Meanwhile, during the privacy calculation, users' perceived benefits in OHCs had a positive effect on both trust in doctors and trust in applications, while perceived risks had a negative effect on both trusts in doctors and trust in applications. Furthermore, in the risk calculation, the perceived threat assessment in OHCs had a significant positive effect on perceived risk, while the response assessment had a significant negative effect on perceived risk, and the effect of users' trust in physicians far exceeded the effect of trust in applications. Finally, users' trust in physicians/applications is a mediating effect between perceived benefits/risks and privacy disclosure intentions. Conclusion: We combine risk calculus and privacy calculus theories to construct a dual-calculus model, which divides trust into trust in physicians and trust in applications, in order to explore the intrinsic motivation and decision-making mechanism of users' participation in privacy disclosure in OHCs. On the one hand, this theoretically compensates for the fact that privacy computing often underestimates perceived risk, complements the research on trust in OHCs, and reveals the influencing factors and decision transmission mechanisms of user privacy disclosure in OHCs. On the other hand, it also provides guidance for developing reasonable privacy policies and health information protection mechanisms for platform developers of OHCs.

AI-assisted Method for Efficiently Generating Breast Ultrasound Screening Reports.

BACKGROUND: Ultrasound is one of the preferred choices for early screening of dense breast cancer. Clinically, doctors have to manually write the screening report, which is time-consuming and laborious, and it is easy to miss and miswrite. AIM: We proposed a new pipeline to automatically generate AI breast ultrasound screening reports based on ultrasound images, aiming to assist doctors in improving the efficiency of clinical screening and reducing repetitive report writing. METHODS: AI efficiently generated personalized breast ultrasound screening preliminary reports, especially for benign and normal cases, which account for the majority. Doctors then make simple adjustments or corrections based on the preliminary AI report to generate the final report quickly. The approach has been trained and tested using a database of 4809 breast tumor instances. RESULTS: Experimental results indicate that this pipeline improves doctors' work efficiency by up to 90%, greatly reducing repetitive work. CONCLUSION: Personalized report generation is more widely recognized by doctors in clinical practice than non-intelligent reports based on fixed templates or options to fill in the blanks.

Value of 18F-FDG-PET/CT radiomics combined with clinical variables in the differential diagnosis of malignant and benign vertebral compression fractures.

BACKGROUND: Vertebral compression fractures (VCFs) are common clinical problems that arise from various reasons. The differential diagnosis of benign and malignant VCFs is challenging. This study was designed to develop and validate a radiomics model to predict benign and malignant VCFs with 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). RESULTS: Twenty-six features (9 PET features and 17 CT features) and eight clinical variables (age, SUVmax, SUVpeak, SULmax, SULpeak, osteolytic destruction, fracture line, and appendices/posterior vertebrae involvement) were ultimately selected. The area under the curve (AUCs) of the radiomics and clinical-radiomics models were significantly different from that of the clinical model in both the training group (0.986, 0.987 vs. 0.884, p < 0.05) and test group (0.962, 0.948 vs. 0.858, p < 0.05), while there was no significant difference between the radiomics model and clinical-radiomics model (p > 0.05). The accuracies of the radiomics and clinical-radiomics models were 94.0% and 95.0% in the training group and 93.2% and 93.2% in the test group, respectively. The three models all showed good calibration (Hosmer-Lemeshow test, p > 0.05). According to the decision curve analysis (DCA), the radiomics model and clinical-radiomics model exhibited higher overall net benefit than the clinical model. CONCLUSIONS: The PET/CT-based radiomics and clinical-radiomics models showed good performance in distinguishing between malignant and benign VCFs. The radiomics method may be valuable for treatment decision-making.

Crosstalk between arterial components and bioresorbable, 3-D printed poly-L-lactic acid scaffolds.

Bioresorbable scaffolds (BRSs) are designed to provide a temporary support that subsequently leaves behind native vessels after its complete degradation. The accumulation of mechanical changes influences the vascular histological characteristics and vice versa, leading to crosstalk and various behaviors in BRSs in different arterial components, which is different from that observed in traditional metal stents. Hence, we analyzed typical elastic and muscular arteries, the abdominal aorta of Sprague-Dawley rats and carotid arteries of New Zealand rabbits, after both received 3-D printed poly-L-lactic acid BRSs. We observed a lower level of scaffold degradation and severe intimal hyperplasia in the carotid arteries of rabbits because of the synthetic phenotypic transformation of vascular smooth muscle cells (SMCs) and endothelial-to-mesenchymal transition of endothelial cells (ECs). Extracellular matrix remodeling and endothelial repair occurred in a less rapid manner in the abdominal aorta of rats. These results suggest that muscular arterial components such as SMCs and ECs are more sensitive to BRS degradation-induced mechanical changes compared to those of elastic arteries. Therefore, the rat abdominal aorta might be more suitable for assessing BRS degradation and safety, while the carotid artery of rabbits could be used to evaluate drug coatings on BRSs, as it closely reflects the recovery of ECs and proliferation of SMCs. Our study also confirmed that the histological characteristics of vasculature should be considered while choosing an animal model for BRS evaluation.

The endothelium permeability after bioresorbable scaffolds implantation caused by the heterogeneous expression of tight junction proteins.

As one of the main functions of vascular endothelial cells, Vascular permeability is determined by four tight junction proteins (TJPs): Zonula Occludens-1 (ZO-1), Claudin-5, Occludin and Tricellulin. The barrier function of blood vessels will be reconstructed after they are damaged by endothelial mechanical injuries caused by vascular interventions. In this study, the effects of balloon expansion (transient mechanical injury) on four TJPs and vascular permeability were compared with those of poly-l-lactic acid bioresorbable scaffolds (BRSs) implantation (continuous mechanical stimulation). We found that BRSs do not affect vascular permeability, while the recovery of vascular barrier function was found to be only related to the mechanical injuries and repair of endothelium. Mechanical stimulation affects and accelerates the recovery process of vascular permeability with the heterogeneous expression levels of TJPs induced after BRSs implantation. Different TJPs have different sensitivity to different loyal mechanical stimuli. ZO-1 is more sensitive to shear stress and tension than to static pressure. Occludin is sensitive to static pressure and shear stress. Tricellulin is more sensitive to tension stretching. Compared with the other three TJPs, Claudin-5 can respond to mechanical stimulation, with relatively low sensitivity, though. This difference in sensitivity determines the heterogeneous expression of TJPs. Mechanical stimulation of different kinds and strengths can also cause different cell morphological changes and inflammatory reactions. As an important element affecting endothelial function, the mechanical factors emerging after BRSs implantation are worthy of more attention.

Improved FCOS for Detecting Breast Cancers.

PURPOSE: Breast cancer ranks first among cancers affecting women's health. Our goal is to develop a fast, high-precision, and fully automated breast cancer detection algorithm to improve the early detection rate of breast cancer. METHODS: We compare different object detection algorithms, including anchor-based and anchor-free object detection algorithms for detecting breast lesions. Finally, we find that the fully convolutional onestage object detection (FCOS) showed the best performance in the detection of breast lesions, which is an anchor-free algorithm. 1) Considering that the detection of breast lesions requires the context information of the ultrasound images, we introduce the non-local technique, which models long-range dependency between pixels to the FCOS algorithm, providing the global context information for the detection of the breast lesions. 2) The variety of shapes and sizes of breast lesions makes detection difficult. We propose a new deformable spatial attention (DSA) module and add it to the FCOS algorithm. RESULTS: The detection performance of the original FCOS is that the average precision (AP) for benign lesions is 0.818, and for malignant lesions is 0.888. The FCOS with a non-local module improves the performance of the breast detection; the AP of benign lesions was 0.819, and that of malignant lesions was 0.894. Combining the DSA module with the FCOS improves the performance of breast detection; the AP for benign lesions and malignant lesions is 0.840 and 0.899, respectively. CONCLUSION: We propose two methods to improve the FCOS algorithm from different perspectives to improve its performance in detecting breast lesions. We find that FCOS combined with DSA is beneficial in improving the localization and classification of breast tumors and can provide auxiliary diagnostic advice for ultrasound physicians, which has a certain clinical application value.

Two-stage degradation and novel functional endothelium characteristics of a 3-D printed bioresorbable scaffold.

Bioresorbable scaffolds have emerged as a new generation of vascular implants for the treatment of atherosclerosis, and designed to provide a temporary scaffold that is subsequently absorbed by blood vessels over time. Presently, there is insufficient data on the biological and mechanical responses of blood vessels accompanied by bioresorbable scaffolds (BRS) degradation. Therefore, it is necessary to investigate the inflexion point of degradation, the response of blood vessels, and the pathophysiological process of vascular, as results of such studies will be of great value for the design of next generation of BRS. In this study, abdominal aortas of SD rats were received 3-D printed poly-l-actide vascular scaffolds (PLS) for various durations up to 12 months. The response of PLS implanted aorta went through two distinct processes: (1) the neointima with desirable barrier function was obtained in 1 month, accompanied with slow degradation, inflammation, and intimal hyperplasia; (2) significant degradation occurred from 6 months, accompanied with decreasing inflammation and intimal hyperplasia, while the extracellular matrix recovered to normal vessels which indicate the positive remodeling. These in vivo results indicate that 6 months is a key turning point. This "two-stage degradation and vascular characteristics" is proposed to elucidate the long-term effects of PLS on vascular repair and demonstrated the potential of PLS in promoting endothelium function and positive remodeling, which highlights the benefits of PLS and shed some light in the future researches, such as drug combination coatings design.

Preparation, Characteristics, Toxicity, and Efficacy Evaluation of the Nasal Self-assembled Nanoemulsion Tumor Vaccine In Vitro and In Vivo.

Epitope peptides have attracted widespread attention in the field of tumor vaccines because of their safety, high specificity, and convenient production; in particular, some MHC I-restricted epitopes can induce effective cytotoxic T lymphocyte activity to clear tumor cells. Additionally, nasal administration is an effective and safe delivery technique for tumor vaccines due to its convenience and improved patient compliance. However, epitope peptides are unsuitable for nasal delivery because of their poor immunogenicity and lack of delivery efficiency. Nanoemulsions (NEs) are thermodynamically stable systems that can be loaded with antigens and delivered directly to the nasal mucosal surface. Ile-Lys-Val-Ala-Val (IKVAV) is the core pentapeptide of laminin, an integrin-binding peptide expressed by human respiratory epithelial cells. In this study, an intranasal self-assembled epitope peptide NE tumor vaccine containing the synthetic peptide IKVAV-OVA257-264 (I-OVA) was prepared by a low-energy emulsification method. The combination of IKVAV and OVA257-264 can enhance antigen uptake by nasal mucosal epithelial cells. Here, we establish a protocol to study the physicochemical characteristics by transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS); stability in the presence of mucin protein; toxicity by examining the cell viability of BEAS-2B cells and the nasal and lung tissues of C57BL/6 mice; cellular uptake by confocal laser scanning microscopy (CLSM); release profiles by imaging small animals in vivo; and the protective and therapeutic effect of the vaccine by using an E.G7 tumor-bearing model. We anticipate that the protocol will provide technical and theoretical clues for the future development of novel T cell epitope peptide mucosal vaccines.

[Histopathology changes in mice infected with Toxoplasma gondii Prugniaud strain].

OBJECTIVE: To observe the symptoms and dynamic changes of histopathology in the organs from ICR mice infected by Toxoplasma gondii Prugniaud strain. METHODS: Thirty ICR mice were infected intraperitoneally with cysts, 10 cysts per mouse. 16 mice were injected with PBS. Incidence of the mice was observed. Three mice from the infected group and two mice from the control group were sacrificed, and the liver, spleen, lung, brain, kidney and heart were collected for pathology and immunohistochemistry examinations on the day 5, 10, 15, 20, 25, 30, 60 and 90 post-infection. RESULTS: The infected mice began to fall ill at 6 d post-infection, symptoms including decreased appetite, pilomotor fur, sloth, shakes and diarrhea, with a mortality rate of 20%. From 5 d to 20 d post-infection, microscopic examination for HE stain-slides showed the destroyed liver structure, cellular edema, ballooning change, focal necrosis, sinus hepatic expansion and hyperemia, and inflammatory infiltration. Splenic corpuscles demolished and disappeared, red pulp widened and white pulp atrophied, splenic sinusoid extended with hyperemia. Lungs showed destruction of the structure and pathological changes of interstitial pneumonia. The pathological changes began to alleviate until recovery after 20 d post-infection. In the brain, neuronal degeneration and necrosis were found at 10 d post-infection. Some neuroglial cell tubercle, blood vessel sleeve cuffing, inflammatory cell infiltration on cavitas subarachnoidealis and cysts were observed from 15 d to 90 d. Granulation tissue was seen at 90 d post-infection. By immunohistochemistry test, internal organs showed toxoplasma antigen at 5 d post-infection, and the positive reaction was remarkable at 10 d post-infection, then began to taper until negative. Toxoplasma antigen was revealed in the brain from 10 d to 90 d post-infection. CONCLUSION: Non-specific clinical manifestation and the degeneration, necrosis and inflammatory cell infiltration in poly-organs appear in earlier period of toxoplasma tachyzoite infection in the ICR mice, followed by the co-existing phenomenon of non-specific infection with cysts in the brain.

Nonstationary signal extraction based on BatOMP sparse decomposition technique.

Sparse decomposition technique is a new method for nonstationary signal extraction in a noise background. To solve the problem of accuracy and efficiency exclusive in sparse decomposition, the bat algorithm combined with Orthogonal Matching Pursuits (BatOMP) was proposed to improve sparse decomposition, which can realize adaptive recognition and extraction of nonstationary signal containing random noise. Two general atoms were designed for typical signals, and dictionary training method based on correlation detection and Hilbert transform was developed. The sparse decomposition was turned into an optimizing problem by introducing bat algorithm with optimized fitness function. By contrast with several relevant methods, it was indicated that BatOMP can improve convergence speed and extraction accuracy efficiently as well as decrease the hardware requirement, which is cost effective and helps broadening the applications.

EHMT2 (G9a) activation in mantle cell lymphoma and its associated DNA methylation and gene expression.

OBJECTIVE: The function of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) has been studied in several cancers; however, little is known about its role in mantle cell lymphoma (MCL). Thus, this study aimed to characterize the significance and function of EHMT2 in MCL. METHODS: EHMT2 expression in MCL and reactive hyperplasia (RH) were investigated by immunohistochemistry. Genome-wide analysis of DNA methylation was performed on EHMT2 + MCL samples. The function of EHMT2 was determined by CCK8, flow cytometry, and western blot assays. Gene expression profile analysis was performed before and after EHMT2 knockdown to search for EHMT2-regulated genes. Co-immunoprecipitation (Co-IP) experiments were conducted to identify the proteins interacting with EHMT2. RESULTS: EHMT2 was expressed in 68.57% (24/35) of MCLs but not in any RHs. Genome-wide analysis of DNA methylation on EHMT2 + MCLs revealed that multiple members of the HOX, FOX, PAX, SOX, and CDX families were hypermethylated or hypomethylated in EHMT2 + MCLs. BIX01294, a EHMT2 inhibitor, inhibited MCL cell growth and stalled cells in the G1 phase. Additionally, BIX01294 downregulated the expressions of cell cycle proteins, cyclin D1, CDK4, and P21, but upregulated the expressions of apoptosis-related proteins, Bax and caspase-3. Co-IP experiments revealed that EHMT2 interacted with UHRF1, HDAC1, and HDAC2 but not with HDCA3. After EHMT2 knockdown, multiple genes were regulated, including CD5 and CCND1, mostly enriched in the Tec kinase signaling pathway. In addition, several genes (e.g., MARCH1, CCDC50, HIP1, and WNT3) were aberrantly methylated in EHMT2 + MCLs. CONCLUSIONS: For the first time, we determined the significance of EHMT2 in MCL and identified potential EHMT2-regulated genes.

PRMT5 promotes progression of endometrioid adenocarcinoma via ERα and cell cycle signaling pathways.

Protein arginine methyltransferase 5 (PRMT5) has previously been reported to be upregulated in many malignant tumors. This study investigated the significance of PRMT5 in endometrial carcinoma (EC) and explored its function in tumorigenesis. Immunohistochemistry was performed to evaluate PRMT5 expression in 62 EC and 66 endometrial hyperplasia samples. The functions of PRMT5 were investigated by cell counting kit-8, plate colony formation, wound healing, and transwell and flow cytometry assays. Quantitative reverse transcription-polymerase chain reaction and western blotting were used to measure the expression of PRMT5, changes in estrogen receptor α (ERα), and related functional proteins. Coimmunoprecipitation was performed to examine the interaction of PRMT5 with ERα and its coactivator steroid receptor coactivator-1 (SRC1). Compared to endometrial hyperplasia tissue, PRMT5 was overexpressed in endometrioid adenocarcinoma (EAC) but not overexpressed in mucinous EC. The main expression pattern of PRMT5 in EAC was cytoplasmic. However, the positive cases of endometrial hyperplasia showed both cytoplasmic and nuclear positivity in the endometrial glands or were mainly positive in stromal cells. Knockdown of PRMT5 significantly inhibited the growth and migration ability of EAC cells and promoted their apoptosis by regulating cyclin D1, c-myc, p53, and Bcl2 proteins. Furthermore, PRMT5 could form a complex with ERα and SRC1 to promote the expression of ERα. In conclusion, PRMT5 plays a significant role in the progression of EAC by interacting with ERα and impacting the cell cycle signaling pathways.