Viral communities locked in high elevation permafrost up to 100 m in depth on the Tibetan Plateau.

Permafrost serves as a natural cold reservoir for viral communities. However, little is known about the viromes in deep permafrost soil, as most studies of permafrost were restricted to shallow areas. Here, permafrost soil samples of up to 100 m in depth were collected from two sites in the Tuotuo River permafrost area on the Tibetan Plateau. We investigated the viral composition in these permafrost soil samples and analyzed the relationship of viral composition and diversity along with depths. Our study revealed that greater permafrost thickness corresponds to higher diversity within the viral community. Bacteriophages were found to be the dominant viral communities, with "kill the winner" dynamics observed within the Siphoviridae and Myoviridae. The abundance and diversity of viral communities may follow a potential pattern along soil layers and depths, influenced by pH, trace elements, and permafrost thickness. Notably, strong correlations were discovered between the content of inorganic elements, including B, Mg, Cr, Bi, Ti, Na, Ni, and Cu, and the viral composition. Moreover, we discovered highly conserved sequences of giant viruses at depth of 10, 20, and 50 m in permafrost, which play a crucial role in evolutionary processes. These findings provide valuable insights into the viral community patterns from shallow to 100-m-depth in high-elevation permafrost, offering crucial data support for the formulation of strategies for permafrost thaw caused by climate change and anthropogenic activities.

CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro.

BACKGROUND: Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. METHODS: The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. RESULTS: The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CONCLUSIONS: CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.

Bibliometric Analysis of Development Trends and Research Hotspots in the Study of Data Mining in Nursing Based on CiteSpace.

Backgrounds: With the advent of the big data era, hospital information systems and mobile care systems, among others, generate massive amounts of medical data. Data mining, as a powerful information processing technology, can discover non-obvious information by processing large-scale data and analyzing them in multiple dimensions. How to find the effective information hidden in the database and apply it to nursing clinical practice has received more and more attention from nursing researchers. Aim: To look over the articles on data mining in nursing, compiled research status, identified hotspots, highlighted research trends, and offer recommendations for how data mining technology might be used in the nursing area going forward. Methods: Data mining in nursing publications published between 2002 and 2023 were taken from the Web of Science Core Collection. CiteSpace was utilized for reviewing the number of articles, countries/regions, institutions, journals, authors, and keywords. Results: According to the findings, the pace of data mining in nursing progress is not encouraging. Nursing data mining research is dominated by the United States and China. However, no consistent core group of writers or organizations has emerged in the field of nursing data mining. Studies on data mining in nursing have been increasingly gradually conducted in the 21st century, but the overall number is not large. Institution of Columbia University, journal of Cin-computers Informatics Nursing, author Diana J Wilkie, Muhammad Kamran Lodhi, Yingwei Yao are most influential in nursing data mining research. Nursing data mining researchers are currently focusing on electronic health records, text mining, machine learning, and natural language processing. Future research themes in data mining in nursing most include nursing informatics and clinical care quality enhancement. Conclusion: Research data shows that data mining gives more perspectives for the growth of the nursing discipline and encourages the discipline's development, but it also introduces a slew of new issues that need researchers to address.

Retinal vessel segmentation based on multi-scale feature and style transfer.

Retinal vessel segmentation is very important for diagnosing and treating certain eye diseases. Recently, many deep learning-based retinal vessel segmentation methods have been proposed; however, there are still many shortcomings (e.g., they cannot obtain satisfactory results when dealing with cross-domain data or segmenting small blood vessels). To alleviate these problems and avoid overly complex models, we propose a novel network based on a multi-scale feature and style transfer (MSFST-NET) for retinal vessel segmentation. Specifically, we first construct a lightweight segmentation module named MSF-Net, which introduces the selective kernel (SK) module to increase the multi-scale feature extraction ability of the model to achieve improved small blood vessel segmentation. Then, to alleviate the problem of model performance degradation when segmenting cross-domain datasets, we propose a style transfer module and a pseudo-label learning strategy. The style transfer module is used to reduce the style difference between the source domain image and the target domain image to improve the segmentation performance for the target domain image. The pseudo-label learning strategy is designed to be combined with the style transfer module to further boost the generalization ability of the model. Moreover, we trained and tested our proposed MSFST-NET in experiments on the DRIVE and CHASE_DB1 datasets. The experimental results demonstrate that MSFST-NET can effectively improve the generalization ability of the model on cross-domain datasets and achieve improved retinal vessel segmentation results than other state-of-the-art methods.

Viromes of Haemaphysalis longicornis reveal different viral abundance and diversity in free and engorged ticks.

Haemaphysalis longicornis ticks, commonly found in East Asia, can transmit various pathogenic viruses, including the severe fever with thrombocytopenia syndrome virus (SFTSV) that has caused febrile diseases among humans in Hubei Province. However, understanding of the viromes of H. longicornis was limited, and the prevalence of viruses among H. longicornis ticks in Hubei was not well clarified. This study investigates the viromes of both engorged (fed) and free (unfed) H. longicornis ticks across three mountainous regions in Hubei Province from 2019 to 2020. RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging to unclassified viruses and seven RNA viral families, namely Chuviridae, Nairoviridae, Orthomyxoviridae, Parvoviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae. Viral abundance and diversity in these ticks were analysed, and phylogenetic characteristics of the Henan tick virus (HNTV), Dabieshan tick virus (DBSTV), Okutama tick virus (OKTV), and Jingmen tick virus (JMTV) were elucidated based on their full genomic sequences. Prevalence analysis demonstrated that DBSTV was the most common virus found in individual H. longicornis ticks (12.59%), followed by HNTV (0.35%), whereas JMTV and OKTV were not detected. These results improve our understanding of H. longicornis tick viromes in central China and highlight the role of tick feeding status and geography in shaping the viral community. The findings of new viral strains and their potential impact on public health raise the need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.

Dysfunctional Bladder Morphology and Functional Impairments Are Identified in the Alzheimer's Disease APPNL-G-F/NL-G-F Murine Model.

BACKGROUND: While symptoms related to lower urinary tract dysfunction (LUTD) are common in individuals with Alzheimer's disease (AD), pathophysiological links between AD and LUTD remain unclear. OBJECTIVE: This study aimed to investigate whether AD neuropathology would cause autonomic dysfunction along the spinal cord-bladder axis, which could result in alterations in bladder muscle kinetics. METHODS: We utilized APPNL-G-F/NL-G-F knock-in (APP KI) and APPwt/wt (wild-type) mice at two different ages, 4- and 10-month-old, to investigate how AD impacts bladder tissue function by immunohistochemistry, western blotting, and pharmacomyography. RESULTS: We showed that the mucosal layer partially separated from the detrusor in 10-month-old APP KI mouse bladders. Although there was no detectable amyloid deposition in the APP KI bladder, we found amyloid plaques in APP KI lumbar spinal cord. Further immunoblot analysis revealed that tyrosine hydroxylase protein levels were significantly reduced in both 4- and 10-month-old bladder tissues, suggesting reduction of norepinephrine synthesis in APP KI mouse bladders. In contrast, the level of ß2 adrenergic receptor was increased in 4-month-old but not 10-month-old APP KI bladders. In bladder strips, the adrenergic agonist isoproterenol induced increased relaxation in 4- but not 10-month-old APP KI bladders. With 10 Hz electrical field stimulation, 10-month-old APP KI bladder strips were more responsive than wild-type controls, with no differences observed in 4-month-old APP KI bladders. CONCLUSIONS: APP KI mice exhibit LUTD, which is likely arising from amyloid pathology in the spinal cord, and results in maturational declines in presynaptic activity combined with compensatory postsynaptic upregulation.

Prediction and identification of HLA-A*0201-restricted epitopes from cancer testis antigen CT23.

Cancer-testis antigen CT23 is a class of tumor-associated antigens (TAA) characterized by restricted expression in male germ cells and a variety of tumor tissues. Numerous studies have shown that CT23 is closely related to tumor cell viability, proliferation, metastasis and invasion. CT23 is immunogenic and can cause specific immune response in tumor patients. Therefore, it is considered to be one of the best target antigens for designing therapeutic tumor vaccines and T-cell-mediated tumor immunotherapy. In this study, we initially obtained seven HLA-A*0201-restricted CT23 epitope candidate peptides through the T cell epitope prediction program. Subsequently, a T2 cell binding assay revealed the potential binding of all candidate peptides with HLA-A2 molecules. Notably, peptide P7 (ALLVLCYSI) exhibited the highest affinity, as evidenced by a fluorescence index (FI) of 2.19. Dendritic cells (DCs) loaded with CT23 candidate peptide can stimulate CD8+T cell activation and proliferation, and compared with other candidate peptides, candidate peptide P7 is superior. The cytotoxic T lymphocytes (CTLs) stimulated by the peptide P7 had killing effect on tumor cells (HLA-A*0201+, CT23+), but no killing effect on tumor cells (HLA-A*0201-, CT23+). The CTLs induced by the peptide P7 also had a specific killing effect on T2 cells bearing the peptide P7. In summary, our findings suggest that the CT23 peptide P7 (ALLVLCYSI) can induce immune responses and holds potential for tumor-specific CTL therapy.

Application and challenges of a metaverse in medicine.

Metaverse has been confirmed as a relatively amorphous concept of innovation, which refers to technological advancement. Metaverse, i.e., a coalition between reality world and virtual world, has created significant significance and convenience in education, communication, economy, etc. The COVID-19 outbreak has stimulated the growth of metaverse applications in medicine. The above-mentioned technology has broad applications while comprising online remote medical treatment, online conferences, medical education, preparation of surgical plans, etc. Moreover, technical, security, and financial challenges should be tackled down by the future widespread use of metaverse. Metaverse is limitlessly promising, and it will exert a certain effect on future scientific and technological advancements in the medical industry. The review article primarily aims to summarize the application of the metaverse in medicine and their challenge in the future of medicine.

Bace1 Deletion in the Adult Reverses Epileptiform Activity and Sleep-wake Disturbances in AD Mice.

Alzheimer's disease (AD) increases the risk for seizures and sleep disorders. We show here that germline deletion of ß-site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) in neurons, but not in astrocytes, increased epileptiform activity. However, Bace1 deletion at adult ages did not alter the normal EEG waveform, indicating less concern for BACE1 inhibition in patients. Moreover, we showed that deletion of Bace1 in the adult was able to reverse epileptiform activity in 5xFAD mice. Intriguingly, treating 5xFAD and APPNL-G-F/NL-G-F (APP KI) mice of either sex with one BACE1 inhibitor Lanabecestat (AZD3293) dramatically increased epileptiform spiking, likely resulting from an off-target effect. We also monitored sleep-wake pathologies in these mice and showed increased wakefulness, decreased non-rapid eye movement sleep, and rapid eye movement sleep in both 5xFAD and APP KI mice; BACE1 inhibition in the adult 5xFAD mice reversed plaque load and sleep disturbances, but this was not seen in APP KI mice. Further studies with and without BACE1 inhibitor treatment showed different levels of plaque-associated microgliosis and activated microglial proteins in 5xFAD mice compared with APP KI mice. Together, BACE1 inhibition should be developed to avoid off-target effect for achieving benefits in reducing epileptic activity and sleep disturbance in Alzheimer's patients.SIGNIFICANCE STATEMENT BACE1 is widely recognized as a therapeutic target for treating Alzheimer's disease patients. However, BACE1 inhibitors failed in clinical trials because of inability to show cognitive improvement in patients. Here we show that BACE1 inhibition actually reduces sleep disturbances and epileptic seizures; both are seen in AD patients. We further showed that one of clinically tested BACE1 inhibitors does have off-target effects, and development of safer BACE1 inhibitors will be beneficial to AD patients. Results from this study will provide useful guidance for additional drug development.

The Influence of Informal Caregivers' Preparedness on Psychological Symptoms and Quality of Life Among Patients With Heart Failure And Insufficient Self-care.

BACKGROUND: Most patients with heart failure find self-care difficult to perform and rely on family caregivers for support. Informal caregivers, however, often face insufficient psychological preparation and challenges in providing long-term care. Insufficient caregiver preparedness not only results in psychological burden for the informal caregivers but may also lead to a decline in caregiver contributions to patient self-care that affects patient outcomes. OBJECTIVE: Our objective was to test (1) the association of baseline informal caregivers' preparedness with psychological symptoms (anxiety and depression) and quality of life 3 months after baseline among patients with insufficient self-care and (2) the mediating effects of caregivers' contributions to self-care of heart failure (CC-SCHF) on the relationship of caregivers' preparedness with patients' outcomes at 3 months. METHODS: A longitudinal design was used to collect data between September 2020 and January 2022 in China. Data analyses were conducted using descriptive statistics, correlations, and linear mixed models. We used model 4 of the PROCESS program in SPSS with bootstrap testing to evaluate the mediating effect of CC-SCHF of informal caregivers' preparedness at baseline with psychological symptoms or quality of life among patients with HF 3 months later. RESULTS: Caregiver preparedness was positively associated with CC-SCHF maintenance ( r = 0.685, P < .01), CC-SCHF management ( r = 0.403, P < .01), and CC-SCHF confidence ( r = 0.600, P < .01). Good caregiver preparedness directly predicted lower psychological symptoms (anxiety and depression) and higher quality of life for patients with insufficient self-care. The associations of caregiver preparedness with short-term quality of life and depression of patients with HF with insufficient self-care were mediated by CC-SCHF management. CONCLUSIONS: Enhancing the preparedness of informal caregivers may improve psychological symptoms and quality of life of heart failure patients with insufficient self-care.

Identification of potential biomarkers in cancer testis antigens for glioblastoma.

OBJECTIVE: To screen and validate cancer testis antigens (CTAs) as potential biomarkers and explore their molecular mechanisms in glioblastoma (GBM). METHODS: Ribonucleic acid sequencing (RNA-seq) and bioinformatics analyses were utilized to screen the highly expressed CTAs in GBM. Correlation analysis was used to identify potential biomarkers associated with tumor purity and prognosis. Immunohistochemistry was applied for detection of protein expression. Protein-protein interaction (PPI) network construction, functional enrichment analysis, and binding domain prediction were performed to investigate the underlying molecular mechanisms of GBM. RESULTS: A total of 8 highly expressed CTAs were identified in GBM. One of them was PDZ-binding kinase (PBK). PBK messenger RNA (mRNA) was most highly expressed in GBM and associated with tumor purity and prognosis, PBK protein expression was also significantly increased in GBM tissues and correlated with p53 expression. Functional enrichment analysis revealed that the PBK related genes were predominantly enriched in cell cycle pathway with 38 genes enriched. The proteins encoding by these 38 genes were performed by binding domain prediction analysis, which demonstrated 15 proteins interacting with PBK. Most of these proteins were up regulated in GBM. CONCLUSION: PBK is highly expressed in GBM. It may serve as a potential biomarker for GBM targeting therapy and the cell cycle modulator by interacting with certain key molecules of cell cycle in GBM.

Self-Assembly of Two Tubular Metalloligand-Based Palladium-Organic Cages as Hosts for Polycyclic Aromatic Hydrocarbons.

Herein we report two tubular metal-organic cages (MOCs), synthesized by the self-assembly of bidentate metalloligands with different lengths and PdII. These two MOCs feature Pd4L8-type square tubular and Pd3L6-type triangular cage structures, respectively. Both MOCs have been fully characterized by NMR spectroscopy, mass spectrometry, and theoretical calculation. Both cages can be employed for encapsulating polycyclic aromatic hydrocarbons and show high binding affinity toward coronene.

A bibliometric analysis of the global trends and hotspots for the ketogenic diet based on CiteSpace.

The ketogenic diet (KD) is a potential nutritional therapy that is frequently utilized in various conditions. More and more studies are being done on KD in recent years. However, as far as we know, few studies have made an effort to offer a thorough synthesis and assessment of this topic. This paper aims to do a rigorous and thorough evaluation of the knowledge structure, development trend, and research hotspot of scientific outputs connected to KD. The bibliographic records connected to KD from January 1, 2001 to April 22, 2022 were collected using the core collection database of Web of Science. The complex data input, that consisted of the amount of publications, journals, authors, institutions, countries, keywords and cited references, was generated and analyzed visually using CiteSpace. A total of 2676 literatures on the KD were published between 2001 and 2022. The most KD-related publications were found in Epilepsia and Epilepsia Research. The authors with the most KD-related papers are Kossoff EH and Rho J. The United States is the country with the most publications, and Johns Hopkins University, Johns Hopkins University Hospital, and Johns Hopkins Medical Institutions are the institutions with the most articles. The high frequency keywords are "KD," "ketone body," "children," "efficacy," "weight loss," "low carbohydrate diet," "metabolism," "epilepsy," "beta hydroxybutyrate," and "modified atkins diet." The 2018 study by Kossoff EH on epilepsia and the 2017 study by Puchalska P on ketone body metabolism earned 127 and 114 citations, respectively. The results of this bibliometric analysis provide information on the state and trends in KD and may be used by researchers to pinpoint hot issues and discover new areas of study.

Postnatal neuronal Bace1 deletion impairs neuroblast and oligodendrocyte maturation.

Beta amyloid cleaving enzyme 1 (BACE1) is largely expressed by neurons and is the sole ß-secretase for initiating the production of neuronal ß-amyloid peptides (Aß). To fully understand the physiological functions of neuronal BACE1, we used mouse genetic approach coupled with unbiased single nucleus RNA sequencing (snRNAseq) to investigate how targeted deletion of Bace1 in neurons, driven by Thy-1-Cre recombinase, would affect functions in the nervous system. Our transcriptome results revealed that BACE1 is essential for maturation of neural precursor cells and oligodendrocytes in mice. RNA velocity analysis confirmed deficit in the trajectory of neuroblasts in reaching the immature granule neuron state in young Bace1fl/fl; Thy1-cre mice. Further analysis of differential gene expression indicated changes in genes important for SNARE signaling, tight junction signaling, synaptogenesis and insulin secretion pathways. Morphological studies revealed a hypomyelination in Bace1fl/fl;Thy1-cre sciatic nerves, but no detectable myelination changes in the corpus callosum, despite clear reduction in myelination proteins in the brain. Functional studies showed reduction in long-term potential, defects in synaptogenesis and learning behavioral. Altogether, our results show that neuronal BACE1 is critical for optimal development of central and peripheral nervous system, and inhibition of neuronal BACE1 will result in deficits in synaptic functions and cognitive behaviors.

The impact of informal caregivers' preparedness on short-term outcomes of heart failure patients with insufficient self-care.

AIMS: Even though self-care is essential in the long-term management of heart failure (HF), it is often not performed adequately in HF populations. Mobilizing informal caregivers may be one way to help patients perform self-care, support individual needs, and maintain health. However, informal caregivers often face insufficient preparation for providing long-term care. This insufficient caregiver preparedness may lead to a decline in caregiver contributions and affect the outcomes of care in patients with HF. This study aimed to explore whether informal caregivers' preparedness is a predictor that influences short-term outcomes of HF patients; to analyse whether caregiver contribution to self-care of HF (CC-SCHF) plays a mediating role between informal caregivers' preparedness and HF short-term outcomes. METHODS AND RESULTS: A prospective observational study was conducted in China. After controlling for covariates, higher levels of informal caregivers' preparedness were significantly associated with lower 3-month mortality [odds ratio (OR) = 0.919, 95% confidence interval (CI) = (0.855-0.988), P = 0.022] and 3-month readmission rate [OR = 0.883, 95% CI = (0.811-0.961), P = 0.004] and shorter length of hospital stay (ß = -0.071, P < 0.001). The informal caregiver's preparedness was positively associated with CC-SCHF maintenance (r = 0.708, P < 0.01), CC-SCHF management (r = 0.431, P < 0.01), and CC-SCHF confidence (r = 0.671, P < 0.01). The CC-SCHF management was a mediator in the relationship between informal caregivers' preparedness and 3-month readmission rate [effect 95% CI = (-0.054 to -0.001)] and length of hospital stay [effect 95% CI = (-0.235 to -0.042)]. CONCLUSION: A higher level of informal caregivers' preparedness is associated with better short-term outcomes of HF patients with insufficient self-care.

Knockdown of hsa_circ_0008922 inhibits the progression of glioma.

Background: A glioma is a tumor originating from glial cells in the central nervous system. Although significant progress has been made in diagnosis and treatment, most high-grade glioma patients are prone to recurrence. Therefore, molecular targeted therapy may become a new direction for adjuvant therapy in glioma. In recent years, many studies have revealed that circular RNA (circRNA) may play an important role in the occurrence and development of many tumors including gliomas. Our previous study found that the expression of hsa_circ_0008922 was up-regulated in glioma tissues upon RNA sequencing. The biological mechanism of circ_0008922 is still unreported in gliomas. Therefore, in this study, we preliminarily outlined the expression of hsa_circ_0008922 in glioma and explored its biological functions. Methods: The expression of hsa_circ_0008922 in forty glioma tissues and four glioma cell lines (A172, U251, SF763 and U87) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between hsa_circ_0008922 expression and clinicopathological features of glioma patients was evaluated by Fisher's exact test. To understand the potential function of hsa_circ_0008922 in glioma, we constructed small interfering RNA (siRNA) to hsa_circ_0008922 to downregulate its expression in glioma cell lines A172 and U251. With these hsa_circ_0008922 downregulated cells, a series of assays were carried out as follows. Cell proliferation was detected by CCK8 assay, migration and invasion were determined by wound healing assay and transwell assay, respectively. Colony formation ability was evaluated by plate clonogenic assay. Moreover, flow cytometry combined with Western blot was performed to analyze apoptosis status and the expression of apoptotic related proteins (caspase 3 and caspase 9). Finally, the possible biological pathways and potential miRNA targets of hsa_circ_0008922 were predicted by bioinformatics. Results: We found that the expression of hsa_circ_0008922 in glioma tissues was 3.4 times higher than that in normal tissues. The expression of has_circ_0008922 was correlated with WHO tumor grade. After down-regulating the expression of hsa_circ_0008922, malignant biological behavior of glioma cells was inhibited, such as cell proliferation, colony formation, migration, and invasion. At the same time, it also induced apoptosis of glioma cells. Predicted analysis by bioinformatics demonstrated that hsa_circ_0008922 may be involved in tumor-related pathways by acting as a molecular sponge for multiple miRNAs (hsa-let-7e-5p, hsa-miR-506-5p, hsa-let-7b-5p, hsa-let-7c-5p and hsa-let-7a-5p). Finally, we integrated our observation to build a circRNA-miRNA-mRNA predictive network.

Combined treatment with epigenetic agents enhances anti-tumor activity of MAGE-D4 peptide-specific T cells by upregulating the MAGE-D4 expression in glioma.

Objective: The study evaluated the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA), and trichostatin A (TSA) on immunotherapy against glioma. Methods: The expression and prognosis of MAGE-D4 in glioma were analyzed online, and the expression of MAGE-D4 and HLA-A2 in glioma induced by epigenetic drugs was detected by qRT-PCR, Western blot, and flow cytometry. The methylation status of the MAGE-D4 promoter was determined by pyrosequencing. An HLA-A2 restricted MAGE-D4 peptide was predicted and synthesized. An affinity assay and a peptide/HLA complex stability assay were performed to determine the affinity between peptide and HLA. CCK8 assay, CFSE assay, ELISA and ELISPOT were performed to detect the function of MAGE-D4 peptide-specific T cells. Flow cytometry, ELISA, and cytotoxicity assays were used to detect the cytotoxicity effect of MAGE-D4 peptide-specific T cells combined with epigenetic drugs against glioma in vitro. Finally, the glioma-loaded mouse model was applied to test the inhibitory effect of specific T cells on gliomas in vivo. Results: MAGE-D4 was highly expressed in glioma and correlated with poor prognosis. Glioma cells could be induced to express MAGE-D4 and HLA-A2 by epigenetic drugs. MAGE-D4-associated peptides were found that induce DCs to stimulate the highest T-cell activities of proliferation, IL-2 excretion, and IFN-γ secretion. MAGE-D4 peptide-specific T cells treated with TSA only or combining TSA and DAC had the most cytotoxicity effect, and its cytotoxicity effect on glioma cells decreased significantly after HLA blocking. In vivo experiments also confirmed that MAGE-D4-specific T cells inhibit TSA-treated glioma. Conclusion: MAGE-D4 is highly expressed in glioma and correlated with the prognosis of glioma. The novel MAGE-D4 peptide identified was capable of inducing MAGE-D4-specific T cells that can effectively inhibit glioma growth, and the epigenetic drug application can enhance this inhibition.

FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy.

OBJECTIVE: Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer, but not in normal tissues except for testis. This study aimed to investigate the expression and functional role of FMR1NB in glioma. METHODS: The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry, respectively, in glioma specimens from 83 patients at follow-up. The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines A172 and U251. RESULTS: FMR1NB mRNA and protein expression was detected in 58.8% (77/131) and 46.34% (57/123) of glioma tissues, respectively. FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome. Knockdown of FMR1NB induced apoptosis and suppressed proliferation, adhesion, migration, and invasion by modulating the expression of cyclin A, CDK2, caspase-3, E-cadherin, and N-cadherin in A172 and U251 cells. CONCLUSION: Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.

Microrna-1224-5p Is a Potential Prognostic and Therapeutic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Analyses.

OBJECTIVE: Glioblastoma (GBM) is the most common, invasive, and malignant primary brain tumor with a poor prognosis and high recurrence rate. It's known that some microRNAs (miRNAs) which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM. This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker. METHODS: Differentially expressed miRNAs (DEmiRNAs) were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus (GEO) database through bioinformatics tools. The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas (CGGA). Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database. TAM2.0 database, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the function of the dysregulated miRNAs. Subsequently, protein-protein interaction (PPI) network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs, respectively. Then, core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks. Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues. Furthermore, the potential biomarkers were identified by clinical correlation analysis and survival analysis. RESULTS: Totally, 68 intersecting DEmiRNAs were identified, 40 of which were upregulated and the other 28 miRNAs were downregulated. Two upregulated and 4 downregulated miRNAs showed prognostic significance. Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p, which were respectively upregulated and downregulated in GBM. The correlation between miR-1224-5p level and recurrence was statistically significant (P=0.011). Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis. Moreover, high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis. CONCLUSION: MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.

Self-Assembly of a Pd4Cu8L8 Cage for Epoxidation of Styrene and Its Derivatives.

Herein we report a discrete heterometallic Pd4Cu8L8 cage with a tubular structure, which was synthesized by the assembly of copper metalloligands and PdII ions in a stepwise manner. The Pd4Cu8L8 cage has been unequivocally characterized by single-crystal X-ray diffraction, electrospray ionization-mass spectroscopy, and energy dispersive spectroscopy. The cage showed excellent catalytic activity in the epoxidation of styrene and its derivatives under conditions without using additional solvent, providing potential material for catalyzing the oxidation reactions.