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BackgroundThe preservation of the Lingguizhugan (LGZG) decoction and patient compliance issue often limit the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Hence, herein, an LGZG oral solution was developed for alleviating MASLD. Additionally, the potential mechanisms underlying LGZG-mediated MASLD mitigation were explored.MethodsA MASLD mouse model was constructed using oleic and palmitic acid-induced LO2 cells and a high-fat diet. The apoptosis, lipid deposition, and mouse liver function were analyzed to assess the therapeutic effects of the LGZG oral solution on MASLD. Serum untargeted metabolomics, gut microbiota, bile acid (BA) metabolism, immunohistochemistry, and Western blotting analyses were performed to investigate the potential mechanism of action of LGZG oral solution on MASLD.ResultsThe LGZG oral solution ameliorated lipid deposition, oxidative stress, inflammation, and pathological damage. Serum untargeted metabolomics results revealed the LGZG-mediated regulation of the primary BA biosynthetic pathway. The 16S ribosomal RNA sequencing of the fecal microbiota showed that LGZG oral solution increased the relative abundance of the BA metabolism-associated Bacteroides, Akkermansia, and decreased that of Lactobacillus. Additionally, the BA metabolism analysis results revealed a decrease in the total taurine-α/β-muricholic acid levels, whereas those of deoxycholic acid were increased, which activated specific receptors in the liver and ileum, including farnesoid X receptor (FXR) and takeda G protein-coupled receptor 5 (TGR5). Activation of FXR resulted in an increase in short heterodimer partner and subsequent inhibition of cholesterol 7α-hydroxylase and sterol regulatory element-binding protein-1c expression, and activation of FXR also results in the upregulation of fibroblast growth factor 15/19 expression, and consequently inhibition of cholesterol 7α-hydroxylase, which correlated with hepatic BA synthesis and lipogenesis, ultimately attenuating lipid deposition and bile acid stasis, thereby improving MASLD.ConclusionAltogether, the findings of this study suggest that modulating microbiota–BA–FXR/TGR5 signaling pathway may be a potential mechanism of action of LGZG oral solution for the treatment of MASLD.

Abstract Background The high invasiveness and infiltrative nature of Glioblastoma (GBM) pose significant challenges for surgical removal. This study aimed to investigate the role of KCNA1 in GBM progression. Methods CCK8, colony formation assay, scratch assay, transwell assay, and 3D tumor spheroid invasion assays were to determine how KCNA1 affects the growth and invasion of GBM cells. Subsequently, to confirm the impact of KCNA1 in ferroptosis, western blot, transmission electron microscopy and flow cytometry were conducted. To ascertain the impact of KCNA1 in vivo, patient-derived orthotopic xenograft models were established. Results In functional assays, KCNA1 promotes the growth and invasion of GBM cells. Besides, KCNA1 can increase the expression of SLC7A11 and protect cells from ferroptosis. The vivo experiments demonstrated that knocking down KCNA1 inhibited the growth and infiltration of primary tumors in mice and extended survival time. Conclusion Therefore, our research suggests that KCNA1 may promote tumor growth and invasion by upregulating the expression of SLC7A11 and inhibiting ferroptosis, making it a promising therapeutic target for GBM.

BackgroundMicroRNAs (miRNAs) have pivotal roles in gene regulation. Circulating miRNAs have been developed as novel candidate non-invasive biomarkers for diagnosis, prognosis, and treatment response for diseases. However, miRNAs that have causal effects on Parkinson’s Disease (PD) remain largely unknown. To investigate the causal relationships between miRNAs and PD, here we conduct a Mendelian randomization (MR) study.MethodsThis study utilized the summary-level data of respective genome-wide association studies (GWAS) for 2083 miRNAs and seven PD-related outcomes to comprehensively reveal the causal associations between the circulating miRNAs and PD. Two-sample MR design was deployed and the causal effects were estimated with inverse variance weighted, MR-Egger, and weighted median. Comprehensively sensitive analyses were followed, including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis, to validate the robustness of our results. Finally, we investigated the potential role of the MR significant miRNAs by predicting their target genes and functional enrichment analysis.ResultsInverse variance weighted estimates suggested that two miRNAs, miR-205-5p (β = −0.46, 95%CI: −0.690 to −0.229, p = 9.3 × 10−5) and miR-6800-5p (β = −0.389, 95%CI: −0.575 to −0.202, p = 4.32 × 10−5), significantly decreased the rate of cognitive decline among PD patients. In addition, eight miRNAs were nominally associated with more than three PD-related outcomes each. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. Gene Ontology (GO) analysis showed that the targets of these causal miRNAs were significantly enriched in cell cycle, apoptotic, and aging pathways.ConclusionThis MR study identified two miRNAs whose genetically regulated expression might have a causal role in the development of PD dementia. Our findings provided potential miRNA biomarkers to make better and early diagnoses and risk assessments of PD.

Abstract Background The intra‐ and inter‐tumoral heterogeneity of gliomas and the complex tumor microenvironment make accurate treatment of gliomas challenging. At present, research on gliomas mainly relies on cell lines, stem cell tumor spheres, and xenotransplantation models. The similarity between traditional tumor models and patients with glioma is very low. Aims In this study, we aimed to address the limitations of traditional tumor models by generating patient‐derived glioma organoids using two methods that summarized the cell diversity, histological features, gene expression, and mutant profiles of their respective parent tumors and assess the feasibility of organoids for personalized treatment. Materials and Methods We compared the organoids generated using two methods through growth analysis, immunohistological analysis, genetic testing, and the establishment of xenograft models. Results Both types of organoids exhibited rapid infiltration when transplanted into the brains of adult immunodeficient mice. However, organoids formed using the microtumor method demonstrated more similar cellular characteristics and tissue structures to the parent tumors. Furthermore, the microtumor method allowed for faster culture times and more convenient operational procedures compared to the Matrigel method. Discussion Patient‐derived glioma organoids, especially those generated through the microtumor method, present a promising avenue for personalized treatment strategies. Their capacity to faithfully mimic the cellular and molecular characteristics of gliomas provides a valuable platform for elucidating tumor biology and evaluating therapeutic modalities. Conclusion The success rates of the Matrigel and microtumor methods were 45.5% and 60.5%, respectively. The microtumor method had a higher success rate, shorter establishment time, more convenient passage and cryopreservation methods, better simulation of the cellular and histological characteristics of the parent tumor, and a high genetic guarantee.

BackgroundThis study investigates the complex interplay between Intrapreneurial Self Capital, Cultural Intelligence, and gender, and their collective influence on the flourishing of Chinese international students in foreign academic settings. As global interconnectivity intensifies, the increasing number of Chinese students seeking education abroad presents a unique opportunity to examine the psychological and sociocultural dynamics of this demographic.AimCentral to our investigation is the role of Cultural Intelligence, a crucial competency for navigating diverse environments, and Intrapreneurial Self Capital, a composite of psychological resources instrumental in educational and career success. The study also explores the mediating role of Cultural Intelligence in the relationship between Intrapreneurial Self Capital and student flourishing, and examines how gender moderates this dynamic.MethodThe research engaged 508 Chinese international students, utilizing a variety of social networks for participant recruitment. The survey, conducted via Qualtrics, focused on a diverse range of students across different educational levels and disciplines. A moderated mediation model was tested to examine the mediation effect of cultural intelligence on the relationship between intrapreneurial self-capital and flourishing, with gender serving as a moderating variable.ResultsOur findings reveal significant insights into how Intrapreneurial Self Capital and Cultural Intelligence contribute to the personal and professional development of Chinese international students. Overall, the results suggest that the impact of Intrapreneurial Self Capital on various cognitive qualities (Metacognitive Cultural Intelligence, Cognitive Cultural Intelligence, Motivational Cultural Intelligence and Behavioral Cultural Intelligence) is moderated by gender, highlighting the importance of considering gender differences in this context. Related to the prediction of Flourishing, the direct effect of Intrapreneurial Self Capital on flourishing is notably strong. However, the mediating roles of Metacognitive, Cognitive, and Behavioral aspects of Cultural Intelligence show different levels of influence.ImplicationsThe study underscores the need for educational institutions to adopt holistic approaches in fostering student well-being and success, accounting for the nuanced effects of cultural and gender dynamics. These results have significant implications for the development of targeted educational programs and training, aimed at enhancing the international educational experience for students and professionals.

Abstract Background Sex-related differences in cancer epidemiology, tumor biology, immune system activity, and pharmacogenomics have been suggested to be important considerations for precision cancer control. Here we elucidated systematically sex biases in genetic variants, gene expression profiles, and immunological landscapes of lung adenocarcinoma patients (LUADs) with different ancestry and smoking status. Methods Somatic mutation and mRNA expression data of Asian and Non-Asian LUADs were obtained from public databases. Sex-biased genetic mutations, gene expression, biological pathways, and immune infiltration were identified in the context of smoking status and race. Results Among nonsmokers, male-biased mutations were prevalent in Asian LUADs, while few sex-biased mutations were detected in Non-Asian LUADs. EGFR was the only mutation whose frequency was significantly higher in females than males in both Asian and Non-Asian nonsmokers. More genes exhibited sex-biased expression in Non-Asian LUADs compared to Asian LUADs. Moreover, genes distinctly expressed in females were mainly related to immune-related pathways, whereas those in males were more involved in activation of DNA repair, E2F_targets, and MYC_targets pathways. We also detected sex-specific immune infiltration in the context of genetic variation. In EGFR-mutant LUADs, males had a significantly increased infiltration of CD8 + T cells, whereas resting CD4 + memory T cells were more abundant in females. Additionally, in KRAS-mutant LUADs, CD8 + and CD4 + T cells were more abundant in females than males. In addition, we detected all female patients with high SCGB3A2 expression were exclusively sensitive to immunotherapy, while this phenomenon was not observed in male patients. Conclusions Our findings provided evidence that sex-related molecular and cellular components are involved in shaping tumor distinct genetic and immune features, which might have important impact on personalized targeted and immune therapy.

Abstract Introduction The activation of STING (stimulator of interferon genes) pathway enhances antitumor immunity in small‐cell lung cancer (SCLC), while the DNA damage induced by non‐cGAMP‐based agonists is a potent inducer of STING activity. Here, we investigate the intrinsic expression of STING in cancer cells and evaluate the value of the combination of ATR and TOP1 inhibitors in enhancing antitumor immunity. Methods STING expression was assessed at mRNA and protein levels in SCLC and normal lung tissues. Transcriptomic subsets of SCLC were identified based on STING‐related genes. Distinct mutation and immunogenomic profiles of these subsets were determined. The direct antitumor efficacy and the potential of enhancing antitumor immunity of the strategy using the ATR‐TOP1‐inhibitor combination were tested in SCLC cell lines. Results The intrinsic expression of STING was significantly reduced in SCLC compared to normal lung tissues (p

Abstract Glioma stem cells (GSCs) are the important cause of tumorigenesis, recurrence, and chemo(radio)resistance in glioma. Targeting GSCs helps improve the outcomes of glioma treatment. Polo-like kinase 1 (PLK1) is a member of the serine/threonine protein kinase family, which is highly conserved. In recent years, it has been suggested that increased levels of PLK1 and its activity are associated with tumor progression and poor prognosis. We aimed to identify whether PLK1 plays a critical role in stemness maintenance and apoptosis regulation in GSCs. Here we identify that PLK1 inhibition can induce apoptosis and DNA damage of GSCs, we have also delineat the possible underlying molecular mechanisms: PLK1 interacts with YBX1 and directly phosphorylates serine 174 and serine 176 of YBX1. Inhibition of PLK1 reduces the phosphorylation level of YBX1, and decreased phosphorylation of YBX1 prevents its nuclear translocation, thereby inducing apoptosis and DNA damage of GSCs. We confirmed that YBX1 knockdown resulted in the apoptosis and DNA damage of GSCs. These findings uncover that PLK1 inhibition induces cell apoptosis and DNA damage in GSCs through YBX1 phosphorylation, providing new insights into the mechanism by which PLK1 inhibition contributes to the apoptosis of and DNA damage in gliomas.

IntroductionTranscatheter aortic valve replacement (TAVR) is the first-line treatment for patients with moderate-to-high surgical risk of severe aortic stenosis. Paravalvular leakage (PVL) is a serious complication of TAVR, and aortic valve calcification contributes to the occurrence of PVL. This study aimed to investigate the effect of location and quantity of calcification in the aortic valve complex (AVC) and left ventricular outflow tract (LVOT) on PVL after TAVR.MethodWe performed a systematic review and meta-analysis to evaluate the effect of quantity and location of aortic valve calcification on PVL after TAVR using observational studies from PubMed and EMBASE databases from inception to February 16, 2022.ResultsTwenty-four observational studies with 6,846 patients were included in the analysis. A high quantity of calcium was observed in 29.6% of the patients; they showed a higher risk of significant PVL. There was heterogeneity between studies (I2 = 15%). In the subgroup analysis, PVL after TAVR was associated with the quantity of aortic valve calcification, especially those located in the LVOT, valve leaflets, and the device landing zone. A high quantity of calcium was associated with PVL, regardless of expandable types or MDCT thresholds used. However, for valves with sealing skirt, the amount of calcium has no significant effect on the incidence of PVL.ConclusionOur study elucidated the effect of aortic valve calcification on PVL and showed that the quantity and location of aortic valve calcification can help predict PVL. Furthermore, our results provide a reference for the selection of MDCT thresholds before TAVR. We also showed that balloon-expandable valves may not be effective in patients with high calcification, and valves with sealing skirts instead of those without sealing skirts should be applied more to prevent PVL from happening.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354630, identifier: CRD42022354630.

In this article, we construct an evaluation index system based on the DPSIRM framework to determine the water resources carrying capacity of Shiyan City. Then, we use an obstacle model to calculate and analyze the factors that constrain the improvement in the water resources carrying capacity in the city. The research results are as follows: (1) The water resources carrying capacity of Shiyan City was on the rise during 2011–2021, and the water resources carrying capacity of Shiyan City was continuously improved. (2) The management system is the primary obstacle subsystem, followed by the driving force system, the response system, the pressure system, the state system, and the influence system. (3) Among the specific factors, the top three obstacles are sewage treatment investment, the proportion of guaranteed harvest area in drought and flood, and the average annual fertilizer applied per unit of cultivated land. These primary factors restrict Shiyan City from improving its water resources carrying capacity. This study has important practical significance for understanding the resilience of the water system in Shiyan City; exploring the changes in the water resources carrying capacity and its obstacle factors; and guiding the development, utilization, and management of water resources in Shiyan City.

Abstract We determined the antitumor mechanism of apatinib in glioma using a patient-derived orthotopic xenograft (PDOX) glioma mouse model and glioblastoma (GBM) cell lines. The PDOX mouse model was established using tumor tissues from two glioma patients via single-cell injections. Sixteen mice were successfully modeled and randomly divided into two equal groups (n = 8/group): apatinib and normal control. Survival analysis and in vivo imaging was performed to determine the effect of apatinib on glioma proliferation in vivo. Candidate genes in GBM cells that may be affected by apatinib treatment were screened using RNA-sequencing coupled with quantitative mass spectrometry, data mining of The Cancer Genome Atlas, and Chinese Glioma Genome Atlas databases, and immunohistochemistry analysis of clinical high-grade glioma pathology samples. Quantitative reverse transcription-polymerase chain reaction (qPCR), western blotting, and co-immunoprecipitation (co-IP) were performed to assess gene expression and the apatinib-mediated effect on glioma cell malignancy. Apatinib inhibited the proliferation and malignancy of glioma cells in vivo and in vitro. Thrombospondin 1 (THBS1) was identified as a potential target of apatinib that lead to inhibited glioma cell proliferation. Apatinib-mediated THBS1 downregulation in glioma cells was confirmed by qPCR and western blotting. Co-IP and mass spectrometry analysis revealed that THBS1 could interact with myosin heavy chain 9 (MYH9) in glioma cells. Simultaneous THBS1 overexpression and MYH9 knockdown suppressed glioma cell invasion and migration. These data suggest that apatinib targets THBS1 in glioma cells, potentially via MYH9, to inhibit glioma cell malignancy and may provide novel targets for glioma therapy.

Abstract Background Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a short median overall survival. Effective induction of GBM cell death is difficult because the GBM cell population is genetically unstable, resistant to chemotherapy and highly angiogenic. In recent studies, ubiquitin-specific protease 7 (USP7) is shown to scavenge ubiquitin from oncogenic protein substrates, so effective inhibition of USP7 may be a potential key treatment for GBM. Methods Immunohistochemistry and western blotting were used to detect the expression of USP7 in GBM tissues. In vitro apoptosis assay of USP7 inhibition was performed by western blotting, immunofluorescence, and flow cytometry. Anti-apoptotic substrates of USP7 were defined by Co-IP and TMT proteomics. Western blotting and IP were used to verify the relationship between USP7 and its substrate. In an in vivo experiment using an intracranial xenograft model in nude mice was constructed to assess the therapeutic effect of target USP7. Results Immunohistochemistry and western blotting confirmed that USP7 was significantly upregulated in glioblastoma samples. In in vitro experiments, inhibition of USP7 in GBM induced significant apoptosis. Co-IP and TMT proteomics identified a key anti-apoptotic substrate of USP7, ADP-ribosylation factor 4 (ARF4). Western blotting and IP confirmed that USP7 interacted directly with ARF4 and catalyzed the removal of the K48-linked polyubiquitinated chain that binded to ARF4. In addition, in vivo experiments revealed that USP7 inhibition significantly suppressed tumor growth and promoted the expression of apoptotic genes. Conclusions Targeted inhibition of USP7 enhances the ubiquitination of ARF4 and ultimately mediates the apoptosis of GBM cells. In a clinical sense, P5091 as a novel specific inhibitor of USP7 may be an effective approach for the treatment of GBM.

Abstract Background Beckwith–Wiedemann syndrome (BWS) is an inherited disorder affecting 1 in 10,500 to 13,700 newborns worldwide. The disease is caused in a vast majority of patients by a molecular defect in the imprinted chromosome 11p15.5. Hereditary spherocytosis (HS) is a form of hemolytic anemia associated with a variety of mutations leading to congenital red blood cell (RBC) membrane defects. The prevalence of HS varies by geographic regions around the world, ranging from 1.2 in 100,000 in Asia to 1 in 2000 in Northern Europe. Methods and Results Herein, we report for the first time a rare case diagnosed with co‐existing BWS and HS. Based on the classical presentations, including macroglossia, hepatosplenomegaly, and macrosomia, the patient was first suspected with BWS. MS‐MLPA confirmed the BWS diagnosis based on hypomethylation of maternal 11p15.5 (KCNQ1OT1), but no copy number variations in chromosome 11 was detected by CNV‐seq. Nevertheless, to scrutinize molecular causes of other symptoms of the patient, including anemia, hyperbilirubinemia, and jaundice, a whole exome sequencing (WES) was performed. We identified a novel and de novo mutation in ANK1 gene (c.520delC). This frameshift mutation of ANK1 gene results in a truncated protein without important functional domains and impaired membrane stability and structure of the resultant red blood cells (RBCs), leading to a definitive diagnosis of HS. Conclusion The present case demonstrated that multiple genetic and epigenetic aberrations might co‐exist in the complex genetic diseases. For such kind of complicated cases, the different types of molecular tests, such as WES and MS‐MLPA, should be utilized in combination to reveal independent causal molecular events. The identifications from this study added new insights into the understanding of molecular mechanisms underlying the co‐existing HS and BWS.

Abstract Early detection and diagnosis are the key to successful clinical management of pancreatic cancer and improve the patient outcome. However, due to the absence of early symptoms and the aggressiveness of pancreatic cancer, its 5-year survival rate remains below 5 %. Compared to tissue samples, liquid biopsies are of particular interest in clinical settings with respect to minimal invasiveness, repeated sampling, complete representation of the entire or multi-site tumor bulks. The potential of liquid biopsies in pancreatic cancer has been demonstrated by many studies which prove that liquid biopsies are able to detect early emergency of pancreatic cancer cells, residual disease, and recurrence. More interestingly, they show potential to delineate the heterogeneity, spatial and temporal, of pancreatic cancer. However, the performance of liquid biopsies for the diagnosis varies largely across different studies depending of the technique employed and also the type and stage of the tumor. One approach to improve the detect performance of liquid biopsies is to intensively inspect circulome and to define integrated biomarkers which simultaneously profile circulating tumor cells and DNA, extracellular vesicles, and circulating DNA, or cell free DNA and proteins. Moreover, the diagnostic validity and accuracy of liquid biopsies still need to be comprehensively demonstrated and validated.

With the rapid development of technologies such as big data, intelligent data analysis and cloud computing, the application of Internet financial technology has become more and more extensive, and with the advent of the era of large asset management in the domestic wealth management industry, in order to improve the efficiency of financial services, traditional finance is needed. The products and services provided by the industry have been innovated, resulting in smart investment. Compared with traditional investment, smart investment as a new business model has the advantages of low threshold, low cost and high efficiency. However, as far as its nature is concerned, smart investment must first play the role of an investment adviser. Therefore, for enterprises or individuals who invest, the investment efficiency of smart investment is the most important. At present, the research on the efficiency analysis of smart investment, due to the improper selection of algorithm models or the lack of deep data mining, leads to the analysis of the investment efficiency of smart investment products is inconsistent with or even deviated from the actual situation. In view of these problems, this paper selects China Merchants Bank's Capricorn Intelligence as the research object, and analyzes the investment efficiency of smart investment based on K-means cluster analysis and data mining technology. The results show that Capricorn has a certain randomness in the selection process of the fund, and chooses to reduce the rate of return in order to control the risk. The investment portfolio formulated for the customer has obvious timing. The results show that the machine learning based on K-means algorithm makes a concrete analysis of the investment efficiency of Capricorn Smart Investment, this method can also be used for the efficiency analysis of other smart investment products.

The benefit of cultivated land use is an essential indicator for measuring the optimal allocation of cultivated land resources and the high-quality development of agriculture. Taking Shiyan City, Xiangyang City, and Suizhou City in Northern Hubei as the research objects, this paper presents an evaluation index system for cultivated land use efficiency from the perspectives of ecology, economy, and society. The entropy TOPSIS method and the obstacle degree model were applied to estimate the cultivated land use efficiency and identify obstacle factors in the three study areas from 2010 to 2020, and the results were as follows. (1) The comprehensive benefit level of cultivated land utilization in Northern Hubei showed an upward trend, and the individual benefit levels of cultivated land utilization in different cities were significantly different. Xiangyang City had outstanding economic performance, Shiyan City had the fastest growth rate of ecological benefits, and various benefits of Suizhou City were “steady”. (2) The fluctuation ranges of the obstacle factors for cultivated land use were relatively large in the Northern Hubei region. From 2010 to 2016, the effective irrigation index, land-averaged fertilizer input level, agricultural input–output ratio, and per capita income of farmers were the main factors restricting the improvement of cultivated land utilization efficiency in Northern Hubei. During 2017–2020, the per capita pesticide input level, per capita grain output, forest coverage rate, land output rate, and agricultural mechanization efficiency became the main obstacles restricting the improvement of cultivated land-use efficiency. (3) All cities of Northern Hubei should take measures according to local conditions, implement specific policies to address the restrictive factors of cultivated land use, improve the level of cultivated land-use benefit in the region, and promote the coordination and unity of the economic, ecological, and social benefits of cultivated land use.

Abstract Background Cancer‐specific autoantibodies found in serum of cancer patients have been characterized as potential predictors of the high risk of recurrence and treatment response. The objective of this study is to investigate the clinical utility of serum O‐6‐methylguanine‐DNA methyltransferase (MGMT) autoantibodies as novel biomarkers for prediction of recurrence and treatment response for glioma through MGMT peptides microarray. Methods A total of 201 serum samples of glioma patients with various WHO grade and 311 serum samples of healthy donors were examined for the detection of MGMT autoantibodies by peptides microarray. The clinical value of MGMT autoantibodies was studied through univariable and multivariable analyses. Results Autoantibodies to MGMT peptides were detected in sera from glioma patients and five highly responsive autoantibodies to peptides were identified in the glioma group. The positive rate of MGMT autoantibody to 20 peptides in glioma groups is compared with healthy individuals, the positive rate of MGMT‐02 (45%), MGMT‐04 (27%), MGMT‐07 (21%), MGMT‐10 (13%), and MGMT‐18 (24%) were significantly elevated in patients with glioma. MGMT autoantibody and its protein expression exhibited a significant correlation. The levels of MGMT autoantibodies decreased on the 30th day after operation, reaching preoperative levels, similar to those when tumor recurrence developed. Univariable and multivariable analyses revealed that the only preoperative autoantibodies to MGMT‐02 peptide were independently correlated with recurrence‐free survival. Preoperative seropositive patients were more likely than seronegative patients to have shorter recurrence times and to be resistant to chemoradiotherapy or chemotherapy with temozolomide. Conclusion Monitoring the levels of preoperative serum autoantibodies to MGMT‐02 peptide was useful for predicting patients at high risk of recurrence and treatment response.

Abstract Bromodomain and extraterminal domain (BET) family proteins are considered to be epigenetic readers that regulate gene expression by recognizing acetyl lysine residues on histones and nonhistone chromatin factors and have been classified as curative targets for a variety of cancers. Glioma‐initiating cells (GICs), which commit self‐renewal, perpetual proliferation, multidirectional differentiation, and vigorous tumorigenicity, sustain the peculiar genetic and epigenetic diversification in the GBM patients, thus, GICs result in tumor recurrence. Abundant evidence demonstrates that BET proteins regulate differentiation of stem cells. However, it endures ambiguous how individual BET proteins take part in GIC advancement, and how do small molecule inhibitors like I‐BET151 target functional autonomous BET proteins. Here, we validated that BRD4, not BRD2 or BRD3, has value in targeted glioma therapy. We announce a signaling pathway concerning BRD4 and Notch1 that sustains the self‐renewal of GICs. Moreover, in‐depth mechanistic research showed that BRD4 was concentrated at the promoter region of Notch1 and may be involved in the process of tumor metabolism. Furthermore, in intracranial models, I‐BET151 eliminated U87 GICs’ tumorigenicity. The outcomes of this research could be conducive to design clinical trials for treatment of glioma based on BRD4.

Abstract Background Recently, minimal invasive surgery (MIS) has been applied as a common therapeutic approach for treatment of hypertensive intracerebral hemorrhage (HICH). However, the efficacy and safety of MIS is still controversial compared with conservative medical treatment or conventional craniotomy. This meta-analysis aimed to systematically assess the safety and efficacy of MIS compared with conservative method and craniotomy in treating HICH patients. Methods PubMed, Embase, Web of Science, and Cochrane Controlled Trials Register were used to identify relevant studies on MIS treatment of HICH up to November 2017. This study evaluated Glasgow Outcome Scale (GOS) score, Activities of Daily Living (ADL) score, pulmonary infection rate, mortality rate, and rebleeding rate for patients who underwent MIS, or conservative method, or craniotomy. Subgroup analyses were performed to compare randomization versus non-randomization and large hematoma versus small or mild hematoma. Begg’s test and Egger’s test were used to determine the potential presence of publication bias. Results Sixteen studies consisting of 1912 patients were included in this study to compare the efficacy and safety of MIS to conservative method or craniotomy. MIS contributed to a significant improvement on the prognosis of the patients comparing with conservative group or craniotomy group. Patients undergoing MIS had a lower mortality rate when compared to those receiving conservative method. Also, MIS led to a notable reduction of rebleeding rate and an effective improvement of the patient’s quality of life by contrast with craniotomy. No obvious difference was found in terms of the pulmonary infection rate among the comparisons of three treatment methods. Randomization is not the potential source of heterogeneity, but hematoma volume may be a risk factor for post-operative mortality rate. No statistical evidence of publication bias among studies was found under most of comparison models. Conclusion This meta-analysis suggests that minimal invasive surgery is an efficient and safe method for the treatment of hypertensive intracerebral hemorrhage, which is associated with a low mortality rate and rebleeding rate, as well as a significant improvement of the prognosis and the quality life of patients when compared with conservative medical treatment or craniotomy.

Improvement of the hot stamping process is important for reducing processing costs and improving the productivity and tensile properties of final components. One major approach to this has been to conduct all or part of the process at lower temperatures. The present paper reviews the state of the art of hot stamping techniques and their applications, considering the following aspects: (1) conventional hot stamping and its advanced developments; (2) warm stamping approaches in which complete austenitisation is not attained during heating; (3) hot stamping with a lower forming temperature, i.e., low-temperature hot stamping (LTHS); (4) advanced medium-Mn steels with lower austenitisation temperatures and their applicability in LTHS. Prospects for the further development of LTHS technology and the work required to achieve this are discussed.

Background: Glioblastoma multiforme (GBM), the most malignant tumor of the central nervous system, is characterized by poor survival and high recurrence. Glioma stem cells (GSCs) are key to treating GBM and are regulated by various signaling pathways. Ubiquitination, a post-translational modification, plays an important regulatory role in many biological processes. Ring finger protein 138 (RNF138) is an E3 ubiquitin-protein ligase that is highly expressed in several tumors; however, its role in GBM is unclear. This study investigated whether RNF138 regulates the self-renewal ability of glioma stem GSCs to treat GBM. Materials and Methods: The expression of RNF138 in glioma tissues and its correlation with GSCs were analyzed using bioinformatics. Short hairpin ribonucleic acid (RNA) was designed to downregulate the expression of RNF138 in GSCs, and immunofluorescence, secondary pellet formation, and western blotting were used to detect changes in GSC markers and self-renewal ability. The effects of RNF138 on p53 protein expression were determined by immunofluorescence and western blotting. The effects of RNF138 on the self-renewal and tumorigenic abilities of GSCs were evaluated in vivo. Results: RNF138 expression was higher in glioma tissues than in normal brain tissues, and was highly expressed in GSCs. RNF138 downregulation significantly decreased the expression of the GSC markers cluster of differentiation 133 (CD133) and nestin. Mechanistically, RNF138 may interfere with the self-renewal ability of GSCs by regulating the expression of p53. RNF138 downregulation in vivo prolonged survival time and regulated the expression of p53 protein in tumor-bearing mice. Conclusion: RNF138 may regulate the expression of p53 protein through ubiquitination, thereby affecting the self-renewal and tumorigenic ability of GSCs. This study provides a scientific basis for the treatment of glioblastoma by targeting RNF138 to inhibit GSCs. [ABSTRACT FROM AUTHOR]