Cellular models of stress resistance may pave ways to fight neurodegenerative diseases

Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron demise.The entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to neurodegeneration.Interestingly,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.

Aggresome-aggrephagy transition process:geting closer to the functional roles of HDAC6 and BAG3

Misfolding of proteins as well as their aggregation is a major driver of age-related neurodegenerative diseases.Hence,cells have evolved sophisticated protein quality control mechanisms.Mainly the ubiquitin-proteasome-system(UPS)and the autophagosome-lysosome-system,specifically a macroautophagy pathway called“aggrephagy”,govern the disposal of aggregates.However.

Entropy‑Conservative Discontinuous Galerkin Methods for the Shallow Water Equations with Uncertainty

In this paper,we develop an entropy-conservative discontinuous Galerkin(DG)method for the shallow water(SW)equation with random inputs.One of the most popular methods for uncertainty quantifcation is the generalized Polynomial Chaos(gPC)approach which we consider in the following manuscript.We apply the stochastic Galerkin(SG)method to the stochastic SW equations.Using the SG approach in the stochastic hyperbolic SW system yields a purely deterministic system that is not necessarily hyperbolic anymore.The lack of the hyperbolicity leads to ill-posedness and stability issues in numerical simulations.By transforming the system using Roe variables,the hyperbolicity can be ensured and an entropy-entropy fux pair is known from a recent investigation by Gerster and Herty(Commun.Comput.Phys.27(3):639–671,2020).We use this pair and determine a corresponding entropy fux potential.Then,we construct entropy conservative numerical twopoint fuxes for this augmented system.By applying these new numerical fuxes in a nodal DG spectral element method(DGSEM)with fux diferencing ansatz,we obtain a provable entropy conservative(dissipative)scheme.In numerical experiments,we validate our theoretical fndings.

New High-Order Numerical Methods for Hyperbolic Systems of Nonlinear PDEs with Uncertainties

In this paper,we develop new high-order numerical methods for hyperbolic systems of nonlinear partial differential equations(PDEs)with uncertainties.The new approach is realized in the semi-discrete finite-volume framework and is based on fifth-order weighted essentially non-oscillatory(WENO)interpolations in(multidimensional)random space combined with second-order piecewise linear reconstruction in physical space.Compared with spectral approximations in the random space,the presented methods are essentially non-oscillatory as they do not suffer from the Gibbs phenomenon while still achieving high-order accuracy.The new methods are tested on a number of numerical examples for both the Euler equations of gas dynamics and the Saint-Venant system of shallow-water equations.In the latter case,the methods are also proven to be well-balanced and positivity-preserving.

Confucius and American Democracy

UPON the establishment of European universities in the Middle Ages,the educational system in Western countries became characterized by an essentially Eurocentric worldview.This was reflected in the study of Latin and Greek in high school,and in basing public life and political systems on philosophies of classical antiquity.The work of the influential Chinese philosopher Confucius(551-479 B.C.),a near-contemporary of the major Greek philosophers Socrates(469-399 B.C.),Plato(428-348 B.C.)and Aristotle(384-322 B.C.),whose ethical and political ideas entered into the constitutions of European states,remained unknown.

Exploring International Media and Information Literacy Initiatives: Insights From DW Akademie’s MIL Model

Media and Information Literacy(MIL)is one of the most important topics in today’s mediatized world.Under the leadership of United Nations Educational,Scientific and Cultural Organization(UNESCO),many international organizations in the world,as foreign donors,annually announce many projects and grants for the promotion and development of the field of MIL in the countries of the world.One of the main actors of this movement is DW Akademie with different media and MIL projects several countries of the world.This research paper delves into the role of DW Akademie’s MIL model in shaping a media-savvy generation.The study explores the theoretical underpinnings and practical applications of Deutsche Welle(DW)Akademie’s MIL model,analysing its effectiveness in fostering media literacy skills.The research employs a multi-faceted approach,incorporating case studies to assess the model’s impact across diverse demographics.The paper also considers the model’s alignment with global educational policies and proposes recommendations for its integration into broader frameworks.By investigating DW Akademie’s MIL model,this research contributes to the ongoing discourse on media literacy education,providing valuable insights for educators,policymakers,and researchers.The findings offer a nuanced understanding of the model’s position in cultivating a media-savvy generation poised to navigate the complexities of the information age.

Unlocking the decomposition limitations of the Li2C2O4 for highly efficient cathode preliathiations

The development of high-energy-density Li-ion batteries is hindered by the irreversible capacity loss during the initial charge-discharge process.Therefore,pre-lithiation technology has emerged in the past few decades as a powerful method to supplement the undesired lithium loss,thereby maximizing the energy utilization of LIBs and extending their cycle life.Lithium oxalate(Li_(2)C_(2)O_(4)),with a high lithium content and excellent air stability,has been considered one of the most promising materials for lithium compensation.However,the sluggish electrochemical decomposition kinetics of the material severely hinders its further commercial application.Here,we introduce a recrystallization strategy combined with atomic Ni catalysts to modulate the mass transport and decomposition reaction kinetics.The decomposition potential of Li_(2)C_(2)O_(4)is significantly decreased from~4.90V to~4.30V with a high compatibility with the current battery systems.In compared to the bare NCM//Li cell,the Ni/N-rGO and Li_(2)C_(2)O_(4)composite(Ni-LCO)modified cell releases an extra capacity of~11.7%.Moreover,this ratio can be magnified in the NCM//SiOx full cell,resulting in a 30.4%higher reversible capacity.Overall,this work brings the catalytic paradigm into the pre-lithiation technology,which opens another window for the development of high-energy-density battery systems.

贝叶斯因子及其在JASP中的实现

统计推断在科学研究中起到关键作用,然而当前科研中最常用的经典统计方法——零假设检验(Null hypothesis significance test,NHST)却因难以理解而被部分研究者误用或滥用。有研究者提出使用贝叶斯因子(Bayes factor)作为一种替代和(或)补充的统计方法。贝叶斯因子是贝叶斯统计中用来进行模型比较和假设检验的重要方法,其可以解读为对零假设H_0或者备择假设H_1的支持程度。其与NHST相比有如下优势:同时考虑H_0和H_1并可以用来支持H_0、不"严重"地倾向于反对H_0、可以监控证据强度的变化以及不受抽样计划的影响。目前,贝叶斯因子能够很便捷地通过开放的统计软件JASP实现,本文以贝叶斯t检验进行示范。贝叶斯因子的使用对心理学研究者来说具有重要的意义,但使用时需要注意先验分布选择的合理性以及保持数据分析过程的透明与公开。

Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC patients were submitted to surgery (log-odds, ADC: -2.1206 ± 0.6249 vs SCC: 4.1356 ± 0.4038, P < 0.05). The odds for re-classification of tumor stage after endoscopic resection were 53% and 39% for ADC and SCC, respectively. Local tumor recurrence was best predicted by grade 3 differentiation and piecemeal resection, metachronous cancer development by the carcinoma in situ component, and lymph node positivity by lymphovascular invasion. With regard to surgically resected patients: Significant differences in patients with positive lymph nodes were observed between ADC and SCC [coefficient: 1.889569, 95%CI: (0.3945146, 3.384624), P<0.01). In contrast, lymphovascular and microvascular invasion and grade 3 patients between histologic types were comparable, the respective rank order of the predictors of lymph node positivity was: Grade 3, lymphovascular invasion (L+), microvascular invasion (V+), submucosal (Sm) 3 invasion, Sm2 invasion and Sm1 invasion. Histologic type (ADC/SCC) was not included in the model. The best predictors for SCC lymph node positivity were Sm3 invasion and (V+). For ADC, the most important predictor was (L+). CONCLUSION: Local tumor recurrence is predicted by grade 3, metachronous cancer by the carcinoma insitu component, and lymph node positivity by L+. T1b cancer should be treated with surgical resection.

High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells

AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction（RT-PCR） after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectalcancer samples, mucosa samples and diverse cancercell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo.RESULTS： HoxA7, HoxB8, HoxC8 and HoxD8 wererestricted by miR-196a in a dose-dependent andgene-specific manner. High levels of miR-196aactivated the AKT signaling pathway as indicated byincreased phosphorylation of AKT. In addition, highlevels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towardsplatin derivatives but did not impact on proliferationor apoptosis. Furthermore, miR-196a increased thedevelopment of lung metastases in mice after tail veininjection.

Genetics of hepatocellular carcinoma

The completely assembled human genome has made it possible for modern medicine to step into an era rich in genetic information and high-throughput genomic analysis. These novel and readily available genetic resources and analytical tools may be the key to unravel the molecular basis of hepatocellular carcinoma (HCC). Moreover, since an efficient treatment for this disease is lacking, further understanding of the genetic background of HCC will be crucial in order to develop new therapies aimed at selected targets. We report on the current status and recent developments in HCC genetics. Special emphasis is given to the genetics and regulation of major signalling pathways involved in HCC such as p53, Wnt- signalling, TGFβ, Ras, and Rb pathways. Furthermore, we describe the influence of chromosomal aberrations as well as of DNA methylation. Finally, we report on the rapidly developing field of genomic expression profiling in HCC, mainly by microarray analysis.

Biotechnology Applications of Plant Callus Cultures

In ethnopharmacology, and especially in traditional Chinese medicine, medicinal plants have been used for thousands of years. Similarly, agricultural plants have been used throughout the history of mankind. The recent development of the genetic engineering of plants to produce plants with desirable features adds a new and growing dimension to humanity’s usage of plants. The biotechnology of plants has come of age and a plethora of bioengineering applications in this context have been delineated during the past few decades. Callus cultures and suspension cell cultures offer a wide range of usages in pharmacology and pharmacy (including Chinese medicine), as well as in agriculture and horticulture. This review provides a timely overview of the advancements that have been made with callus cultures in these scientific fields. Genetically modified callus cultures by gene technological techniques can be used for the synthesis of bioactive secondary metabolites and for the generation of plants with improved resistance against salt, draft, diseases, and pests. Although the full potential of callus plant culture technology has not yet been exploited, the time has come to develop and market more callus culture-based products.

Multidisciplinary management of gastric and gastroesophageal cancers

Carcinomas of the stomach and gastroesophageal junction are among the five top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer, surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer （UICC） stages in Western countries because of the high risk of recurrence and metachronous metastases. However, recent large phase-Ⅲ studies improved the diagnostic and therapeutic options in gastric cancers, indicating a more multidisciplinary management of the disease. Multimodal strategies combining different neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular, the perioperative （neoadjuvant, adjuvant） chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection, mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastroesophageal cancer, and discusses future strategies toimprove Iocoregional failures.

Update on autoimmune hepatitis

Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features,hyperglobulinemia (IgG),and the presence of circulating autoantibodies,as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years,a couple of new insights into the genetic aspects,clinical course and treatment of AIH have been reported,which will be the focus of this review. In particular,we concentrate on genome-wide microsatellite analysis,a novel mouse model of AIH,the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH,and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab

AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metastases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab.

Type 1 diabetes and polyglandular autoimmune syndrome: A review

Type 1 diabetes(T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1 D as a monoglandular disease and the relation to polyglandular autoimmune syndrome(PAS) have also been wellexplored. The incidence of T1 D has steadily increased in most parts of the world, especially in industrialized nations. T1 D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1 D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterialinduced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type Ⅲ, which encompasses T1 D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1 D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome.

变量间的网络分析模型及其应用

变量间的网络分析模型近年来被广泛应用于心理学研究。不同于将潜变量作为观测变量的共同先导因素的潜变量模型,网络分析模型将观测变量作为初级指标,采用图论的方法建立观测变量之间的关系网络,其中变量为网络的节点,而变量间的关系是节点之间的连线。因此网络分析可以突显观测变量之间的联系以及观测变量相互影响而形成的系统。通过变量网络中基于各个节点特征的指标(如中心性)以及基于整体结构特征的指标(如小世界性),网络分析为研究各种心理现象提供了新的可视化的描述方式和理解视角。近10年来,网络分析的方法已在人格心理学、社会心理学和临床心理学等领域得到一定的应用。未来研究应继续发展和完善网络分析模型的理论和方法,使之运用到更多的数据类型和更广的研究领域中。

Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors

To review the implication of CXCR4 for gastrointestinal cancer, a ＂Pubmed＂ analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were ＂cancer, malignoma, esophageal, gastric, colon, colorectal, hepatic, pancreatic, CXCR4, SDF- 1α, and SDF-1β＂. CXCR4 expression correlated with dissemination of diverse gastrointestinal malignomas. The CXCR4 ligand SDF-1α might act as ＂chemorepellent＂ while SDF-1β might act as ＂chemorepellent＂ for CTLs, inducing tumor rejection. The paracrine expression of SDF-1α was furthermore closely associated with neoangiogenesis. CXCR4 and its ligands influence the dissemination, immune rejection, and neoangiogenesis of human gastrointestinal cancers. Inhibition of CXCR4 might be an interesting therapeutic option.

Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?

AIM： To define the （co-）expression pattern of target receptor-tyrosine-kinases （RTK） in human gastric adenocarcinoma. METHODS： The （co-）expression pattern of VEGFR1-3, PDGFR（α/β and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS： The majority of samples revealed a VEGFR1 （98%）, VEGFR2 （80%）, VEGFR3 （67%）, PDGFRα （82%） and PDGFRβ （82%） expression, whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells, accompanied by an additional nuclear staining for VEGFR3, EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes, which also depicted a PDGFRα expression. CONCLUSION： Our results reveal a high rate ofreceptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy.

Hepatocellular carcinoma in patients with autoimmune hepatitis

AIM: To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare. METHODS: In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH. RESULTS: Eighty-nine patients (32%) were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded. CONCLUSION: We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer.