bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Analysis and Identification of Key Driver Genes for Distinguishing Between Esophageal Adenocarcinoma and Squamous Cell Carcinoma
Authors: Wang Feng , Zhang Lan , Xu Yue , Xie Yilin , Li Shenglei
Published: May 2021

Background: Esophageal cancer (EC) is one of the deadliest cancers in the world. However, the mechanism that drives the evolution of EC is still unclear. On this basis, we identified the key genes and molecular pathways that may be related to the progression of esophageal adenocarcinoma and squamous cell carcinoma to find potential markers or therapeutic targets.

Methods: GSE26886 were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) among normal samples, EA, and squamous cell carcinoma were determined using R software. Then, potential functions of DEGs were determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The STRING software was used to identify the most important modules in the protein–protein interaction (PPI) network. The expression levels of hub genes were confirmed using UALCAN database. Kaplan–Meier plotters were used to confirm the correlation between hub genes and outcomes in EC.

Results: In this study, we identified 1,098 genes induced in esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC), and 669 genes were reduced in EA and ESCC, suggesting that these genes may play an important role in the occurrence and development of EC tumors. Bioinformatics analysis showed that these genes were involved in cell cycle regulation and p53 and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. In addition, we identified 147 induced genes and 130 reduced genes differentially expressed in EA and ESCC. The expression of ESCC in the EA group was different from that in the control group. By PPI network analysis, we identified 10 hub genes, including GNAQ, RGS5, MAPK1, ATP1B1, HADHA, HSDL2, SLC25A20, ACOX1, SCP2, and NLN. TCGA validation showed that these genes were present in the dysfunctional samples between EC and normal samples and between EA and ESCC. Kaplan–Meier analysis showed that MAPK1, ACOX1, SCP2, and NLN were associated with overall survival in patients with ESCC and EA.

Conclusions: In this study, we identified a series of DEGs between EC and normal samples and between EA and ESCC samples. We also identified 10 key genes involved in the EC process. We believe that this study may provide a new biomarker for the prognosis of EA and ESCC.
Expression and Function of Organic Cation Transporter 2 in Pancreas
Authors: Schorn Sandra , Dicke Ann-Kristin , Neugebauer Ute , Schröter Rita , Friedrich Maren , Reuter Stefan , Ciarimboli Giuliano
Published: May 2021

Organic cation transporters (OCT) play an important role in mediating cellular uptake of several pharmaceuticals, such as the antidiabetic drug metformin and the platinum-derived chemotherapeutics. Since these drugs can also affect the pancreas, here it was investigated whether these transporters are expressed in this organ. An interaction between OCT2 and the glucose transporter 2 (GLUT2), which is expressed with important functional consequences in the kidneys and in the pancreas, has already been demonstrated elsewhere. Therefore, here it was further investigated whether the two proteins have a functional relationship. It was demonstrated that OCT2 is expressed in pancreas, probably in β cells of Langerhans islets, together with GLUT2. However, a co-localization was only evident in a cell-line model of rat pancreatic β cells under incubation with high glucose concentration. High glucose stimulated OCT2 expression and activity. On the other side, studies conducted in human embryonic kidney cells stably expressing OCT2, showed that overexpression of GLUT2 decreased OCT2 activity. Unfortunately, pull-down experiments aimed to confirm a physical OCT2/GLUT2 interaction were not successful. Renal glucose excretion was reduced in mice with genetic deletion of OCT2. Nonetheless, in these mice no regulation of known kidney glucose transporters was measured. Therefore, it may be speculated that OCT2 may influence cellular trafficking of GLUT2, without changing its amount. OCT2 may play a role in drug uptake of the pancreas, and its activity may be regulated by glucose and GLUT2. Vice versa, GLUT2 activity may be regulated through an interaction with OCT2.
Photochemical Reactivity of Humic Substances in an Aquatic System Revealed by Excitation-Emission Matrix Fluorescence
Authors: Wang Xin-yuan , Yang Qi-peng , Tian Shi-jie , Song Fan-hao , Guo Fei , Huang Nan-nan , Tan Wei-qiang , Bai Ying-chen
Published: May 2021

The photochemical reactivity of humic substances plays a critical role in the global carbon cycle, and influences the toxicity, mobility, and bioavailability of contaminants by altering their molecular structure and the mineralization of organic carbon to CO2. Here, we examined the simulated irradiation process of Chinese standard fulvic acid (FA) and humic acid (HA) by using excitation-emission matrix fluorescence combined with fluorescence regional integration (FRI), parallel factor (PARAFAC) analysis, and kinetic models. Humic-like and fulvic-like materials were the main materials (constituting more than 90%) of both FA and HA, according to the FRI analysis. Four components were identified by the PARAFAC analysis: fulvic-like components composed of both carboxylic-like and phenolic-like chromophores (C1), terrestrial humic-like components primarily composed of carboxylic-like chromophores (C2), microbial humic-like overwhelming composed of phenolic-like fluorophores (C3), and protein-like components (C4). After irradiation for 72 h, the maximum fluorescence intensity (Fmax) of C1 and C2 of FA was reduced to 36.01–58.34%, while the Fmax of C3 of both FA and HA also decreased to 0–9.63%. By contrast, for HA, the Fmax of its C1 and C2 increased to 236.18–294.77% when irradiated for 72 h due to greater aromaticity and photorefractive tendencies. The first-order kinetic model (R2 = 0.908–0.990) fitted better than zero-order kinetic model (R2 = 0–0.754) for the C1, C2, and C3, of both FA and HA, during their photochemical reactivity. The photodegradation rate constant (k1) of C1 had values (0.105 for FA; 0.154 for HA) that surpassed those of C2 (0.059 for FA, 0.079 for HA) and C3 (0.079 for both FA and HA) based on the first-order kinetic model. The half-life times of C1, C2, and C3 ranged from 6.61–11.77 h to 4.50–8.81 h for FA and HA, respectively. Combining an excitation-emission matrix with FRI and PARAFAC analyses is a powerful approach for elucidating changes to humic substances during their irradiation, which is helpful for predicting the environmental toxicity of contaminants in natural ecosystems.
A Microfluidic Chip-Based MRS Immunosensor for Biomarker Detection via Enzyme-Mediated Nanoparticle Assembly
Authors: Yin Binfeng , Qian Changcheng , Wang Songbai , Wan Xinhua , Zhou Teng
Published: May 2021

Conventional immunoassay methods have their common defects, such as tedious processing steps and inadequate sensitivity, in detecting whole blood. To overcome the above problems, we report a microfluidic chip–based magnetic relaxation switching (MRS) immunosensor via enzyme-mediated nanoparticles to simplify operation and amplify the signal in detecting whole blood samples. In the silver mirror reaction with catalase (CAT) as the catalyst, H2O2 can effectively control the production of Ag NPs. The amount of Ag NPs formed further affects the degree of aggregation of magnetic nanoparticles (MNPS), which gives rise to the changes of transverse relaxation time (T2). Both sample addition and reagent reaction are carried out in the microfluidic chip, thereby saving time and reagent consumption. We also successfully apply the sensor to detect alpha-fetoprotein (AFP) in real samples with a satisfied limit of detection (LOD = 0.56 ng/ml), which is superior to the conventional ELISA.
Nanogold Functionalized With Lipoamide-isoDGR: A Simple, Robust and Versatile Nanosystem for αvβ3-Integrin Targeting
Authors: Sacchi Angelina , Gasparri Anna Maria , Monieri Matteo , Anderluzzi Giulia , Colombo Barbara , Gori Alessandro , Corti Angelo , Curnis Flavio
Published: May 2021

Gold nanoparticles functionalized with isoDGR, a tripeptide motif that recognizes αvβ3 integrin overexpressed in tumor vessels, have been used as nano-vectors for the delivery of cytokines to tumors. Functionalization of nanogold with this peptide has been achieved by coating nanoparticles with a peptide-albumin conjugate consisting of heterogeneous molecules with a variable number of linkers and peptides. To reduce nanodrug heterogeneity we have designed, produced and preclinically evaluated a homogeneous and well-defined reagent for nanogold functionalization, consisting of a head-to-tail cyclized CGisoDGRG peptide (iso1) coupled via its thiol group to maleimide-PEG11-lipoamide (LPA). The resulting iso1-PEG11-LPA compound can react with nanogold via lipoamide to form a stable bond. In vitro studies have shown that iso1, after coupling to nanogold, maintains its capability to bind purified αvβ3 and αvβ3-expressing cells. Nanogold functionalized with this peptide can also be loaded with bioactive tumor necrosis factor-α (TNF) to form a bi-functional nanodrug that can be stored for three days at 37°C or >1 year at low temperatures with no loss αvβ3-binding properties and TNF-cytolytic activity. Nanoparticles functionalized with both iso1 and TNF induced tumor eradication in WEHI-164 fibrosarcoma-bearing mice more efficiently than nanoparticles lacking the iso1 targeting moiety. These results suggest that iso1-PEG11-LPA is an efficient and well-defined reagent that can be used to produce robust and more homogeneous nano-vectors for the delivery of TNF and other cytokines to αvβ3 positive cells.
Gut Microbiota Aberration in Patients of Systemic Sclerosis and Bleomycin-Induced Mice Model
Authors: Tang Jungen , Zhou Xin , Wu Xuefen , Lin Shengyan , Ming Bingxia , Zhong Jixin , Wang Baoju , Dong Lingli
Published: May 2021

Systemic sclerosis (SSc) is an immune-mediated systemic autoimmune disease with unknown etiology, which has high morbidity and mortality. Current treatments to dispose of this disorder are limited. And there are still no ideal animal models that can fully replicate the four basic pathophysiological features of SSc, including vascular lesions, fibrosis, inflammation, and autoimmunity, let alone animal models specifically designed to study gastrointestinal lesions. It’s essential to seek and establish appropriate animal models to explore the role of gut microbiota in the pathogenesis of SSc. In this study, we found similar gut microbiota aberration in patients of SSc and bleomycin (BLM)-induced mice model through 16S rRNA gene sequencing. In terms of phylum-level differences, the relative abundance of Bacteroidetes was significantly decreased and Firmicutes increased in the SSc patients and the mice. Notably, the genera of Lactobacillus, commonly used as a probiotic additive, was also elevated in SSc patients and BLM mice, which was consistent with a few of studies. Therefore, the model can likely mimic the pathological changes of gut microbiota in patients with SSc, which may offer an important potential platform for the in-depth understanding of gut microbiota aberration in patients with SSc and to devise potential disease-modifying treatments.
Osteomyelitis and Septic Arthritis Due to Burkholderia pseudomallei: A 10-Year Retrospective Melioidosis Study From South China
Authors: Wu Hua , Wang Xuming , Zhou Xiaojun , Chen Shaowen , Mai Wenhui , Huang Hui , You Zelin , Zhang Suling , Zhang Xiuxia , Lu Binghuai
Published: May 2021

Burkholderia pseudomallei is the causative agent of melioidosis, endemic mainly in tropical and subtropical areas. Its clinical manifestation is broad ranging from a localized skin lesion to a life-threatening systemic disease. Osteomyelitis and septic arthritis caused by B. pseudomallei
are a rare, fatal illness, whose clinical features have not been illustrated in mainland China. Over 10 years (2010 to 2019), of 334 culture-confirmed melioidosis in Hainan province, China, 44 patients (13.2%) were confirmed to have osteomyelitis and septic arthritis through the combination of clinical features, imaging examination and microbiological culture. Herein, we summarized these 44 patients’ clinical manifestations, demographical features, antibiotic treatment, and outcomes. Of them, osteomyelitis and septic arthritis accounted for 25 (56.8%) and 15 (34.1%), respectively, and 4 patients (9.1%) had both. The gender ratio of male/female was approximately 13.7:1; diabetes mellitus was the most common risk factor (38/44, 86.4%); imipenem and trimethoprim/sulfamethoxazole were the most frequently used antibiotics. Most B. pseudomallei strains were isolated from blood samples (41/44, 93.2%). After surgical handling, antibiotic treatment, or both, 9 patients died, with a mortality rate of 20.5%. In summary, in melioidosis endemic areas, for patients with both localized manifestations of joint and bone and a positive B. pseudomallei
blood culture, increased awareness is required for melioidotic osteomyelitis and septic arthritis.
Could Changing the DNA Methylation Landscape Promote the Destruction of Epstein-Barr Virus-Associated Cancers?
Authors: Sinclair Alison J.
Published: May 2021

DNA methylation at CpG motifs provides an epigenetic route to regulate gene expression. In general, an inverse correlation between DNA hypermethylation at CpG motifs and gene expression is observed. Epstein Barr-virus (EBV) infects people and the EBV genome resides in the nucleus where either its replication cycle initiates or it enters a long-term latency state where the viral genome becomes hypermethylated at CpG motifs. Viral gene expression shows a largely inverse correlation with DNA hypermethylation. DNA methylation occurs through the action of DNA methyl transferase enzymes: writer DNA methyl transferases add methyl groups to specific regions of unmethylated DNA; maintenance DNA methyl transferases reproduce the pattern of DNA methylation during genome replication. The impact of DNA methylation is achieved through the association of various proteins specifically with methylated DNA and their influence on gene regulation. DNA methylation can be changed through altering DNA methyl transferase activity or through the action of enzymes that further modify methylated CpG motifs. Azacytidine prodrugs that are incorporated into CpG motifs during DNA replication are recognized by DNA methyl transferases and block their function resulting in hypomethylation of DNA. EBV-associated cancers have hypermethylated viral genomes and many carcinomas also have highly hypermethylated cellular genomes. Decitabine, a member of the azacytidine prodrug family, reactivates viral gene expression and promotes the recognition of lymphoma cells by virus-specific cytotoxic T-cells. For EBV-associated cancers, the impact of decitabine on the cellular genome and the prospect of combining decitabine with other therapeutic approaches is currently unknown but exciting.
Sponge Takeover from End-Permian Mass Extinction to Early Induan Time: Records in Central Iran Microbial Buildups
Authors: Baud Aymon , Richoz Sylvain , Brandner Rainer , Krystyn Leopold , Heindel Katrin , Mohtat Tayebeh , Mohtat-Aghai Parvin , Horacek Micha
Published: May 2021

The end-Permian mass extinction was the most severe biotic crisis in Earth’s history. In its direct aftermath, microbial communities were abundant on shallow-marine shelves around the Tethys. They colonized the space left vacant after the dramatic decline of skeletal metazoans. The presence of sponges and sponge microbial bioherms has largely gone unnoticed due to the sponges’ size and the cryptic method of preservation. In addition to sponge dominated facies recently described in South Armenia and Northwestern Iran, we describe here sponge-microbial bioherms cropping out in two well-known Permian-Triassic boundary localities: the Kuh-e Hambast section, south-east of Abadeh city and the more distal Shahreza section, near Isfahan. In both sections, the extinction horizon is located at the top of an upper Changhsingian ammonoid-rich nodular limestone, calledParatiroliteslimestone. At Kuh-e Hambast, the overlying decimetric thick shale deposit called “boundary clay,” the latest Permian in age, is conformably overlain by well-dated transgressive basal Triassic platy limestone containing four successive levels of decimeter to meter scale, elongated to form cup-shaped mounds made of branching columnar stromatolites. Sponge fibers from possibly keratose demosponge, are widely present in the lime mudstone matrix. At the Shahreza section, above the extinction level, the boundary clay is much thicker (3 m), with thin platy limestone intervals, and contains two main levels of decimeter to meter scale mounds of digitate microbialite crossing the Permian-Triassic boundary with similar sponge fibers. Three levels rich in thrombolite domes can be seen in the overlying 20 m platy limestone of earliest Triassic age. Sponge fibers and rare spicules are present in their micritic matrix. These sponge fibers and spicules which are abundant in the latest Permian post-extinction boundary clay, followed microbial buildups during the Griesbachian time.
A 3D printing Short Course: A Case Study for Applications in the Geoscience Teaching and Communication for Specialists and Non-experts
Authors: Ishutov Sergey , Hodder Kevin , Chalaturnyk Rick , Zambrano-Narvaez Gonzalo
Published: May 2021

3D printing developed as a prototyping method in the early 1980s, yet it is considered as a 21st century technology for transforming digital models into tangible objects. 3D printing has recently become a critical tool in the geoscience research, education, and technical communication due to the expansion of the market for 3D printers and materials. 3D printing changes the perception of how we interact with our data and how we explain our science to non-experts, researchers, educators, and stakeholders. Hence, a one-day short course was designed and delivered to a group of professors, students, postdoctoral fellows, and technical staff to present the application of 3D printing in teaching and communication concepts in the geoscience. This case study was aimed at evaluating how a diverse group of participants with geoscience and engineering background and no prior experience with computer-aided modeling (CAD) or 3D printing could understand the principles of different 3D printing techniques and apply these methods in their respective disciplines. In addition, the course evaluation questionnaire allowed us to assess human perception of tangible and digital models and to demonstrate the effectiveness of 3D printing in data communication. The course involved five modules: 1) an introduction lecture on the 3D printing methods and materials; 2) an individual CAD modeling exercise; 3) a tour to 3D printing facilities with hands-on experience on model processing; 4) a tour to experimentation facilities where 3D-printed models were tested; and 5) group activities based on the examples of how to apply 3D printing in the current or future geoscience research and teaching. The participants had a unique opportunity to create a digital design at the beginning of the course using CAD software, analyze it and 3D print the final model at the end of the course. While this course helped the students understand how rendering algorithms could be used as a learning aid, educators gained experience in rapid preparation of visual aids for teaching, and researchers gained skills on the integration of the digital datasets with 3D-printed models to support societal and technical objectives.
The Truong Son, Loei-Phetchabun, and Kontum Terranes in Indochina: Provenance, Rifting, and Collisions
Authors: Burrett Clive , Udchachon Mongkol , Thassanapak Hathaithip
Published: May 2021

The three main regions of Indochina are defined as the Truong Son, Loei-Phetchabun, and Kontum terranes. The aim of this review is to integrate numerous petrological studies with sedimentary, palaeontological, and provenance studies in order to construct a preliminary tectonic model which shows the terranes docked in the earliest Carboniferous (Truong Son with Loei-Phetchabun) and in the Permian (Kontum). The Kontum Terrane is characterized by Proterozoic magmatism, mid-Ordovician to Early Devonian granites, and Permian charnockites. Major carbonate platforms developed in the Givetian to earliest Tournaisian on Truong Son and from the Visean to mid-Permian across Truong Son and Loei-Phetchabun terranes. The Truong Son has Silurian granites and a Late Ordovician to Silurian magmatic arc along its southern and western borders caused by subduction of oceanic lithosphere, the remnants of which are now partially preserved in the Loei and Tamky sutures. A region to the east of the Loei Suture in the Loei Foldbelt has a similar-age volcanic arc extending northwards into Laos and is included in Truong Son. A platform-margin coral-stromatoporoid reef developed on Truong Son in the Frasnian and was coincident with a gap in magmatism until the Pennsylvanian with granite magmatism became widespread until the Late Triassic. In the Loei-Phetchabun Terrane, Devonian siliciclastics, volcanics are overlain by Givetian limestones and patch reefs and in turn overlain by Late Devonian to earliest Tournaisian radiolarian cherts and siliciclastics. Tournaisian to early Visean siliciclastic turbidites were coincidental with initial uplift and deformation and were replaced by Visean terrestrial evaporites and coal and marine limestones. Arc magmatism along the Loei-Phetchabun Terrane indicates intermittent eastward subduction from mid-Devonian to mid-Triassic. Carboniferous-Triassic volcanism extends eastward along the northern margin of Cambodia and is probably an extension of Loei-Phetchabun. Ordovician within-plate basalts in Kontum and the transition from shallow marine Ordovician siliciclastics to Silurian deep-marine sediments and a volcanic arc in Truong Son suggest rifting of both terranes from Gondwana in the Late Ordovician. Initial docking of Truong Son with South China was probably in the late Silurian to Early Devonian and docking of Loei-Phetchabun and Truong Son was in the late Tournaisian to early Visean.
Singular Spectrum Analysis of the Total Electron Content Changes Prior to M ≥ 6.0 Earthquakes in the Chinese Mainland During 1998–2013
Authors: Chen Hongyan , Miao Miao , Chang Ying , Wang Qiao , Shen Xuhui , Hattori Katsumi , Han Peng
Published: May 2021

Early studies have shown evidence of the seismo-ionospheric perturbations prior to large earthquakes. Due to dynamic complexity in the ionosphere, the identification of precursory ionospheric changes is quite challenging. In this study, we analyze the total electron content (TEC) in the global ionosphere map and investigate the TEC changes prior to M ≥ 6.0 earthquakes in the Chinese Mainland during 1998–2013 to identify possible seismo-ionospheric precursors. Singular spectrum analysis is applied to extract the trend and periodic variations including diurnal and semi-diurnal components, which are dominated by solar activities. The residual ΔTEC which is mainly composed of errors and possible perturbations induced by earthquakes and geomagnetic activities is further investigated, and the root-mean-square error is employed to detect anomalous changes. The F10.7 and Dst index is also used as criterion to rule out the anomalies when intense solar or geomagnetic activities occur. Our results are consistent with those of previous studies. It is confirmed that the negative anomalies are dominant 1–5 days before the earthquakes at the fixed point (35°N, 90°E) during 0600–1000 LT. The anomalies are more obvious near the epicenter area. The singular spectrum analysis method help to establish a more reliable variation background of TEC and thus may improve the identification of precursory ionospheric changes.
The Value of Pre-Ablative I-131 Scan for Clinical Management in Patients With Differentiated Thyroid Carcinoma
Authors: van der Boom Trynke , Zandee Wouter T. , Dekkers Claire C. J. , van der Horst-Schrivers Anouk N. A. , Jansen Liesbeth , Kruijff Schelto , Brouwers Adrienne H. , Links Thera P.
Published: May 2021

Background

A diagnostic I-131 (Dx) scan is used to detect a thyroid remnant or metastases before treatment of differentiated thyroid cancer (DTC) with I-131. The aim of this study is to specify in which patients with DTC a Dx scan could have an additional value, by studying the effect of the Dx scan on clinical management.

Methods

Patients with DTC, treated with I-131 after thyroidectomy were included in this retrospective cohort study. Twenty-four hours after administration of 37 MBq I-131 a whole body Dx scan and an uptake measurement at the original thyroid bed were performed. Outcomes of the Dx scan and the subsequent changes in clinical management, defined as additional surgery or adjustment of I-131 activity, were reported. Risk factors for a change in clinical management were identified with a binary logistic regression.

Results

In 11 (4.2%) patients clinical management was changed, including additional surgery (n=5), lowering I-131 activity (n=5) or both (n=1). Risk factors for a change in clinical management were previous neck surgery (OR 5.9, 95% CI: 1.4-24.5), surgery in a non-tertiary center (OR 13.4, 95% CI: 2.8 – 63.8), TSH <53.4 mU/L (OR 19.64, 95% CI: 4.94-78.13), thyroglobulin ≥50.0 ng/L (OR 7.4, 95% CI: 1.6-34.9) and free T4 ≥4.75 pmol/L (OR 156.8, 95% CI: 128.4-864.2)

Conclusion

The Dx scan can potentially change clinical management before treatment with I-131, but the yield is low. A Dx-scan should only be considered for patients with a high pre-scan risk of a change in management, based on patient history and prior center-based surgical outcomes.
Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition
Authors: Sarli Polyxeni-Maria , Manousopoulou Antigoni , Efthymiou Elias , Zouridis Andreas , Potiris Anastasios , Pervanidou Panagiota , Panoulis Konstantinos , Vlahos Nikolaos , Deligeoroglou Efthymios , Garbis Spiros D. , Eleftheriades Makarios
Published: May 2021

Background

Fetal growth restriction (FGR) has been associated with adverse perinatal outcomes and epigenetic modifications that impact gene expression leading to permanent changes of fetal metabolic pathways and thereby influence development of disease in childhood and adult life. In this study, we investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups.

Materials & Methods

Ten (n = 10) timed pregnant Wistar rats on their 14th day of gestation were randomly assigned to either control (n = 4) or food restricted group (n = 6). The control group had ad libitum access to food. In the food restricted group, maternal diet was limited in a moderate fashion (50%) from day 15 of pregnancy until delivery. All rats delivered spontaneously on day 21 and newborn pups were immediately weighed. Pups born to normally nourished mothers were considered as controls, while pups born to food restricted mothers were subdivided into two groups, based on their birth weight: growth restricted (FGR) and appropriately grown (non-FGR). Rats were euthanized immediately after birth and liver tissues of 11 randomly selected male offspring (FGR n = 4, non-FGR n = 4, control n = 3) were collected and analyzed using quantitative proteomics.

Results

In total 6,665 proteins were profiled. Of these, 451 and 751 were differentially expressed in FGR and non-FGR vs. control, respectively, whereas 229 proteins were commonly expressed. Bioinformatics analysis of the differentially expressed proteins (DEPs) in FGR vs. control revealed induction of the super-pathway of cholesterol biosynthesis and inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway. Analysis of DEPs in non-FGR vs. control groups showed inhibition of thyroid hormone metabolism, fatty acid beta oxidation, and apelin liver signaling pathway.

Conclusion

This study demonstrates the impact of prenatal food restriction on the proteomic liver profile of FGR and non-FGR offspring underlying the importance of both prenatal adversities and birth weight on liver-dependent postnatal disease.
Comprehensive Profiling Reveals Distinct Microenvironment and Metabolism Characterization of Lung Adenocarcinoma
Authors: Li Chang , Tian Chen , Liu Yangyang , Liang Jinyan , Zeng Yulan , Yang Qifan , Liu Yuting , Wu Di , Wu Jingjing , Wang Juanjuan , Zhang Kai , Gu Feifei , Hu Yue , Liu Li
Published: May 2021

Lung adenocarcinoma has entered into an era of immunotherapy with the development of immune checkpoint inhibitors (ICIs). The identification of immune subtype is crucial to prolonging survival in patients. The tumor microenvironment (TME) and metabolism have a profound impact on prognosis and therapy. The majority of previous studies focused on only one aspect, while both of them are essential to the understanding of tumorigenesis and development. We hypothesized that lung adenocarcinoma can be stratified into immune subgroups with alterations in the TME infiltration. We aimed to explore the “TME-Metabolism-Risk” patterns in each subtypes and the mechanism behind. Glycolysis and cholesterol were selected for the analysis of metabolic states based on the first half of the study. Bioinformatic analysis was performed to investigate the transcriptomic and clinical data integrated by three lung adenocarcinoma cohorts (GSE30219, GSE31210, GSE37745, N = 415). The results were validated in an independent cohort (GSE50081, N = 127). In total, 415 lung adenocarcinoma samples were integrated and analyzed. Four major immune subtypes were indentified using bioinformatic analysis. Subtype NC1, characterized by a high level of glycolysis, with extremely low microenvironment cell infiltration. Subtype NC2, characterized by the “Silence” and “Cholesterol biosynthesis Predominant” metabolic states, with a middle degree infiltration of microenvironment cell. Subtype NC3, characterized by the lack of “Cholesterol biosynthesis Predominant” metabolic state, with abundant microenvironment cell infiltration. Subtype NC4, characterized by “Mixed” metabolic state, with a relatively low microenvironment cell infiltration. Least absolute shrinkage and selection operator (LASSO) regression and multivariate analyses were performed to calculate the risk of each sample, and we attempted to find out the potential immune escape mechanism in different subtypes. The result revealed that the lack of immune cells infiltration might contribute to the immune escape in subtypes NC1 and NC4. NC3 was characterized by the high expression of immune checkpoint molecules and fibroblasts. NC2 had defects in activation of innate immune cells. There existed an obviously survival advantage in subtype NC2. Gene set enrichment analysis (GSEA) and Gene Ontology analysis indicated that the PI3K-AKT-mTOR, TGF-β, MYC-related pathways might be correlated with this phenomenon. In addition, some differentially expressed genes (DEGs) were indentified in subtype NC3, which might be potential targets for survival phenotype transformation.
REW-ISA V2: A Biclustering Method Fusing Homologous Information for Analyzing and Mining Epi-Transcriptome Data
Authors: Zhang Lin , Chen Shutao , Ma Jiani , Liu Zhaoyang , Liu Hui
Published: May 2021

Background: Previous studies have shown that N6-methyladenosine (m6A) is related to many life processes and physiological and pathological phenomena. However, the specific regulatory mechanism of m6A sites at the systematic level is not clear. Therefore, mining the RNA co-methylation patterns in the epi-transcriptome data is expected to explain the specific regulation mechanism of m6A.

Methods: Considering that the epi-transcriptome data contains homologous information (the genes corresponding to the m6A sites and the cell lines corresponding to the experimental conditions), rational use of this information will help reveal the regulatory mechanism of m6A. Therefore, based on the RNA expression weighted iterative signature algorithm (REW-ISA), we have fused homologous information and developed the REW-ISA V2 algorithm.

Results: Then, REW-ISA V2 was applied in the MERIP-seq data to find potential local function blocks (LFBs), where sites are hyper-methylated simultaneously across the specific conditions. Finally, REW-ISA V2 obtained fifteen LFBs. Compared with the most advanced biclustering algorithm, the LFBs obtained by REW-ISA V2 have more significant biological significance. Further biological analysis showed that these LFBs were highly correlated with some signal pathways and m6A methyltransferase.

Conclusion: REW-ISA V2 fuses homologous information to mine co-methylation patterns in the epi-transcriptome data, in which sites are co-methylated under specific conditions.
RETRACTED: “Crisis Within the Walls”: Rise of Intimate Partner Violence During the Pandemic, Indian Perspectives
Authors: Nair Vasundharaa S. , Banerjee Debanjan
Published: May 2021

The ongoing coronavirus disease 2019 pandemic has been a social “un-equalizer,” besides being a global health threat. Gender inequality has been globally prominent during the outbreak and the consequent lockdown. Although domestic abuse and intimate partner violence have increased due to chronic entrapment, overcrowding in families, enhanced substance use, distorted relationship dynamics, travel restrictions, and reduced healthcare access, coercive sexual practices have also been on the rise. In low- and middle-income countries, the lack of awareness, societal pressure, administrative apathy, fear of legal hassles, and inadequate knowledge–attitude–practice related to help-seeking lead to underreporting and mismanagement of domestic abuse, which can perpetuate its vicious cycle during the ongoing crisis. India, with its socio-culturally diverse population, has been one of the nations worst hit by the pandemic. With the rise in reports of gender-based violence on the premise of preexisting gender inequality and minority stress, concerns behind “closed doors” are as threatening as the infection itself. With this background, the authors highlight the backdrop of domestic violence as a “hidden pandemic” during the coronavirus disease 2019 crisis, drawing on perspectives from India and briefly reviewing the data from other nations. The role of mental health education and digital literacy as mitigating strategies is subsequently discussed.
RETRACTED: Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation
Authors: Zhou Jiajun , Yao Mengtian , Zhu Minghui , Li Mengchao , Ke Qiwei , Wu Bing , Wang Daming
Published: May 2021

Fibrosis contributes to graft loss in chronic renal allograft injury. Endothelial‐to‐mesenchymal transition (EndMT) plays an important role in the development of fibrosis following kidney transplantation. Autophagy plays an important role in the homeostasis of diverse cell types including endothelial cells. Here we demonstrate that inhibition of autophagy by treatment with 3-methyladenine (3-MA) or by silencing autophagy-related (ATG)5 promoted interleukin (IL)-6–dependent EndMT in human umbilical vein endothelial cells (HUVECs) and human renal glomerular endothelial cells (HRGECs), and autophagy inactivation was associated with EndMT in patients with chronic allograft dysfunction. IL-6 level was significantly higher in the culture medium of HUVECs transfected with ATG5 siRNA or treated with 3-MA compared to the respective control groups. IL-6 application induced EndMT in HUVECs and HRGECs, whereas antibody-mediated neutralization of IL-6 suppressed EndMT induced by ATG5 silencing. The protective role of curcumin (Cur) against allograft fibrosis was confirmed in a rat kidney transplantation model of F344 donors to Lewis recipients. Curcumin—a natural polyphenol compound with known antifibrotic effects in various tissues—alleviated IL-6–induced EndMT and promoted autophagy in the allografted organ and in HUVECs. This is the first demonstration of the role of autophagy in renal allograft fibrosis; our findings indicate that curcumin can alleviate chronic renal allograft injury by suppressing IL-6–dependent EndMT via activation of autophagy.
Immune Checkpoint Inhibitor-Associated Pneumonitis in Non-Small Cell Lung Cancer: Current Understanding in Characteristics, Diagnosis, and Management
Authors: Zhang Qin , Tang Liansha , Zhou Yuwen , He Wenbo , Li Weimin
Published: May 2021

Immunotherapy that includes programmed cell death-1 (PD-1), programmed cell death- ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors has revolutionized the therapeutic strategy in multiple malignancies. Although it has achieved significant breakthrough in advanced non-small cell lung cancer patients, immune-related adverse events (irAEs) including checkpoint inhibitor pneumonitis (CIP), are widely reported. As the particularly worrisome and potentially lethal form of irAEs, CIP should be attached more importance. Especially in non-small cell lung cancer (NSCLC) patients, the features of CIP may be more complicated on account of the overlapping respiratory signs compromised by primary tumor following immunotherapy. Herein, we included the previous relevant reports and comprehensively summarized the characteristics, diagnosis, and management of CIP. We also discussed the future direction of optimal steroid therapeutic schedule for patients with CIP in NSCLC based on the current evidence.
Integrated Analysis of Omics Data Reveal AP-1 as a Potential Regulation Hub in the Inflammation-Induced Hyperalgesia Rat Model
Authors: Zhu Xiang , Li Feng , Wang Miqun , Su Huibin , Wu Xuedong , Qiu Haiyan , Zhou Wang , Shan Chunli , Wang Cancan , Wei Lei
Published: May 2021

Inflammation-associated chronic pain is a global clinical problem, affecting millions of people worldwide. However, the underlying mechanisms that mediate inflammation-associated chronic pain remain unclear. A rat model of cutaneous inflammation induced by Complete Freund’s Adjuvant (CFA) has been widely used as an inflammation-induced pain hypersensitivity model. We present the transcriptomics profile of CFA-induced inflammation in the rat dorsal root ganglion (DRG) via an approach that targets gene expression, DNA methylation, and post-transcriptional regulation. We identified 418 differentially expressed mRNAs, 120 differentially expressed microRNAs (miRNAs), and 2,670 differentially methylated regions (DMRs), which were all highly associated with multiple inflammation-related pathways, including nuclear factor kappa B (NF-κB) and interferon (IFN) signaling pathways. An integrated analysis further demonstrated that the activator protein 1 (AP-1) network, which may act as a regulator of the inflammatory response, is regulated at both the transcriptomic and epigenetic levels. We believe our data will not only provide drug screening targets for the treatment of chronic pain and inflammation but will also shed light on the molecular network associated with inflammation-induced hyperalgesia.
Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis
Authors: Deng Chong , Peng Na , Tang Yuan , Yu Na , Wang Cuicui , Cai Xiaoyan , Zhang Lijun , Hu Dajun , Ciccia Francesco , Lu Liwei
Published: May 2021

Interleukin-17E (IL-25) is a member of the IL-17 cytokine family that includes IL-17A to IL-17F. IL-17 family cytokines play a key role in host defense responses and inflammatory diseases. Compared with other IL-17 cytokine family members, IL-25 has relatively low sequence similarity to IL-17A and exhibits a distinct function from other IL-17 cytokines. IL-25 binds to its receptor composed of IL-17 receptor A (IL-17RA) and IL-17 receptor B (IL-17RB) for signal transduction. IL-25 has been implicated as a type 2 cytokine and can induce the production of IL-4, IL-5 and IL-13, which in turn inhibits the differentiation of T helper (Th) 17. In addition to its anti-inflammatory properties, IL-25 also exhibits a pro-inflammatory effect in the pathogenesis of Th17-dominated diseases. Here, we review recent advances in the roles of IL-25 in the pathogenesis of inflammation and autoimmune diseases.
Effects of the Invasion of Caulerpa cylindracea in a Cymodocea nodosa Meadow in the Northern Adriatic Sea
Authors: Najdek Mirjana , Korlević Marino , Paliaga Paolo , Markovski Marsej , Ivančić Ingrid , Iveša Ljiljana , Felja Igor , Herndl Gerhard J.
Published: May 2021

Graphical Abstract

Effects of the presence of the invasive macroalgae C. cylindracea in the seagrass meadow evidenced by substantial loss in below-ground biomass of C. nodosa and lowering of the redox transition depth in the sediment underlying the mixed settlement.
Integrating Diel Vertical Migrations of Bioluminescent Deep Scattering Layers Into Monitoring Programs
Authors: Chatzievangelou Damianos , Bahamon Nixon , Martini Séverine , del Rio Joaquin , Riccobene Giorgio , Tangherlini Michael , Danovaro Roberto , De Leo Fabio C. , Pirenne Benoit , Aguzzi Jacopo
Published: May 2021

The deep sea (i.e., >200 m depth) is a highly dynamic environment where benthic ecosystems are functionally and ecologically connected with the overlying water column and the surface. In the aphotic deep sea, organisms rely on external signals to synchronize their biological clocks. Apart from responding to cyclic hydrodynamic patterns and periodic fluctuations of variables such as temperature, salinity, phytopigments, and oxygen concentration, the arrival of migrators at depth on a 24-h basis (described as Diel Vertical Migrations; DVMs), and from well-lit surface and shallower waters, could represent a major response to a solar-based synchronization between the photic and aphotic realms. In addition to triggering the rhythmic behavioral responses of benthic species, DVMs supply food to deep seafloor communities through the active downward transport of carbon and nutrients. Bioluminescent species of the migrating deep scattering layers play a not yet quantified (but likely important) role in the benthopelagic coupling, raising the need to integrate the efficient detection and quantification of bioluminescence into large-scale monitoring programs. Here, we provide evidence in support of the benefits for quantifying and continuously monitoring bioluminescence in the deep sea. In particular, we recommend the integration of bioluminescence studies into long-term monitoring programs facilitated by deep-sea neutrino telescopes, which offer photon counting capability. Their Photo-Multiplier Tubes and other advanced optical sensors installed in neutrino telescope infrastructures can boost the study of bioluminescent DVMs in concert with acoustic backscatter and video imagery from ultra-low-light cameras. Such integration will enhance our ability to monitor proxies for the mass and energy transfer from the upper ocean into the deep-sea Benthic Boundary Layer (BBL), a key feature of the ocean biological pump and crucial for monitoring the effects of climate-change. In addition, it will allow for investigating the role of deep scattering DVMs in the behavioral responses, abundance and structure of deep-sea benthic communities. The proposed approach may represent a new frontier for the study and discovery of new, taxon-specific bioluminescence capabilities. It will thus help to expand our knowledge of poorly described deep-sea biodiversity inventories and further elucidate the connectivity between pelagic and benthic compartments in the deep-sea.
Policy Approaches Toward Combatting Venereal Diseases in the Soviet Occupation Zone in Germany (1945–1949), the German Democratic Republic (1949–1989), and the Polish People's Republic (1945–1989)
Authors: Orzechowski Marcin , Woniak Katarzyna , Schochow Maximilian , Steger Florian
Published: May 2021

The spread of venereal diseases after the Second World War constituted a grave public health danger in Europe. Especially in all four occupation zones in Germany and the Polish People's Republic high morbidity rates were observed. In order to limit the spread of diseases, respective administrations adopted specific regulations. The aim of this research is the analysis and comparison of legal regulations for controlling and combating venereal diseases in these countries. We have analyzed legislative and administrative acts concerning combatting venereal diseases issued by the official organs of the Soviet Occupation Zone, the German Democratic Republic, and the Polish People's Republic from 1945 to 1989. Subsequently, the analyzed sources were evaluated in light of the existing literature on the topic. Our analysis shows that policy approaches in both countries were based the Soviet Union's model for fighting venereal diseases. Visible are similarities of the approaches. They include organization of anti-venereal services, compulsory hospitalization, and actions against social groups perceived as sources of venereal diseases. Beside the purpose of breaking the spread of the epidemics, the approaches had also a political aim of sanctioning behavior that diverged from prescribed socialist moral norms.
Spike in Rhino-Orbital-Cerebral Mucormycosis Cases Presenting to a Tertiary Care Center During the COVID-19 Pandemic
Authors: Fouad Yousef A. , Abdelaziz Tougan Taha , Askoura Anas , Saleh Mohamed Ibrahim , Mahmoud Mohammad S. , Ashour Doaa Maamoun , Ashour Manar Maamoun
Published: May 2021

Objective: To determine if there was an increase in the rate of cases presenting with rhino-orbital-cerebral mucormycosis (ROCM) to a tertiary care center during the first wave of the coronavirus disease 2019 (COVID-19) pandemic and the characteristics of the presenting cases.

Methods: Retrospective observational study reviewing ROCM cases presenting from March 25 until September 25, 2020. Cases fulfilling the clinical, radiological, and pathological/microbiological criteria for diagnosis with ROCM were included. The number of cases presenting during the designated interval, their COVID-19 status, comorbidities, and clinical presentation were analyzed. The number of cases during the corresponding interval in the previous 3 years was used as reference to detect if there was a recent spike.

Results: Of the 12 ROCM cases identified, 5 had a concurrent positive reverse transcription PCR (RT-PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 1 had a prior positive result, and 6 did not have concurrent nor prior positive test results. Nine of the 12 cases had poorly controlled diabetes mellitus, and 2 cases had a hematological malignancy. All cases had orbital invasion, and eight cases had cerebral invasion. The number of cases identified during the interval is much higher than the numbers presenting in the prior 3 years during equivalent intervals (range, one to two cases) than those reported in the literature in different settings in the pre-pandemic era.

Conclusions: There is an increased rate of ROCM cases presenting to our center during the first wave of the COVID-19 pandemic. This is a preliminary report, and further studies are needed to corroborate the findings and explain possible underlying links.