bluuebunny/crossref_metadata_2025 huggingface dataset:
Controversial Role of Transferrin in the Transport of Ruthenium Anticancer Drugs
Authors: Levina Aviva , Chetcuti Anthony R. M. , Lay Peter A.
Published: September 2022

Ruthenium complexes are at the forefront of developments in metal-based anticancer drugs, but many questions remain open regarding their reactivity in biological media, including the role of transferrin (Tf) in their transport and cellular uptake. A well-known anticancer drug, KP1019 ((IndH)[RuIIICl4(Ind)2], where Ind = indazole) and a reference complex, [RuIII(nta)2]3− (nta = nitrilotriacetato(3−)) interacted differently with human apoTf, monoFeTf, or Fe2Tf. These reactions were studied by biolayer interferometry (BLI) measurements of Ru–Fe–Tf binding to recombinant human transferrin receptor 1 (TfR1) in conjunction with UV-vis spectroscopy and particle size analysis. Cellular Ru uptake in human hepatoma (HepG2) cells was measured under the conditions of the BLI assays. The mode of Tf binding and cellular Ru uptake were critically dependent on the nature of Ru complex, availability of Fe(III) binding sites of Tf, and the presence of proteins that competed for metal binding, particularly serum albumin. Cellular uptake of KP1019 was not Tf-mediated and occurred mostly by passive diffusion, which may also be suitable for treatments of inoperable cancers by intratumoral injections. High cellular Ru uptake from a combination of [RuIII(nta)2]3− and Fe2Tf in the absence of significant Ru–Tf binding was likely to be due to trapping of Ru(III) species into the endosome during TfR1-mediated endocytosis of Fe2Tf.
Roles of Two-Component Signal Transduction Systems in Shigella Virulence
Authors: Pasqua Martina , Coluccia Marco , Eguchi Yoko , Okajima Toshihide , Grossi Milena , Prosseda Gianni , Utsumi Ryutaro , Colonna Bianca
Published: September 2022

Two-component signal transduction systems (TCSs) are widespread types of protein machinery, typically consisting of a histidine kinase membrane sensor and a cytoplasmic transcriptional regulator that can sense and respond to environmental signals. TCSs are responsible for modulating genes involved in a multitude of bacterial functions, including cell division, motility, differentiation, biofilm formation, antibiotic resistance, and virulence. Pathogenic bacteria exploit the capabilities of TCSs to reprogram gene expression according to the different niches they encounter during host infection. This review focuses on the role of TCSs in regulating the virulence phenotype of Shigella, an intracellular pathogen responsible for severe human enteric syndrome. The pathogenicity of Shigella is the result of the complex action of a wide number of virulence determinants located on the chromosome and on a large virulence plasmid. In particular, we will discuss how five TCSs, EnvZ/OmpR, CpxA/CpxR, ArcB/ArcA, PhoQ/PhoP, and EvgS/EvgA, contribute to linking environmental stimuli to the expression of genes related to virulence and fitness within the host. Considering the relevance of TCSs in the expression of virulence in pathogenic bacteria, the identification of drugs that inhibit TCS function may represent a promising approach to combat bacterial infections.
Sex-Differences in Pain and Opioid Use Disorder Management: A Cross-Sectional Real-World Study
Authors: Escorial Mónica , Muriel Javier , Margarit César , Agulló Laura , Morales Domingo , Peiró Peiró Ana M.
Published: September 2022

(1) Background: It is essential to focus attention on sex-specific factors which are clinically relevant in pain management, especially with regards to opioid use disorder (OUD) risk. The aim of this study was to explore potential sex-differences in chronic non-cancer pain (CNCP) outpatients. (2) Methods: An observational cross-sectional study was conducted under CNCP outpatients with long-term prescribed opioids (n = 806), wherein 137 patients had an OUD diagnosis (cases, 64% females) and 669 did not (controls, 66% females). Socio-demographic, clinical, and pharmacological outcomes were analyzed. (3) Results: Female controls presented an older age and less intensive pain therapy but higher psychotropic prescriptions and emergency department visits compared to male controls. Meanwhile, cases demonstrated a younger age, higher work disability, double morphine equivalent daily dose, and benzodiazepine use compared with controls. Here, female cases showed an 8% greater substance use disorder (OR 2.04 [1.11–3.76]) and 24% lower tramadol use, while male cases presented a 22% higher fentanyl use (OR 2.97 [1.52–5.81]) and reported the highest number of adverse drug reactions (24%, OR 2.40 [1.12–5.16]) compared with controls. (4) Conclusions: An OUD individual risk profile was evidenced with sex-differences to take into consideration to design equal prevention programs.
Prognostic Role of Post-Induction Fecal Calprotectin Levels in Patients with Inflammatory Bowel Disease Treated with Biological Therapies
Authors: Facciorusso Antonio , Ramai Daryl , Ricciardelli Cristina , Paolillo Rosa , Maida Marcello , Chandan Saurabh , Mohan Babu P. , Domislovic Viktor , Sacco Rodolfo
Published: September 2022

Background: There is currently scarce knowledge about markers of early therapeutic response in patients with inflammatory bowel disease (IBD) treated with biologics. The aim of this study was to evaluate the role of fecal calprotectin (FC) as an early predictor of mucosal healing and clinical remission. Methods: Data from a multicenter series of 172 IBD patients treated with biologics between 2017 and 2020 were analyzed. Treatment outcomes were mucosal healing and clinical remission assessed at 2 years. FC levels were assessed at 14 weeks (post-induction), at 6 months, and yearly. The receiver operating characteristic (ROC) curve analysis was performed to calculate the best cut-off in % change of FC levels between post-induction and baseline predicting treatment outcomes. Sensitivity, specificity, and accuracy for several post-induction FC cut-off points were also calculated. Results: At 2 years, mucosal healing was noted in 77 patients (44.7%), of whom were 41 Crohn’s disease (CD) and 36 ulcerative colitis (UC) patients, whereas 106 patients experienced clinical remission (61.6%), of whom were 59 CD and 47 UC patients. Both baseline and post-induction FC levels were significantly higher in non-responders as compared to responders. On the other hand, FC decrease was less pronounced in non-responders. Similar results were observed in all subgroups, namely according to disease (CD vs. UC), or treatment used (TNF-inhibitors vs. vedolizumab). The best cut-off points were −86% in % change in FC levels to predict mucosal healing and −83% for clinical remission. Conclusions: The current study suggests a predictive role of post-induction FC assessment to predict treatment response in IBD patients treated with biologics.
High Prevalence of Primary Aldosteronism in Patients with Type 2 Diabetes Mellitus and Hypertension
Authors: Tyfoxylou Ernestini , Voulgaris Nick , Gravvanis Chris , Vlachou Sophia , Markou Athina , Papanastasiou Labrini , Tentolouris Nikolaos , Kassi Eva , Kaltsas Gregory , Chrousos George P. , Piaditis George P.
Published: September 2022

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. The prevalence of hypertension is higher in patients with diabetes mellitus-2 (DM-2). Following the limited existing data, we prospectively investigated the prevalence of aldosterone excess either as autonomous secretion (PA) or as a hyper-response to stress in hypertensive patients with DM-2 (HDM-2). A total of 137 HDM-2 patients and 61 non-diabetics with essential hypertension who served as controls (EH-C) underwent a combined, overnight diagnostic test, the Dexamethasone–captopril–valsartan test (DCVT) used for the diagnosis of PA and an ultralow dose (0.3 μg) ACTH stimulation test to identify an exaggerated aldosterone response to ACTH stimulation. Twenty-three normotensive individuals served as controls (NC) to define the normal response of aldosterone (ALD) and aldosterone-to-renin ratio (ARR) to the ultralow dose ACTH test. Using post-DCVTALD and ARR from the EH-C, and post-ACTH peak ALD and ARR from the NC, 47 (34.3%) HDM-2 patients were found to have PA, whereas 6 (10.4%) HDM-2 patients without PA (DCVT-negative) exhibited an exaggerated aldosterone response to stress—a prevalence much higher than ever reported. Treatment with mineralocorticoid receptor antagonists (MRAs) induced a significant and permanent reduction of BP in all HDM-2 patients. Early diagnosis and targeted treatment of PA is crucial to prevent any aggravating effect on chronic diabetic complications.
The Role of Intraamygdaloid Oxytocin and D2 Dopamine Receptors in Reinforcement in the Valproate-Induced Autism Rat Model
Authors: László Kristóf , Vörös Dávid , Kiss Orsolya , László Bettina Réka , Ollmann Tamás , Péczely László , Mintál Kitti , Tóth Attila , Kovács Anita , Zagoracz Olga , Kertes Erika , Kállai Veronika , Berta Beáta , Karádi Zoltán , Lénárd László
Published: September 2022

Background: autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting around 1 out of 68 children and its incidence shows an increasing tendency. There is currently no effective treatment for ASD. In autism research, the valproate (VPA)-induced autism rodent model is widely accepted. Our previous results showed that intraamygdaloid oxytocin (OT) has anxiolytic effects on rats showing autistic signs under the VPA-induced autism model. Methods: rats were stereotaxically implanted with guide cannulae bilaterally and received intraamygdaloid microinjections. In the present study, we investigated the possible role of intraamygdaloid OT and D2 dopamine (DA) receptors on reinforcement using VPA-treated rats in a conditioned place preference test. OT and/or an OT receptor antagonist or a D2 DA antagonist were microinjected into the central nucleus of the amygdala (CeA). Results: valproate-treated rats receiving 10 ng OT spent significantly longer time in the treatment quadrant during the test session of the conditioned place preference test. Prior treatment with an OT receptor antagonist or with a D2 DA receptor antagonist blocked the positive reinforcing effects of OT. The OT receptor antagonist or D2 DA antagonist in themselves did not influence the time rats spent in the treatment quadrant. Conclusions: Our results show that OT has positive reinforcing effects under the VPA-induced autism rodent model and these effects are OT receptor-specific. Our data also suggest that the DAergic system plays a role in the positive reinforcing effects of OT because the D2 DA receptor antagonist can block these actions.
The Influence of SARS-CoV-2 Infection on Lipid Metabolism—The Potential Use of Lipid-Lowering Agents in COVID-19 Management
Authors: Kowalska Klaudia , Sabatowska Zofia , Forycka Joanna , Młynarska Ewelina , Franczyk Beata , Rysz Jacek
Published: September 2022

Several studies have indicated lipid metabolism alterations during COVID-19 infection, specifically a decrease in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) concentrations and an increase in triglyceride (TG) levels during the infection. However, a decline in triglycerides can also be observed in critical cases. A direct correlation can be observed between a decrease in serum cholesterol, HDL-C, LDL-C and TGs, and the severity of the disease; these laboratory findings can serve as potential markers for patient outcomes. The transmission of coronavirus increases proportionally with rising levels of cholesterol in the cell membrane. This is due to the fact that cholesterol increases the number of viral entry spots and the concentration of angiotensin-converting enzyme 2 (ACE2) receptor, crucial for viral penetration. Studies have found that lower HDL-C levels correspond with a higher susceptibility to SARS-CoV-2 infection and infections in general, while higher HDL-C levels were related to a lower risk of developing them. However, extremely high HDL-C levels in serum increase the risk of infectious diseases and is associated with a higher risk of cardiovascular events. Low HDL-C levels are already accepted as a marker for risk stratification in critical illnesses, and higher HDL-C levels prior to the infection is associated with a lower risk of death in older patients. The correlation between LDL-C levels and disease severity is still unclear. However, TG levels were significantly higher in non-surviving severe patients compared to those that survived; therefore, elevated TG-C levels in COVID-19 patients may be considered an indicator of uncontrolled inflammation and an increased risk of death.
Development of New Simple Compositions of Silver Inks for the Preparation of Pseudo-Reference Electrodes
Authors: Camargo Jéssica R. , Fernandes-Junior Wilson S. , Azzi Déborah C. , Rocha Raquel G. , Faria Lucas V. , Richter Eduardo M. , Muñoz Rodrigo A. A. , Janegitz Bruno C.
Published: September 2022

Silver materials are known to present excellent properties, such as high electrical and thermal conductivity as well as chemical stability. Silver-based inks have drawn a lot of attention for being compatible with various substrates, which can be used in the production uniform and stable pseudo-reference electrodes with low curing temperatures. Furthermore, the interest in the use of disposable electrodes has been increasing due to the low cost and the possibility of their use in point-of-care and point-of-need situations. Thus, in this work, two new inks were developed using Ag as conductive material and colorless polymers (nail polish (NP) and shellac (SL)), and applied to different substrates (screen-printed electrodes, acetate sheets, and 3D-printed electrodes) to verify the performance of the proposed inks. Measurements attained with open circuit potential (OCP) attested to the stability of the potential of the pseudo-reference proposed for 1 h. Analytical curves for β-estradiol were also obtained using the devices prepared with the proposed inks as pseudo-references electrodes, which presented satisfactory results concerning the potential stability (RSD < 2.6%). These inks are simple to prepare and present great alternatives for the development of pseudo-reference electrodes useful in the construction of disposable electrochemical systems.
Comparative Analysis of Cell Metabolic Activity Sensing by Escherichia coli rrnB P1-lux and Cd Responsive-Lux Biosensors: Time-Resolved Experiments and Mechanistic Modelling
Authors: Delatour Eva , Pagnout Christophe , Zaffino Marie L. , Duval Jérôme F. L.
Published: September 2022

Whole-cell bacterial sensors are used in medical/environmental applications to detect chemicals, and to assess medium toxicity or stress. Non-specific constitutive biosensors generally serve the latter purpose, whereas chemical detection is performed with biosensors involving a specific chemical-inducible promoter. Herein, we show that functioning principles of specific and non-specific whole-cell biosensors are not exclusive as both can probe modulations of cell metabolic activity under stressing conditions. The demonstration is based on (i) time-resolved measurements of bioluminescence produced by constitutive rrnB P1-luxCDABE Escherichia coli biosensor in media differing with respect to carbon source, (ii) theoretical reconstruction of the measured signals using a here-reported theory for bioluminescence generated by constitutive cells, (iii) comparison between time-dependent cell photoactivity (reflecting metabolic activity) retrieved by theory with that we reported recently for cadmium-inducible PzntA-luxCDABE E. coli in media of similar compositions. Whereas signals of constitutive and non-constitutive biosensors differ in terms of shape, amplitude and peak number depending on nutritional medium conditions, analysis highlights the features shared by their respective cell photoactivity patterns mediated by the interplay between stringent response and catabolite repressions. The work advocates for the benefits of a theoretical interpretation for the time-dependent response of biosensors to unravel metabolic and physicochemical contributions to the bioluminescence signal.
Efficacy of Liquid Embolic Agent Treatment in Hemorrhagic Peripheral Intracranial Aneurysms: A Single-Center Experience
Authors: Zhuang Zong , Zhu Qi , Liu Xun-Zhi , Ling Hai-Ping , Na Shi-Jie , Liu Tao , Zhang Yu-Hua , Hang Chun-Hua , Liu Kai-Dong , Zhang Qing-Rong
Published: September 2022

Objective: To evaluate the efficacy of liquid embolization agents for treating various hemorrhagic peripheral intracranial aneurysms. Methods: We retrospectively analyzed 38 patients who suffered from hemorrhagic peripheral intracranial aneurysms and were treated with liquid embolization agents. We used the modified Rankin scale for follow-up at 6 months postoperatively, and digital subtraction angiography follow-up was performed 6 months postoperatively. Results: Of the 38 patients (ten of simple peripheral intracranial aneurysms, six of Moyamoya disease (MMD), and 22 of arteriovenous malformation (AVM)), posterior circulation accounted for the most significant proportion (57.9%), followed by anterior circulation (21.1%) and intranidal aneurysms (21.1%). Intraoperative hemorrhage occurred in four cases, postoperative cerebral infarction occurred in four cases, two patients encountered microcatheter retention, and intraoperative thrombosis took place in the basilar artery of a patient with an arteriovenous malformation. A postoperative hemorrhage occurred in only one patient. At 6-month follow-up, 84.2% of patients had good prognosis outcomes, and 13.5% had poor outcomes. Conclusion: Liquid embolization agents are effective for hemorrhagic peripheral intracranial aneurysms; however, safety depends on the subtypes. For peripheral hemorrhagic aneurysms in MMD, the vessel architecture must be carefully evaluated before embolization.
Optimization of the Seismic Performance of a Steel-Concrete Wind Turbine Tower with the Tuned Mass Damper
Authors: Yue Yanchao , Li Changxin , Jia Kai , Zhang Yuhang , Tian Jingjing
Published: September 2022

To optimize the seismic performance of a new type of steel-concrete tower, a 120 m steel-concrete composite tower model with a tuned mass damper (TMD) was constructed in ABAQUS for simulation analysis. Firstly, a time history analysis was conducted to study the towers with and without a TMD to determine the difference in their accelerations, velocities, and displacements. Then, a frequency spectrum analysis was performed to determine the tower vibration reduction effect of TMDs with different mass ratios. Five different cases were considered to explore the impact of different layouts on the dynamic performance of the tower. The results showed that the TMD had a significant vibration reduction effect on the tower accelerations, velocities, and displacements. The acceleration was reduced the most, while the vibration reduction effect in the middle of the tower was more significant than that at the top of the tower. For the steel-concrete tower studied in this paper, the optimal mass ratio of TMD was found to be 0.01. Placing one TMD at the top and another in the middle of the tower was found to be the optimal TMD arrangement for tower vibration reduction.
Analysis of Particulate and Microbiological Filtration Performance of Air Handling Unit Filters in a Low-Energy Office Building over 12 Months
Authors: Pavard Gaëtan , Joubert Aurélie , Andrès Yves , Le Cann Pierre
Published: September 2022

Indoor air quality is an important consideration for the health and well-being of building occupants, and the SARS CoV-2 pandemic highlighted the importance of maintaining proper ventilation in buildings. Air handling units (AHUs) are used to provide fresh air and maintain occupant comfort. The objective of this work was to study the evolution of filtration efficiency in an AHU fitted with bag filters, installed to treat office air in a low-energy building, over a 12-month period. The particulate filtration efficiency (PFE) and the microbial filtration efficiency (MFE) were quantified by measuring particle size distribution and bacterial and fungal concentration in the air circulating in the AHU. The resulting microbial concentration measurements in the fresh air (between 10²–103 CFU/m3 for fungi and around 103 CFU/m3 for bacteria) were higher than those in the extracted air from the offices (between 101 and 102 CFU/m3 for fungi and around 102 CFU/m3 for bacteria). The PFE and MFE measured were almost constant throughout the 12 months, with an increase of the filter pressure drop from 70 to 90 Pa. The PFE and MFE were quite comparable for a particle diameter. Therefore, the measurement of PFE is a reliable indicator of the MFE.
LncRNA H19 Promotes Lung Adenocarcinoma Progression via Binding to Mutant p53 R175H
Authors: Zhou Yaodong , Xia Qing
Published: September 2022

Background: Accumulating data suggest that long non-coding RNA (lncRNA) H19 and p53are closely related to the prognosis of lung cancer. This study aims to analyze the association and interaction betweenH19 and mutant p53 R175H in lung adenocarcinoma (LAC). Methods: Mutant-type (Mt) p53 R175H was assessed by using RT-PCR in LAC cells and 100 cases of LAC tissue samples for association with H19 expression. Western blot, RNA-pull down, immunoprecipitation-Western blot and animal experiments were used to evaluate the interaction between H19 and mtp53. Results: Mtp53 R175H and H19 were over-expressed in LAC tissues and cells, while H19 over-expression extended the p53 half-life and enhanced transcriptional activity. Combined with anti-p53, ShH19 can significantly inhibit tumor growth in vivo. Conclusions: H19 over-expression may induce the elevated expression of mtp53 and interact with mtp53, leading to LAC progression. In addition, the high expression of mtp53 R175H is associated with poor overall survival inpatients. The simultaneous inhibition of H19 and mtp53 may provide a novel strategy for the effective control of LAC clinically.
Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples
Authors: Alorda-Clara Marina , Torrens-Mas Margalida , Hernández-López Reyniel , Ibarra de la Rosa Javier M. , Falcó Esther , Fernández Teresa , Company Maria Margarita , Sastre-Serra Jorge , Oliver Jordi , Pons Daniel Gabriel , Roca Pilar
Published: September 2022

Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.
CTRP1 Knockout Attenuates Tumor Progression in A549 and HCT116 Cancer Cells
Authors: Park Rackhyun , Park Yea-In , Park Yeonjeong , Lee Siyun , So Jaeyeon , Park Junsoo
Published: September 2022

C1q and TNF-related 1 (C1QTNF1/CTRP1) is an adiponectin-associated protein belonging to the C1q/TNF-related protein family. Recent studies have shown that the C1q and TNF-related protein (CTRP) family is involved in cancer progression; however, the specific role of CTRP1 in tumor progression has not yet been elucidated. To examine the role of CTRP1 in tumor progression, we generated CTRP1 knockout A549 and HCT116 cell lines, which reduced the expression levels of nuclear factor (NF)-κB-dependent and metastasis-promoting transcripts. We demonstrated that CTRP1 knockout inhibited the cell proliferation and invasion and tumor growth. Finally, database analysis showed that CTRP1 expression was upregulated in metastatic cancers and elevated levels of CTRP1 were associated with poor prognosis. These results suggest that CTRP1 expression contributes to NF-κB signaling and promotes tumor progression.
Preface of the Special Issue “COVID-19 Infection and Hematological Malignancies”
Authors: Chen Mingyi , Anderson Larry D.
Published: September 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020 [...]
Identification of Novel Molecular Subgroups in Esophageal Adenocarcinoma to Predict Response to Neo-Adjuvant Therapies
Authors: Hoefnagel Sanne J. M. , Koemans Willem J. , Khan Hina N. , Koster Jan , Meijer Sybren L. , van Dieren Jolanda M. , Kodach Liudmila L. , van Sandick Johanna W. , Calpe Silvia , del Sancho-Serra Carmen M. , Correia Ana C. P. , Van Berge Henegouwen Mark I. , Gisbertz Suzanne S. , Hulshof Maarten C. C. M. , Mattioli Sandro , Spaander Manon C. W. , Krishnadath Kausilia K.
Published: September 2022

Esophageal adenocarcinoma (EAC) is a highly aggressive cancer and its response to chemo- and radiotherapy is unpredictable. EACs are highly heterogeneous at the molecular level. The aim of this study was to perform gene expression analysis of EACs to identify distinct molecular subgroups and to investigate expression signatures in relation to treatment response. In this prospective observational study, RNA sequencing was performed on pre-treatment endoscopic EAC biopsies from a discovery cohort included between 2012 and 2017 in one Dutch Academic Center. Four additional cohorts were analyzed for validation purposes. Unsupervised clustering was performed on 107 patients to identify biological EAC subgroups. Specific cell signaling profiles were identified and evaluated with respect to predicting response to neo-adjuvant chemo(radio)therapy. We identified and validated three distinct biological EAC subgroups, characterized by (1) p38 MAPK/Toll-like receptor signaling; (2) activated immune system; and (3) impaired cell adhesion. Subgroup 1 was associated with poor response to chemo-radiotherapy. Moreover, an immune signature with activated T-cell signaling, and increased number of activated CD4 T memory cells, neutrophils and dendritic cells, and decreased M1 and M2 macrophages and plasma cells, was associated with complete histopathological response. This study provides a novel molecular classification for EACs. EAC subgroup 1 proved to be more therapy-resistant, while immune signaling was increased in patients with complete response to chemo-radiotherapy. Our findings give insight into the biology of EACs and in cellular signaling mechanisms underlying response to neo-adjuvant treatment. Future implementation of this classification will improve patient stratification and enhance the development of targeted therapies.
Epigenetic Dysregulations in Arsenic-Induced Carcinogenesis
Authors: Islam Ranakul , Zhao Lei , Wang Yifang , Lu-Yao Grace , Liu Ling-Zhi
Published: September 2022

Arsenic is a crucial environmental metalloid whose high toxicity levels negatively impact human health. It poses significant health concerns to millions of people in developed and developing countries such as the USA, Canada, Bangladesh, India, China, and Mexico by enhancing sensitivity to various types of diseases, including cancers. However, how arsenic causes changes in gene expression that results in heinous conditions remains elusive. One of the proposed essential mechanisms that still has seen limited research with regard to causing disease upon arsenic exposure is the dysregulation of epigenetic components. In this review, we have extensively summarized current discoveries in arsenic-induced epigenetic modifications in carcinogenesis and angiogenesis. Importantly, we highlight the possible mechanisms underlying epigenetic reprogramming through arsenic exposure that cause changes in cell signaling and dysfunctions of different epigenetic elements.
Neurofibroma Development in Neurofibromatosis Type 1: Insights from Cellular Origin and Schwann Cell Lineage Development
Authors: Ge Ling-Ling , Xing Ming-Yan , Zhang Hai-Bing , Wang Zhi-Chao
Published: September 2022

Background: Neurofibromatosis type 1 (NF1), a genetic tumor predisposition syndrome that affects about 1 in 3000 newborns, is caused by mutations in the NF1 gene and subsequent inactivation of its encoded neurofibromin. Neurofibromin is a tumor suppressor protein involved in the downregulation of Ras signaling. Despite a diverse clinical spectrum, one of several hallmarks of NF1 is a peripheral nerve sheath tumor (PNST), which comprises mixed nervous and fibrous components. The distinct spatiotemporal characteristics of plexiform and cutaneous neurofibromas have prompted hypotheses about the origin and developmental features of these tumors, involving various cellular transition processes. Methods: We retrieved published literature from PubMed, EMBASE, and Web of Science up to 21 June 2022 and searched references cited in the selected studies to identify other relevant papers. Original articles reporting the pathogenesis of PNSTs during development were included in this review. We highlighted the Schwann cell (SC) lineage shift to better present the evolution of its corresponding cellular origin hypothesis and its important effects on the progression and malignant transformation of neurofibromas. Conclusions: In this review, we summarized the vast array of evidence obtained on the full range of neurofibroma development based on cellular and molecular pathogenesis. By integrating findings relating to tumor formation, growth, and malignancy, we hope to reveal the role of SC lineage shift as well as the combined impact of additional determinants in the natural history of PNSTs.
Surgical and Functional Outcome after Resection of 64 Petroclival Meningiomas
Authors: Wagner Arthur , Alraun Marie , Kahlig Victoria , Dorier Anne-Sophie , Aftahy Amir Kaywan , Bernhardt Denise , Combs Stephanie E. , Gempt Jens , Shiban Ehab , Meyer Bernhard , Negwer Chiara
Published: September 2022

Objective: The management of petroclival meningiomas (PCMs) remains notoriously difficult due to their close association with neurovascular structures and their complex anatomy, hence the surgical paradigm change from radical to functional resection in the past. With this study, we aimed to analyze surgical and functional outcomes of a modern consecutive series of patients with PCMs. Methods: We reviewed patient charts and imaging data of 64 consecutive patients from 2006 to 2018 with a PCM resected at our institution and compared surgical and functional outcomes between subgroups stratified by surgical approach. Results: Females comprised 67.2% of patients (n = 43), with a mean age of 55 years (median 56; range 21–84). Follow-up data were available for 68.8% and reached a mean of 42.3 months (range 1–129) with a median of 28.5 months. The mean tumor diameter was 37.3 mm (standard deviation (SD) 15.4; median 37.0). Infiltration of the cavernous sinus was observed in 34 cases (53.1%), and the lesions affected the brain stem in 28 cases (43.8%). Preoperative cranial nerve palsy was observed in 73.4% of cases; trigeminal neuropathy (42.2%), hearing loss (32.8%), and impairment of vision (18.8%) were the most common. A retrosigmoid approach was employed in 47 cases (78.1%), pterional in 10 (15.6%), combined petrosal in 2 (3.1%), and transnasal and subtemporal in 1 (1.6%). Fifteen cases (23.4%) were resected in a two-staged fashion. Gross total resection (GTR) was attempted in 30 (46.9%) cases without cavernous sinus infiltration and was achieved in 21 (70.0%) of these cases. Surgical complications occurred in 13 cases (20.3%), most commonly meningitis (n = 4; 6.3%). Postoperatively, 56 patients (87.5%) developed new cranial nerve palsy, of which 36 (63.6%) had improved or resolved on last follow up. Achieving GTR was not significantly associated with higher rates of surgical complications (chi-square; p = 0.288) or postoperative cranial nerve palsy (chi-square; p = 0.842). Of all cases, 20 (31.3%) underwent postoperative radiation. Tumor progression was observed in 10 patients (15.9%) after a mean 102 months (median 124). Conclusions: Surgical resection remains the mainstay of treatment for PCMs, with perioperative cranial neuropathies exhibiting favorable recovery rates. Most essentially, the preselection of patients with hallmarks of brain stem affection and cavernous sinus infiltration should dictate whether to strive for a functionally oriented strategy in favor of radical resection.
Pan-Cancer Analysis and Experimental Validation Identify ACOT7 as a Novel Oncogene and Potential Therapeutic Target in Lung Adenocarcinoma
Authors: Zheng Chao , Zhang Guochao , Xie Kai , Diao Yifei , Luo Chao , Wang Yanqing , Shen Yi , Xue Qi
Published: September 2022

Background: Acyl-CoA thioesterase 7 (ACOT7) is of great significance in regulating cell cycle, cell proliferation, and glucose metabolism. The function of ACOT7 in pan-cancer and its capacity as a prognostic indicator in lung adenocarcinoma (LUAD) remains unknown. We intended to perform a comprehensive pan-cancer analysis of ACOT7 and to validate its value in LUAD. Methods: The expression levels, prognostic significance, molecular function, signaling pathways, and immune infiltration pattern of ACOT7 in 33 cancers were explored via systematic bioinformatics analysis. Multivariate Cox regression was applied to construct nomograms to predict patients’ prognoses. Moreover, we conducted in vitro experiments including CCK8, scratch, Transwell, and Matrigel assays to further explore the function of ACOT7 in LUAD. Results: Patients with high ACOT7 expression have notably poorer long-term survival in many cancer types, including LUAD. Further enrichment analyses reveal that ACOT7 is involved in immune cells’ infiltration and is substantially related to the cancer–immune microenvironment. ACOT7 could influence drug sensitivities, including afatinib, gefitinib, ibrutinib, lapatinib, osimertinib, sapitinib, taselisib, and PLX-4720 (all p < 0.01). A nomogram demonstrated a fair predictive value of ACOT7 in LUAD (C-index: 0.613, 95% CI: 0.568–0.658). The proliferation and migration of PC9 cells were significantly repressed when ACOT7 expression was downregulated. Conclusion: As an oncogene, ACOT7 is critical in the tumor microenvironment of pan-cancer and might be a novel therapeutic target for LUAD.
Thermogravimetry Applied for Investigation of Coke Formation in Ethanol Conversion over Heteropoly Tungstate Catalysts
Authors: Verdeş Orsina , Popa Alexandru , Borcănescu Silvana , Suba Mariana , Sasca Viorel
Published: September 2022

Thermogravimetric analysis (TGA) was used to evaluate the thermal stability and the amount of coke deposition resulting from the deactivation of catalysts during ethanol dehydration reaction in a fixed bed continuous flow reactor. In this study, a series of catalysts containing 30% of Pd doped and pure 12-tungstophosphoric acid and its insoluble Cs2.5H0.5PW12O40 salt supported on SBA-15 were prepared. The catalytic efficiency of ethanol dehydration reaction was also evaluated. Two types of coke are identified from the TPO (Temperature programmed oxidation) profiles and assigned to the coke precursor and hard coke, respectively. The results indicate that cesium salts reduced the formation of hard coke. The amount of total coke formed was significantly reduced by supporting the catalysts on mesoporous SBA-15 molecular sieves.
Effective Removal of Refractory Pollutants through Cinnamic Acid-Modified Wheat Husk Biochar: Experimental and DFT-Based Analysis
Authors: Habiba Umme , Mutahir Sadaf , Khan Muhammad Asim , Humayun Muhammad , Refat Moamen S. , Munawar Khurram Shahzad
Published: September 2022

The removal of refractory pollutants, i.e., methylene blue (MB) and ciprofloxacin (CIP), relies heavily on sorption technologies to address global demands for ongoing access to clean water. Because of the poor adsorbent–pollutant contact, traditional sorption procedures are inefficient. To accomplish this, a wheat husk biochar (WHB), loaded with cinnamic acid, was created using a simple intercalation approach to collect dangerous organic pollutants from an aqueous solution. Batch experiments, detecting technologies, and density functional theory (DFT) calculations were used to investigate the interactions at the wheat husk biochar modified with cinnamic acid (WHB/CA) and water interface to learn more about the removal mechanisms. With MB (96.52%) and CIP (94.03%), the functionalized WHB exhibited outstanding adsorption capabilities, with model fitting results revealing that the adsorption process was chemisorption and monolayer contact. Furthermore, DFT studies were performed to evaluate the interfacial interaction between MB and CIP with the WHB/CA surface. The orbital interaction diagram provided a visual representation of the interaction mechanism. These findings open up a new avenue for researchers to better understand adsorption behavior for the utilization of WHB on an industrial scale.
Effect of Modified Alumina Support on the Performance of Ni-Based Catalysts for CO2 Reforming of Methane
Authors: Alreshaidan Salwa Bader , Ibrahim Ahmed A. , Fakeeha Anis H. , Almutlaq Abdulaziz M. , Ali Fekri Abdulraqeb Ahmed , Al-Fatesh Ahmed S.
Published: September 2022

The CO2 reforming of methane to syngas was examined over five different supported catalysts. In this study, 5% Ni was used as the active metal part of the catalyst. To better comprehend the impact of the supports on the catalytic properties, 5% Ni-based catalysts were characterized using nitrogen adsorption–desorption isotherms, XRD, H2-TPR, CO2-TPD, TGA, TPO, FTIR, and Raman. The results showed that the catalyst support with the highest surface area provided the best catalytic activity. The acquired CH4 and CO2 conversions at 700 °C were 58.2% and 67.6%, respectively, with a hydrogen/carbon ratio of 0.85. The TGA investigation of the high-surface-area sample produced a minimum carbon deposition of 11.2 wt.%, and in the CO2-TPD investigation, the high-surface-area sample exhibited the absence of a peak in the strong-basic-sites zone. The formation of NiAl2O4 spinel, moderate basicity, and the high surface area explained the outperformance of the high-surface-area catalyst sample.
Drepmel—A Multi-Omics Melanoma Drug Repurposing Resource for Prioritizing Drug Combinations and Understanding Tumor Microenvironment
Authors: Thompson Zachary J. , Teer Jamie K. , Li Jiannong , Chen Zhihua , Welsh Eric A. , Zhang Yonghong , Ayoubi Noura , Eroglu Zeynep , Tan Aik Choon , Smalley Keiran S. M. , Chen Yian Ann
Published: September 2022

Although substantial progress has been made in treating patients with advanced melanoma with targeted and immuno-therapies, de novo and acquired resistance is commonplace. After treatment failure, therapeutic options are very limited and novel strategies are urgently needed. Combination therapies are often more effective than single agents and are now widely used in clinical practice. Thus, there is a strong need for a comprehensive computational resource to define rational combination therapies. We developed a Shiny app, DRepMel to provide rational combination treatment predictions for melanoma patients from seventy-three thousand combinations based on a multi-omics drug repurposing computational approach using whole exome sequencing and RNA-seq data in bulk samples from two independent patient cohorts. DRepMel provides robust predictions as a resource and also identifies potential treatment effects on the tumor microenvironment (TME) using single-cell RNA-seq data from melanoma patients. Availability: DRepMel is accessible online.
Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization
Authors: Schrenk-Siemens Katrin , Pohle Jörg , Rostock Charlotte , Abd El Hay Muad , Lam Ruby M. , Szczot Marcin , Lu Shiying , Chesler Alexander T. , Siemens Jan
Published: September 2022

Somatosensation, the detection and transduction of external and internal stimuli such as temperature or mechanical force, is vital to sustaining our bodily integrity. But still, some of the mechanisms of distinct stimuli detection and transduction are not entirely understood, especially when noxious perception turns into chronic pain. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. However, it is in particular the access to human pluripotent stem cells and the possibility of generating and studying human sensory neurons that has enriched the somatosensory research field. Based on our previous work, we describe here the generation of human stem cell-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations with different responsiveness to nociceptive stimuli such as capsaicin. Functional as well as deep sequencing analysis demonstrated that one protocol in particular allowed the generation of a mechano-nociceptive sensory neuron population, homogeneously expressing TRPV1. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation. The efficient and homogenous generation of these neurons make them an ideal translational tool to study mechanisms of sensitization, also in the context of chronic pain.
Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update
Authors: Müller Isabel , Alt Philipp , Rajan Suhasini , Schaller Lena , Geiger Fabienne , Dietrich Alexander
Published: September 2022

Our respiratory system is exposed to toxicants and pathogens from both sides: the airways and the vasculature. While tracheal, bronchial and alveolar epithelial cells form a natural barrier in the airways, endothelial cells protect the lung from perfused toxic compounds, particulate matter and invading microorganism in the vascular system. Damages induce inflammation by our immune response and wound healing by (myo)fibroblast proliferation. Members of the transient receptor potential (TRP) superfamily of ion channel are expressed in many cells of the respiratory tract and serve multiple functions in physiology and pathophysiology. TRP expression patterns in non-neuronal cells with a focus on TRPA1, TRPC6, TRPM2, TRPM5, TRPM7, TRPV2, TRPV4 and TRPV6 channels are presented, and their roles in barrier function, immune regulation and phagocytosis are summarized. Moreover, TRP channels as future pharmacological targets in chronic obstructive pulmonary disease (COPD), asthma, cystic and pulmonary fibrosis as well as lung edema are discussed.
Thermal, Physical, and Optical Properties of the Solution and Melt Synthesized Single Crystal CsPbBr3 Halide Perovskite
Authors: Agrawal Kirti , Hasan Syed Mohammad Abid , Blawat Joanna , Mehta Nishir , Wang Yuming , Cueto Rafael , Siebenbuerger Miriam , Kizilkaya Orhan , Prasad Narasimha S. , Dorman James , Jin Rongying , Gartia Manas Ranjan
Published: September 2022

Inorganic lead-halide perovskite, cesium lead bromide (CsPbBr3), shows outstanding optoelectronic properties. Both solution- and melt-based methods have been proposed for CsPbBr3 crystal growth. The solution-based growth was done at low-temperature, whereas the melt-based growth was done at high-temperature. However, the comparison of optical, physical, and defect states using these two different growth conditions has been scarcely studied. Here, we have compared the thermal and optical properties of solution-grown and melt-grown single crystals of CsPbBr3. Positron Annihilation Lifetime Spectroscopy (PALS) analysis showed that melt-grown crystal has a relatively smaller number of defects than the chemical synthesis method. In addition, crystals grown using the chemical method showed a higher fluorescence lifetime than melt-grown CsPbBr3.
Elemental Analysis of V, Mo, Cr, Mn, Al, Ni, and Cu in Steel Alloy with Femtosecond Laser Ablation Spark-Induced Breakdown Spectroscopy
Authors: He Xiaoyong , Yang Qi , Ling Dongxiong , Wei Dongshan , Wang Hongcheng
Published: September 2022

Femtosecond laser ablation spark-induced breakdown spectroscopy (fs LA-SIBS) was developed to quantitatively analyze vanadium, molybdenum, chromium, manganese, aluminum, nickel, and copper in a steel alloy. In the experiment, a femtosecond laser operating at a repetition rate of 1 kHz was used as the laser ablation source, and spark discharge was utilized to re-excite the plasma and enhance the atomic intensity. A compact fiber spectrometer was used to record and analyze the plasma emission spectra in a nongated signal-recording mode. The calibration curves of V, Mo, Cr, Mn, Al, Ni, and Cu elements in steel alloy samples were established, and the detection limits of these elements were determined to be 10.9, 12.6, 4.0, 5.7, 8.7, 7.9, and 3.1 ppm with fs LA-SIBS, respectively, which were 4–12-fold better than those achieved with femtosecond laser-induced breakdown spectroscopy (fs LIBS). Compared with conventional LIBS, the fs LA-SIBS technique provided a rapid and high spatial resolution approach to quantitative elemental analysis, with better analytical sensitivity.
Self-Assembly of Ultrathin Nickel Oxysulfide for Reversible Gas Sensing at Room Temperature
Authors: Ha Nam , Xu Kai , Cheng Yinfen , Ou Rui , Ma Qijie , Hu Yihong , Trinh Vien , Ren Guanghui , Yu Hao , Zhang Lei , Liu Xiang , Zhang Jiaru , Li Zhong , Ou Jian Zhen
Published: September 2022

Two-dimensional (2D) or ultrathin metal sulfides have been emerging candidates in developing high-performance gas sensors given their physisorption-dominated interaction with target gas molecules. Their oxysulfide derivatives, as intermediates between oxides and sulfides, were recently demonstrated to have fully reversible responses at room temperature and long-term device stability. In this work, we explored the micro-scale self-assembly of ultrathin nickel oxysulfide through the calcination of nickel sulfide in a controllable air environment. The thermal treatment resulted in the replacement of most S atoms in the Ni-S frameworks by O atoms, leading to the crystal phase transition from original hexagonal to orthorhombic coordination. In addition, the corresponding bandgap was slightly expanded by ~0.15 eV compared to that of pure nickel sulfide. Nickel oxysulfide exhibited a fully reversible response towards H2 at room temperature for concentrations ranging from 0.25% and 1%, without the implementation of external stimuli such as light excitation and voltage biasing. The maximum response factor of ~3.24% was obtained at 1% H2, which is at least one order larger than those of common industrial gases including CH4, CO2, and NO2. Such an impressive response was also highly stable for at least four consecutive cycles. This work further demonstrates the great potential of metal oxysulfides in room-temperature gas sensing.